Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Medicinteknikdagarna Stockholm, 2013 ABSTRAKT Egentillverkning, ansvar, hur och vem? Session 1B Moderator: Heikki Teriö 2 2 Egentillverkning – En viktig del av innovationsarbetet 1 1 1 1 1 1 2 Jimmy Johansson , Maria Olsson , Lisa Nilsson , Thomas Hajdu , Jörgen Larsson , Anna Grahn 2 Medicinsk teknik, Skånes universitetssjukhus, Lund/Malmö, Sverige. Bild- och funktionsdiagnostiskt centrum Lund, Skånes universitetssjukhus, Lund/Malmö, Sverige. Inledning Möjligheten till tidig klinisk användning av medicinsktekniska produkter är ett viktigt verktyg i landstingens innovationsarbete. Att tidigt kunna använda egentillverkade produkter i begränsad omfattning ökar sannolikheten för att det är slutanvändarens behov som styr utformningen av framtidens produkter. Positivt resultat från den begränsade kliniska användningen ökar produktens trovärdighet längs den ofta krokiga vägen genom olika innovationssystem och minimerar de ständigt återkommande frågorna om hur vidare det finns ett reellt behov eller ej. Bakgrund Medicinsk teknik vid Skånes universitetssjukhus har sedan ett tiotal år tillbaka arbetat med egentillverkning inom elektronik och finmekanik i stor utsträckning. Det har funnits rutiner och mallar för riskhantering och uppfyllandet av väsentliga krav men det har saknats fullständiga processer för t.ex. produktutveckling samt en övergripande kvalitetsmanual. Under åren 2008-2011 ökade antalet projekt inom medicinteknisk mjukvara avsevärt och arbetet med att hitta effektiva metoder för detta inledes. Vi uppmärksammade att de flesta regulatoriska aktiviteterna genomfördes precis innan driftsättning, vilken inte bara ger en obalans i arbetsbelastning utan även minskar möjligheten att förbättra produkten utifrån t.ex. riskanalysens resultat. Vi såg därmed över ordningsföljden för de övergripande aktiviteterna och framförallt riskhanteringsprocessen som ofta förbrukar mycket resurser. Under arbetet med att skapa effektivare processer för riskhantering och användbarhet använde vi ett projekt som tog fram en applikation för beräkning och presentation av blodflöde i hjärnan som pilot där en professor och två doktorander från Lunds Tekniska Högskola följde och studerade analysarbetet. Resultatet har publicerats i tre artiklar1,2,3 och använts för att förbättra processerna för riskhantering och användbarhet på Medicinsk teknik. Utveckling Till följd av att Medicinsk teknik utökat sin verksamhet inom forskning och utveckling och nu leder eller medverkar i flertalet stora forsknings- och utvecklingsprojekt har det varit möjligt och tvunget att lägga ännu större fokus kvalitetsarbetet. Nyligen har upprättandet av ett fullständigt kvalitetsledningssystem för utveckling av medicintekniska produkter enligt ISO13485 avslutats. Detta arbete gjordes stegvis genom inledande utbildningsinsatser inom vår verksamhet, därefter i form av praktiskt genomförande i mindre skala samt analys av ett företags ISO-certifierade ledningssystem. Slutligen upprättade en mindre grupp bestående av processanvariga och slutanvändare ett fullständigt ledningssystem som ska passa väl in vår verksamhet. Ledningssystemet innehåller alla tillämpliga processer men pekar i så stor utsträckning som möjligt på befintliga rutiner inom verksamheten. Processen för användarvänlighet och utveckling av medicinteknisk programvara, enligt EN 62366 respektive EN 62304, har t.ex. använts inom det VINNOVA-finansierade projektet ”IT-stöd för Avancerad Cancervård i Hemmet” där stort fokus lagts på användarvänlighet och det har genomförts aktiviteter med både vårdpersonal och patienter. Det fortsatta arbetet med ledningssystemet på Medicinsk teknik kommer inrikta sig på att lägga respektive projekt på korrekt nivå samt att utbildning av berörda medarbare sker i den takt som krävs. Resultat och slutsatser Ledningssystem ger universitetssjukhuset kontroll över egentillverkade produkter och öppnar upp för innovativt arbete i flera olika projekt. I projektet ”IT-stöd för Avancerad Cancervård i Hemmet” har flera mindre delar av det medicintekniska systemet tagits i kliniskt bruk. I flera fall har den kliniska användningen endast varit ett mellansteg för att få feedback för den framtida utvecklingen. T.ex. används teknik, som i framtiden är tänkt att flyttas hem till patienterna, kliniskt inom sjukhuset. Det kan även handla om begränsad användning där man har bra kontroll på utbildningsgrad osv. Därmed kan man på ett säkert och relativt tidigt stadium få återkoppling på produktens utformning och prestanda från tänkta slutanvändare. Medicinsk teknik verksamhet inom forskning och utveklings stödjer även regionens innovations- och testbäddsverksamhet med detta arbetssätt, vilket med stor sannolikhet medför att fler och bättre produkter når marknaden och därmed tillgodoser fler användare och patienters behov. 1 "A Case Study on Software Risk Analysis and Planning in Medical Device Development" ”Introducing Usability Testing in the Risk Management Process in Software Development” 3 "A Case Study on Software Risk Analysis in Medical Device Development" 2 3 Ehälsa/IKT I Session 2B Moderator: Bengt Arne Sjöqvist 4 2B2 E-Health in Developing Countries to Manage illnesses through Patient Education and Empowerment of Rural Health Workers Mannan Mridha1, Björn Erik Erlandsson1, Mohammad Islam2, Mandalika B. Srinivas3 1 School of Technology and Health, the Royal Institute of Technology, Stockholm, Sweden 2 BSM Medical University, Dhaka, Bangladesh 3 Birla Institute of Technology and Sciences, BITS, Hyderabad, India 1 Introduction In developing countries, the vast majority of the people are living in the rural areas with limited access to quality care. In fact, village doctors with limited training, community health workers, unqualified allopathic providers and drug store sales people are largely responsible for providing the rural medical care. Severe sufferings and increased healthcare cost of the patients are caused due to either inadequate information, choice of drugs and treatment strategies etc. Some relatively well to do rural patients go the cities for medical care. The private hospitals and clinics offer adequate services but are out of reach for the common people. The government hospitals and clinics are affordable for all but offer poor quality services. Most of the medical equipment are imported but often do not function effectively due poor quality of service and maintenance Physicians order expensive and sometimes unnecessary investigations because they receive incentives for their referrals from the diagnostic centers. Doctors' tendency to prescribe fashionable and expensive drugs or irrational drugs with limited therapeutic value is also of concern for patients’ care and safety. Currently a burning question is how to bring a rapid improvement for rural people in the developing countries that have no or limited access to safe health care? The application of Internet and Communication Technology, ICT in healthcare is growing rapidly in an attempt to find cost effective solutions for providing quality healthcare (1). We are working with the integration of smart, affordable medical devices with telemedicine using modern ICT tools, for improving the rural health care situations (2). 2 Method The rural people depend on village doctors and paramedics. But they have limited capacity for providing relevant healthcare. In order to improve health care facilities and achieve health equity and patient safety, we together with the local partners are using Innovative, Relevance, Acceptability, Affordability and Effective ICT tools to address some of the health problems in rural areas. We are working to improve rural health workers’ capacity, quality and performance by creating enabling environment to provide services that are. Our actions include development of a) reliable, robust and cost effective medical devices, b) proper education and training to use the diagnostic equipment, c) connectivity to the medical experts for disease prevention and treatment advice and d) health education to teach how to prevent and treat health problems which routinely afflict them. We have developed and deployed reliable and affordable diagnostic devices integrated with the communication systems and have developed care services nearest to the homes that have the capacity to diagnose the common chronic illnesses, formulate in consultation with distant specialists a Home-care Plan, follow-up care, identify secondary risks and make referrals. We have also initiated to organize Health Clubs to create scope for collective approach for management of these illnesses that ensures access and patient education and empowerment. Female health worker are visiting rural women at the homes with: i) relevant and user-friendly health care content to educate to manage health, ii) portable and affordable diagnostic and iii) communication platform to connect the health workers and patients with medical experts for advice. 3 Results We find our model of e-Health activities to be appropriate for India and Bangladesh and believe to be suitable for other resource-constrained countries. Rural people find great satisfaction from the face to face video-consultation with the medical experts. They appreciate the just in time, cost-effective and quality treatment without any need for travelling. This has greatly reduced the earlier errors due to wrong diagnosis or wrong medication or too much medication for a too long time. Some other positive impacts of our work are: a) Better monitoring of the progress of health programmes and achievements of health MDGs. b) Increased understanding of the importance of e-Health by the policy-makers c) Rural doctors and paramedics benefit from a satisfying professional experience thanks to connectivity to medical experts and avoiding harmful mistakes. This rural e-Health service decreases their professional isolation, reduce number of unnecessary referrals and facilitate for continuous education and empowerment, d) A creative environment of health around the Point of Care to strengthen the confidence of the community for seeking health and start sharing the responsibility of health care by all stake holders; 4 Discussions While working with ICT tools for empowering the rural people in Bangladesh and India, some of the challenges that we faced include, unreliability of electricity supply, weak internet backbone, high internet access cost, financial constraints preventing the purchase of an appropriate number and type of ICT equipment, unavailability of adequate number of computer-literate employees to implement e-health programme, resistance to changes. Work should be intensified to: a) raise awareness of existing e-Health tools and services, b) develop an knowledge exchange network to share practical experiences on the application and impact of e-Health initiatives, c) create an e-Health information resource to support the needs of the rural people and d) promote the use of e-Learning for rural health workers and rural people. Acknowledgment: This work was financially supported by the Swedish International Development Agency, SIDA. References [1] Chandrasekhar, C.P. and Ghosh, J. “Information and communication Technologies and health in low income countries: the potential and the constraints”. Bull World Health Org 79(9): 850-855, 2001 [2] Mridha M. and Pehrson Björn, “To develop a telemedicine system to improve remote diagnoses and to deliver cost effective, better quality specialist services in developing countries”, International conference on Wide Open Access, 2004, Stockholm, Sweden. 5 2B3 A cross-sectional pilot study assessing needs and attitudes to implementation of Information and Communication Technology for rational use of medicines among healthcare staff in rural Tanzania Jessica Nilseng, Lars L Gustafsson, Amos Nungu, Pia Bastholm-Rahmner, Dennis Mazali, Björn Pehrson, Jaran Eriksen In resource-poor countries access to essential medicines, and suboptimal prescribing and use of medicines are major public health problems. Health workers lack updated medical information and treatment support. Information and Communication Technology (ICT) could help tackle this. The impact of ICT on health systems in resource-poor countries is likely to be significant and transform the practice of medicine just as in high-income countries. However, research for finding the best way of doing this is needed. We assessed current approaches to and use of ICT among health workers in two rural districts of Tanzania in relation to the current drug distribution practices, as well as assessing the feasibility of using ICT to improve ordering and use of medicines. This pilot study was conducted in 2010-2011, mapping the drug distribution chain in Tanzania, including its problems and barriers. The study was conducted in Bunda and Serengeti districts, both part of a nationally supported ICT for rural development project. Health workers involved in drug procurement and use at 13 health facilities were interviewed on use of and knowledge about ICT, and their attitudes to its use in their daily work. They were also showed a potential ICT tool. This tool was a prototype application for android tables developed at the KTH Royal Institute of Technology in Stockholm. It consisted of two parts; inventory of drug stock and drug ordering, based on the Tanzanian Medical Stores Department (MSD) current paper forms. Interviewees reported stable drug supply as their main challenge: Drug supplies were often delayed and incomplete, resulting in stock-outs of essential medicines and equipment. The 20 interviewed health workers all used mobile phones, 8 of them Smartphones that they connected to the Internet. All were very positive to the drug tracking application, and expressed a great need and wish for continuous medical education by distance. New ways to order and distribute drugs, and support their use with updated knowledge are increasingly needed as soaring medicine costs and chronic diseases add to the burden on health systems. This makes it important to test and evaluate how simple ICT-technology integrated into the health-care system can improve the quality of drug ordering, distribution and use in rural parts of Africa. Studying this in a systematic way is pertinent, e.g. using the Technology Acceptance Model (TAM). 1 6 6 2B4 Exploring the potential of mobile phone and web based technology to promote the Sexual & Reproductive Health of high school aged youths in Zimbabwe 1 1 2 3 Comfort Sithole , Leif Sandsjö , Bengt Arne Sjöqvist 3 M.Sc. Chalmers Univ. Of Technology. Assist. Prof. Medtech West/School of Engineering, University of Borås. Prof. of Practice, Dept. of Signals & Systems, Chalmers Univ. Of Technology 2 1. Introduction and Background Telemedicine or eHealth by definition encompasses the communication of health practices via technology, and the advent of the internet and mobile phone technology brought seemingly endless possibilities for telemedicine. Such technologies may be instrumental to promote health in hard to engage groups, especially young people, as interventions that make use of the internet tend to influence young people as they frequently use the internet to find information pertaining to their health. Generally, youths are put off by more traditional means of engaging with health care services, and this applies more so to accessing Sexual and Reproductive Health (SRH) services. The general consensus is that most youths appreciate the anonymity, confidentiality and convenience factors associated with accessing SRH information from the internet. 2. Aim, Method and Results This work, undertaken as a Master Thesis, is aimed at systematically exploring the potential that is offered by mobile phone technology in promoting the Sexual & Reproductive Health of high school aged youths in Zimbabwe. Youth SRH services are sparsely available in Zimbabwe and the exploitation of available and future technologies in youth SRH services has not been widely explored. The use of mobile phones in Zimbabwe is on the rise and broadband internet is becoming widely available, thus this technology can be utilized efficiently to offer services that are aimed at accurately informing the young people of Zimbabwe about their sexual and reproductive health. From the research carried out, only 10% of youths had accessed available SRH services, but given that 97% and 86% of survey participants have access to a mobile phone and the internet respectively, it would suggest that employing an SRH intervention that exploits this readily available media would be more effective. Taking into account perspective user requirements and the technological environment in Zimbabwe, the Youth Sex Health Online (YSHO) web-based SRH clinic and the complimentary Just Ask! Text messaging services were designed. YSHO is aimed at being a non-commercial one-stop shop for all adolescent SRH needs that meets identified needs in a relevant, efficient and effective manner. 3. Conclusion Feedback on the mock-up of proposed services suggests that the proposed service is effective and of particular benefit to its intended users. This work has shown that eHealth applications offer solutions to existing needs. The need for a relevant and effective youth SRH service was identified in Zimbabwe, with so many teens seemingly unsure about where to access vital information about their SRH needs. By making use of web-based and mobile phone technology that is readily available to these youths, YSHO as an eHealth application offers a solution to the need. Even though the state of eHealth in Zimbabwe is in its infancy stage, it can be suggested that investing in a national eHealth strategy and solutions like YSHO would invariably lead to a decrease in state spending in addressing some health issues. Keywords: Sexual & Reproductive Health, technology in youth SRH services, eHealth in developing countries, web-based clinic, text messaging service, mobile phone application. 7 2B5 M-Health Application Product Development for Physiological Disorders Based on Interaction Design Helen Sørheim 1, B.Sc., Ankica Babic 1,2, Ph.D. 1. Institute for Information and Media Science, University of Bergen, Norway 2. Department of Biomedical Engineering, Linkoping University, Sweden Introduction: The paper identifies a multidisciplinary nature of the team work needed to put in place to reassure project, design and product development that could meet needs of patients and health care givers and sustain upgrades and future development. The project is focused on patients with severe conditions such as schizophrenia in which constant monitoring and support is central to the patient well-being. There are two aspects that the development should follow: self-monitoring in stabile periods and instant help in cases of crises. Background: System development is strongly based on interaction design using input of all stakeholders (patients, patient groups, care givers, health and patient networks). It takes into account existing healthcare tools (treatment and crisis plan) and well-established treatment approaches which help utilizing good clinical resources known to all involved stakeholders. Methods & Expected Results: The Figure 1 presents the product development phases that were used as one of the development tools besides scientific and clinical ones. Figure 1 includes key activities, resources, partners and values, customer relationships and segments, channels, cost structure and revenue streams, which is identified by Osterwalder, Pigneur and Tucci (2005). Figure 1: Application business model Discussion: We have studied the business perspective of the application to sustain the product life in a demanding clinical reality. We have identified the strength of having multiple stakeholders involved from the very beginning and made the user input central to the application product development. Literature: Osterwalder, A., Pigneur, Y., & Tucci, C. L. 2005. Clarifying business models: Origins, present and future of the concept. Communications of the Association for Information Science (CAIS), 16: 1-25. 8 8 2B6 IT-baserad hemvård av djur med hjärtfel 2 1 Clarence Kvart1, Anna Gund , Andreas Wahl3 2 SLU, Uppsala, Sweden. Chalmers Göteborg, Sweden, 3Karlstads djursjukhus, Sweden 1. Introduktion Studiens målsättning var att utvärdera om ett internetbaserat system benämt Petheart utvecklat från ”Care at Distance” (Gund 2008,2011) kunde användas för att förbättra vården av hjärtsjuka hundar och katter. Detta med huvudsyfte att på ett tidigare stadium kunna upptäcka en hälsoförsämring samt visa om eftersträvad effekt uppnås vid behandling och medicinering av hjärtsvikt. 2. Metod Systemet som används i studien är internetbaserat och består av en webportal som kan nås från datorer och även nyare mobiltelefoner som har tillgång till internet. Genom att logga in på webbportalen med sitt användarnamn och lösenord kan djurägarna föra in sitt djurs mätvärden angående puls och andningsfrekvens samt svara på hälsorelaterade frågor. Väl inloggade på webbportalen kan både djurägare och vårdgivare i en spalt till vänster välja att klicka sig vidare till ett flertal olika sidor. Djurägarna kan här välja fliken ” Lägg in ditt djurs data” för att föra in resultat från mätningar men också besvara frågor samt fliken ”Dialog” för att kontakta vårdgivaren om de har några frågor gällande systemet eller sitt djurs hälsa. Här finns även ett hjälpavsnitt där djurägarna i text och bilder instrueras hur de på enklaste sätt utför mätningarna hemma. Fliken ”Dialog” kan även nyttjas av vårdgivaren för att kontakta djurägaren om systemet indikerar en försämring av djurets hälsa. Inlagd data skickas över internet till en databas där den lagras. Väl lagrad kan vårdpersonal och även djurägare när som helst genom att logga in på webbportalen få tillgång till informationen. I studien ingick totalt 26 patienter, varav 17 hjärtsjuka och 9 friska individer . Samtliga djurägare hade deklarerat att de ville delta i studien och mottagit information om dess utformning. Bild 1. Exempelbild av grafer över valda fysiologiska parametrar. Andnings- och hjärtfrekvens är uppmätt och visas per 20 sekunder. Genom att markera en viss punkt på grafen erhålls inrapporterade värden aktuell dag i rutan till höger i bilden 3. Resultat och diskussion PetHearts höga acceptans och användande bland djurägarna i studien i kombination med möjligheterna till bättre hälsoövervakning och kommunikation indikerar att det skulle kunna vara ett bra komplement vid vård av hjärtsjuka hundar och katter.PetHeart bidrar till att en hälsoförsämring hos hjärtsjuka katter och hundar kan upptäckas i ett tidigare skede, vilket bidrar till en ökad livskvalitet, bl.a. genom att behov av att initiera eller justera medicinering kan upptäckas tidigt. Andningsfrekvensen är den bästa enskilda parametern för att upptäcka hjärtsvikt. PetHeart skapade en ökad trygghet bland djurägare till hjärtsjuka hundar och katter. En synnerligen intressant användning av systemet var att djurägare fick rapportera sitt djurs data dagligen vid ändring av hjärtmedicinering för att kunna kontrollera effekt på hälsotillståndet på distans. Speciellt användbart är detta vid utsättning av en medicinering som bedöms att sannolikt vara onödig eller insatt på felaktiga grunder. Med hjälp av det beskrivna systemet kan man lättare, även i poliklinisk verksamhet, våga sätta ut pågående medicineringar. Detta då en god kontroll av responsen kan erhållas på distans. Ett ”Care at Distance” system, som det ovan beskrivna, kan ge ökat kurage hos veterinärer och läkare att våga sätta ut medicineringar som ej gör någon nytta men kanske försämrar patientens hälsotillstånd och livslängd. Det beskrivna systemet skulle kunna göra stor samhällsnytta om det utvecklades och kom till utbredd användning. References [1] Gund, A. (2011) On the Design and Evaluation of an eHealth System for Management of Patients in Out-of-Hospital Care. Diss. Göteborg: Chalmers Tekniska Högskola. [2] Gund, A. (2008) Design of an Internet-Based Disease Management System for Chronic Heart Failure. Akad.lic. avh. Göteborg: Chalmers Tekniska Högskola 9 Sammanfattningar Diagnos och behandling Session 4B Moderator: 10 10 4B1 CEREBRAL BIOIMPEDANCE SPECTROSCOPY: STEPS TOWARDS STROKE DETECTION 1 Seyed Reza Atefi1, Fernando Seoane1,2, Kaj Lindecrantz1,3 KTH Royal Institute of Technology ,Huddinge , Sweden, 2University of Borås, Borås, Sweden. 3 Karolinska institutet, Stockholm, Sweden3 1. Introduction Following cancer and cardio-vascular disease stroke is considered as the third cause of death world-wide [1]. Considering the limitations of the most widely used diagnostic technologies for stroke detection, in particular imaging modalities, the need for portable non-invasive and less expensive diagnosis technologies that will fill the gap between current clinical routines and patient needs leading to faster and better treatment outcome is crucial. Earlier studies have demonstrated that electrical bioimpedance spectroscopy (EBIs) measurements from the cerebral tissue contain useful clinical information related to changes imposed to the cerebral tissue after the onset of the stroke [2] making EBIS a suitable candidate for this purpose. 2. Method 720 EBI measurements were collected from two different volumes ( Mc Central and larger, ML lateral and smaller) of 18 hemispheres of 9 subjects, three of whom suffering from unilateral stroke. These measurements were fitted into the Cole function consisting of four parameters R0, resistance at DC, R∞, resistance at frequency infinity, α and fc i.e. the characteristic frequency.. Based on Cole parameters, structural and intrinsic frequency dependent properties of the cerebral tissue reported to be altered after the onset of stroke a number of features are extracted [3], see table 1. Later on these features are fed into a tree classifier to evaluate the possibility of stroke detection based on these features. Feature1 Table 1 Features Feature2 Feature 3 ( ( ⁄ ⁄ ) ) 3. Results Final results with high degree of accuracy shows that after three hierarchical classification steps using the tree classifier a full classification of healthy and damaged cerebral tissue is achieved. Feature 2 Feature 3 Feature 1 Figure 1 Classification tree, at each node a threshold based on the features is applied and results are in leaves of the tree 4. Conclusion Using three features originated from the spectral information and geometry dependency of electrical bioimpedance data based on Cole parameters and a simple classification tree, an accurate classification between healthy brain hemispheres and stroke damaged ones has been performed. Despite the small size of the database available these results are sufficient to show that bioimpedance spectroscopy contains useful information to asses on stroke brain damage. References [1] G. A. Donnan, M. Fisher, M. Macleod, and S. M. Davis, "Stroke," Lancet, vol. 371, pp. 1612-23, May 10 2008. [2] G. Bonmassar, S. Iwaki, G. Goldmakher, L. M. Angelone, J. W. Belliveau, and M. H. Lev, "On the Measurement of Electrical Impedance Spectroscopy (EIS) of the Human Head," Int J Bioelectromagn, vol. 12, pp. 32-46, Jan 1 2010. [3] S. R. Atefi, F. Seoane, and K. Lindecrantz, "Electrical Bioimpedance cerebral monitoring. Preliminary results from measurements on stroke patients," in Engineering in Medicine and Biology Society (EMBC), 2012 Annual International Conference of the IEEE, 2012, pp. 126-129 11 4B2 TOWARDS AMBULANCE BASED STROKE DIAGNOSTICS Mikael Persson1,4, Andreas Fhager1,4, Hana Dobsicek Tréfna1,4, Yinan Yu1, Tomas McKelvey1, Göran Pegenius2, Jan-Erik Karlsson3, Mikael Elam2,3,4 1 2 3 4 Signal Processing and Biomedical Engineering, Dept. of Signals and Systems, Chalmers University of Technology, Göteborg, Sweden Inst of Neuroscience and Physiology, Dept. of Clinical Neurophysiology, Sahlgrenska Academy, Göteborg University, Sweden Neuro-division, Sahlgrenska University Hospital, Göteborg, Sweden MedTech West, Göteborg, Sweden 1. Introduktion Around 15 million people suffer a stroke each year. The global cost of stroke is hard to assess but the total European cost has been estimated to 64.1 billion € per year. The human cost of stroke is horrific with 5 million deaths/year and another 5 million are permanently disabled. Most stroke patients are not receiving optimal treatment. The majority of these are Ischemic stroke patients and should ideally receive acute thrombolytic treatment, dramatically reducing or abolishing symptoms. Today, less than 5% of these patients reach diagnosis and treatment in time, mainly due to long lead times in transport to and from the diagnostic instruments. Such treatment must be initiated within 4.5h after stroke onset, preceded by safe differentiation of haemorrhagic vs. ischemic stroke since thrombolysis can severely aggravate a haemorrhagic condition. Today this requires brain scans, calling for hospitalization before treatment. In a close collaboration between biomedical engineering, signal processing and medical scientists we have developed a system for screening patients for the presence, location and size of an intracranial haemorrhage with the ambition to create a device that could be used upon arrival in the emergency room, or by ambulance personnel at the scene of incident. 2. Methods The technology developed is a result of a long-term project dealing with microwave propagation in human tissues. The simplicity and size of a microwave-based diagnostic system underlined the possibility of creating an ambulance-based pre-hospital diagnostic system for stroke patients. The system, shown in the picture to the right, further has the advantage of being completely safe and without side effects since the power levels used are only a fraction of what is transmitted by a mobile phone. The stroke detection system consisted of antennas sending and receiving microwave signals, mounted on a helmet-like supporting structure. In order to provide a comfortable fit of the system, patch antennas with a flat surface facing the skull were used. These antennas had a rectangular shape with the radiating metallic structure of the antennas in the form of isosceles triangle with a height of 37 mm and a width of 25 mm, printed on the surface facing the skull. A total of 12 antennas were used and distributed uniformly over the surface of the skull to ensure good coverage of the brain. To accommodate varying skull sizes shapes of the patients, containers of soft plastic were placed between skull and antennas and filled with water to fill the gap. The use of the plastic containers ensured a good electromagnetic coupling between the antennas and the skull. In the measurement procedure each antenna is consecutively used as a transmitter, with all remaining antennas in receive mode. In total 66 independent transmit-receive channels were measured over a large band of frequencies, 0.3-3.0 GHz. The classification algorithm is derived by using a labelled set of training data with purpose of delivering estimates of specific subspaces for each of the two classes. The estimated subspaces are the reduced by removing a number of dimensions for each subspace in order to increase the smallest principal angle between the subspaces. The classification algorithm projects the measurement data vector onto both the subspaces and selects the predicted class label based on which of the projections results in the longest vector. The accuracy of the classifier is evaluated on the clinical data by combining the leave-one-out cross validation method with a bootstrap sampling technique to reduce the variance of the performance estimates. 3. Results We have performed a clinical study using the above described brain diagnostic devices based on microwave technology. With the detector aimed at identifying all 10 patients with haemorrhagic stroke, 13 out of 15 ischemic stroke patients were clearly separated from haemorrhagic stroke patients whereas 2 were not. The results show that this type of device and the associated algorithms can differentiate haemorrhagic from ischemic stroke patients. In summary we have reported on a new system and a clinical studies that set the stage for pre-hospital diagnosis and treatment in ambulances for the 15 million yearly stroke patients around the world thus helping society to meat one of the major unmet challenges of the global health care system. 12 12 4B3 ASSESSING OBSTRUCTIVE AIRWAY DISORDERS BY MEANS OF COMPUTATIONAL FLUID DYNAMICS (CFD) Mihai Mihăescu1, Laszlo Fuchs1, Nelson Powell2 1.Background and Motivation The upper respiratory tract is susceptible to obstructionlike abnormalities that can be caused by various mechanisms at one or multiple locations and can affect the airway functions. Often, the interaction between the flow and the obstruction involves dynamic changes in the flow regime, flow recirculation regions, flowinduced instabilities, nonlinear pressuredrop/flow rate relations, selfexcited oscillations of the soft tissue, and flowinduced noise. It is believed that the changes in the flow patterns associated with an obstruction are playing an important role for the progress of the disorder over the time. Obstructive Sleep Apnea (OSA) is the most common obstructive airway disorder, affecting more than 12 million people in US alone. It is characterized by partial or complete narrowing of the pharyngeal airway during sleep (hypopneas and apneas), resulting in partial or complete airflow cessation and Oxygen desaturation. Overnight Polysomnography is considered the goldstandard for its diagnosis. It is an expensive and time consuming process for both patient and evaluator. The OSA severity is expressed using ApneaHypopnea Index (AHI), which represents the total number of hypopneas and apneas occurring in one hour of sleep. A mild OSA is indicated by an AHI between 5 and 15, while severe conditions are those for which AHI is greater than 30. Medical imaging techniques (e.g. Computed Tomography, Magnetic Resonance Imaging) facilitated anatomical measurement of the airway, but they have little clinical utility for quantifying the functional impact of an airway obstruction. These techniques cannot offer details about the effect of the airway’s anatomical features on the airflow or on airway resistance to assess obstruction’s severity. 2.Methodology An upper respiratory tract simulator based on medical imaging for extracting patientspecific upper respiratory tract anatomy and Computational Fluid Dynamics (CFD) for computing the airflow through the pharyngeal airway are employed [1]. CFD is able to predict fluid flow characteristics by solving the physical laws of fluid mechanics (NavierStokes equations) using numerical methods and algorithms embodied in the form of a computer code. The tool is proposed as a nonintrusive and inexpensive diagnosis technique for obstructive airway disorders. Thus, not only the specific anatomic measurements are acquired (i.e. pharyngeal airway dimensions, crosssectional area, and volume) but also pertinent data to the airflow are computed (e.g. airway resistance, flow patterns, velocity, pressure, turbulence production, or wall shearstresses). The data obtained in normal healthy pharyngeal respiratory tracts (Controls) are averaged and used to generate a “Baseline” against which the results obtained in sleepdisordered breathing patients at pre and posttreatment are compared and contrasted. 3.Results Clinical and CFD based data concerning four healthy adult subjects and four OSA patients at pre and posttreatment conditions are presented in the Figure 1. The medical imaging and the AHI data were obtained at the Sleep and Research Center, Stanford University. Despite of the low number of subjects considered, a strong correlation is observed between the CFD data (mean pharyngeal airway resistance) and the clinically obtained AHI values. A correlation coefficient of was calculated. About an order of magnitude difference between the pre (red) and the posttreatment resistances (green) is found. The posttreatment airway resistances are bellow or in the range of the averaged airway resistance estimated for the healthy subjects (blue). The proposed approach allows thus differentiating between healthy subjects and individuals with OSA. Figure 1: Predicted airway resistance and clinically measured AHI plotted for four Controls and four OSA patients at pre and posttreatment conditions. 4.Discussion The present study represents an important step in building a tool for quantifying OSA and for assessing treatment outcome. Such a computational model shall enable to determine and understand the pathophysiology of the sleep disorder and the risks for airway collapse and flow induced obstruction at pre and posttreatment conditions. The simulation of the pharyngeal airflow may allow the surgeon to add quantitative data into his/her decision making, which is often based on semiquantitative or qualitative clinical findings. Acknowledgments The work is supported by the Swedish Research Council (VR 62120124256). Also, the financial support from the Göran Gustafsson Stiftelse by means of “The Göran Gustafsson Young Scientist Award (UU/KTH)” conferred to Dr. Mihaescu is greatly acknowledged. References [1] M. Mihăescu, G. Mylavarapu, E. Gutmark, and N. Powell, Large Eddy Simulation of the pharyngeal airflow associated with Obstructive Sleep Apnea Syndrome at pre and postsurgical treatment. , 44, 22212228, (2011). 13 4B4 DEVELOPING A WEARABLE MICROWAVE INSTRUMENT FOR DETECTING THORAX INJURIES—TESTS ON A PNEUMOTHORAX PHANTOM 1–3 1 1 1, 2 1, 2 1, 2 Stefan Candefjord , Prateek Saraswat , Robert Samo , Tomas McKelvey , Andreas Fhager , Mikael Persson Chalmers tekniska högskola, Göteborg, Sweden 2MedTech West, Göteborg, Sweden 3SAFER Vehicle and Traffic Safety Centre at Chalmers 1 1. Introduction Traumatic injuries is the leading cause of death for young people. A quarter of these deaths are a consequence of thorax injuries [1]. Pneumothorax (PTX) is a collection of air in the thoracic cavity caused by a rupture in the membranes surrounding the lung. Failure to diagnose and swiftly treat a PTX that is enlarging may cause patient death [1]. There is a need for an instrument to be used in the prehospital setting for objective detection of PTX. 2. Materials and Methods A wearable microwave instrument with six antennas was constructed using a leather belt and in-house fabricated patch antennas; measurements were performed on healthy volunteers (Figure 1). A simplified model of the human thorax was constructed using plastic containers of suitable sizes, filled with an appropriate mixture of ethanol and deionized water to obtain realistic dielectric properties; a container in the shape of an elliptical frustum (inner volume 12 L, with the smaller ellipse as the base) represented the thoracic cavity, and two cylindrical containers (inner volume 2 L) formed the lung space (Figure 1). To simulate a PTX, the lung space was left empty and a plastic bag resembling a collapsed lung filled with a dielectrically suitable liquid was placed inside. Measurements were performed for PTX sizes of 10%, 20% and 50% in the left or the right lung; sixty measurements were randomly drawn from this dataset and represented the PTX observations. An additional sixty measurements were performed on a phantom without PTX. The belt was repositioned after every third measurement. Measurements were conducted in a random order. A classification algorithm based on finding the minimum distance to the subspace bases, which were calculated by singular value decomposition of the training data matrix, was used to distinguish between the measurements of No PTX and PTX. The leave-one-out approach was used, i.e. the sample to be classified was not included in the training data matrix, in order to not overestimate the classification performance. 3. Results & Discussion Measurements of the human thorax and the thorax model showed similar characteristics. The classification algorithm differentiated PTX and No PTX (Figure 2). All No PTX and all except two PTX observations were correctly classified. This is an encouraging result for pursuing the development of an instrument for PTX detection in the prehospital setting. References [1] A. Sharma and P. Jindal, Journal of Emergencies, Trauma, and Shock, 71, 34–41 (2008). Figure 1: Left: The wearable microwave device (earlier version with four antennas). Right: Top view of the human thorax model, antenna locations are labelled A1–A6. PTX Subspace distance [−] Subspace distance [−] No PTX 2 1 0 d No PTX d PTX 3 2 1 0 d No PTX d PTX Figure 2: Box plots showing the distance to each subspace basis for the two classes, i.e. No PTX or PTX. The line in the middle of the box shows the median, and the bottom and the top of the box show the 25th and 75th percentile, respectively. 14 14 4B5 A compact wideband antenna for microwave hyperthermia system 1 Pegah Takook1, Hana Dobsicek Trefna2, Mikael Persson3 Chalmers university of technology, Göteborg, Sweden. 2 Chalmers university of technology, Göteborg, Sweden. 3 Chalmers university of technology, Göteborg, Sweden 1. Introduction Hyperthermia treatment is a medical treatment during which the temperature is raised in tumours for a sufficient period of time, to kill the cancer cells or make them more sensitive to ionizing radiation or chemotherapy. Different type of antennas have been used so far in deep hyperthermia applicators, such as water-filled waveguide antennas, dipole antennas or probe-fed patch antennas. These antennas are either large and heavy (like as the waveguide antennas) or present very narrow bandwidth which are not desired characteristics. In this paper we present a compact, wideband antenna to be used in hyperthermia antenna applicator. This applicator is developed for microwave hyperthermia of deep seated tumours in head and neck. The antenna should be of small size, with wide frequency band and directive radiation pattern. The desired wide bandwidth of 0.4 to 0.9 GHz, is due to multiple frequency approach in our treatment strategy. 2. Method The antenna consists of two parts: the self-grounded Bow-tie antenna and the balun. The Bow-tie antenna covered, by teflon from the upper-side, is completely immersed in water. The Teflon improves the antenna's reflection coefficients and high permittivity of the water leads to a significantly reduced size antenna. To transform the 30-ohm-impedance feed-line of Bow-tie in the background of water to a 50-ohm-impedance microstrip line, a wideband balun has been designed. Finally the shape and size of the water bolus is quantified by 50% iso-SAR contours as indicators of penetration depth and the directivity. 3. Results Our designed wideband balun presents a return loss of better than 10 dB and the transmission coefficient about -0.5 dB over a bandwidth from 0-1 GHz. Also the simulations results of the antenna shows the best performance in terms of the S11 for the bow-tie of size 18*27*7 mm3 and conical shape water bolus of size 40*80*30 mm3 (diameters of the upper and lower circular bases and height). The obtained reflection coefficients are below -10 dB over most of the desired bandwidth, and below -5 dB for less than 0.45 GHz and higher than 0.85 GHz. Figure 1: Simulated bow-tie antenna in water bolus with the designed balun 4. Discussion and conclusion The presented self-grounded bow-tie antenna with added teflon, immersed in water-filled conical shape bolus and with the designed wideband balun, presents a wideband performance over the desired frequency range of 0.4-0.9 GHz. References [1] H.D. Trefna, J.F. Bakker, J. Vrba, Mikael. Persson. ''Evaluation of a patch antenna applicator for time reversal hyperthermia.''International Journal of Hyperthermia, March 2012 . [2] M.M. Paulides, J.F. Bakker, N. Chavannes, G.C. Van Rhoon. ''A patch antenna designed for application in a phased-array head and neck hyperthermia applicator.'' IEEE Trans. Biom. Eng. 15 4B6 APPLICATOR FÖR MIKROVÅGSBASERAD BEHANDLING AV HUVUD- OCH HALSTUMÖRER 1 1 2 Hana Dobšíěek Trefná , Pegah Takook , Johanna Gellermann , Mikael Persson 1 2 Chalmers University of Technology, Sweden. University Hospital Tubingen 1 1. Introduction Hyperthermia is presently used as an adjuvant to the radiation therapy in the treatment of certain types of cancers. Recently, randomised trials have shown a significant advantage of combining hyperthermia with radiotherapy and/or chemotherapy in the treatment of solid tumours [1,2]. The objective of hyperthermia treatment is to raise the temperature in the tumour to a therapeutic level 41 – 44 C for a sufficient period of time to achieve cell death or render the cells more sensitive to ionizing radiation and chemical toxins. In this contribution, we present a novel design of an antenna applicator for hyperthermia treatment in Head & Neck region. 2. Method The applicator consists of 12 to 18 elements arranged in one to three ring set-ups. The distance between the rings is 30 mm. The self-grounded Bow-Tie immersed in conical water bolus serves as an applicator element,. The operating frequency range is from 400 to 1000 MHz. In order to keep distance in terms of wavelength between radiating elements body at different frequencies, the diameter of the applicator is adjustable and varies between 340 and 460 mm. In order to cool down the body surface, an additional water layer is placed between the body and water boli of the antennas. This layer has thickness of 1-2 cm and contain circulating cold water. 3. Results The focusing abilities of the applicator are evaluated by using a numerical model of an anthropomorgical phantom of H&N region. The phantom, containing small laryngeal tumor of volume approx. 15 mm 3 consists of 6 tissues. The treatment plans were calculated by using the time reversal algorithm [3]. The results show a considerable heating in terms of SAR in the target region with a remarkably low heating in critical tissues (i.e. spinal column). The obtained SAR distribution is favorable, although a relatively high level of energy is also absorbed on the surface of the body. It is apparent that this heating is local and not expected to cause problems as it can be cooled by blood perfusion and water bolus. The obtained results also justify advantages of using the multi-frequency approach in treatment planning. 4. Conclusions The results presented in this study are promising, awaiting the experimental evaluation on the physical version of the phantom. References [1] J. Van der Zee, D. Gonzáles Gonzáles, et al.,” Comparison of radiotherapy alone with radiotherapy plus hyperthermia in locally advanced pelvic tumours: a prospective, randomised, multicentre trial”, Lancet, vol. 355, pp. 1119-1125, 2000. [2] R.D. Issels, L.H. Lindner, J. Verweil , et al.,”Neo-adjuvant chemotherapy alone or with regional hyperthermia for localised high-risk softtissue sarcoma: a randomised phase 3 multicentre study.”, Lancet Oncol., Vol.11(6), pp. 561-70, 2010. [3] H. Dobšíček Trefná, J. Vrba, and M. Persson, ”Time-Reversal Focusing in Microwave Hyperthermia for Deep-Seated Tumours”, Phys Med Biol, vol 55, pp. 2167-85, 2010. Figure 1: Applicator design and SAR distribution in phantom containing laryngeal tumor. 16 16 Sammanfattningar Ehälsa/IKT II Session 2C Moderator: Bengt Arne Sjöqvist 17 17 2C1 itACiH - it-stöd för Avancerad Cancervård i Hemmet 1 1 2 3 4 Jimmy Johansson , Boris Magnusson , Rickard Fredin , Hlin Thorgeirsson 2 Medicinsk teknik, Skånes universitetssjukhus, Lund/Malmö, Sweden. Datavetenskap, Lunds Tekniska Högskola, Lund, Sweden. 3,4 Palliativa enheten, Primärvården Skåne, Lund, Sweden. Inledning Ett integrerat it-stöd för avancerad cancervård i hemmet är nu i klinisk drift inom den palliativa enheten i Lund. Den mobila vårdpersonalen har en mobil enhet med uppdaterad information för respektive patient de ska besöka samt stöd för dokumentering. Den mobila enheten utbyter kontinuerligt information med en avdelningsenhet som är placerad på verksamhetens expedition. På så sätt kan den rondande vårdpersonalen få en uppdaterad bild av patienternas status. Den mer avancerade medicintekniska utrustningen i form av provtagningsutrustning, infusionspumpar och monitoreringsutrustning är också uppkopplad mot systemet och tekniken utvärderas i en simulerad hemmiljö, tillsammans med patienter inom den palliativa slutenvårdavdelningen. På så sätt kan vi ta med oss feedback i vidareutvecklingen och bemöta de krav som ställs för att på ett säkert sätt integrera denna typ av utrustning i hemmet. Vi lägger stor vikt vid användbarhet och har experter i projektet som fortlöpande utvärderar detta. Bakgrund Projektet, it-stöd för Avancerad Cancervård i Hemmet (itACiH), syftar till att upprätta en avancerad vårdplats i hemmiljö med inriktning mot cancervård. Antalet cancerfall beräknas öka, även oberoende av den ökande andelen äldre i befolkningen. En av tre svenskar drabbas av cancer och med allt bättre möjligheter till behandling lever allt fler längre med sin sjukdom vilket innebär ökade krav på avancerad sjukvård i livets slutskede. För att det ska vara möjligt att ge kvalitativ vård med den ökande belastningen på samhället som detta innebär måste det finnas nya vägar för omvårdnad både under aktiv behandling och i livets slutskede. Ny teknik kommer att öka antalet patienter som kan ges möjlighet att vårdas hemma, vilket en stor del av dagens patienter önskar. Det huvudsakliga målet för projektet är att göra det möjligt för fler patienter med cancer att vårdas hemma. Detta förutsätter att det kännas lika tryggt att vara hemma som på en vårdavdelning. Genom att utveckla tekniker för övervakning av utrustning som finns runt patienten, i vissa fall fjärrstyrning av utrustningen, kombinerat med kommunikation mellan hem och vårdpersonal, såväl vårdavdelning som mobila vårdteam, hoppas vi kunna åstadkomma en sådan situation. Projektet finansieras genom VINNOVA:s program för utmaningsdriven innovation som riktar sig till breda sektors- och ämnesöverskridande konstellationer som gemensamt vill arbeta för att möta samhällets utmaningar. Konstellationen består av företag från olika sektorer, tvärdisciplinär forskning från universitet, forskningsinstitut, offentlig sektor och ideella organisationer enligt bilden nedan. Projektet, itACiH, har en budget på 22 miljoner, varav 10 miljoner från VINNOVA och 12 miljoner i form av medfinansiering från partners, och en tidsplan som sträcker sig över 2012 och 2013. Utveckling I detta tvärvetenskapliga projekt samverkar datatekniker, medicintekniker, sjukvårdspersonal och företag från olika discipliner för att tillsammans lösa detta komplexa problem. Projektet drivs efter en iterativ modell där två delprojekt, utveckling och kravställning, fortgår parallellt. Processer för utveckling, riskhantering och användbarhet etablerats för att hantera de regulatoriska kraven för medicintekniska produkter. Fram till nu har fokus legat på att etablera en underliggande infrastuktur samt tillhandahålla ett integrerat it-stöd för vårdpersonalen. Nästa steg blir att även integrera enheter som stödjer patienter och anhöriga. Vi har genom samarbetet med Nätverket mot cancer genomfört workshops tillsammans med patienter och anhöriga för att designa ett system som utgår från de viktigaste behoven och för att ta hänsyn till de integritetsaspekterna man tidigt stöter på. Det pågår ett antal examensarbete inom ramen för projektet som syftar till att anpassa produkter som idag är avsedda för sjukhusbaserad vård och behöver anpassas vad gällande både säkerhet och mobilitet. Resultat och slutsatser Ungefär 1,5 år in i projektet ser vi att det som tas fram både är välkommet i verksamheten och med stor sannolikhet är ett måste för att avancerad sjukvård i hemmet ska kunna växa i den omfattningen som prognoserna pekar på. Utöver behovet, av ett integrerat it-stöd, som identifierats inom verksamheten för avancerad sjukvård i hemmet har ett tydligt behov identifierats i andra ambulerande verksamheter som t.ex. primärvården och kommunen. Även andra verksamheter inom sjukhusbaserad specialiserad öppenvård såsom diabetesmottagningen, hemdialysenheten och barnkliniken har visat stort intresse. Nu arbetar vi för att i första hand slutföra utvecklingen som möter den avancerade cancervården i hemmet men tittar även på möjligheten att specialanpassa systemet för barn och andra vårdområden. 18 2C2 A Novel Data-Mining Approach Using Social Media to Respond to Outcomes of Diabetes Treatment 1 1 2 3 ALTUG R. AKAY , ANDREI DRAGOMIR BJÖRN-ERIK ERLANDSSON 2 3 KTH Royal Institute of Technology, Huddinge, Sweden. University of Houston, Houston, Texas KTH Royal Institute of Technology, Huddinge Sweden. 1. Heading (eg Introduction) Social media, ranging from personal messaging to live foras, is providing limitless opportunities for patients to discuss their experiences with drugs and devices. It is also providing limitless opportunities for companies to receive feedback on their products and services [1]. Pharmaceutical companies are already looking at social network monitoring as a top priority within their IT departments, potentially creating an opportunity for rapid dissemination and feedback of products and services to optimize and enhance delivery, and reduce costs [2]. Traditional social sciences use surveys and involve subjects in the data collection process. Limited by this process, data collected is of small sizes and typically hundreds of subjects in one study. By contrast, thousands of users of social media produce inordinate amounts of data with rich user interactions. There are two simple ways to extract this information: 1) crawling using site provided APIs, or 2) scraping needed information from rendered html pages. Many social media sites provide APIs: Twitter, Facebook, YouTube, Flickr, etc. We can also follow how its properties change over time, which would greatly interest public health studies. 2. Heading (eg Method) We used text and data-mining tools in Rapidminer (www.rapidminer.com) to develop opinion labels about each drug and device (positive, negative, neutral) per node within a network, build networks from the search results of the forum, and developed a network ranking system reflecting the degree to which the respective network is involved in the opinion formation about the drug/disease. Each forum group (separated by drugs and/or devices discussed) was fed into Rapidminer and preprocessed by removing unwanted characters (HTML tags, punctuation, numbers) and common stop words (e.g. a, the, it, etc.), breaking down words into token words, stem tokens into ‘root words’ (e.g. working ->work; lost, lose->los). The end result was a wordlist per vector using a binary system to identify words within a vector (‘1’ = the word was present, ‘0’ = the word was absent). 3. Results The following figure is the graphical representation of the SOM of the positive words group. We used a 10 x 10 map size with thirty variables present. Fig. 1. Positive Words The clustering resulting from the SOM analysis reveal that the positive words (along with positive words and drugs) have a larger presence in the cluster groups. Negative words (along with negative words and drugs) had a much lower presence in the cluster groups. We developed a list of words dominating the clusters. 4. Discussion The goal of this study was to transform forum posts into vectors to scan for patterns in the responses to gauge consumer opinion of the drugs and devices used to treat diabetes mellitus. The clusters belonging to the ‘Positive’ and ‘Positive + Drugs’ categories contained more positive words (per vector and per frequency) compared to the ‘Negative’ and ‘Negative + Drugs’ group. This gives the impression of an overall positive user satisfaction and experience with the specified drugs and devices. A future study will go more deeply into the interaction amongst the users to develop a more thorough web of user influence and opinion and how user influence (based on quality of posts and ranking within the forum) affects interactions with other users (replies, friendships, the timing and quality of posts in threads) [3]. Future research will expand to include other diseases such as oncology. With social media becoming an expanding venue for people to express their thoughts, ideas, and reactions, it represents a goal mine for companies seeking to optimize health delivery and reduce costs. References [1] [2] [3] Alberto Ochoa, Arturo Hernández, Laura Cruz, Julio Ponce, Fernando Montes, Liang Li and Lenka Janacek (2010). Artificial Societies and Social Simulation Using Ant Colony, Particle Swarm Optimization and Cultural Algorithms, New Achievements in Evolutionary Computation, Peter Korosec (Ed.), ISBN: 978-953-307-053-7, InTech (http://www.intechopen.com/articles/show/title/artificialsocieties-and-social-simulation-using-ant-colony-particle-swarm-optimization-and-cultural) “Pharma 2.0 – Social Media and Pharmaceutical Sales and Marketing” Identifying influential users in an online healthcare social network, X. Tang, C.C Yang, ISI 2010 19 2C3 Case Based Reasoning in Support of the LVAD Surgical Treatment Ankica Babic, PhD, Department of Biomedical Engineering, Linköping University Introduction. In approximately 1-3% of patients undergoing open-heart surgery, there is a need for Left Ventricular Assist Device (LVAD) due to heart failure when weaning from cardiopulmonary bypass (CPB) [1]. To minimize the high mortality and morbidity rates it is important to chose the right treatment for the particular patient situation. The amount of the data collected in electronic patient records might be limited for an elaborate statistical analysis, but it is very critical for assuring a timely and accurate clinical insight into a patient particular situation. Case Based Reasoning (CBR) methodology provides means of collecting patients cases and retrieving them following the clinical criteria [2]. By studying previously treated patients with similar backgrounds, the physician can get a better support for deciding on treatment and be better prepared for complications that might occur during and after surgery. Case Based Reasoning (CBR) engine was developed using an extended version of the Nearest Neighbor'a algorithm, which uses logarithms that emphasize small differences between similar cases. A patient case (Figure 1) is represented as a combination of perioperative variable values and operation reports. Physicians could review a selected number of cases by browsing through the electronic patient records and operational narratives which provides an exhaustive insight into the previously treated cases. Figure 1. A Patient Case. Results. An evaluation of the search algorithm suggests good functionality: an experienced physician retrieves cases using fewer clinical variables while the novice selects more variables which influences the distance calculation and consequently the set of the K nearest cases. The CBR engine had been implemented as a part of a web-based decision support system for thoracic surgery. Literature. 1. B Peterzén, U Lönn, A Babic, H Granfeldt, H Casimir-Ahn, H Rutberg. Postoperative Management of Patients With Hemopump Support After Coronary Artery Bypass Grafting. Ann. Thorac. Surg. 1996;62: 495-500 2. Holt A et al., The Knowledge Engineering Review / Volume 20 / Issue 03 / September 2005, pp 289-292 20 2C4 UTVECKLING AV BESLUTSSTÖD FÖR HJÄRTPUMPSINSTÄLLNING 1 2 3 4 5 6 7 Lisa Nilsson , Boris Magnusson , Lars Algotsson , Jimmy Johansson , Matilda Landgren , Anders Heyden , Ida Rasmark , Erik 8 Lindsten 1 Projektledare, Skånes universitetssjukhus, Medicinsk Teknik, Lund, Sverige. 2 Professor, Lunds Tekniska Högskola, Institutionen för datavetenskap, Lund, Sverige 3 Överläkare, biträdande klinikchef, Skånes Universitetssjukhus, Kliniken för Thoraxkirurgi, Anestesi och Intensivvård, Lund, Sverige 4 Ansvarig för Forskning och Utveckling, Skånes universitetssjukhus, Medicinsk Teknik, Lund, Sverige 5 Doktorand, Lunds Tekniska Högskola, Matematikcentrum, Lund, Sverige 6 Professor, Lunds Tekniska Högskola, Matematikcentrum, Lund, Sverige 7 Examensarbetare, Lunds Tekniska Högskola, Institutionen för datavetenskap, Lund, Sverige 8 Examensarbetare, Lunds Tekniska Högskola, Institutionen för datavetenskap, Lund, Sverige 1. Introduktion Hjärttransplantation är sista utvägen för patienter som lider av allvarlig hjärtsvikt. Antalet patienter som väntar på hjärttransplantation är många fler än tillgången på donatorhjärtan. I väntan på ett nytt hjärta får vissa patienter en hjärtpump inopererad för att avlasta det egna hjärtat. Hjärtpumpens hastighet är kontinuerlig, och behöver justeras många gånger innan man har hittat en lämplig hastighet. För att ställa in hjärtpumpens hastighet inhämtar man information både från olika uppmätta tryck, såsom centralt venöst blodtryck och kapillärt inkilningstryck i lungkretsloppet, samt ultraljudsbilder av hjärtat. Att bara utgå från de tryck man mäter är vanskligt då dessa tryck ökar både då pumpen går för fort och för långsamt. Med hjälp av ultraljudsbilder av de fyra kamrarna i hjärtan är det möjligt att avgöra om pumpens hastighet är för hög eller för låg. En ideal hastighet resulterar i att vänster hjärtkammares storlek inte är abnormal och att kammarskiljeväggen inte är förskjuten för mycket åt något håll. Dock kan ett fyrkammarultraljud vara svårt att tolka då vinkeln mellan ultraljudsapparaten och hjärtan kan variera beroende på hur den appliceras, men också på grund av patienternas variation i form och storlek, eller hjärtats placering i kroppen. 2. Bakgrund Forskningsprojektet syftar till att hitta nya metoder för optimering av hastighet för en inopererad hjärtpump. Projektet drivs genom ett samarbete mellan Thoraxintensiven och Medicinsk Teknik vid Skånes Universitetssjukhus, samt institutionen för datavetenskap, institutionen för reglerteknik och Matematikcentrum vid Lunds Tekniska Högskola. 3. Metod och resultat Att ställa in hjärtpumpens hastighet optimalt är idag komplicerat, och trots de supportsystem man har idag råder fortfarande osäkerhet om den hastighet man väljer är korrekt. Målet med projektet är att utveckla ett beslutsystem för att lättare kunna avgöra om pumpens hastighet skall ökas eller minskas. Beslutsstödet skall kombinera insamlad information från patientövervakningssystemet med information från ultraljudsbilder i realtid och analysera denna. Återkoppling skall kunna ges i realtid till de närvarande läkarna och kunna ge en indikation på om pumpens varvtal bör ökas eller minskas. Beslutsstödet skall utformas på sådant sätt att det är intuitivt att använda och har hög användbarhet för de läkare det är tänkt att stödja. Projektet består av två delar, dels analysen av ultraljudsbilderna, och dels av sammanställningen av ultraljudsbildernas resultat med de fysiologiska parametrarna som utläses från patientövervakningen och analysen och presentationen av denna samlade data. I projektet ingår att identifiera vilka parametrar i ultraljudsbilden som är vitala, såsom kammarskiljeväggens rörlighet och kamrarnas storlek, och att i analysen översätta detta till en, eller flera, numeriska parametrar som går att använda i en algoritm. Denna bildanalys görs med hjälp av variationsmetoder. Projektet baserar sig i tidigare arbeten på Lunds Tekniska Högskola och Medicinsk teknik. Ett tidigare projekt har resulterat i en databas där en patients alla mätvärden från patientmonitorn sparas och långtidslagras. Från denna databas hämtas de övervakningsparametrar som används i analysen. Man använder sig också av PalCom för kommunikation mellan beslutsstödsprogrammet, ultraljudsapparat och databas. PalCom är resultatet av ett EU-projekt som pågick 2004-2007 och involverade flera länder och universitet, däribland Lunds Tekniska Högskola och institutionen för datavetenskap. PalCom tillhandahåller ramverk för att skapa flexibla anslutningspunkter för enheter och applikationer. För att underlätta integrationen ytterligare använder applikationerna formatet HL7 för kommunikation sinsemellan och mot externa system. 4. Diskussion Projektet är avgränsat till att utveckla en prototyp som kan testas och utvärderas av sjukvårdspersonal på Thoraxintensiven. I förlängningen kan man tänka sig att detta arbete kan leda till förfinade metoder att analysera de fysiologiska parametrar som är av intresse för hjärtpumpsinställning. Prototypen skulle kunna användas till att utvärdera olika algoritmer för att stödja hjärtpumpsinställning, och kanske i förlängningen att inte bara ge indikation om huruvida pumpens hastighet skall justeras uppåt eller nedåt, utan också kunna ge förslag på hastighet. 21 Sammanfattningar Medicinska bilder I Session 3C Moderator: Thomas Jansson 22 22 3C1 DETECTION OF IRON OXIDE NANOPRTICLES IN RAT LYMPH NODES USING MAGNETOMOTIVE ULTRASOUND IMAGING Maria Evertsson1, Magnus Cinthio1, Sarah Fredriksson2, Pontus Kjellman2, Rene in 't Zandt2, Fredrik Olsson2, Hans W. Persson1, Tomas Jansson3 1 Electrical Measurements, Faculty of Engineering LTH at Lund University, Lund, Sweden. 2 Genovis AB, Lund, Sweden. 3 Clinical Sciences, Lund University, Lund, Sweden 1. Introduction Breast cancer and malignant melanoma spread mainly through the lymphatic system. If the cancer has spread it is most likely to find metastases in the sentinel lymph node (SLN), the first lymph node draining the tumor. The SLN is by invasive surgery removed and histologically examined. It is desirable to find new methods and tracers to localize SNLs to improve the accuracy of the detection and removal of cancer infected lymph nodes. In this study we aim to detect multimodal superparamagnetic iron oxide nanoparticles (SPIO-NP) in rat SLNs in situ, using the new imaging technique magnetomotive ultrasound imaging (MMUS). In MMUS a time-varying external magnetic field acts to move the NPs and, thus, the NP-laden tissue. This movement can be detected by proper processing of ultrasound data. Recently we developed a frequency and phase gated algorithm which efficiently reduce motion artifacts. The algorithm has shown promising results in phantom studies [1], but has not yet been verified in animals. If presence of adequate signal can be established in an animal model, there is a potential for MMUS to be used as a bed-side surgical guide, imaging the very same particles that were used in prior staging with other imaging techniques (e.g MRI and SPECT). 2. Method Seven Wistar rats were injected with 100µL nanoparticle solution in one of their hind paws, four with 31nm NPs and three with 67 nm NPs. Further, the injections were given as a low or a high concentration (0.3 and 3 mg iron oxide/mL respectively). Only one animal received the high concentration 67nm NPs. 24 hours post injection the animals were sacrificed and imaged with a high frequency ultrasound scanner (Visualsonics VEVO 2100). Each rat was positioned between the transducer (center frequency 21 MHz) and a solenoid with a cone shaped iron core, imaging the lymph node in the fold of the knee, proximal to the injection site. The solenoid was excited with various voltages (10, 20, 30Vpp) and frequencies (5-15Hz, in steps of 2.5Hz). Displacements were calculated from acquired RF IQ-data. Signal to clutter ratios were given as average displacement in the lymph node divided with that in the fat capsule surrounding the node. 3. Results and discussion Fig. 1 shows: (a) a B-mode image of a rat lymph node after injection of 100µl 0.3mg/mL solution of 31nm NPs; (b) the total magnetomotive displacement at 5Hz 30V coil excitation; (c) the phase distribution at the detected frequency and (d) the frequency and phase-discriminative displacement. The displacement and phase magnitudes can be read from the color bars, note the different scales. The displacement is in the same order as in previous phantom studies. The signal to clutter ratio in the case depicted in Fig. 1 (d) was 16.7 dB compared to an average of 6.7dB for all measurements. The displacement tended to decrease with increasing frequency, and to increase with increasingexcitation voltage. For example it was approximately twice as large at 5Hz than 15Hz, and three times larger at 30V compared to 10V. There was also a tendency that smaller particles induced a larger magnetomotive displacement. From the phase map 1(c) it can be seen that the magnetomotive displacement of NP-laden tissue induces a counteracting motion with opposite phase in tissue surrounding the lymph node. The phase discriminative algorithm however effectively suppresses this counteracting motion. 4. Conclussion In breast cancer and malignant melanoma it is important to localize SLNs to investigate if the cancer has spread. We have here established magnetic excitation parameters for successful MMUS imaging in a preclinical SLN model. Further, the results show that MMUS has potential as a stand-alone modality for other imaging applications, besides from SLN, such as stem cell tracking and cardiovascular research. References References [1] M. Evertsson, M. Cinthio, S. Fredriksson, F. Olsson, H. W. Persson, and T. Jansson, “Frequency- and Phase-Sensitive Magnetomotive Ultrasound Imaging of Superparamagnetic Iron Oxide Nanoparticles,” IEEE Trans. UFFC, vol 60, no.3, pp 481-491, 2013. 23 3C2 ULTRASOUND SPECKLE TRACKING FOR ARTERIAL STRAIN IMAGING – A VALIDATION STUDY IN-SILICO, IN-VITRO AND IN-VIVO 1,2 1 2 1 2 Matilda Larsson , Brecht Heyde , Lars-Åke Brodin , Jan D’hooge KTH-Royal Institute of Technology, School of Technology and Health, Stockholm, Sweden. 2 Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium 1. Introduction Ultrasound-based speckle tracking for estimation of arterial wall strain has potential to be used for assessment of arterial stiffness to improve cardiovascular risk stratification. However, most speckle tracking algorithms have been developed and validated for cardiac applications, whereas strain assessment in the artery wall is more challenging due to lower strain amplitudes combined with poor spatial resolution. This project aimed to develop and test an ultrasound-based speckle tracking algorithm for strain estimation of the artery wall in simulated data sets, in an experimental setup and in an animal model. 2. Method A speckle tracking algorithm tuned for the vascular setting was developed in Matlab (normalized cross-correlation for 2D motion estimation across frames, kernel size: 5λ×2λ, axial and lateral kernel overlap: 40% and spline interpolation for subsample motion detection). Accumulation of the displacement maps throughout the cardiac cycle was performed and longitudinal and radial strains were then obtained by linear regression after averaging in one direction of the selected region of interest (radially for longitudinal strain and vice versa). The strain curves were then drift compensated and low-pass filtered. The speckle tracking algorithm was validated in three steps: in-silico, in-vitro and in-vivo. First, it was applied on simulated ultrasound images from a kinematic cylindrical model of the carotid artery with realistic dimensions and movement pattern. The ultrasound images were simulated using a generalized convolution model (COLE) with realistic image properties and the estimated strain was then compared with the ground truth from the model. In the experimental validation, the algorithm was applied on ultrasound images from polyvinyl alcohol phantoms mimicking the carotid artery. The phantoms were connected to a pulsatile pump, programmed to generate carotid flow profiles. Sonomicrometry crystals were glued on the phantom walls and used to acquire reference values of strain. In the in-vivo validation, the algorithm was applied on ultrasound images obtained in a sheep model. The left carotid arteries of 3 sheep were exposed during isofluran anesthesia and two sonomicrometry crystals were sutured onto the artery wall to obtain reference values of longitudinal strain. The wound was closed and filled with ultrasound gel followed by ultrasound imaging at baseline and stress. 3. Results An overall good agreement was found between the strain estimated with the speckle tracking algorithm and the reference strain in the three validation setups. In-silico, the peak systolic radial strain was estimated to be -13.15 ± 0.99% (ground truth 13.89%) while longitudinal strain was 5.25 ± 1.20% (ground truth 5.30%). The correlation between estimated mean peak strain values and reference peak strain values was r = 0.92 (p < 0.001) for radial strain and r = 0.72 (p = 0.006) for longitudinal strain in the experimental setup. The results from the in-vivo validation are shown in Fig. 1. 4. Discussion This study shows the feasibility of estimating radial and longitudinal strain in the carotid artery using ultrasound speckle tracking. However, the step from in-silico and in-vitro to in-vivo estimation is challenging and the surgical exposure in the in-vivo validation may have affected the artery wall properties since lower strain values than previously observed in-vivo were obtained. Moreover, further studies are needed to test the algorithm on human in-vivo data and to investigate the potential of the method to estimate arterial stiffness and detect cardiovascular diseases at an early stage. 24 3C4 ARTIC – ETT FLEXIBELT PROGRAM FÖR KARAKTERISERING AV ARTÄRER I ULTRALJUDSBILDER 1 Simon Segstedt1, Tobias Nilsson1, Åsa Rydén Ahlgren2, Tomas Jansson3, Hans W Persson1, Magnus Cinthio1 Elektrisk Mätteknik, Lunds Tekniska Högskola, Lund 2Klinisk Fysiologi, Lunds Universitet, Malmö, 3Institutionen för Kliniska Vetenskaper, Lund Universitet, Lund 1. Introduktion Ultraljudsmätningar av diameter, distension och väggtjocklek (intima-media thickness, IMT) hos artärer med hjälp av ultraljud är en viktig metod inom kardiovaskulär forskning. Vi har utvecklat en automatisk metod, ARTerIal Characterization (ARTIC), för att mäta diameter, distension och IMT, där målet har varit att göra en generell och lättanvänd metod som fungerar på så många olika typer av kärl som möjligt. Tidigare utvärderingar har gjorts på halspulsådern med filformat som är specifika för var ultraljudsapparat. I denna utvärdering har vi studerat det standardiserade bildformatet (DICOM) samt studerat flera andra kärl. 2. Metod ARTIC är baserad på segmentering där de olika lagren i kärlväggen detekteras med hög upplösning, se figur 1. Till skillnad från standardiserade manuella mätningar där enskilda bilder används, mäter ARTIC diameter, distension och IMT i hela bildsekvenser. Detta möjliggör automatisk mätning av diameter, distension och IMT under hela hjärtcykeln. Vi har tidigare gjort en utvärdering av ARTIC och jämfört den med en fantomvaliderad metod. I den utvärderingen användes bilder på halspulsådern från både gamla och unga individer tagna med olika ultraljudsapparater. För att kunna implementeras i större vetenskapliga studier har vi nu också gjort en utvärdering med DICOM-bilder. Dessutom har vi gjort en inledande utvärdering där ARTIC har använts för att mäta diameter, distension och IMT hos aorta, brachialis och poplitea. I DICOMutvärderingen mättes halspulsådern med två olika frekvenser, 9 MHz (12 individer, medelålder 39 år, 25-54 år) och 12 MHz (20 individer, medelålder 41 år, 21-62 år). I den andra utvärderingen mättes totalt 10 kärl hos 6 individer (medelålder 38 år, 27-62 år). Varje kärl mättes två gånger varpå repeterbarheten mättes med hjälp av coefficient of variation (CV). 3. Resultat DICOM-utvärderingen visade CV-värden på 0.6% för diameter (medel±SD 5613±562 µm), 3.9% för distension (604±145 µm) och 3.2% för IMT (592±91 µm) för 9 MHz samt 0.7% för diameter (5466±534 µm), 4.2% för distension (566±166 µm) och 2.4% för IMT (609±86 µm) för 12 MHz. Utvärderingen av olika kärl gav CV-värden på 0.9% för diameter (6812±4149 µm), 13,1% för distension (368±472 µm) och 2.8% för IMT (514±240 µm). 4. Diskussion Utvärderingarna, i kombination med tidigare studier [1, 2], visar att ARTIC är en generell metod som fungerar för olika typer av bilder och olika typer av kärl. Parametrarna beräknas automatiskt efter att operatören markerat blodkärlets mitt med ett musklick. Beräkningstiden är kort (~1ms/bildruta) och ett flertal markörer för kardiovaskulär hälsa kan sparas. Även andra funktioner finns implementerade, såsom möjligheten till manuell mätning och uppskattning av lokalt tryck, i t.ex. aorta, med hjälp av den beräknade distensionskurvan [3]. Genom att vara en generell och användarvänlig metod kommer ARTIC kunna vara ett värdefullt hjälpmedel inom kardiovaskulär forskning. Figur 1. Till vänster visas en ultraljudsbild (DICOM) där de olika lagren är markerade med svart (adventitia) respektive vitt (intima). Till höger visas resultatet, heldragen linje markerar diameter-resultat och streckad linje markerar IMT-resultat. Referenser [1] T. Nilsson, S. Segstedt, Å. R. Ahlgren, S. Ricci, G. Östling, P. Tortoli, J. Nilsson, T. Jansson, H. W. Persson, and M. Cinthio, "A robust and fast method for arterial lumen diameter and intima-media thickness measurements," in IEEE Ultrasonics Symposium, 2012, p. In Press. [2] S. Segstedt, T. Nilsson, P. Milton, S. Sveinsdottir, T. Jansson, H. W. Persson, D. Ley, and M. Cinthio, "Arterial diameter change measurements in premature rabbit pups using B-Mode images," in IEEE Ultrasonics Symposium, 2012, p. In Press. [3] J. Kips, F. Vanmolkot, D. Mahieu, S. Vermeersch, I. Fabry, J. de Hoon, L. Van Bortel, and P. Segers, "The use of diameter distension waveforms as an alternative for tonometric pressure to assess carotid blood pressure," Physiological Measurement, vol. 31, pp. 543-553, Apr 2010. 25 3C6 A FAST 2D TISSUE MOTION ESTIMATOR BASED ON THE PHASE OF THE INTENSITY ENABLES VISUALIZATION OF THE PROPAGATION OF THE LONGITUDINAL MOVEMENT IN THE CAROTID ARTERY WALL 1 Tobias Nilsson , Åsa Rydén Ahlgren2, John Albinsson1, Simon Segstedt1, Jan Nilsson2, Tomas Jansson3, Hans W Persson1, Magnus Cinthio1 1 2 Electrical Measurements, Faculty of Engineering, LTH, Lund University, Sweden. Department of Clinical Sciences Malmö, Lund 3 University, Sweden. Department of Clinical Sciences Lund, Lund University, Sweden. 1. Introduction A fast 2D motion estimator applied on ultrasound B-mode images has been developed and evaluated. As oppose to most other methods this method does not utilize block-matching or iterative solutions. The method is thus computationally efficient and suitable for real-time motion estimation over the entire image. Further the method has enabled visualization of the propagation of the longitudinal movement in the carotid artery wall. 2. Method The 2D motion estimator converted the B-mode intensity to phase information in the vertical and horizontal directions. For each direction, the intensity was first differentiated and the Hilbert transform was applied to extract the spatial phase. Then the average temporal phase difference between two frames and the average spatial phase gradient was calculated using a convolution with a 2D kernel of ones. The motion of each pixel was then calculated as the quotient between these two matrices. The method has been evaluated on 1) phantom measurements and 2) in vivo on the carotid artery wall of 17 subjects, where measurements of the longitudinal displacement of the intima-media complex were compared to our previously validated method. 3. Results The error of the phantom measurements was 1.6±15.7% (velocities between 5-10 mm/s; approx. 9.5 million estimations). In the in vivo measurements the mean difference (validated-proposed) was 18±44µm. Several different phases of the longitudinal propagation, which seem to be connected to the multi-phasic pattern of the longitudinal movement, can be seen. All phases of the longitudinal propagation seem to originate from the direction of the heart. Figure 1 show four consecutive frames (FR = 54 Hz; kernel size ~1x1 mm) where two phases of the propagation of the longitudinal movement can be visualized. 4. Discussion In conclusion, conversion of B-mode intensity to spatial phase information enables fast tissue motion estimation in two dimensions. The method is simple and well suited for real time implementation for tracking in entire images in various applications. An interesting application is the visualization of the propagation of the longitudinal movement in the carotid artery wall which, to our knowledge, has not been visualized before. All phases during a cardiac cycle seem to originate from the direction of the heart. Figure 1: Four consecutive frames (A-D) of a carotid artery. The horizontal velocity of the longitudinal movement is colorcoded and overlaid on the grey-scale image. In these frames, two phases of the propagation of the longitudinal movement can be visualized, one with negative velocity and one with positive velocity relative to the heart. The direction of the heart is to the right. 26 Sammanfattningar Mätteknik Session 4C Moderator: Gösta Hellström 27 27 4C1 COMPREHENSIVE ASSESSMENT OF LEFT VENTRICULAR RELATIVE PRESSURE FIELDS 1 1 2 Jonatan Eriksson , Ann F Bolger , Carl-Johan Carlhäll1, Tino Ebbers1 2 Linköpings University and Center for Medical and Image Science (CMIV), Linköping, Sweden. Department of Medicine, University of California, San Francisco, California, USA Introduction Blood flow within the cardiovascular system is driven by pressure differences, where blood accelerates from higher to lower pressure areas. Absolute pressure may not be measured non-invasively, but relative pressure fields can be calculated from velocity fields [1] acquired using MRI or ultrasound. Although relative pressure fields may be visually analyzed, such assessment is highly user dependent and qualitative. In this study we utilized pressure fields based on three-dimensional, three-directional, time-resolved (3D + time = 4D) MRI (magnetic resonance imaging) data to investigate the distribution of pressure gradients in the left heart and present a comprehensive analysis approach. Methods Ten healthy subjects underwent an MRI examination (1.5T, Philips Achieva) where 4D velocity and morphological data were acquired. Time-resolved velocity data was acquired in a 3D volume encompassing the heart with a spatial resolution of 3x3x3 mm3 and a temporal resolution of 50.4 ms. Data was reconstructed into 40 time frames and corrections were made for concomitant gradient field effects on the scanner. In-house written Matlab software was used to correct for background errors and phase-wraps. The left ventricle (LV) and atrium (LA) were segmented based on the morphological short axis images at all diastolic time frames and LV only during the systolic time frames, using freely available software, Segment (http://segment.heiberg.se). The segmentation was used as boundary condition for computation of the 4D relative pressure fields from the pressure Poisson equation. Computations were performed by the use of a multigrid solver [2]. The LV blood pool was divided into 17 segments in a similar way fashion as customary for myocardial assessment [3].In short, the segments are defined based on 4 short axis slices covering the LV from apex to base. The slice through the apex contains one segment. The basal and mid slices were divided into six 60 degrees pie segments, while the remaining apical segment was divided into four 90 degrees segments. The median and range of the pressure was computed for every segment, after the median pressure of the 17th segment (apex) was subtracted from the pressures of the other segments. Figure 1. Relative pressure fields in a three-chamber view at time of peak early filling. A healthy 50 y.o. female with a heart rate of 66 bpm. Pressure is in mmHg. LV, Left Ventricle; LA, Left Atrium. Results For every subject, the median pressure in all segments, except the apex, were plotted over the cardiac cycle (figure 3). Distinct positive and negative pressure gradients could be recognized during the acceleration and deceleration respectively, of both early and late diastolic LV filling, as well as during LV ejection. For interesting phases, as early filling, the median and range of the pressures were visualized in a so-called bullseye plot (figure 2). The bullseye plots clearly showed that the main pressure gradients were directed in the base-apex direction, while the pressure differences within the short axis were considerable smaller. Discussion Visual assessment of time-resolved intracardiac velocity vector fields is user dependent and time consuming. Computation of 3D relative pressure fields, which are scalar field, may present a deobfuscated comprehensive approach for analysis of intracardiac blood flow dynamics and may open the doors for larger clinical studies of function. References [1] Ebbers T et al. Estimation of relative cardiovascular pressures using time-resolved three-dimensional phase contrast MRI. Magn Reson Med 2001;45(5):872-879. [2] Ebbers T and Farnebäck G. Improving computation of cardiovascular relative pressure fields from velocity MRI. J Magn Reson Imaging 2009;30(1):54-61 [3] Cerqueira MD et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. Int J Figure 3. Median for all segments minus apex over time, in mmHg. Cardiovasc Imaging 18: 539-542, 2002. Black lines, basal segments; Red lines, mid segments; Magenta lines, apical segments. Subject is a 50 y.o. healthy female. Figure 2. Bullseye-plot showing a time frame of early filling in a representative 50 year old female. The median of apex are subtracted from all the segments. Each segment is represented by median and range. 28 4C2 STEGRÄKNAR-APPAR FÖR ATT FRÄMJA FOLKHÄLSAN - MEN MÄTER DE RÄTT? Anna Åkerberg1, Mia Folke1, Anne Söderlund2, Maria Lindén1 Mälardalens Högskola, Akademin för Innovation, Design och Teknik, Västerås, Sweden 2 Mälardalens Högskola, Akademin för Hälsa, Vård och Välfärd, Västerås, Sweden 1 1. Bakgrund Fast forskning visar att det är farligt för hälsan att ha en stillasittande livsstil [1], blir människor mer fysiskt inaktiva i många länder [2]. Det är väl känt att fysisk aktivitet har positiva effekter på kroppen [3-4], minskar risken för kroniska sjukdomar [5], samt har positiv påverkan på en mängd medicinska tillstånd [6]. Ett vanligt sätt att mäta fysisk aktivitet är med stegräknare, vilka har påvisat samband med ökad fysisk aktivitet [7]. Idag använder de flesta mobiltelefon och stegräknarappar möjliggör att dessa mobiltelefoner kan användas som stegräknare. Det saknas idag underlag för huruvida stegräknarappar mäter korrekt, vilket är en förutsättning för att kunna motivera till ökad fysisk aktivitet. Syftet med studien var att utvärdera noggrannhet i mätning av sex stegräknar-appar för tre mobiltelefoner, vilka bars på tre olika positioner. 2. Metod Tio testpersoner (5 kvinnor/5 män), medelålder 38 år (23-51), medel BMI 25.8 (19.9-36.6) och medellängd 1.76 m (1.671.92), gick 200 steg nio gånger i normal gånghastighet på en plan och rak väg. Stegen räknades manuellt, distansen mättes med mäthjul och tiden klockades med stoppur. Tre mobiltelefoner användes; Iphone 4 (Apple Inc., USA), HTC Sensation (HTC Corp., Taiwan) och Sony Ericsson Xperia Arc (Sony Mobile Com., UK/Sverige). Sex stegräknar-appar testades, varav tre var utvecklade för Iphone och utvärderades endast på Iphone; Ipedometer LITE (app 1), Pedometer Ultimate GPS+ (app 2) och Pedometer 24/7 FREE (app 3). Resterande tre var kompatibla med både HTC och Sony E, och utvärderades därför på båda androidtelefonerna; Pedometer by LexApps (app 4), Pedometer Levente Bagi (app 5) och Pedometer Luminant Software Inc. (app 6). Samtliga appar var tillgängliga för gratis nerladdning (laddades ner febr. 2012) och ansågs populära. För app 2-5 var känsligheten ställbar, vilken ställdes till medium/medel. Mobiltelefonerna bars i höger jackficka, i höger byxficka och i ett sportarmband på höger överarm. 3. Resultat Tabell 1. Medel antal steg och SD för varje mobiltelefon, app och position. Testpersonerna höll i genomsnitt en fart på 1.6 m/s (1.4-1.9). I en jämförelse mellan telefonerna mätte Iphone mest noggrant och den överestimerade inte heller stegen någon gång. HTC mätte mer varierat men oftast med högre SD. Sony E underestimerade stegen grovt för alla appar och positioner (se tabell 1). Mobiltelefon Iphone App Nr 1 Iphone 2 Iphone HTC 3 4 Bröstficka 124 ±96.8 Byxficka 152 ±140.8 Sportarmband 73 ±57.7 162 ±16.0 100 ±18.6 195 ±28.4 143 ±23.6 144 ±52.0 90 ±9.8 206 ±79.3 302 ±108.4 159 ±27.0 4. Diskussion 5 230 ±72.6 290 ±73.6 162 ±24.1 Majoriteten av apparna som utvärderats i denna studie klarade inte HTC 6 att utföra noggranna mätningar. Endast en kombination av HTC 128 ±57.8 139 ±90.6 145 ±61.1 mobiltelefon och app (Iphone med app 2) påvisade noggranna Sony E 4 2 ±2.7 12 ±12.6 4 ±6.0 mätningar med godtagbar SD, speciellt i byxfickan (195±28.4). En Sony E 5 3 ±1.9 43 ±92.8 15 ±14.8 svårighet med stegräknarappar är att mobiltelefonen kan bäras på ett Sony E 6 14 ±29.6 81 ±54.4 74 ±58.6 flertal sätt, jämfört med traditionella stegräknare. Eventuell inverkan av vinkeln på mobiltelefonen har därför undersökts, vilka visade att vinkeln kan ha betydelse för hur mobiltelefonen registrerar stegen, men att utförligare studier behövs för att påvisa detta. En rekommendation är därför att mobiltelefonen alltid skall bäras på samma sätt när den används som stegräknare [8]. Utvärderade stegräknar-appar kan bli praktiska, trovärdiga och användbara redskap för att mäta fysisk aktivitet då en stor del av befolkningen som redan äger en mobiltelefon då kan övervaka sin vardagliga fysiska aktivitet på ett korrekt sätt. Detta kan i ett vidare perspektiv främja folkhälsan. Referenser [1] P. Katzmarzyk, T. Church, C. Craig, C. Boouchard. Sitting Time and Mortality from All Causes, Cardiovascular Disease and Cancer, Medicine in Science and Sports & Exercise, 42, 998-1005 (2009). [2] WHO, Global Recommendations on Physical Activity for Health. Available from: http://whqlibdoc.who.int/publications/2010/9789241599979_eng.pdf, latest access on 2013; Apr 18 (2010). [3] WHO, Global Strategy on Diet, Physical Activity and Health. Available from: http://www.who.int/dietphysicalactivity/strategy/eb11344/strategy_english_web.pdf, latest access on 2013; Apr 5 (2004). [4] C. H. Hillman, K. I. Erickson, A. F. Kramer. Be smart, exercise your heart: exercise effects on brain and cognition, Nature Reviews Neuroscience, 9, 58-65 (2008). [5] ISPAH, The Toronto Charter for Physical Activity and Health: A Global Call for Action. Available from: http://wwwcflri.ca/icpah/en/dokument/CharterDocument3 ENG draft3.pdf , latest access on 2013; Mars 10 (2010). [6] K. Johansen, P. Painter. Exercise in individuals with CKD. American Journal of Kidney Diseases, 59, 126-134 (2012). [7] D. M. Bravata, C. Smith-Spangler, V. Sundaram, A. L. Gienger, N. Lin, R. Lewis, C. D. Stave, I. Olkin, J. R. Sirard. Using Pedometers to Increase Physical Activity and Improve Health: A systematic Review, JAMA, 298, 2296-2304 (2007). [8] A. Åkerberg, M. Lindén, M. Folke. Pedometer Cell Phone Applications and Future Trends in Measuring Physical Activity. In R. Martinho, R. Rijo, M. Cruz-Cunha, J. Varajão (Eds.), Information Systems and Technologies for Enhancing Health and Social Care (pp. 324-339), latest access on 2013; April 25. doi:10.4018/978-1-4666-3667-5.ch021 29 29 4C3 Ett multifunktionelt mätsystem som kan efterlikna förhållanden under en stroke: hur försvarar sig neuroner mot akut syrebrist? 1,2 1 1,2 1,2.3 Kerstin Ramser , Ahmed Alrifaiy , Olof A. Lindahl 2 3 Luleå Tekniska Universitet, Luleå, Sverige. CMTF, Center för Medicinsk Teknik och Fysik, Luleå och Umeå, Sverige. Norrlands Universitetssjukhus, Umeå, Sweden. 1. Introduktion På senare tid har aktuell forskning gett inblick i hur vår kropp fungerar på den biokemiska nivån. Det har lett till nya terapeutiska strategier för att förhindra eller bota neurologiska sjukdomar såsom hjärncancer, stroke, Alzheimers och Parkinsons. Framstegen beror till stor grad på utvecklandet av mätmetoder som ger kunskap om hur små organismer beter sig på den biomolekylära nivån. Vår tvärvetenskapliga forskning är inriktad på att utveckla metoder för att undersöka hur levande biologiska neuroner eller hjärnvävnad försvarar sig mot syrebrist eller andra stressituationer. Vi har inriktat oss på hemoproteiner då det nyligen har visat sig att de kan förhindra skador som uppstår vid syrebrist. Vi sammankopplar ett flertal mätmetoder och ett mikroflödessystem under ett mikroskop för att undersöka hemoproteiners verkan på enstaka neuroner i nära fysiologiska miljöer, det vill säga så likt det levande som möjligt. Det har visat sig vara viktigt att kunna studera nervcellernas elektriska signaler som är ett mått på stressnivån samtidigt som man mäter hur hemoproteiner samverkar med olika molekyler och proteiner. De elektriska signaleringsegenskaperna hos nervceller eller tunna hjärnsnitt mäts lämpligen genom patch-clamp teknik [1]. Optisk Raman spektroskopi och UV-Vis spektroskopi fungerar väl för att studera haemoproteiner och de första Ramanmätningarna på tunna hjärnskivor visade att det går att skilja åt olika hemoproteiner [2]. För att kunna kontrollera syrehalten krävs det en sluten gastät flödeskammare med möjlighet till patch-clamp där man snabbt kan flöda olika lösningar av varierande syre-, och salthalt. I detta system är patch-clamp pipetten fixerad till en position och cellerna förs till pipetten med hjälp av en optisk pincett [3] som är en beröringsfri optisk manipuleringsmetod där biologiska celler fångas i ett starkt fokuserat laserljus som här förflyttas med hjälp av ett xyz-bord. Vi kommer att presentera de senaste framstegen i utvecklandet av mätsystemet där röda blodceller användes som modell. 2. Metod och resultat Ca 10 microliter blod tappas ur fingret från en frivillig och blandas ut i fysiologisk fosfatbuffertlösning. Lösningen sattes in i en spruta som kopplades till en kontinuerlig pump med ett flertal sprutor som reglerades genom individuellt programmerbara tryckkolvar (Cetoni, Tyskland). Mikroflödessystemet i plexiglas (PMMA) ritades upp i ett CAD program och frästes i en CNC styrd maskin. Mikroflödessystemet hade en kanal med en gastät ingång för patch-clamp pipetten som fördes in till en fix position med en mikrometerskruv. Pipetten var dragen med en pipettdragare (Kopf750, David Kopf Instuments, USA) och fylldes med intracellulär lösning och en elektrod. Pipetten kopplades till pipetthållaren (Axon Digitada, USA) utrustad med signalförstärkaren (Heka 7, Tyskland). Signalerna behandlades av mjukvara (pclamp 7, Axon, USA). Raman spektrometern (Schamrock 303, Andor technology, UK, våglängd 532 och 830 nm) eller UV-Vis spektrometern (HR 400 Ocean Optics, USA) kopplades till sidoporten av det inverterade mikroskopet (IX71, 100x, 1.4 NA, Olympus, Japan). Mikroflödessystemet sattes på xyz-bordet. Syrehalten kontrollerades genom att införa fysiologisk buffert med 0% eller 21 % syrehalt, uppmätt av syresensorn (FOXY AL 300, Ocean Optics, USA), med en kontinuerlig peristaltisk pump (Knauer, HPLC K-501, Knauer, Tyskland) in i mikroflödessystemet. Referenselektroden sattes i en utgångskanal som fungerade som utlopp. En optisk pincett, bestående av en strålexpander (1:5) och en NIR laser (200mW, 808nm, IQ1A, Power Technology, USA) tillfördes genom bakre ingången av mikroskopet. 3. Resultat och diskussion Patch-clamp pipetten justerades till att generera en pipettspets som gav en resistans mellan 10-15 MΩ vilket motsvarar en diameter som ligger under en micrometer, vilket är nödvändigt för att studera deformerbara röda blodceller. Pipetten sattes på pipetthållaren som var kopplad till en vinklad mikrometerskruv. Genom mikrometerskruven kunde pipetten sättas i exakt och fix position inne i kanalsystemet vilket observerades genom mikroskopet. Resistansen uppmättes och registrerades i mjukvaran. Efter det kunde de röda blodcellerna lätt införas i systemet. Genom den optiska pincetten kunde de fångas och föras fram till pipettspetsen där de med undertryck sögs fast vid pipettspetsen för att åstadkomma en hög resistans (200-1500 MΩ). Buffert med varierande syrehalt (21% - ca 0-1%) pumpades in i flödeskammaren till den röda blodcellen. Den minsta uppmätta syrehalten låg mellan 0-1% vilket skall jämföras med tidigare mätningarna där den minsta syrehalten varit bäst 7%, vilket motsvarar normala syrehaltnivåer i hjärnan. Detta är en klar förbättring. Optisk spektroskopi kunde utföras samtidigt som den röda blodcellen var patchad, dvs fäst vid pipettspetsen. Experiment på att få en högre kontaktresistans för att kunna utföra ett komplett protokoll för patch-clamp mätningar är pågående. 4. Slutsats Framstegen med den första prototypen av den syretäta mikroflödeskammaren är lovande [4]. Syrehalten kunde sänkas rejält jämfört med konventionella system. På så sätt blir mätningarna mer likt de förhållanden som råder i hjärnan under en stroke. Det är viktigt för att kunna se i realtid hur hjärnan försvarar sig mot syrebrist och de första Ramanmätningarna har visat att det är möjligt att studera hemoproteiner i realtid [2]. Vårt slutgiltiga mål är att förstå hur proteinet fungerar för att kunna utveckla preventiva mediciner, som aktiverar eller bromsar Ngb, för att hjälpa människor i riskzonen för hjärncancer, stroke, Alzheimers eller Parkinsons. References [1] E. Malinina, M. Druzin, K. Ramser, S.Johansson, 7th Forum of European NeuroScience FENS, Amsterdam, Netherlands, 2010, pp. 014.020. [2] K. Ramser, E. Malinina, S. Candefjord, Applied Spectroscopy, 2010, 66(12), pp 1454-1600. [3] K. Ramser, H. Dagtorp, Journal of Biophotonics, 2010, 3 (4), pp 187-206. [4] A. Alrifay, K. Ramser, Biomedical Optics Express, 2012, 2(8), pp 2299-2306 30 4C5 DISPOSABLE CHIP TO ENABLE METERING IN DRIED BLOOD SPOT SAMPLING Gabriel Lenk1, Anton Pohanka2, Göran Stemme1, Olof Beck3, Niclas Roxhed1 1 Micro and Nanosystems, KTH Royal Institute of Technology, SWEDEN 2 Dept. of Laboratory Medicine, Karolinska Institutet, SWEDEN 3 Dept. of Medicine, Division of Clinical Pharmacology, Karolinska University Hospital, SWEDEN This work presents a disposable chip for metering and transferring an exactly defined liquid volume into a paper matrix using self-actuated dissolvable valves. Once a liquid droplet of 20-50 µl is applied to the chip, a volume of 1 µl is automatically metered, separated from the applied volume and subsequently transferred into conventional Whatman 903 paper used in Dried Blood Spot (DBS) sampling. Background: With increased sensitivity in analysis techniques such as HPLC-MS/MS, DBS sampling is considered to be a simple and convenient alternative to venous blood sampling, especially interesting for Therapeutic Drug Monitoring (TDM) [1]. However, conventional DBS sampling stores an unknown volume of blood from a fingerprick in a paper matrix, thus making quantitative analysis inaccurate. The problem with quantitative analysis of DBS stems from the unknown volume that is stored in a punched out disk from the spot. Inhomogeneous distribution of analytes within the spot is caused by hematocrit and chromatographic effects in the paper [2,3]. An engineered solution to ensure exact blood volume sampling directly from a fingerprick into conventional DBS paper has, to the best of our knowledge, not been reported yet. This work: The chip we present consists of a combination of DBS paper, structured transparencies and a dissolvable thin film (DTF). The DTF separates a microfluidic layer (inlet, channel, outlet) from a paper storage layer and controls by its thickness the timing sequence of different events (fig.2). When a droplet is applied to the chip inlet, capillary filling of a microchannel occurs which defines a precise volume. Once the barrier between the microfluidic layer and the storage layer is broken up, the fluid is absorbed by the paper matrix. This cause a pinch of at the beginning of the channel where the excess volume is first absorbed and separates the defined volume, which is then sucked out from the channel through the outlet by the capillary forces in the paper matrix. The whole stored spot at the outlet can now be punched out. Since the volume has been metered in the microchannel, spot inhomogeneity is no longer a concern. Results: From 64 tested chips 55 showed a successful filling sequence. Quantitative measurements using HPLCMS/MS showed metered dried liquid spots (DI-water spiked with amphetamine) with a volume of 0.86 µl (±0.099 µl). The working principle was also demonstrated with blood from a fingerprick. Conclusion: This paper demonstrates a disposable and accurate low cost chip for microliter metering of liquid samples into a DBS paper matrix. The presented method offer a viable solution to achieve quantitative measurements from simple and convenient DBS sampling which may have an enormous impact on individualized drug therapy and TDM. [1] Edelbroek et al., Dried Blood Spot Method in Therapeutic Drug Monitoring: Methods, Assays, and Pitfalls., The Drug Monit. 2009. [2] Spooner et al., Dried Blood Spots as a Sample Collection Technique of pharmcokinteics in Clinical Studies…, Anal Chem, 2009 [3] O`Mara et al., The effect of hematocrit and punch location on assay bias during quantitative bioanalysis of DBS samples, Bioanal, 2011. Figure 1: Comparision of DBS on Whatman 903. Left side: a DBS paper with the punch taken from its center, the dark outline of the spot indicates inhomogeneous spot properties. On the right: punched out chip-DBS of ~1 μl, the whole outline of the spot is on the sampled disk. 31 Figure 2: Illustration of the metering sequence showing the cross-section of the chip with the corresponding top view picture during application of a undefined blood volume from a fingertip. The chip extracts a defined volume from the applied droplet, separates it and transfers it to the paper matrix. 31 4C6 VIRTUELL VIT KÄPP FÖR DEN SEENDE RULLSTOLEN 1 2 2 2 Daniel Innala Ahlmark , Maria Prellwitz , Jenny Röding , Lars Nyberg , Kalevi Hyyppä 1 2 Institutionen för system- och rymdteknik Institutionen för hälsovetenskap Luleå tekniska universitet 1. Bakgrund Att ge sig ut på okända platser är en stor utmaning för synskadade. Färdtjänst och ledsagarservice underlättar, men då krävs tidig planering för varje utflykt. Detta kan resultera i att man helt enkelt hoppar över vissa utflykter man annars skulle tänkas göra. Vi utvecklar en virtuell vit käpp som kan användas för att på flera meters avstånd och utan fysisk kontakt upptäcka hinder och riktmärken i omgivningen. Detta gör att man får en bättre överblick över ett större område, i likhet med hur synen används. Med denna information blir det lättare att hålla koll på var man är och vart man ska. Många navigationshjälpmedel för synskadade har utvecklats men ytterst få används. Detta kan bero på att de är för svåra eller ansträngande att använda i förhållande till vad de tillför, eller att den underliggande tekniken inte är eller upplevs tillräckligt tillförlitlig. Ett lättanvänt och tillförlitligt navigationshjälpmedel bör leda till ökad trygghet, möjlighet till en mer spontan livsstil, sänkt ledsagarbehov och bättre livskvalitet. 2. Vår lösning Systemet bygger på ett naturligt användningssätt som påminner om den vita käppen. Detta bör resultera i att systemet är lättare att lära sig använda och lita på. Det använder varken GPS eller kartinformation och kan därmed användas överallt och utan oro över att systemets karta inte stämmer med verkligheten. Vi låter synskadade användare utvärdera systemet tidigt och påverka utvecklingsprocessen. Detta görs i samarbete med forskare från institutionen för hälsovetenskap vid Luleå tekniska universitet. 3. En första utvärdering En handfull synskadade personer har testat systemet. Syftet med detta var framför allt att avgöra huruvida det är intuitivt att ta till sig och använda information om närliggande hinder via haptik. Försökspersonerna observerades och intervjuades efteråt. På detta sätt framkom många värdefulla synpunkter för framtida utveckling av systemet. 4. Resultat Försökspersonerna var alla vana vid den vanliga vita käppen. Detta märktes i hur snabbt de förstod och började använda systemet. Ingen uttryckte otrygghet, men en del kommenterade att det krävdes mycket koncentration att använda systemet. Att bedöma avstånd till hinder upplevdes som svårt, troligen främst på grund av att de aldrig testat systemet tidigare. Att kunna känna på ett längre avstånd sågs som den primära nyttan med systemet. Fortsatt forskning kommer fokusera på en bärbar enhet som bygger på liknande användningssätt. 32 1 Figur 1: Laserskannern mäter avstånd till föremål i omgivningen. Figur 2: En förenklad 3D-modell av omgivningen skapas. Figur 3: 3D-modellen upplevs via känseln, med hjälp av en haptisk robot. Sammanfattningar Medicinska Bilder II Session 1D Moderator: Anna Bjällmark 33 1D1 A NEW METHOD FOR OBTAINING HIGH-RESOLUTION VELOCITY DATA FROM MAGNETIC RESONANCE IMAGING? Jonas Lantz, Tino Ebbers Department of Science and Technology (ITN), and Center for Medical Image Science and Visualization (CMIV), Linköping University 1. Introduction With phase-contrast magnetic resonance imaging (PC-MRI), it is possible to measure blood flow in vivo. Besides the three velocity components, it has also been shown that the turbulent kinetic energy can obtained [1]. The spatial resolution of flow measurements is typically on the order of millimetres, while the temporal resolution is on the order of 20-40 milliseconds. In addition to the relatively low resolution (15-20 voxels over a typical aortic diameter), partial-volume effects close to the arterial wall can have a detrimental effect on the flow measurement. In order to obtain high-resolution MRI-data, naïve interpolation between measurement points will not reproduce small flow scales, but instead introduce unphysical flow features and violate conservation of mass and momentum. To overcome this, and obtain high-resolution MRI-data, we here present a new method of obtaining a high-resolution flow field from PC-MRI-measurements using the governing flow equations to fill in the gaps, while at the same time obey the laws of physics. 2. Method The Navier-Stokes equations are the governing equations for any flow field and completely describe the fluid flow. They can be used to compute the flow field inside large vessels using 2D PC-MRI data as inflow boundary conditions [2]. This approach, computational fluid dynamics (CFD), may become inaccurate due to sensitivity to uncertainties in boundary conditions and unavoidable modelling assumptions in the numerical algorithms, which makes its use challenging for complex flow fields due to e.g. diseases. We developed a new technique, which utilizes the full potential of 4D flow MRI, where internal conditions are used together with standard boundary conditions. These internal conditions are based on the 4D PC-MRI measurement and act as momentum sources or sinks. In this study, this approach was tested on a part of the abdominal aorta with a renal artery, see Figure 1. The time-resolved 3D velocity field and anatomy were measured using a 1.5 T Philips Achieva MRI system. From this measurement, a time-resolved 3D high-resolution velocity field was computed using the proposed approach. For comparison, a conventional CFD simulation was performed, utilizing solely the inflow boundary condition from PC-MRI. The simulation software was Ansys CFX 14.5. Figure 1: Surface of the artery in the study. 3. Results Initial results are presented in Figure 2, where it can be seen that the MRI-enhanced CFD simulation with internal conditions agree better with the MRI simulation compared with the standard CFD simulation that only used MRI-data as boundary conditions. [m/s] Figure 2: Cross-section of the artery just proximal the branching renal vessel (see Figure 1), color showing velocity magnitude at peak flow rate. Left: MRI measurement, middle: MRI-enhanced CFD simulation, right: conventional CFD simulation. 4. Discussion The initial results show that the method may allow for enhancement of time-resolved 3D flow MRI data and yields the expected effects. The MRI-enhanced flow field corresponds to the MRI-measured flow, while the conventional CFD simulation gives a somewhat different velocity distribution. In addition to the enhanced MRI-data, flow parameters such as wall shear stress, which is very sensitive to the near-wall resolution as it depends on the velocity gradient at the wall, can easily be computed directly from the PC-MRI data without any assumptions on the velocity profile. This study shows the potential of this approach for PC-MRI, but may also be used in combination with other imaging techniques such as ultrasound Doppler. Further research is necessary to extend and evaluate this approach for other geometries, noisy data, data with artefacts due to e.g. the present of prosthetic devices, and turbulent flow. References [1] P. Dyverfeldt et al. MRM 28, p 655-663, 2008 [2] J. Lantz et al. J Biomech Eng. 45, 537-542, 2012 34 1D2 Intra-Cardiac 4D flow MRI using spiral k-space trajectories 1 S. Petersson1, A. Sigfridsson2, C. Carhäll1, T. Ebbers1 2 Linköpings universitet, Linköping, Sweden. ETH Zürich, Zürich, Switzerland 1. Introduction Time-resolved three-dimensional phase contrast MRI (4D flow) is a powerful tool for hemodynamic assessment in the cardiovascular system. However, the application of the method has been hindered by long scan times. By using spiral k-space trajectories, improved efficiency provides a means of reducing scan times without decreasing SNR. Spiral readouts have previously been used for 4D flow measurements in the aorta using prospective ECG gating [1]. Using retrospective gating, the entire cardiac cycle is covered, which allows analysis of late diastole and tracking of blood over a complete cardiac cycle. These are crucial for cardiac 4D flow studies, and allow for pathline based data quality assessment. The aim of this work is to develop a retrospectively gated 4D flow sequence using a stack of spiral readouts for the measurement of intra-cardiac velocities. 2. Methods A retrospectively gated 4D flow sequence using a stack of spirals was implemented on a Philips Achieva 1.5T. Six healthy volunteers (age 28±3 years) were imaged. The following parameters were used for the spiral measurements: field of view 280x280x101-112 mm3; voxel-size 2.8 mm isotropic; VENC 1.2 m/s; temporal resolution 48 ms; spiral duration 5.5 ms; 10 spiral interleaves. A Cartesian scan with the same spatial resolution using a SENSE reduction factor of 2 was carried out for comparison. The data quality was evaluated by comparison with 2D through–plane velocity measurements in the proximal ascending aorta and quantitative pathline analysis. Pathlines were released backward and forward from the left ventricle (LV) to compute inflow and outflow volumes for the LV [2]; a small difference between the inflow and outflow values indicates good data quality. Furthermore, to facilitate aortic flow comparison, the 4D flow data was reformatted to the same slice location as the 2D data. 3. Results Using spiral k-space trajectories, a 57% reduction in scan time could be achieved compared to the Cartesian scan, as shown in Table 1. Comparison with the 2D through-plane measurement does not show any decrease in data quality. The outflow values from the pathline analysis were slightly lower for some of the spiral acquisitions. Visual inspection of the pathlines did not reveal any major differences in data quality (see Figure 1). Table 1. Results for 6 healthy volunteers (mean ± std). Scan time [min] |Outflow-Inflow| [ml] Spiral 13±3 7.7±7.5 Cartesian 30±7 4.9±3.7 Inflow [ml] 91±21 Outflow [ml] 84±22 Aortic flow [ml] 92±12 91±16 89±16 91±11 2D Cartesian - - 93±20 - - Figure 1: Pathlines visualizing the blood flow going from the left atrium, trough the ventricle, out in the aorta from 4D flow measurements from one of the healthy volunteers using a) spiral readouts and b) Cartesian readouts. 4. Conclusion A retrospectively gated spiral 4D flow sequence was successfully implemented. The spiral readouts resulted in more than a two-fold reduction in scan time compared to a conventional Cartesian scan, which was already accelerated using parallel imaging, without any notable loss in data quality. Additional improvements in scan time and resolution can be obtained by using parallel imaging. References [1] Sigfridsson MRM 2012 [2] Eriksson JCMR 2010 35 1D3 BLOCK-MATCHING METHODOLOGIES USING BLOCK EXPANSION IN THE TIME DOMAIN FOR IMPROVED SPATIAL RESOLUTION AND INCREASED ROBUSTNESS – AN IN VIVO EVALUATION 1 1 2 1 John Albinsson , Åsa Rydén Ahlgren , Magnus Cinthio 2 Electrical Measurements, Lund University, Lund, Sweden. Clinical Physiology, Lund University, Malmö, Sweden. 1. Introduction The dynamics of the arterial wall is an important component of the dynamics of the cardiovascular system and an important investigative tool for studying the effects of vascular disease and aging. The radial movement, i.e. arterial diameter change, has been extensively investigated by ultrasound since the 1970’s and forms the basis for estimation of arterial wall stiffness. Presently, measurement of the longitudinal movement of the arterial wall has shown a distinct bi-directional multi-phasic movement of the same magnitude as the diameter change in the common carotid artery. Moreover, the inner layers of the arterial wall showed a larger movement than the outer layer thus introducing an intramural shearing in the arterial wall. We propose the hypothesis that the use of an extra block will lead to motion estimations in ultrasound B-mode images with an increased spatial resolution while the accuracy is maintained. The hypothesis was tested on clinical ultrasound cineloops consisting of in vivo measurements of the longitudinal movements of the intima-media complex of the common carotid artery. The motion estimation was compared to both the basic method without use of an extra block and to our golden standard method [1] for measurement of the longitudinal movement of the arterial wall. 2. Method The basic tracking method [2] incorporated 1) a sparse iterative block-matching algorithm and 2) a sub-pixel determination method. The primary block was expanded in the time domain by use of the information the block had in the previous frame. A full-search block-matching scheme for the extra block was conducted within a limited search range (±2 pixels). The two resulting positions (not necessarily the same) were used for sequent sub-pixel determination. The position of the tracked block was then calculated as the spatially averaged sub-pixel position over both blocks. The size of the blocks was set individually and independently by the operator for each tracking method and cineloop to obtain an acceptable level of tracking accuracy. The size of the primary block and the extra block were equal in each measurement. The common carotid artery on the right side of the volunteers was scanned in the longitudinal direction with a horizontal orientation in the image. On each of the 20 healthy volunteers (10 males; age 27–57 years and 10 females; age 25–49 years), two independent measurements were made. Electrocardiogram was recorded during all the measurements. All investigations were performed with a commercial ultrasound system (HDI5000, Philips Medical Systems, Bothell, WA, USA). 3. Result In the in vivo measurements (n = 40) the antegrade movement, i.e., a displacement in the direction of the blood flow, in early systole was mean 312 µm (SD 197) using the basic method with the use of an extra block. The following retrograde movement, i.e., a displacement in the direction opposite of the blood flow, was mean -706 µm (SD 222). The subsequent antegrade movement was mean 577 µm (SD 218). The intraobserver variation (CV) was 22%, 18% and 22% for the different phases of movement, respectively, using the basic tracking method and 21%, 13% and 17%, respectively, using the basic tracking method with the use of an extra block. Though the mean area of the block was decreased, the intra-observer variation when using the basic method was maintained when the basic method with the use of an extra block is used. Using the Figure 1: Difference against mean for the basic method, the area of the block was mean 0.31 mm2 (SD 0.13) in the measurements of the three major longitudinal 2 range of 0.15–0.76 mm , whereas using the basic method with the use of displacements. an extra block, the area of the block was mean 0.25 mm2 (SD 0.09) in 2 the range of 0.09–0.51 mm . This equals a decrease in the area of the block by 19% (p<0.01). Figure 1 shows the difference against the mean between the basic method using an extra block and the golden standard method. Six cineloops were excluded as they contained no specific echo structure with enough stability and thus the golden standard method was not able to track the echoes in them. 4. Discussion The incorporation of an extra block in the tracking was hypothesized in this study to increase the spatial resolution of a tracking method while maintaining the tracking accuracy. The basic method with the use of an extra block was compared to our golden standard method; a tracking method specialized for estimating arterial wall movements. The estimated movements of the two methods are compared in Figure 1. Reported CV values for the golden standard method are 14%, 13%, and 16% for the first antegrade, the retrograde, and the second antegrade movement respectively [3]. The figure and the CVvalues show that the basic method with the use of an extra block has a tracking accuracy of the same magnitude as the golden standard method without any discernible bias. As can be seen, the golden standard method gave CV-values that are lower than those from the proposed method, but with a higher demand on the stability of the echo structures in the cineloops. In six of the 40 in vivo cineloops, the stability of the echo structures was too low for the golden standard method to successfully estimate the movements. Please note that the proposed method successfully estimated the movements in these cineloops. References [1] M. Cinthio, Å. R. Ahlgren, T. Jansson, A. Eriksson, H. W. Persson, and K. Lindström, IEEE Trans. Ultrason. Ferroelectr. Freq. Control, 52, 1300-1311 (2005). [2] J. Albinsson, S. Brorsson, F. Lindgren, Å. R. Ahlgren, and M. Cinthio, Proc. IEEE Ultrason. Symp., 2000-2003 (2010). [3] M. Cinthio and Å. R. Ahlgren, Ultrasound Med. Biol., 36, 697-704 (2010). 36 1D4 IMAGE ENHANCEMENT AND REDUCTION OF RADIATION DOSE FOR PANORAMIC DENTAL X-RAY IMAGING 1 1 Hamed Hamid Muhammed School of Technology and Health (STH), Royal Institute of Technology (KTH), Alfred Nobel Allé 10, SE-141 52 Huddinge, Sweden Keywords: Image enhancement, X-ray dose, PCI-operation, panoramic dental X-ray 1. Background Reducing the X-ray dose too much produces images with low quality; Noisy, blurred, faded, under exposed. The approach used in this work aims at enhancing image quality by using advanced automatic image processing algorithms. 2. Purpose To minimize X-ray dose exposure during panoramic dental X-ray imaging, in addition to automatically enhancing the acquired X-ray images to achieve high quality images that can be viewed using ordinary monitors. 3. Method An automatic, adaptive image enhancement algorithm was developed and implemented on multi-core CPU as well as GPU to achieve real time performance. 4. Results The method was tested on panoramic dental X-ray images acquired with varying radiation dose. The results were promising and indicated the possibility of obtaining diagnostically usable images using a reduced dose by 50%. A group of ten dentists and specialists evaluated the resulted images. Figure (1) shows a comparison between an enhanced panoramic dental X-ray acquired with reduced dose by 50% and an original (unprocessed) panoramic dental X-ray acquired with a standard dose. 5. Discussion and conclusions This study shows the possibility to achieve a number of goals that can lead to better patient safety and better healthcare in general, such as: • • Minimized X-ray dose to the patient, which can lead to reduced risk of physical damage (e.g. cancer) and psycological consequences (e.g. stress). Better image quality which can lead to better, faster and more accurate and confident diagnostic. The resulted enhanced images can be automatically produced without any noticeable waiting time and viewed using any ordinary monitor (LCD/LED TV or computer screens) without any need for any expensive/exclusive high-dynamic-range displays. Figure 1: comparison between (a) an enhanced panoramic dental X-ray acquired with reduced dose and (a) another original one acquired with a standard dose. 37 1D5 MICROWAVE IMAGING SYSTEM UNDER DEVELOPMENT FOR BREAST CANCER DETECTION 1 1 1 Andreas Fhager , Mikael Persson Chalmers University of Technology, Göteborg, Sweden Abstract Microwave imaging for breast cancer detection is investigated. Through numerical and experimental studies an imaging system has been studied and evaluated for use in breast cancer imaging. Results are promising and clinical trials are within reach. Keywords: microwave imaging, breast cancer, image reconstruction 1. Introduction Breast cancer is a serious health problem for women. According to national statistics of Sweden from year 2007 it is the most common cause of death from cancer among women, with about 30 yearly deaths per 100,000 inhabitants, (1). The standard method for breast cancer diagnosis today is X-ray mammography. Despite its recognized ability to detect tumors it suffers from some limitations. Neither the false positive nor the false negative detection rates are negligible. This leads to a number of unnecessary additional investigations and, more seriously, a fraction of the tumors are not detected at an early stage which is a prerequisite for efficient treatment. An interesting alternative being researched extensively today is microwave tomography. From measurements on excised tissue a significant dielectric contrast has been observed between the healthy and malignant tissue. 2. Theory In microwave tomography the object under investigation is surrounded by a number of transmitting and receiving antennas. In the measurements each antenna is operated as a transmitter as well as a receiver for every possible combination of antennas. In this work an iterative algorithm has been used for reconstructing the dielectric parameters of the target object under test. It is based on electromagnetic simulations of the antenna system and the image is reconstructed based on a comparison with the scattering measurements of pulses for the different transmitter/receiver combinations. The difference between the measured and the simulated signals is used to update the dielectric properties in the target region. As the reconstruction of the target object is iteratively refined, the simulated and measured signals converge. The assumption is that when the difference is sufficiently small the reconstruction is completed. 4. Results and discussion In this paper we will present results from our investigation and evaluation of the design of a clinical prototype for reaching the performance required for accurate image reconstruction in the clinical situation. See figure 1 for an illustration of the proposed imaging system. 5. Conclusions There is a need for novel breast cancer detection systems to overcome the limitations with today’s modalities. Microwave based system has the potential to become both sensitive and specific in this application. We have studied and evaluated a possible design for a clinical system as well as developed an accurate image reconstruction algorithm to work with this system. References [1] Sweden’s National Board of Health and Welfare: “Causes of death 2007”, (Access at: www.sos.se). Figure 1: Illustration of the proposed microwave system. 38 1D6 A NEW METHOD FOR VESSEL SEGMENTATION BASED ON A PRIORI INPUT FROM MEDICAL EXPERTISE IN PHASE-CONTRAST MAGNETIC RESONANCE IMAGING SEQUENCES Sebastian Bidhult1, Marcus Carlsson1, Håkan Arheden1, Einar Heiberg1,2 Department of Clinical Physiology, Skåne University Hospital Lund, Lund University, Sweden. 2 Centre for Mathematical Sciences, Lund University, Sweden 1 Keywords: cardiovascular flow, segmentation, principal component analysis, magnetic resonance, active contours 1. Introduction Phase contrast magnetic resonance imaging (PC-MRI) is the current gold standard for quantification of blood flow in the cardiovascular system. Using this technique it is possible to quantify cardiac output, stroke volume, shunts and valve insufficiencies. The accuracy of flow quantification is highly dependent on the manual delineation of the vessels of interest. Therefore, the purpose of this study is to develop an automatic method for vessel segmentation in PC-MRI sequences. 2. Method A total of 161 patients with ejection fraction below 40% from a previous study [1] were included. For all patients manual delineations of the aorta ascendens were available in all timeframes. The subjects were randomly divided into a training set of 40 patients and a test set of 121 patients. The manual delineations in the training set were parameterized and from this parameter set a principle component analysis (PCA) were performed to extract a priori information regarding shape change and motion during the cardiac cycle for the aorta ascendens. The proposed algorithm is an active contour model initialized by a manual delineation in one timeframe. The active contour deformations are guided by vessel probability maps calculated by a statistical image classification algorithm (expectation maximization). Every third deformation is followed by a projection onto a subset of linearly independent components of the a priori dataset. This procedure is repeated 10 times. Validation was performed by comparing automated delineations with manual delineations of the aorta ascendens in the test set consisting of the 121 remaining patients. All automatic segmentations were initiated with the manual delineation in the first timeframe. Calculated stroke volume and a similarity measure (Dice coefficient) were used as performance measure. The Dice coefficient ranges from 0.0 to 1.0, where 1.0 corresponds to perfect agreement between manual and automatic delineations. Inter observer variability for manual observers was analysed for 20 patients in the previous study [1]. 3. Results The result for stroke volume is shown in Figure 1. The stroke volume from the automated method agreed well with manual delineations, with a correlation coefficient of r2 = 0.97. Bias between automated and manual delineation was -1.9 ± 3.2 ml, or -2.2 ± 4.6 % of the stroke volume. This should be compared to an inter observer variability of 3 ± 4 % [1]. The mean Dice coefficient was 0.93 ± 0.02 (range 0.83-0.97). 4. Conclusions In conclusion, the proposed method performs vessel segmentation with bias and variability comparable to gold standard manual delineations. References [1]. M. Carlsson, R. Andersson, K. Markenroth, K. Steding, H. Mosen, F. Stahlberg, B Ekmehag, H. Arheden. "Cardiac output and cardiac index measured with cardiovascular magnetic resonance in healthy subjects, elite athletes and patients with congestive heart failure." Journal of Cardiovascular Magnetic Resonance, 14(51), 2012. Figure 1: Left panel shows a scatter plot of automatically measured stroke volume, and gold standard (manual delineation). The solid line indicates line of identity. Right panel shows the Bland-Altman plot of manual and automated delineation. The dashed lines indicate ±2SD and the solid line indicates bias between the two methods. 39 Sammanfattningar Patientsäkerhet & utbildning Session 2D Moderatorer: 40 40 2D1 Patient Safety: A Measure on Reporting System and Accident Investigation in Bangladesh 1 Md Shafiqur Rahman Jabin1, Mohammad Saiful Islam2 ,Mannan Mridha1 KTH, School of Health and Technology, Stockholm, Sweden. 2BSM Medical University, Dhaka, Bangladesh 1 Introduction Bangladesh, like many other developing countries in the world, has inadequate access to safe health care not only in the rural areas but also in different hospitals, especially in public ones in the cities. Every year, a very large number of people die or get severely injured due to preventable adverse events associated with medical devices, medication error, unsafe blood collection or transfusion, surgery, anesthesia and obstetric trauma that occur during treatment or due to the negligence of the healthcare personnel or incompetent practices used in regard to the safety of the patients. As a result, patients in Bangladesh lose their trust in both public and private hospitals due to poor quality and unsafe care that cause a growing outflow of Bangladeshi patients to the hospitals of neighboring countries. Therefore, to promote patient safety, effective research studies are required to help healthcare professionals and policy makers to understand the complex causes that lead to unsafe care. 2 Method The aims of the project were to describe safety issues in selected safety-healthcare domain, lining up a measure on reporting systems of three private and three public hospitals and to make recommendations leading to the development or local adaptation of appropriate, affordable and effective solutions. The method included three different case studies. The first case study (CS1) compared rural healthcare services [1] in a village (Magura) with that of in the available in the city (Dhaka) The second case study (CS2) included a measure on safety case practices in six different public and private hospitals in Dhaka. It surveyed safety case practices, for example, suspected adverse drug reaction and its reporting system, systematic review of complex Diagnostic Laboratory and Intensive Care Unit (ICU) set up, infection control, medical devices domain and their respective reporting system on adverse events. Thus, this study assessed the main drivers and barriers and made recommendations for the adoption of safety cases and general reporting system in healthcare sectors [2]. Our third case study (CS3) involved a measure on accident investigation of a particular case in order to understand and interlink with first two case studies. Preparation of a protocol was developed initially in consultation with local experts. Information and data were collected through interviews firstly, by visiting the village doctors at their private chambers in Magura district and later from the doctors, laboratory chief, technicians and nurses in different private and public hospitals. Data evaluation and management were performed using written notes, cross tabular analysis, SPSS for all three case studies. However, the accident investigation was analyzed using RCA-MTO method and FRAM [3]. Recommendations from both these methods were generated and compared with each other. 3 Results Our project work have shown promising results indicating that the entire method has the ability to measure the extent of harm caused during healthcare delivery and subsequently prevent them and thus improve the patient safety. CS1 indicated that the most rural health care providers are neither well educated not adequately trained. Therefore, severe health hazards are common practice. Incorrect diagnosis due to lack of medical devices, unethical practices of prescribing inappropriate and unnecessary drugs by the village doctors often cause severe harm to the patients. This can be avoided by training the underskilled village doctors, and some positive impacts of e-Health activities in this area have been identified. CS2 has pointed out that the limitations of infrastructure, technology, resources and management including reporting, feedback and training cause greater risks of patient harm resulting in breakdown of entire system of patient care. It also showed that there was a complete absence of safety management and reporting system of medical adverse events especially in the public hospitals. CS3 helped to find out how adverse events occur during treatment; either due to lack of communication between surgical team members or informal methods used by the healthcare personnel. 4 Discussion Study of regulatory process was not included in the main scope of this work. However, during the course of the study, it was identified that, government regulations to report accidents are essential to ensure reporting of adverse events. Moreover, all the field studies held as part of this project brought together academicians and experts in healthcare safety along with clinicians, patient safety managers, laboratory chiefs and regulators. The dialogue resulted in bringing new insights and concerns to identify enablers and barriers to the useful adoption of safety methods in healthcare. Thus, these attempts and dialogues should continue in order to ensure that the proposed solutions remain clinically relevant and practicable to the current critical healthcare safety conditions in Bangladesh. Patients safety study is a new field in Bangladesh and there remains a considerable amount of work to be done, such as, awareness has to be developed, organizational structure needs to be enhanced, rules for safe use of medical devices have be followed, and a well- structured reporting system in public hospitals has be introduced involving patients and their families too. Acknowledgements: The study was partly supported by Swedish Research Links and MFS References [1] Shehrin S Mahmoud et al, Are Village doctors in Bangladesh a curse or a blessing? (research article), Social and Behavioral Science Unit, Public Health Sciences Division, BMC International h Health and Human Rights, 2010. [2] WHO. Draft Guidelines for Adverse Event Reporting System and Learning System, WHO/EIP/SPO/QPS/05.3 [3] Helen Alm, Woltjer R, Patient safety Investigation through the lens of FRAM; Human Factors: A system view of human, technology and organization, ISBN 978-90-423-0395-9. 41 2D2 PATIENT SAFETY REGARDING MEDICAL DEVICES AT ICUS IN BANGLADESH Tonima Afroze1, Mia I. Palmqvist1, Dr. Mohammad S. Islam2, Dr. Mannan Mridha1 and Dr Björn -Erik Erlandsson1 1 School of Technology and Health, Kungliga Tekniska Högskolan, Stockholm, Sweden 2 BSM Medical University, Dhaka, Bangladesh 1 Introduction: Healthcare errors are a persistent threat to patient safety. Up to 98,000 patients die because of human error in U.S. hospitals each year. Critical care is one of the areas in which human errors occur most frequently. Error rate was 1.7 per patient per day in the intensive care unit (ICU), 45.8 percent of ICU were associated with an adverse event, 45 percent of all error were preventable [1]. To prevent errors made at the ICU, we need to know why they arise. Intensive care units look after patients whose conditions are life-threatening and need constant, close monitoring and support from equipment and medication to keep normal body functions going. They have higher levels of skilled staff, specialist monitoring and treatment equipment. Patients with critical illness suffer from failure of one or more of their systems such as the heart, lung or kidneys. Heart attack, stroke, poisoning, pneumonia, surgical complications, major trauma as a result of road traffic accidents, a fall, burns, an industrial accident or violence are all examples of critical illnesses. Infections are a common cause of ICU admission. ICU patient is weakened and has lessened ability to fight off infections, and is too sick to protect from errors. Managing and learning from error is our priority, and can be achieved with an understanding of the roots, nature and consequences of error. Such an understanding can improve management activities and will lead to fewer care-related injuries and deaths and cost effectiveness, which favors the patient, patient’s family, the hospital and society. 2 Aim of Study: This study aimed to a) Compare the conditions of medical devices at ICUs in private and public hospitals, b) Increase understanding of errors, risks and accidents related to medical devices;, c) Study reporting systems and communication between staff at ICUs, d) Find ways to minimize hazards related to medical equipment to ensure effective and safe use of devices. 3 Method: Data was collected through interviews during field visits to three government and three private hospitals in Dhaka, Bangladesh. We interviewed the chiefs of the ICUs, physicians, nurses and technicians working at the ICUs, to find Human Error, human factors leading to accidents and to prepare a list of error-producing conditions (EPCs) that can affect both performance and the potential to increase the probability of error when a specific task is performed in the presence of these conditions. 4 Results: We found that that the nurses at the public hospitals identified many risk factors such as, work environment, workload, communication within their team, physical and mental well-being, and lack of knowledge. Organizational factors, inadequate training lack of competent technical support were also mentioned as the causes of poor performances. Public hospitals are very cheap whereas the private ones are out of reach for the majority of the population. Public hospitals offer extremely low quality services due to the limited resources. Pronounced differences could also be observed in maintenance and calibration of medical equipment, further education of staff, working environment and infection control. The reporting systems at both types of hospitals were inadequate, and the equipment procurement process was lengthy at all hospitals. Only the private hospitals had a Biomedical Engineering department, which led to better maintenance and calibration of devices. Access to disposable items was limited at several hospitals. It was found that reporting systems for adverse events and communication about patients’ conditions between coworkers was weak at all hospitals. A hierarchical medical team, an absence of self-awareness of errors, and absence of medical technicians makes patient care situation very risky 5 Discussion: Government hospitals are almost free, but the quality of care is extremely poor due to overload. The poor patients seldom question about the quality or safety aspects. Shortage of technical resources, inadequate skilled workers, poor hygienic conditions and the doctors’ conflict of interests due to their private practices at the private hospitals are some of the causes of adverse events. In order to improve the work in the ICU, a number of suggestions have been proposed. An in-house clinical engineering units at all large hospitals will result in better procurement system, proper use, management and maintenance, and adaptation of medical equipment. Educational and organizational improvements should be made, in particular, education in infection control, patient safety and user safety for health care workers. ICT can substantially improve the safety of medical care by structuring actions, catching errors, and bringing evidence-based, patient-centered decision support to the point of care to allow necessary customization [2]. Such tools can also be used for spreading information on the use, management and solutions to common technical problems related to specific devices. An internet forum for consultation on these subjects can be constructed for technicians. Based on the present findings, it appears that questionnaires—in addition to observational approaches used can be useful to identify errors at the ICU. Further study is being conducted to increase our understanding of device-related human error in the ICU. This is an important step toward the goal of reducing hazards and improving patient safety. Acknowledgements: The study was partly supported by Swedish Research Links and Minor Field Studies References: [1] Error Producing Conditions in the Intensive Care Unit by Frank A. Drews, PhD, et al. Kohn LT, Corrigan JM, Donaldson MS editors. To err is human: Building a safer health system. Washington, DC: National Academies Press; 2000. [2] Bates DW, Gawande AA. Patient safety: Improving safety with information technology. N Engl J Med. 2003;348:2526– 2534. [PubMed] 42 2D3 2D4 Renhet i operationsrum – En presentation av SIS-TS 39:2012 1 1 Philip De Geer Swedish Standards Institute 1. Introduktion SIS tekniska specifikation Mikrobiologisk renhet i operationsrum - Förebyggande av luftburen smitta - Vägledning och grundläggande krav (SIS/TS 39:2012) har nu varit tillgänglig sedan augusti 2012. Dokumentet har väckt stort intresse och varit föremål för många frågor och kommentarer. 2. Metod Den tekniska specifikationen ger funktionskrav samt vägledning till teknisk utformning av ventilation och anger metoder för utvärdering av ventilationens förmåga att avlägsna mikroorganismer från luften. Samspelet mellan kläder och ventilation beskrivs också. 3. Resultat Avsikten med denna tekniska specifikation är att ge vägledning för hur luftburen smitta till operationssår och medicintekniska produkter kan minimeras i operationsrum och angränsande lokaler. Syftet är att förebygga postoperativa infektioner förorsakade av luftburna mikroorganismer. Andra viktiga åtgärder för renhet i operationsrum är iordningsställande av rummet före och avveckling efter operation, arbetssätt och flöden för patient och personal. Dessa områden belyses men ligger utanför den egentliga ramen för den tekniska specifikationen. 43 Bättre vård med beslutsstödsystem kopplade till register 2D4 Peter Funk, Professor, Intelligenta system, Mälardalens Högskola, Västerås, [email protected], 021 10 31 53 Ett exempel på beslutsstödsystem för bättre individuell smärtlindring efter operationer är PAIN OUT, ett webbaserat beslutsstödsystem framtaget för bättre postoperativ vård. Vid de cirka 40 miljoner operationer som varje år genomförs i Europa upplever mer än hälften av patienterna höga smärtnivåer, något som ofta förlänger tillfrisknandet. I EUprojektet PAIN OUT är målet att förbättra behandlingen av patienter med smärta efter operationer för vilket vi utvecklat ett webbaserade kliniska beslutsstödsystem. – En bättre smärtbehandling förkortar tillfrisknandet och är ett moraliskt ansvar. Standardmetoder passar kanske 70 procent av alla, men ger samtidigt 30 procent av patienterna en mindre optimal behandling, där kommer PAIN OUT in. Beslutsstödsystemet använder fallbaserat resonerande, bygger på över 13 års forskning inom självlärande algoritmer och fallbaserat resonerande och utgår från patienten. Systemet identifierar liknande patienter i de cirka 37 000 patientjournaler från nio olika länder som finns i systemet och drar slutsatser från dessa. Läkarna kan fatta beslut på individuell basis, med bättre underlag, genom att se uppgifterna om de avidentifierade patienterna i registret som listar uppgifter som ålder, kön, vikt, sjukdomshistoria och annat som kan vara av vikt för smärtbehandlingen. I journalerna inom projektet har patienterna själva bedömt sin smärta före, under och efter operationerna. Beslutsstödsystemet finns på en läsplatta som specialistläkarna och kliniker kan ta med sig ut till patienterna. Där kan beslutsstödsystemet identifiera liknande patienters journaler och dra slutsatser från dessa. Det gör det möjligt för läkarna att få kunskap just i det ögonblick de behöver den, något som de som testat systemet hittills tyckt varit mycket positivt. Beslutsstödsystemet öppnar helt nya möjligheter för de kliniska specialisterna och läkarna. I dag samlas allt större volymer data in inom vården. I framtiden kommer den insamlade informationen bli grunden i fallbaserade beslutsstödsystem och kommer därmed till direkt och omedelbar nytta och värde både lokalt, nationellt och globalt. Nu blir nästa steg att ta forskningsprototypen mot en produkt tillgänglig för klinisk användning. Målet är att alla sjukhus i Europa ska använda systemet inom tre till sex år. Om PAIN-OUT: PAIN-OUT är ett forskningsprojekt med mål att förbättra hanteringen av smärta efter operationer i Europa. Projektet finansierades inom EU:s sjunde ramprogram med närmare tre miljoner euro 2010-2012. Ett konsortium har nu bildats för att få ut resultaten till sjukhusen och över 100 sjukhus i Europa har anslutit sig PAIN OUT. Peter Funk och Mobyen Ahmed ansvarar för vidareutvecklingen av beslutsstödsystemet. 16 sjukhus och kliniska forskningscentra från Spanien, Sverige, Tyskland, Frankrike, England, Italien, Schweiz och Rumänien samt många världsledande experter har aktivt deltagit i projektet. www.pain-out.eu 44 2D5 INTEGRATION AV MEDICINTEKNISK GRUNDUTBILDNING I VÅRDEN Sjoerd Haasl och Bertil Guve Centrum för Teknik i Medicin och Hälsa, KTH/KI/SLL, Stockholm 1. Sammanfattning Clinical Innovation Fellowships är en flerårig satsning där tvärdisciplinära och högkvalificerade team går in i sjukvården för att identifiera behov och utifrån dessa behov både ta fram förbättringar till sin respektive värdklinik och en uppfinning samt affärsplan som kan ligga till grund för ett startupföretag inom medicinteknik. Detta abstract beskriver programmets interaktion och synergier med grundutbildningen på KTH och andra icke-medicinska läroverk. 2. Bakgrund: om Clinical Innovation Fellowships Clinical Innovation Fellowships finansieras av KTH, KI och SLL tillsammans med Erling Perssons stiftelse. Satsningen är inspirerad av ett innovationsprogram för medtech på Stanford som heter BioDesign och som har varit väldigt framgångsrik sedan dess start 2001. CTMH startade med Clinical Innovation Fellowships 2010 och varje år i oktober tar vi in två tvärdisciplinära team som placeras på var sin värdklinik för att på ett strukturerat och systematiskt sätt ta fram kliniska innovationer utifrån kliniska behov. Teamen består av tre till fyra högkvalificerade individer (3-10 år yrkeslivserfarenhet) med kompetenser inom medicin, management, teknik och design som jobbar heltid i åtta månader. 3. Programmets mål 1. Huvudmålet är långsiktigt: vi vill skapa ett aktivt kluster inom klinisk innovation i Stockholm. Vi vill ta vara på förutsättningarna som KI, KTH, SLL och näringslivet inom medicinteknik i regionen ger genom ett nätverk av kliniker, entreprenörer och forskare med ett intresse för medicinteknisk innovation där Fellows utgör centrala noder. 2. Att utbilda framtidens ledare inom klinisk innovation: fellows är innovatörer med en djup förståelse för den kliniska miljön och medtechindustrin 3. Att skapa förbättringar som direkt gynnar värdklinikerna samt innovationer som leder till nya medicintekniska företag i Stockholm 4. Upplägg: åtta månader Tidsschemat för de åtta månaderna speglar designmetoden framtagen av Stanfords Biodesign Fellowships och tillämpas även i Dublin, Barcelona, Singapore och Stockholm: vecka 1-2: En intensiv utbildning i Biodesigns innovationsprocess och i värdklinikens verksamhet, både medicinsk, organisatorisk och finansiell. Utbildningen fortsätter även efter v2 i form av ett seminarium varje vecka kring relevanta ämnen, såsom hälsoekonomi, offentlig upphandling, CE-märkning, affärsplan osv. vecka 3-7: En klinikvistelse där kandidaterna har full tillgång till hela verksamheten och observerar genom att följa och intervjua läkare, sköterskor och patienter vecka 8-10: En formulering och kvantifiering av kliniska behov utifrån observationerna. Behoven kvantifieras utan att de tänker på specifika lösningar: hur mycket lidande skulle man slippa om behovet löstes? Hur många liv skulle sparas? Hur mycket arbetstid sparas? Hur mycket skulle en klinik vara villig att betala för att lösa behovet? Är detta ett behov som bara finns på denna klinik, eller även på andra ställen? Osv. vecka 11-34: Lösningsfasen, framtagning av tre leverabler: a. en rapport till värdkliniken med behov och lösningsförslag b. tre examensarbeten som löser kliniklokala behov, dvs behov som har stor effekt för värdkliniken, men inte nödvändigtvis behöver ligga till grund för ett företag c. en affärsplan för kommersialisering av en medicinteknisk innovation Vid framgångsrik avslutning av programmet diplomeras deltagarna med titeln Clinical Innovation Fellow vid KTH och KI. 5. Synergier med grundutbildning Under de första tre åren har programmet visat sig leda till stora synergier med grundutbildningen. Utgående från behov som de har identifierat under sin klinikvistelse har Fellows handlett: 1. Examensarbeten inom medicinteknikutbildningen på KTH, både på kandidatnivå (22 studenter) som på masternivå (3 studenter) 2. Examensarbeten inom andra områden (Industriell ekonomi, Företagsekonomi, ICT, Matematik) på KTH, Lunds Universitet och Stockholms Universitet, även här på kandidat och masternivå (2 resp 7 studenter) 3. Projektarbeten inom kursen Produktutveckling inom den biomedicinska industrin, på Unit of Bioentrepreneurship på Karolinska Institutet: 42 studenter. Förutom dessa projekt- och examensarbeten involveras fellows vid olika tillfällen i grundutbildningar, både som föreläsare (på KTH, Konstfack) och som sakexperter kring behov. 6. Slutsatser Studenterna får, tack vare dessa behov samt genom fellowshandledningen och de kontaktytor som fellows har mot vården, en ovärderlig relevans till den värld som de utbildas för att verka i. Samtidigt bidrar studenternas arbete direkt till de förbättringar som fellows har som uppdrag att leverera till sin värdklinik. För representanterna från sjukvården är kontakten med projekt- och examensarbetare oftast ett nytt arbetssätt. Värdklinikerna har vid upprepade tillfällen uttryckt en stor uppskattning för det arbete som studenterna utför under ledning av fellows. 45 MEDICINTEKNISKA INGENJÖRER 1 1 2D6 2 Anna Hagman , Karin Nilsson 2 Kungliga Tekniska Högskolan, Stockholm, Sweden. Kungliga Tekniska Högskolan, Stockholm, Sweden 1. Bakgrund Allt fler lever längre, allt fler blir sjuka, allt fler önskar en ökad livskvalitet. Allt fler söker en möjlighet för sjuka att bli friska, och för redan friska att må ännu bättre. Framtidens vision om en högre välfärd gör hälsa och välbefinnande för alla individer till samhällets viktigaste och största utmaning. Med en djup kunskap inom både teknik och medicin, ligger medicintekniska ingenjörer i framkant med en inbyggd vision om att öka graden av medicinsk innovation – medicinsk innovation som skall leda till mer effektiva hjälpmedel och därmed en högre välfärd. Hos medicintekniska ingenjörer finns all den kunskap som behövs för att underhålla och utveckla den allt mer teknologiskt avancerade vården. Detta samspel av medicinsk och teknisk kunskap, skulle genom en interaktion mellan näringsliv och studenter skapa en plattform för framtiden. 2. Utbildning Kungliga Tekniska Högskolan tillhandahåller två unika program vilka är inriktade mot medicinsk teknik – en treårig högskoleingenjörsutbildning samt en femårig civilingenjörsutbildning. Civilingenjörsutbildningen var den första i Sverige, och startade år 2008. Utbildningarna skiljer sig på så sätt att högskoleingenjörsutbildningen är mer praktiskt inriktad, medan civilingenjörsutbildningen är mer teoretisk. Vad de två utbildningarna har gemensamt är den medicintekniska inriktningen. Vid sidan av klassiskt tekniska kurser som matematik, fysik, programmering och reglerteknik, läses kurser som fysiologi, bioteknik, medicinska bildgivande system samt kvalitet och regelverk inom medicinsk teknik. Detta lägger grunden för ett tvärvetenskapligt tänkande, med en inblick i både människa och samhälle. Det skapar en bred kompetens med mycket goda gränsöverskridande kunskaper inom medicin och teknik. Det utvecklar en stark analytisk förmåga – en förmåga att analysera och lösa problem genom innovativt tänkande. 3. Framtid En utbildad medicinteknisk ingenjör har stor kompetens att arbeta inom såväl sjukhusbranschen som vid företag som utvecklar, tillhandahåller eller inriktar sig mot medicinteknisk apparatur. En medicinteknisk ingenjör kan arbeta med forskning och utveckling, med undervisning eller entreprenörskap. En medicinteknisk ingenjör kan vara företagsledare, projektledare, produktutvecklare eller konsult. En medicinteknisk ingenjör är en tillgång i alla företag eller projekt som har en samverkan mellan människa och teknik. Utbildningen är ännu ung och namnet har inte hunnit etableras än, varför många företag inte känner till de kommande ingenjörerna. Att behovet av dessa ingenjörer är stort är dock ett faktum, att sprida studenternas namn och kunskap likaså. Programmet är skräddarsytt efter framtidens behov och önskemål, vilket ger studenterna en exklusiv spetskunskap. Medicintekniska ingenjörer är unika. Genom utbyten som examensarbeten, praktikplatser, sommarjobb eller företagsevenemang ökar interaktionen mellan näringsliv och studenter. Genom att inleda en diskussion och ett samarbete, byggs en bro mellan behov och kunskap - en gemensam väg som leder mot en friskare framtid. 46 Sammanfattningar Sensorer och implantat Session 4D Moderator: Fernando Seoane 47 47 4D1 A micromachined millimeter-wave medical sensor for skin-cancer diagnosis Fritzi Töpfer1, Sergey Dudorov1, Dragos Dancila2, Robin Augustine2, Xin Hu2, Lennart Emtestam3, Kari Gustafsson4, Lars Tenerz5, Anders Rydberg2 and Joachim Oberhammer1 1 2 KTH Royal Institute of Technology, Uppsala University, 3Karolinska Institutet, 4ADAKT AB, 5OPTIGA AB 1. Medical motivation Skin cancer is the most common cancer in the age group of 15-45 years. Incidents are increasing by an average of 3-6% per year since the 1960s, and melanoma are among the most deadliest cancer types with 15-20% mortality. In Sweden, there are about 2500 melanoma and 1200 precursors diagnosed per year, resulting in almost 500 deaths in 2011. A huge screening effort is needed to find skin cancer: about 50-250 screenings have to be done for finding a single melanoma. There is no established sensor technology available, diagnosis is so far been done by highly-trained dermatologists using dermatoscopes, and after extraction verified by histological analysis. In Sweden alone, about 100 000 preventive skin surgeries are performed every year, most of which are unnecessary and could be avoided if a diagnosis tool with high sensitivity/specificity would be available. Specialized dermatology departments are increasingly becoming a bottleneck. 2. Method: a drastically miniaturized, 100-GHz millimeter-wave sensor for skin-cancer diagnosis Electromagnetic waves at microwave frequencies are known to be able to distinguish healthy from tumour cells, as energy absorption above 1 GHz is significantly higher due to increased free and bound water content of fast and uncontrolled growing tissue [1]. The discrimination of healthy/cancer tissue by microwaves has also been shown for skin tumours, incl. BCC [2] and melanoma [3]. Macroscopic microwave sensors, available up to 40 GHz, have a too large interaction volume and are therefore not suitable for analysing shallow and inhomogeneous skin cancer tissue at an early stage. This paper presents the results of a micromachined millimeter-wave probe operating at 100 GHz, which has a probe tip with only 0.9% of the contact area of a conventional microwave probe and with a penetration depth matched to shallow skin cancer tissue layers, and uniquely combines high sensitivity and high resolution. Two different probe designs, a broadband design by KTH and a resonance concept by UU, have been implemented by micromachining and characterized. 3. Results: technical verification, first measurements on skin Probe prototype 1 (KTH design) has successfully been technically verified, resulting in a responsivity of S11/εr=0.47dB in the permittivity range of cancer/healthy tissue at 100GHz, a reproducibility better than 1.4% (1σ), a long-term stability better than 0.6% (1σ) for 8h, and a lateral scanning resolution of about 100μm for a 600x300μm2 probe tip. First tests on human skin revealed that the probe can clearly distinguish skin tissue on different positions of the body (back of hand, palm, arm), can detect skin burns and can monitor the healing process of skin burns (discrimination between burnt skin, newly grown skin, normal skin), and can distinguish benign skin neoplasms from normal skin and subdermal (junctional) nevi. Probe prototype 2 (UU design) is a resonant probe design which has been tested on phantom materials composed of agar, polyethylene powder and TX-15. The probe can successfully distinguish 50%, 75%, and 100% phantom materials. 4. Conclusions, outlook, acknowledgements We presented a new type of microwave wave medical sensor, enabled by micromachining. The probes were optimized for skin cancer, and provide a unique responsivity/resolution performance as compared to conventional microwave probes. The sensor prototypes have been successfully technically characterized and measurements on different skin types and skin anomalies have clearly verified the sensor function. Currently, an application for ethical approval is being filed for continuing the work towards evaluating cancer tissue. The VINNOVA Framtidens Hälsa programme is acknowledged for funding. References [1] Mariya Lazebnik et al., Phys. Med. Biol. 52 (2007) 6093–6115. [2] R. M. Woodwardet al. , J. Invest. Dermatol., vol. 120, pp. 72-78, 2003. [3] A. Ito et al., Cancer Sci., vol 94, no. 3, pp. 308-313, Mar. 2003. (a) (c) (d) (e) (b) Figure 1: Mmicromachined microwave skin-cancer sensor prototypes: (a) broadband sensor, (b) resonant type sensor; (c) responsivity analysis; (d) measurements on skin, discrimination of burnt/new-grown/normal skin; (e) measurements on skin, benign skin neoplasm/subdermal mole/normal skin. 48 4D2 INBYGGDA SENSORSYSTEM FÖR HÄLSA - FORSKNINGSPROFILEN ESS-H Maria Lindén, Mats Björkman Mälardalens högskola, Sverige 1. Introduktion Embedded Sensor Systems for Health (ESS-H), är en 6-årig forskningsprofil inom inbyggda system för hälsa. Profilens hemvist är Mälardalens högskola, Akademin för Innovation, Design och Teknik. Totalt satsar KK-stiftelsen, MDH och företagen 84 miljoner kronor på forskningsprofilen. KKS står för 36 miljoner kronor, företagen för 30 miljoner kronor och MDH för 18 miljoner kronor. Inom ESS-H ska högskolan tillsammans med nio företag samt kommuner och landsting utveckla sensorsystem som främjar hälsa. Sensorsystemen ska monitorera och följa hälsotillståndet hos äldre i hemmiljö, men även monitorera yrkesförare och maskinoperatörer och därigenom åstadkomma säkrare arbetsmiljö. Profilen utgår från ett systemperspektiv och kombinerar multidisciplinära kompetenser. Såväl hårdvaru- som mjukvaruaspekter inkluderas. Målet med ESS-H är att akademi och industri, tillsammans med hälsovård, sjukvård och vårdgivare ska finna nya tekniska lösningar för att främja hälsa speciellt inom två områden: i hemmet och på arbetsplatsen., 2. Motivering Hälso- och sjukvårdskostnaderna ökar i Sverige, liksom i resten av västvärlden. Den åldrande, multisjuka befolkningen står för en stor del av dessa. Intelligenta, adaptiva system som kan monitorera och utvärdera hälsostatusen för dessa patientgrupper är viktiga. Dessa kan bidra till monitorering, prevention och rehabilitering, t ex genom att följa individens hälsotillstånd och tidigt kunna identifiera en försämrad hälsostatus och sätta in åtgärder. En stor del av de arbetsplatsolyckor som inträffar sker i stressiga eller farliga miljöer. Användningen av intelligenta, adaptiva system som monitorerar omgivningen och/eller fysiologiska parametrar kan bidra till att göra arbetsplatserna säkrare. 3. Kärnkompetenser och stödjande teknologier Kärnkompetenserna inom ESS-H är Medicinsk sensorteknik, Medicinteknisk signalbehandling och Intelligent beslutsstöd. Verifierbarhet och säkerhet är viktiga aspekter inom inbyggda sensorsystem för hälsoapplikationer. De stödjande teknologierna utgörs av Mjukvarutestning och Säker trådlös kommunikation och utgör viktiga pusselbitar för att de inbyggda sensorsystemen ska kunna tillämpas inom hälsodomänen. Figur 1. Kärnkompetenserna inom ESS-H. 4. Forskningsutmaningar Inom ESS-H har tre huvudutmaningar identifierats:1) Insamling av tillförlitliga fysiologiska data, 2) Personlig biofeedback och 3) Tillförlitliga distribuerade beslutsstödssystem. Var och en av dessa forskningsutmaningar kräver multidisciplinär forskning. Forskningsutmaningarna adresseras i ett antal samverkande forskningsprojekt där varje delprojekt kombinerar samtliga kompetenserna inom ESS-H, både forskningskompetensen inom kärn- och stödteknologierna, men även expertis från partnerföretagen. 5. Delprojekt Forskningen inom profilen är systemorienterade och samtliga delprojekt adresserar det tre huvudutmaningarna inom ESS-H. Delprojekten är inledningsvis: • Sensorsystem för hälsomonitorering hemma • Sensorsystem för hälsa på jobbet (speciellt farliga yrken) • Infrastruktur för fysiologisk databehandling (inklusive kommunikation) Det kommer att bli stora synergieffekter och samarbeten även mellan delprojekten. 49 49 4D3 PIEZOELEKTRISK TEXTIL FIBER FÖR MEDICINSKA APPLIKATIONER Erik Nilsson1,2, Karin Rundqvist3, Anja Lund2,3, Bengt Hagstöm1,2 Swerea IVF, Textiles and Plastics Department, Box 104, SE-431 22 Mölndal, Sweden 2 Dept. Materials and Manufacturing Technology, Chalmers University of Technology, SE-412 96 Göteborg, Sweden 3 The Swedish School of Textiles, University of Borås, SE-501 90 Borås, Sweden 1 1. Introduktion Övervakning av hjärtslag- och andningsljud är vanligt förekommande i vården och möjligt genom flera olika tekniker. Elektrokardiografi (EKG) som är den mest exakta metoden, är också den vanligaste diagnostiska hjärtundersökningen i sjukvården. Men det finns tillfällen då man vill övervaka hjärtats frekvens över en längre tidsperiod, exempelvis vid längre sjukhusvistelser eller hos personer med hjärtproblem som vårdas i hemmiljö och behöver observeras under en längre tid. Idén med att integrera mätutrustningen i klädesplagget ökar patientens välbefinnande, mobilitet och integritet [1]. Något som rimligtvis bör gynna läknings- och återhämtningsprocessen. Inom det textila området har det nu utvecklats lösningar där sensorer integreras i klädesplagget. Genom att använda metalltrådar insydda i plagget kan de elektriska signalerna från hjärtat registreras [2]. Alternativt kan de mekaniska rörelserna som uppstår vid andning och hjärtats slag övervakas med piezoelektriska sensorer. Detta kan exempelvis ske genom att ett plåster med en piezoelektrisk filmsensor fästs på bröstet [3] eller att en sensor spänns fast med kardborreband på fingret [4]. Ingen av dessa lösningar är varken praktiska eller komfortabla att använda under en längre tid. I denna studie visar vi att det går att skapa en sensor på fibernivå som har egenskaper likvärdiga med en kommersiell textilfiber och därmed inte har negativ påverkan på användarens komfort då sensorfibrerna inte skiljer sig från de övriga fibrerna i textilen. 2. Metod Fibrerna är tillverkade genom smältspinning som är den vanligaste metoden att tillverka syntetiska fibrer. Fibrerna är av bikomponent typ med en ledande kärna av kolkomposit omgiven av ett hölje av polyvinyldifluorid (PVDF), en polymer med piezoelektriska egenskaper. Fibrerna har utvärderats som enstaka garn och vävda till en textil. Signalen från fibern registreras mellan den inre elektroden och en yttre elektrod. Testerna är genomförda i både dragprovare och fastspända på kroppen för att mäta hjärt- och andningsljud. 3. Resultat Mätningar i dragprovare visar att fibrerna är mycket känsliga. Töjningar på 0.07% ger upp till 4 V utsignal från PVDF fibrerna vid en dynamisk belastning på 4 Hz. Fibrerna mäter endast transienta förlopp och frekvensområdet beror på impedansen hos mätutrustningen. För optimal prestanda måste utrustningen anpassas för det aktuella mättillfället. Figur 1 visar hjärtslag och andning från en stillasittande person. Mätningen är gjord genom att en textil klämts mellan resårbandet på sport-BH och huden på en person som är sittande. Mätningar har även utförts med ett band som spänts kring bröstet på testpersonen. Genom att använda ett elektriskt ledande garn som yttre elektrod har ett nytt textilt sensor-koncept utvecklats. Testerna visade att signalstyrkan från PVDF fibrerna påverkas av det ledande garnets konduktivitet, grovlek (Tex) och vävens konstruktion. Bindningstypen som gav högst signalstyrka var twill, som ger god draperbarhet och är mest flexibel av de testade bindningstyperna. 4. Slutsats och diskussion Försöken visar att det är fullt möjligt att att mäta hjärtslag och andning med sensorer integrerade på fibernivå. Genom att integrera sensorer i klädesplagget så ökar patientens komfort. Detta möjliggör övervakning av patienter i deras hemmiljö utan att det inskränker på deras livskvalitet. (Det kan bli möjligt att övervaka patienter i deras hemmiljö utan att det inskränker på livskvaliteten) För att få ut en maximal signal så skall fibrerna vara löst bundna i textilen. För vidare arbete behövs elektronik för datainsamling med ett tillhörande gränssnitt mot fibrerna utvecklas. Figur 1 a) Hjärtslag för en stillasittande person som håller andan och b) både hjärtslag och andning. Referenser [1] F.H. Wilhelm, W.T. Roth, M.A. Sackner, Behavior Modification, 27, 671-‐91 (2003). [2] S. Choi, Z. Jiang, Sensors and Actuators A: Physical, 128, 317-‐26(2006). [3] Y.-‐Y. Chiu, W.-‐Y. Lin, H.-‐Y. Wang, S.-‐B. Huang, M.-‐H. Wu, Sensors and Actuators A: Physical, 189, 328-‐34(2013). [4] Y. Chen, L. Wang, W.H. Ko, Sensors and Actuators A: Physical, 23, 879-‐82(1990). 50 INTEGRATION OF POLYMER MICROFLUIDICS WITH SILICON PHOTONIC BIOSENSORS BY ONE-STEP COMBINED PHOTOPATTERNING AND MOLDING OF OSTE 1,2 1 3 1 4D4 1 Carlos Errando-Herranz , Farizah Saharil , Albert Mola Romero , Niklas Sandström , Reza Zandi Shafagh , 1 1 1 Wouter van der Wijngaart , Tommy Haraldsson , and Kristinn B. Gylfason 1 2 KTH Royal Institute of Technology, Stockholm, Sweden. UPV Polytechnic University of Valencia, Valencia, Spain, 3 University of Barcelona, Barcelona, Spain 1. Introduction Silicon-based sensors have recently demonstrated good performance in terms of biological and chemical analyte detection. Silicon-based photonic ring resonators [1], DNA sequencing devices [2], and nanowire sensors [3] are examples of high performance silicon sensors, featuring low detection limits, high scalability, and mass production capability in dense arrays at low cost. However, for chemical and biological applications, silicon sensor fabrication faces a bottleneck: the integration of liquid sample handling. Here, we present a fast and simple integration of microfluidics onto silicon photonic sensors. By taking advantage of the OSTE polymer [4], we photopattern and mold microfluidics in a single casting step, without squeezefilm formation. By enabling photopatterning of vias both for fluid connections and optical fiber probing, the necessary wafer area is reduced, enabling fabrication of fluidics on the same scale as current silicon sensor arrays. We demonstrate measurements using a silicon photonic refractive index sensor fabricated by this process. 2. Method OSTE with a 70% thiol excess is poured in a PDMS mold, defining connectors, and then sandwiched between the PDMS and a glass mask. The glass mask has chromium dots defining vias, and SU8 reliefs defining microchannels, thus acting both as a mold and photolithography mask. After a UV-exposure time of 15 seconds, the casting process is finished by releasing and developing the OSTE layer with butyl acetate during 30 seconds. Thereby, the unexposed parts dissolve, and the vias for optical and fluidic connections are opened. By taking advantage of the excess thiol functional groups on the OSTE surface, we then covalently bond the fluidic layer to an isocyanate functionalized silicon optical chip, in a reaction that takes 10 minutes. 3. Results and discussion We obtain squeeze-film free vias, and leakage free bonding to flat glass and silicon, including microchannels defined by thin and long walls with bond areas down to 0.12 x 10 mm2 (Fig. 1). Moreover, we demonstrate bonding to silicon photonic chips with 220 nm thick protruding waveguides, and show optical measurements with a Mach-Zehnder interferometer based refractive index sensor. The results show a shift in the interference wavelengths with the introduction of air, isopropanol and ethanol into the fluidic channel (Fig. 2). 4. Conclusions We have demonstrated a one-step microfluidic integration technique for silicon photonic waveguide based sensors with surface grating couplers. We replace the prevalent microfluidic integration solution (PDMS) with one based on the OSTE polymer, and thus, by combined lithography and molding, we enable the integration of photolithographed vias for optical probing with grating couplers (Fig. 1). Moreover, dry bonding of OSTE to silanized silicon photonic chips overcomes the limitations of PDMS in bonding to biofunctionalized surfaces. We show leakage free bonding of microfluidic layers to patterned silicon, together with refractive index measurements using a grating coupled Mach-Zehnder interferometer sensor chip, fabricated by these means (Fig 2).Our demonstration of a functional photonic sensor, packaged by a fast single-step microfluidic layer integration extendable to wafer-level fabrication, illustrates that our novel approach has the potential to accelerate the commercial uptake of silicon based biosensors.. References [1] Rothberg, J. M. et al. Nature 475, 348-352 (2011). [2] Zheng, G. et al. Nature Biotechnology 23, 1294-1301 (2005). [3] Luchansky, M. S. et al. Analytical Chemistry 84, 793-821 (2011). [4] Carlborg, C. F. et al. Lab on a Chip 11, 3136-3147 (2011). Figure 1: The Mach-Zehnder interferometer chip. 51 Figure 2: Transmitted optical power through the sensor. 51 4D5 A NEW BONE CONDUCTION IMPLANT (BCI) SYSTEM USED IN A FIRST CLINICAL STUDY 1 Hamidreza Taghavi1, Bo Håkansson1, Sabine Reinfeldt1, Karl-Johan Fredén Jansson1, Måns Eeg-Olofsson2 Department of Signals and Systems, Chalmers University of Technology, Gothenburg, Sweden. 2 ENT Department, Sahlgrenska University Hospital, Department of Otorhinolaryngology, University of Gothenburg, Gothenburg, Sweden 1. Introduction Patients with conductive and mixed hearing loss can be rehabilitated by percutaneous bone-anchored hearing aids (BAHA). Even though the BAHA has been successful and more than 100,000 patients have been implanted, the skin-penetrating implant site needs life-long daily care and some skin complications may occur. A new Bone Conduction Implant (BCI) system has been designed and developed as an alternative to the percutaneous BAHA and recently implanted for long-term use in four patients. In a BCI the skin and subcutaneous tissue is kept intact and the sound is transmitted via an inductive link [1,2]. 2. Method The study was done on four patients in the clinical study phase. Two patients had bilateral conductive loss and two had unilateral conductive loss. The BCI consists of an externally worn sound processor and an implanted unit called the Bridging Bone Conductor (BBC), which is permanently implanted in the mastoid portion of the temporal bone. The BBC contains a transducer, a tuned demodulator and uses an inductive link for communication with the external sound processor similar to cochlear implants, see Figure 1. The BCI sound processor has been implemented in a very efficient ultra-low power Application Specific Integrated Circuit (ASIC) that optimizes the power and sound transmission through the inductive link. The inductive link gain has been designed to be fairly robust for skin flap thickness variations of 2-8 mm. The output force level and total harmonic distortion of the BCI devices were measured on Skull simulator in an acoustic measurement set-up. To measure the efficiency of the BCI, the battery current consumption of the BCI was also measured based on American National Standards Institute standards. In addition, a nasal sound pressure (NSP) measurement was used as an intraoperative method to verify that the implant operates properly before closing the incision. 3. Results It was found that the BCI can generate high enough output force for the candidate patients with unilateral and bilateral conductive hearing loss. The output force level of the BCI measured on Skull simulator is fairly robust for skin flap thickness range of 2-8 mm. It was found that the battery current consumption of the BCI is in a range that can be used with a single hearing aid battery for 5-7 days based on patients’ use. Moreover, it was shown that the NSP measurement on the patients was a proper method for verification of the implant functionality during surgery and in follow-up sessions. 4. Conclusion The Bone Conduction Implant has been developed and implanted in four patients and the performance and verification methods show that the implant performs as expected after surgery. The NSP will be used as the verification method during coming BCI surgeries. References [1] Håkansson B, Reinfeldt S, Eeg Olofsson M, et al. A novel bone conduction implant (BCI): engineering aspects and preclinical studies. Int J Audiol 2010;49:203-215. [2] Taghavi H, Håkansson B, Reinfeldt S. Analysis and Design of RF Power and Data Link Using Amplitude Modulation of Class-E for a Novel Bone Conduction Implant. IEEE Trans. Biomed. Eng 2012;59:3050-59. Figure 1: The BCI system with an implanted and capsuled transducer with a flat surface contact to the temporal bone. The vibrations are received to the cochlea by means of bone conduction. (BEST: Balanced Electromagnetic Separation Transducer) 52 4D6 BCI - NYTT HÖRSELIMPLANTAT SOM ERSÄTTER SKADAT MELLANÖRA Sabine Reinfeldt1, Bo Håkansson1, Hamidreza Taghavi1, Karl-Johan Fredén Jansson1, Måns Eeg-Olofsson2 1 Chalmers Tekniska Högskola, Göteborg, Sweden. 2 Sahlgrenska Universitetssjukhuset, Göteborg, Sweden 1. Introduktion Patienter med hörselskada i ytter- eller mellanörat rehabiliteras idag med den benförankrade hörapparaten BAHA. Den har blivit framgångsrik med mer än 100 000 opererade patienter. Apparaten fästs i benet med en titanskruv och det blir en hudgenomföring som kan ge upphov till komplikationer. Daglig vård av huden krävs och det kan uppkomma hudinfektioner och skruven kan lossna. En del patienter nekar till BAHA för att de inte vill ha ”en skruv som sticker ut ur huvudet”. Vi har utvecklat ett nytt benledningsimplantat (BCI), där huden hålls intakt. För att implantatet ska passa i temporalbenet bakom örat, så har själva högtalaren gjorts mindre och genom en speciell teknik så är den mer effektiv och ger mindre distortion än vad BAHA-vibratorn gör. Visionen är dels att det nya benledningsimplantatet löser problemen kopplade till den nuvarande hudgenomföringen i BAHA och dels att BCI ska ge lika bra hörselrehabilitering för patienten. BCI-systemet består av en extern ljudprocessor och en implanterad enhet, inkluderande högtalaren som vibrerar för att ge en hörselupplevelse. Signalen transmitteras induktivt från ljudprocessorn, som fästs med magnet mot implantatet genom huden. [1,2] 2. Metod För att utveckla BCI har ett antal prekliniska studier genomförts, och just nu genomförs en klinisk studie med 20 patienter, vilken godkändes hösten 2012 av Läkemedelsverket och Regionala etikprövningsnämnden. I skrivande stund har fyra patienter fått implantaten inopererade och två av dem har även fått den yttre ljudprocessorn, vilken man får efter fyra veckor. Ett stort testbatteri genomförs på varje patient, både före och efter operationen. Innan operationen får patienten använda en referenshörapparat, vilken är en BAHA som fästs med elastiskt band. Vid samtliga besök mäts hörtrösklar för toner och tal, samt uppfattbarhet av tal i brus. För att veta att implantatet fungerar innan operationssåret sys igen så stimuleras implantatet med en elektrisk signal och ljudtrycket i näsan mäts. Detta har visat sig vara en bra metod för kontroll av implantatet och används också i uppföljningsbesöken för att följa implantatets funktion över tid. Själva högtalaren i implantatet sänks ner i benet ungefär 20 mm bakom hörselgången och ljudprocessorn sitter då ungefär 55 mm från hörselgången, vilket är den vanliga positionen för BAHA. Högtalaren fästs med en titantråd; alltså behövs ingen skruv för BCI. 3. Resultat Vi kommer att visa resultatet av de audiometriska mätningarna vi har gjort på de första patienterna. Vi har sett en definitiv förbättring av hörseln med BCI, och att BCI är jämförbar med referenshörapparaten. Operationsproceduren har utvecklats och är säker och enkel för både patient och kirurg. Implantatets placering planeras med hjälp av cone beam computed tomography (CBCT) för att ge bäst möjliga individanpassning. 4. Diskussion Resultaten visar att BCI ger lika bra hörsel som en BAHA gör och har den stora fördelen att huden hålls intakt. Dessutom sitter den närmare huvudet och ger därför inte lika mycket vindbrus. En tredje fördel är att högtalaren sitter längre ifrån mikrofonen än vad den gör i BAHA, och därför ger den mycket mindre återkoppling jämfört med BAHA, vilket medför att det är möjligt att använda mössa med BCI. Operationen är säker och enkel och det är möjligt att kontrollera implantatets funktion med näsljudtryck innan operationssåret sys igen. References [1] Håkansson B, Reinfeldt S, Eeg Olofsson M, et al. A novel bone conduction implant (BCI): engineering aspects and preclinical studies. Int J Audiol 2010;49:203-215. [2] Taghavi H, Håkansson B, Reinfeldt S. Analysis and Design of RF Power and Data Link Using Amplitude Modulation of Class-E for a Novel Bone Conduction Implant. IEEE Trans. Biomed. Eng 2012;59:3050-59. 53 53 Sammanfattningar Plenarföredrag Session E Moderator: 54 E2 NANOMEDICIN – EN (R)EVOLUTION FÖR FRAMTIDENS SJUKVÅRD? Agneta Richter Dahlfors Professor, Director, Swedish Medical Nanoscience Center, Karolinska Institutet, Department of Neuroscience, Stockholm, Sweden Nanomedicin är ett forskningsområde som med stor sannolikhet kommer att revolutionera framtidens sjukvård. Bland annat kommer vi att få se nya metoder för att ställa diagnos, nya behandlingsmetoder och effektivare terapier. Detta möjliggörs genom tät samverkan mellan forskare inom nanoteknik och medicin. Genom nanoteknik kan material skapas och kontrolleras på nanometernivå. Detta öppnar för helt nya sätt att integrera material med nya funktioner i medicinska applikationer, eftersom materialens storlek är tusen gånger mindre än kroppens celler. Nanomedicinens utveckling ställer emellertid även krav på samhället i övrigt. Både politiker och allmänhet måste delta i diskussion om hur vi i framtiden skall utnyttja de oändliga möjligheter som nanomedicin kommer att erbjuda – en viktig debatt som redan initierats i andra länder. 55 Sammanfattningar Regelverk och ekonomi Session 2F 56 56 2F1 Hälsoekonomisk utvärdering av medicinteknik -en permanent verksamhet på nationell nivå? Malin Blixt Tandvårds- och läkemedelsförmånsverket, Stockholm, Sweden 1. Bakgrund Regeringen uppdrog i april 2012 åt Tandvårds- och läkemedelsförmånsverket, TLV att genomföra hälsoekonomiska bedömningar av medicintekniska produkter. Verksamheten skulle bedrivas i form av en försöksverksamhet och omfatta minst två medicintekniska produktgrupper. En av dessa grupper skulle utgöras av insulinpumpar. När det gäller dessa produkter skulle uppdraget delredovisas senast den 30 april 2012. Redovisningen skulle utgöras av ett kunskapsunderlag i form av hälsoekonomisk bedömning av insulinpumpar. Uppdraget ska slutredovisas senast den 31 oktober 2013. Slutredovisningen ska bestå av dels kunskapsunderlag i form av hälsoekonomiska bedömningar av de utvalda medicintekniska produktgrupperna, dels en bedömning av om försöksverksamheten bör permanentas och hur den i så fall bör utformas. Av uppdraget framgår att TLV ska samråda med sjukvårdshuvudmännen och berörda organisationer samt samverka med berörda myndigheter beträffande arbetsformer och det material TLV ska använda vid bedömningarna samt hur myndigheten ska få tillgång till detta. TLV ska även under uppdraget föra en dialog med hälso- och sjukvårdshuvudmännen för att anpassa kunskapsunderlagen till behoven hos mottagarna av dessa underlag. De hälsoekonomiska bedömningarna av medicintekniska produkter förväntas vara ett stöd för hälso- och sjukvårdshuvudmännen vid kliniska beslut och vid upphandling av produkterna. De hälsoekonomiska bedömningarna påverkar dock inte frågan om produkterna ska ingå i läkemedelsförmånerna eller inte. TLV och branschorganisationerna för medicinteknik bör i utvecklingsarbetet föra en dialog om vilket material som ska användas och hur myndigheten ska få tillgång till detta. En fråga som bör diskuteras är vilka priser som ska användas vid bedömningen. Det är angeläget att systemet blir förutsebart för att medicinteknikföretagen ska kunna utveckla rutiner kring framtagande av underlag, samt åtar sig att förse TLV med detta underlag. Regeringens bedömning är att hälsoekonomiska bedömningar av medicintekniska produkter gagnar patienter och vården på flera sätt. Bedömningarna väntas bland annat bidra till - bättre underlag för kliniska beslut och upphandling av medicintekniska produkter, - större transparens kring medicintekniska produkters kostnadseffektivitet och priser, - bättre utnyttjande av existerande resurser för kunskapsutvärdering genom att bedömningarna görs av en nationell myndighet och inte av alla huvudmännen, samt - en mer kunskapsstyrd och likvärdig användning av medicintekniska produkter i hela landet. 2. Reslutat TLV anser att uppdraget bör bli permanent och kommer i slutrapporten att lämna en fullständig bild av hur vi anser att en permanent verksamhet bör utformas. TLV inledde med att göra en marknadsanalys av landsting och andra myndigheter, dels för att se hur de hanterar medicinteknik, dels för att se om de har några prioriteringslistor, eller andra transparenta urvalsprocesser. Det är oklart precis hur mycket pengar medicintekniska produkter omsätter varje år då landstingens redovisning kan ske på flera olika sätt. En kvalificerad uppskattning är att kostnaderna för medicintekniska produkter är drygt 20 miljarder kronor. Olika landsting lägger olika mycket på medicintekniska produkter. Det är stor skillnad på hur prioriteringarna görs, en del landsting utgår enbart från årets budget, vissa landsting tittar på hälsoekonomi, andra landsting lyssnar mer på enskilda läkare. Det finns ett väldigt stort intresse för detta regeringsuppdrag från både organisationer, privatpersoner, andra myndigheter och bransch samt landsting. Projektgruppen har fått många inbjudningar att prata om projektet och många har uttryckt att det är efterlängtat. Bland annat branschföreningen menar att det finns ett undertryckt behov. Den 2 september kommer myndighetens förslag till slutrapport att läggas ut på www.tlv.se för synpunkter för alla som är intresserade. På Medicinteknikdagarna kommer att redogöras för vilka överväganden som har gjorts, hur en permanent verksamhet bör bedrivas, vilka implikationer det får för olika aktörer och förhoppningsvis kommer det då även att vara klart om och i så fall när en permanent verksamhet startar upp i myndighetens regi. 57 2F2 ERFARENHETER AV IT-BEROENDE MEDICINTEKNISKA PRODUKTER I GENERELL IT-STRATEGI OCH FÖRVALTNINGSMODELL 1 1 1 Robert Lorentsson , Roger Lampa , Morgan Andréasson 1 Sahlgrenska Universitetssjukhuset, Göteborg. 1. Introduktion I Västra Götalandsregionen (VGR) har en IT-översyn [1] genomförts som bland annat innebär en ny IS/IT-strategi, ny förvaltningsmodell (pm3) och ny styrmodell. Inom IT-översynsprojektet fanns delprojekt för IT-beroende MTP som beskrivs här. VGR har tre huvuduppdrag: hälso- och sjukvård, främja tillväxt och hållbar utveckling samt kollektivtrafiken. Regionen har ca 50 000 anställda varav 90 procent arbetar i hälso- och sjukvården. IT-organisationen är sedan flera år regional och medarbetarna är lokaliserade utanför sjukhusen centraliserat till de större städerna i regionen. En förstudie [2] som beskrev hur IT-beroende MTP hanterades innan IT-översynen genomfördes och resulterade i ett antal förslag som låg till grund för genomförandeprojektet. Dessa förslag var bland andra: - Förvaltningsobjekt som innehåller mycket MTP bemannas med både Förvaltningsledare MT och Förvaltningsledare IT på utförarsidan som tillsammans bildar funktionen Förvaltningsledning teknik (till skillnad från andra objekt som endast har Förvaltningsledare IT på utförarsidan) - Beredningsprocessen för IT kompletteras med erforderliga aktiviteter och roller för att hantera införande av ITberoende MTP - En roll införs på varje sjukhus som samordnar investeringar i IT-beroende MTP - En regional processägare införs för riskhantering av IT-beroende MTP - Verksamhetsnära IT-stöd införs - Sjukhusens kravställnings- och beställningsfunktion gentemot IT-organisationen kompletteras med MT-kompetens Ett genomförandeprojekt med förstudiens förslag håller på att genomföras och avslutas troligtvis under maj 2013. 2. Avrapportering Ett av förvaltningsobjekten inom hälso- och sjukvård innehåller mycket IT-beroende MTP, rekrytering av förvaltningsledare MT pågår. Regional processägare för riskhantering av IT-beroende MTP ska tillsättas. Ett initialt uppdrag kommer att vara att implementera tillhörande regional process för riskhantering av IT-beroende MTP med stöd av SS-EN 80001-1 [3]. Erfarenheter gjorda vid implementering av styr- och förvaltningsmodellen i VGR ur ett MT-perspektiv: Majoriteten av de IT-beroende MTP som har med diagnostik och terapi att göra hamnade i samma förvaltningsobjekt. Detta objekt har fler IT-komponenter än de andra förvaltningsobjekten. Kravet på regional samsyn avseende IT-beroende MTP möjliggörs med hjälp av förvaltningsledare MT som har informations-, kommunikations- och förankringsansvar mot sjukhusens MT-organisationer. - Förslag att ett regionalt team för verksamhetsnära IT-stöd från IT-organisationen avseende IT-beroende MTP ska etableras. Referenser [1] VGR, IT-översynen. (2011), IS/IT-strategi, RSK 1200-200, Västra Götalandsregionen: VGR. [2] Andréasson, M. (2012), Förstudie: Nuläge avseende MTP/MIS relaterat till regionens nya IT-strategi, http://tiny.cc/c81gkw. [3] SEK TK 62. (2011). Riskhantering tillämpad på IT-nätverk som innehåller eller är kopplade till medicintekniska produkter, Stockholm: SIS. 58 58 2F3 THE ROAD TO CE FOR MEDICAL DEVICES IN COOPERATION WITH INTERTEK ´S SWEDISH MDD NOTIFIED BODY 1 1 Anneli Wiedenkeller Intertek Certification, Regulatory Services, Torshamnsgatan 43, Box 1103, 164 22 Kista, Sweden 1. Introduction As a manufacturer, importer or distributor of medical devices you are obliged to follow a variety of rules and regulations. In order to sell your product(s) in Sweden and other countries within EU it is especially important to know and comply with the applicable medical device directive (93/42/EEC “MDD” or 90/385/EEG “AIMDD” or 98/79/EG “IVDD”) and to understand the supervising role of the Notified Body (products in higher risk classes). 2. Scope and Obligations 93/42/EEC (“MDD”) [1] is the applicable directive for many medical devices and the main scope for Intertek´s Swedish Notified Body. The directive includes definitions, classification rules, requirements on both the manufacturer and the product(s), different conformity roads for CE fulfillment and requirements on national authorities and notified bodies. For a first time reader the directive might give a messy impression, but a good cooperation with your Notified Body can give you the right understanding of the requirements and help you to be in control. To take responsibility of the safety and effectiveness of your product(s). The requirements are extensive but can actually be summarized in a few pages stated in the Essential Requirements (annex I). 3. The road to CE in cooperation with Intertek´s Swedish MDD Notified Body A simplified picture of the Intertek process is: CE: Manufacturer & Product MDD review Step 1: Revision/audit for certification Technical File review* Step 2: Revision/audit for certification EC Certificate Repeated 2 *Answer requested in 30 days/repeated reports until closure of all NonConformities. Optional use of Testing Services Quality System/process review Pre-review •Revision/audit: MDD (+ISO13485, optional) •Sample surveillance Technical File reviews* www.intertek.se References: [1] 93/42/EEC http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CELEX:31993L0042:en:HTML 59 THE IMPACT OF ROHS ON THE MEDICAL DEVICE INDUSTRY 1 2F4 Anna Forsgren1 Intertek Chemistry, Health and Environmental Services, Torshamnsgatan 43, Box 1103, 164 22 Kista, Sweden 1. Introduction The European Union’s RoHS Directive 2011/65/EU, or recast RoHS, (Restriction Of Hazardous Substances in electrical and electronic equipment (EEE)) will from 22nd of July 2014 include medical devices [1]. This abstract outlines the main obligations under RoHS, and discusses their potential impact on the medical device industry. 2. RoHS scope and obligations The aim of RoHS is to reduce the use, in EEE, of certain substances hazardous to the environment and human health. The Directive restricts the use of Lead, Hexavalent Chromium, Mercury, Polybrominated Biphenyls (PBB) and Polybrominated Diphenylethers (PBDE) to a maximum concentration of 0.1 w/w% and the use of Cadmium to 0,01 w/w% . The restrictions apply to each homogenous material in the product. The recast RoHS Directive has a broader and clearer scope than its predecessor, which entered into force in 2006. New categories such as medical devices and monitoring and control instruments are now included and will be phased in over the coming years. One important reason behind the recast of the RoHS Directive was the aim to create a simpler, more effective and more enforceable Directive. With the recast RoHS, conformity assessment and CE marking have been introduced as the way to show compliance. For manufacturers of medical devices with any function dependent on electricity (or electromagnetic fields), the most important new obligations are to ensure that the substance restrictions of the Directive are met, to implement appropriate processes for the conformity assessment and to compile the necessary RoHS documentation for the technical file. The conformity assessment can be done through self-verification, and there is a harmonized standard available; EN 50581:2012 “Technical documentation for the assessment of electrical and electronic products with respect to restriction of hazardous substances” available to explain and clarify this process. 3. Impact on the medical device industry Due to the substance restrictions, it might become necessary to substitute or modify materials and components in the product. Subsequently, these modifications may require reliability testing, validation or clinical trials and submittal of new data to Notified Bodies for compliance with other Directives and standards. This process may take up to 2,5 years [2]. If materials cannot be substituted, it may be necessary to apply for an application exemption. In addition, creating the infrastructure to produce and maintain correct technical documentation on RoHS compliance has proven resource- and time-consuming and may, in addition to substance substitution, take up to a year to complete. It is therefore important to start the compliance work several years before the deadline. The cost to implement RoHS largely depends on the number of suppliers, whether materials need to be substituted or new exemptions will be required etc. For a complex and new product, the cost for RoHS compliance could be 10% of the turnover of the product. The approximate annual compliance cost for the medical devices sector has been estimated to 400 – 1 600 million Euros [3]. Article 2(2) of the recast RoHS requires all medical devices made available on the market (i.e. any supply) to not contain any of the six restricted substances, unless specifically excluded. Medical devices sold before 2014 and later refurbished and sold to second users, would then be non-compliant. This will have a major negative environmental and economic impact and it has therefore been suggested that this article of the recast Directive [4] is modified. 4. Discussion The availability of RoHS compliant medical devices will be affected if the industry does not start the RoHS compliance work well ahead of applicable deadlines, since ensuring that the medical devices are in compliance with RoHS might take up to three years if validations of new materials or new exemptions are required. Also, the availability of secondary equipment will be affected if Article 2(2) of the Directive is not changed. Manufacturers should expect that RoHS compliance will require hard work and investments. However, these costs can be reduced with the implementation of sound processes for RoHS compliance, using the harmonized standard and experience in the field. References [1] Directive 2011/65/EU of the European Parliament and of the Council of 8 June 2011 on the restriction of the use of certain hazardous substances in electrical and electronic equipment (recast) [2] Goodman, P., Review of Directive 2002/95/EC (RoHS) Categories 8 and 9, 5 (2006) [3] Commission staff working paper accompanying the Proposal for a Directive of the European Parliament and of the Council on the restriction of the use of certain hazardous substances in electrical and electronic equipment (2008) [4] Mudgal, S. et.al., BIO Intelligence Service Measures to be implemented and additional impact assessment with regard to scope changes, pursuant to the new RoHS Directive, Final Report prepared in collaboration with ERA Technology for the European Commission, DG ENV, 345 – 354 (2011) Figure 1: The RoHS Directive (2011/65/EU) will have an impact on the medical device industry as manufacturers and other economic operators will need to comply with this environmental legislation from the 22nd of July 2014. 60 60 Sammanfattningar Innovation & utveckling i och med vården Session 4F 61 61 4F1 Biomedical engineering research creates new inventions for the health care industry O.A. Lindahl1,2,3 , B. M. Andersson1,4, R. Lundström1,3, K. Ramser1,2 1 Centre for Biomedical Engineering and Physics, Umeå University, Umeå, Sweden 2 Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology, Luleå, Sweden 3 Department of Radiation Sciences, Biomedical Engineering, Umeå University, Umeå, Sweden 4 Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden Abstract The health care industry is dependent on new innovations for its survival and expansion. Health care innovations are also important for improving patient care. Through activities at the centre for biomedical engineering and physics (CMTF) we have generated growth both in academia at the universities and in the industry in northern Sweden. Fruitful cooperations were generated between 26 research projects and about 15 established companies in the field of biomedical engineering. The established researcher-owned company for business development of the research results from the CMTF, CMTF Business Development Co Ltd, has so far launched three spin-off companies and has 15 new business leads to develop. The activities have also increased the interest for commercialization and entrepreneurship. So far a total of nine spin-off companies have resulted from the CMTF-research since the year 2000 that has improved the health care market in northern Sweden. Keywords: Health care, Biomedical engineering, business development, innovation, science centre. 1. Introduction CMTF (Centre for Biomedical Engineering and Physics) started 2000 at Umeå University (UmU) and since 2007 includes Luleå University of Technology (LTU). It is an organization for triple-helix cooperation between scientific research, biomedical industry and health care, with the aim of commercializing biomedical research in northern Sweden. CMTF has a budget of 12 million Euro through the European Regional Structural Fund, North Sweden (2008-2014) and additional about 0,5 million Euro per year from other funds. The aim was a strong and sustainable organization for scientific research and business development in northern Sweden. A further aim was a model for the development of new biomedical viable spin off companies originated from the research results through the triple-helix activities of the center. . 2. Method The CMTF was organized with a board of directors as-signed by the universities. The board is chosen to give the CMTF a stable leadership and to reinsure a good cooperation in-between the two counties and the two universities as well as with the health care industry in the region. The broad professional expertise of the board members guarantees high competence for decision making on industrial as well as scientific matters. Before joining the CMTF, all original 26 research projects were evaluated by the board concerning three criteria; scientific excellence, clinical and industrial relevance and scientific research management. The evaluated and approved projects could make use of the CMTF logotype and refer to CMTF as their research milieu. About 200 researchers and supporting staff were engaged within CMTF at the start of 2012. A majority of the projects in CMTF has both scientific and industrial cooperation with international partners both outside EU, e.g. Japan and USA, and within EU, e.g. Nor-way, Finland and Italy. An important step was the establishment of a research company CMTF Business Development Co., Ltd. (CMTF BD), in 2007. The owners were the scientists/project managers from CMTF as well as representatives from the regional innovation system in both Umeå and Luleå. This was in order to form an organization that could be a part of the existing innovation system but with a special emphasis to launch the biomedical engineering research results on the health care market. In 2011 the CMTF BD was expanded with two business councils, one in Umeå and one in Luleå. The project leaders signed over the IPR to the CMTF BD through an agreement. For identified research innovations, a contract was signed with the scientists about the sharing of future profit from the innovation, a so called incentive agreement giving a stream of money to the researchers and one stream of money to the company at success. The CMTF research and development was funded by several local and global organizations. The major founder was the EU structural foundation, objective 2. A majority of CMTF BD was funded with support from private means from the scientific leaders, Uminova Innovation Co Ltd, LTU Holding Co. Ltd. and the County councils in Västerbotten and Norrbotten. 3. Results and conclusions CMTF has built an academic and industrial network for triple-helix cooperation. Currently about 15 national and international companies are involved in the CMTF projects. CMTF research has produced nine spin-off companies. Seven of them were based on patented innovations and one is the CMTF BD. CMTF BD has started three new companies. More than eleven patents have been filed within CMTF and 15 innovations are currently under business verification through CMTF BD and the innovation systems in Umeå and Luleå. The triple-helix activities have also increased the knowledge and interest for innovations and entrepreneurship among the scientists in the centre. The CMTF BD has also become a place for the CMTF scientific leaders to meet and discuss business and innovation issues. Thus the company has contributed to the encouragement of entrepreneurship. CMTF has also been successful to attract necessary funding. The CMTF research network and CMTF BD are today an established triple-helix organization for the development of research into spin-off companies in the area of biomedical engineering. This has resulted in an increased growth of the biomedical engineering activities both in academia and in the industry in northern Sweden. Acknowledgement The study was supported by the European Regional Structural Fund, North Sweden 62 Abstract Föreläsning om SLL Innovation 4F2 SLL Innovation är en decentraliserad organisation som arbetar med medarbetare, företag och produktutveckling på plats i den offentligt finansierade hälso- och sjukvården. SLL Innovation vänder sig både till sina egna medarbetare och samtidigt till den privata sektorns företag som vill komma i kontakt med vården. Företag behöver ofta stöd vid CE-märkning,kliniska utvärderingar och prövningar samt riskanalyser etc. För att underlätta introduktionen av nya innovationer i vården har SLL Innovation tillsammans med SLL Upphandling även startat ett Innovationsupphandlingsnätverk som träffas en gång per kvartal. SLL Innovation startade som ett projekt under 2010 med finansiering från Vinnova och Stockholms läns landsting. Sedan starten har ett väl fungerande innovationssystem inom SLL implementerats och idag arbetar fem innovationskoordinatorer och tre produktutvecklare inom SLL Innovation, utplacerade på Danderyds sjukhus, Södersjukhuset, Karolinska sjukhuset, Solna och Huddinge samt Norrtälje sjukhus. För att samordna samtliga innovationskoordinatorer och produktutvecklare spelar det månatliga utvecklingsrådet en viktig roll. Där utvärderas idéer och projekt. Rådet är även ett forum för att diskutera lösningar på organisatoriska frågor som ännu inte finns färdiga utarbetade rutiner för. Den nära kopplingen till sjukhusens medicintekniska avdelningar ger dels tillgång till kompetens men även viktiga kontakter med företag och sjukvårdspersonal. Detaljerade rutiner kring SLL Innovations tjänster har upprättats och avtalsmallar har godkänts av SLL:s jurister Resultat Totalt har ca 450 rådgivningstillfällen, från den 1 april 2010 hållits av innovationskoordinatorerna, varav ca 20 idéer gått vidare för närmare utvärdering. Ett femtiotal förfrågningar från företag/entreprenörer har mottagits, varav ett tjugotal projekt har initierats inom riskanalys, klinisk prövning, behovsutvärdering och stöd vid CEmärkning. Ett stort antal innovatörsavtal och fribrev har utfärdats sedan start i april 2010. Produkten Stickstop som utvecklats inom ramen för SLL Innovation på Södersjukhuset har sålts och kommit ut på marknaden. SLL Innovation har initierat och leder, Kvinnors nätverk för en innovativ hälso- och sjukvård som startades i början av 2010. Ett permanent samarbete med Almi Stockholm/Sörmland har etablerats. SLL Innovation har skrivit ett avtal som ger samtliga SLL Innovations innovationskoordinatorer tillgång till Almis förstudiemedel. Kontakter har knutits med samtliga övriga innovationsslussar som fått tilldelade resurser från Vinnova. Ett Innovationsupphandlingsnätverk har upprättats tillsammans med SLL Upphandling. Syftet är att genom systematisk samverkan med upphandlingscheferna kunna underlätta introduktionen av nya produkter i hälso- och sjukvården. 63 SLL Innovations verksamhet är förankrad i Landstingsstyrelsen och hos samtliga sjukhus- och sjukvårdsdirektörer. Stockholms läns landsting har ca 45 000 anställda, ett universitetssjukhus, flertalet akutsjukhus och närsjukhus, inklusive en stor primärvård. Samtliga verksamhetschefer har informerats om SLL Innovations verksamhet genom särskild marknadsföring via kommunikationsavdelningar inom hela SLL. Vårdpersonal informeras om verksamheten genom nyhetsbrev, informationsträffar och flyers. SLL Innovation har även utbildat ett 40-tal så kallade innovationsambassadörer. Ambassadörerna är medarbetare som tidigare visat intresse för innovationer och dessa fungerar som en länk mellan avdelningarna och SLL Innovation. Sök på www.webbhotell.sll.se 64 4F3 OPPORTUNITIES FOR MEDICAL ENGINEERING INNOVATIONS IN HEALTCARE TO IMPROVE LIFE FOR CHILDREN WITH CANCER 1 Dennis Sturm1,2, Karin Nilsson2, Anna Larsson2 Centre for Technology in Medicine and Health (CTMH), Stockholm, Sweden; 2KTH Royal Institute of Technology, Stockholm, Sweden 1. Introduction Cancer is a disease with an increasing impact on society. The majority of patients treated for cancer are adults, only a small percentage are children (i.e. persons younger than the age of 18 years). Children are often wrongly regarded as small adults. However, their physiology, body composition and pharmacokinetics differ considerably from these of down-scaled adults. The brain mass of an adult, for example, contributes with around 2% to a person’s body mass while this ratio may be 12% for a small child. Approximately 300 children are diagnosed with cancer in Sweden every year [1]. While it can be deemed positive that the numbers for children affected by cancer are low, this small patient share may increase the challenge for businesses to develop and produce profitable concepts for medical devices and solutions adapted to specific needs of children. Despite great improvements in the survival rate of children with cancer to approximately 80% over the last 35 years there are still major opportunities to improve healthcare tools and processes as well as to provide technology aids for daily life of children with cancer and their family. There is thus a need to investigate the specific potentials for innovation in healthcare for children with cancer. This need served as the motivation for this study. 2. Method A solution-complication-question-answer (SCQA) structure governed the study. In order to gather information on existing solutions as well as current difficulties a sequence of interviews was prepared. In total 9 interviews were conducted with a group of selected individuals from healthcare personnel (8) and parents of children with cancer (1). Interviewees were recruited with the help of a department head and emphasis was laid on a heterogeneous distribution amongst the various functions in which personnel served. Each interview was designed as an open interview and lasted between 20min and 80min. Consecutively, the interviews were transcribed. The analysis of this transcribed information focussed on the identification of problems which can be transformed into engineering questions and challenges. In this sense, specific opportunities for new technical devices, processes and services were extracted from a wide set of data. Having sorted these opportunities into categories, the study was finalised by listing suggestions for future work and procedures in order to fulfil or resolve each identified need. 3. Results Potential for new technology was observed and classified into three categories: 1) Needs for information systems and their interfaces, 2) needs for more efficient processes, and 3) needs in improving healthcare devices and products. A major information system challenge is the modification of existing patient systems to facilitate the presentation of information in an optimised way with regard to the needs of cancer healthcare. This includes the ability to visualise a temporal presentation of events in the treatment (e.g. blood test results, tendencies, start- and endpoint of a treatment, etc.) as well as the accumulation and simultaneous presentation of information from different examinations for one patient. While there are many possibilities to improve work processes, last, an example for a potential, new healthcare product is presented. A need for circumventing the entanglement of tubes from the multitude of infusions that a child with cancer often has to be connected to during treatment was emphasised by both hospital personnel and a parent. As a suggestion for reducing this dilemma a method to sort the tubes was designed, see Figure 1. The leaves of colourful and easy-to-clean flowers on a plastic wire hold the tubes in order and allow for more free movements so that a child with cancer is not more than absolutely necessary reduced in its desire and ability to play. Figure 1: Prototype to prevent entanglement of tubes. 4. Discussion The study was designed as a Bachelor Thesis and resources were thus limited, in particular time. Nevertheless, it could be shown that it is possible to identify opportunities for improving healthcare for children with cancer even within this limited scope. A follow-up project to evaluate selected suggestions from this work is scheduled. Furthermore, this project can be regarded as a pre-study to a Clinical Innovation Fellowship programme organised by CTMH and Barncancerfonden in 2013/14. This 8-month programme will address the aforementioned problems with considerably greater resources on time, manpower and budget. The authors would like to express their gratitude to Barncancerfonden and to the Astrid Lindgren Children’s Hospital, a division of the Karolinska University Hospital, for their support and cooperation. References [1] Barncancerfonden. http://www.barncancerfonden.se/PageFiles/11513/Engelska/faktablad%20barncancer%20engelska.pdf Visited 2013-05-16 65 4F4 INNOVATION MOT INFEKTION, ETT INTERDISCIPLINÄRT INNOVATIONSPROJEKT MOT VÅRDRELATERADE INFEKTIONER 1,2 1,2 2 1,2 Ylva Odelberg , Sjoerd Haasl , Malin Hollmark , Bertil Guve Enheten för klinisk innovation, Skolan för teknik och hälsa, Kungliga Tekniska Högskolan, Stockholm, Sweden 2 Centrum för Teknik i Medicin och Hälsa (Karolinska Institutet - Kungliga Tekniska Högskolan – Stockholms Läns Landsting) 1 Vårdrelaterade infektioner (VRI) drabbar ca 9 % av de patienter som behandlas inom hälso- och sjukvården. Trots en ökad medvetenhet om problemet har den siffran sedan 2009 legat stabil i de punktprevalensmätningar av förekomsten av VRI som Sveriges kommuner och landsting genomför två gånger per år [1]. VRI kostar den svenska sjukvården 3.7 miljarder kronor årligen [2,3]. Upp till 30 % av alla vårdskador utgörs av VRI enligt Socialstyrelsens vårdskademätning [2,4] även internationellt sett är VRI den vanligaste avvikelsen inom hälso- och sjukvården. Prevalensen för VRI i Europa ligger mellan 5,7-19,1 % kostnaden för detta beräknas till ca 7 miljarder euro per år [2]. Enligt Socialstyrelsens definition av VRI [3], drabbas patienter av VRI till följd av sitt besök i vården (sjukhusvård eller öppenvård) eller som en följd sin behandling. Det kan röra sig om pneumonier, urinvägsinfektion i samband med användning av kvarsittande urinvägskateter eller postoperativa sårinfektioner, där operationssåret inte läker som det ska. Till VRI räknas även då vårdpersonal drabbas av infektioner som en följd av sitt arbete. VRI leder till ökat lidande för patienter, längre behandlingstider och högre sjukvårdskostnader: infekterade sår kan ta mycket lång tid att läka och utbrott av tarminfektioner kan tvinga sjukhusavdelningar att stänga. Dessutom kan en VRI kräva antibiotikabehandling av en typ som ökar risken för resistensutveckling. Ur ett globalt perspektiv har Sverige förvisso kommit jämförelsevis långt i arbetet med optimal antibiotikaanvändning för att förhindra uppkomst av bakterieresistens, men resistenta bakterier sprids även här. Vad gäller VRI krävs förebyggande arbete för att minska incidensen1 för att i den bästa av världar slippa behandla VRI överhuvudtaget. Problematiken kring VRI handlar alltså både om infektioner som kan komma att kräva antibiotikabehandling och att en VRI är en vårdskada, åsamkad patienten av vården. Innovation mot infektion (IMI) är ett VINNOVA-finansierat multiprofessionellt projekt som tar ett helhetsgrepp om VRIproblematiken. Parterna i IMI kommer från akademi, vård och omsorg samt näringsliv och inkluderar en rad olika professioner såsom läkare, sköterskor och annan sjukvårdspersonal, ingenjörer, designers, beteendevetare, biologer, m.fl. Arbetsgruppen i IMI täcker på så sätt med sin samlade kompetens ett brett område, där folk med olika kompetens, ofta ovana att samarbeta över professionsgränserna, gör gemensam sak och arbetar på ett innovativt sätt för en säkrare vård. IMIprojektet leds av SP Sveriges Tekniska Forskningsinstitut. Detta konferensbidrag fokuserar på den följeforskning som bedrivs genom ett doktorandprojekt på Skolan för teknik och hälsa vid KTH. Mål med projektet är att behovsägare och lösningsägare tillsammans arbetar fram innovativa lösningar som kan minska förekomsten av VRI samt att beskriva en modell för hur parterna fortsättningsvis kan samverka effektivt. Projektet kartlägger hanteringen av postoperativa sår, smittspridning med avseende på hygienteknik, medicintekniska device såsom urinkatetrar, centrala venkatetrar (CVK) och endotrakealtuber och ska testa olika åtgärder såsom tekniska lösningar, processer och tjänster som kan minska risken för VRI. Relevanta effektmått för utvärdering av dessa åtgärder ska tas fram. I Sverige har vi en nollvision för vårdskador. Trots detta avlider varje år ca 1500 personer på grund av, eller som en följd av, sina vårdrelaterade infektioner [2]. Det har vi all anledning att ändra på. Referenser [1] ”Punktprevalensmätning av vårdrelaterade infektioner v.42-43”, 2012, Sveriges kommuner och landsting [2] ”Strategi för att minska vårdrelaterade infektioner i hälso- och sjukvården” HSN 1209-1142, Hälso- och sjukvårdsförvaltningen 2012-09-17 [3] “Att förebygga vårdrelaterade infektioner – Ett kunskapsunderlag”, Socialstyrelsen 2006 [4] “Vårdskador inom somatisk slutenvård”, artikelnr 2008-109-16 Socialstyrelsen 2008 1 Antal patienter som insjuknar i VRI 66 4F5 KLINISKT TESTCENTRUM FÖR MEDICINTEKNIK I VÄSTMANLAND 1 1 2 Elisabet Rodby Bousquet , Maria Lindén 2 Centrum för klinisk forskning Västerås, Sweden. Mälardalens högskola, Västerås, Sweden 1. Samverkan för ökad medicinteknisk utveckling Testcentrum är ett samverkansprojekt mellan Centrum för klinisk forskning, Mälardalens högskola, näringslivet och hälsooch sjukvården i landstinget i Västmanland i syfte att främja utveckling och införande av ny medicinteknik för att höja effektivitet, säkerhet och kvalitet inom hälso- och sjukvården. 2. Vad är problemet? Ett flertal forskare, innovatörer och entreprenörer inom det medicintekniska området upplever svårigheter att få testa sina idéer och lösningar mot slutanvändaren i ett tidigt skede, och processen från idé till färdig produkt kan vara lång. Samtidigt sker en snabb medicinsk utveckling inom hälso-och sjukvården som är beroende av tillgång till nya tekniska lösningar för ökad kvalitet, säkerhet och effektivitet både vad gäller diagnostik, behandling och uppföljning. Möjligheten att med hjälp av slutanvändaren identifiera vilka problem som nya produkter och tjänster verkligen behöver lösa skulle vara mycket viktig, både för innovatören och för slutanvändaren; innovatören skulle få en bättre insikt i slutanvändarens problematik och slutanvändaren skulle beredas möjlighet att få nya lösningar på befintliga problem 3. Hur går vi från idé till handling? För att få till en lösning på detta initierade Centrum för klinisk forskning i samarbete med Mälardalens högskola ett forskaroch entreprenörsnätverk inom medicin och teknik i Västmanland med bl.a. gemensamma föreläsningar och diskussioner. Ett flertal diskussionsgrupper och djupintervjuer genomfördes med nyckelpersoner inom näringslivet, akademin, hälso- och sjukvården, medicintekniska avdelningen, upphandlingsenheten mm för att identifiera svårigheter att komma från idé till färdig lösning och möjligheterna att öka samverkan mellan forskare och entreprenörer inom medicinteknik och hälso- och sjukvården för att snabbare få tillgång till nya tekniska lösningar. 4. Initiala resultat Denna utökade samverkan mellan medicin och teknik bidrog till uppstart av ett flertal nya utvecklingsprojekt bl.a. med innovation, utveckling och utvärdering av nya tekniska lösningar för förbättrad diagnostik inom barn och ungdomspsykiatrin. Ett kliniskt testcentrum byggs nu upp på sjukhuset med sjukhusmiljö, boendemiljö och virtuell miljö för att underlätta klinisk testning av olika medicintekniska lösningar i form av produkter, processer och metoder. Testcentrum drivs via Centrum för klinisk forskning i landstinget Västmanland i ett nära samarbete med Medicintekniska avdelningen, Mälardalens Högskola, NovaMedTech, ALMI, Västerås Science Park, Länsstyrelsen m fl. Testcentrum erbjuder en möjlighet att testa idéer och lösningar i ett tidigt skede men även test och klinisk utvärdering under senare utvecklingsfaser. Det erbjuder en testmiljö riktad mot hälso- och sjukvården med medicinsk specialistkompetens inom ett flertal områden som bl a. psykiatri och onkologisk kirurgi. Testcentrum förbereder även testmiljö för innovationer och produkter riktade mot barn, vuxna och äldre med flerfunktionshinder. 67 4F6 METIS – EN MODELL FÖR REPETERBAR LÅNGSIKTIG INNOVATION OCH UTVECKLING AV EHÄLSA INOM PREHOSPITAL AKUTSJUKVÅRD 1 Bengt Arne Sjöqvist1, Robert Sinclair2, Bo Norrhem3, Marika Hellqvist-Greberg4 Signaler och System, Chalmers, Göteborg 2 Hälso- och sjukvårdsavdelningen, Västra Götalandsregionen, Göteborg 3 Lindholmen Science Park, Göteborg 4 Regionutvecklingssekretariatet, Västra Götalandsregionen, Göteborg Introduktion Den prehospitala akutsjukvården står inför stora utmaningar. Nya vårdprocesser och metoder, samt ökande krav på behandlingsresultat, säkerhet, kvalitet, uppföljning och effektivitet kräver samverkan och informationsutbyte mellan många olika aktörer och system, såväl som stödjande IKT/eHälsa. Denna situation skapar därför stora möjligheter för utveckling och innovation av eHälsa inom området. För att täcka hela kedjan från händelse till vård på rätt plats, i rätt tid och på rätt nivå, krävs ett flertal samverkande komponenter från olika leverantörer. Krav på standardisering, helhetstänkande, vårdkunskap, utvärdering och tester i autentiska miljöer, samt öppenhet mellan alla inblandade aktörer är därför nödvändigt för att nå långsiktig framgång. Dessutom måste även komplexiteten när det gäller teknik, samverkande aktörer, juridiska frågor etc. beaktas i innovations- och utvecklingssammanhang. Projektbeskrivning Projektet Metis drar fördel av en unik regional situation när det gäller tillgång till aktörer och kunskapsdomäner för att skapa en modell för innovation och utveckling av processtödjande eHälsa inom prehospital akutsjukvård. Modellen skall möjliggöra repeterbar långsiktigt hållbar utveckling, innovation, tillväxt och omsorg, men också stärka Sveriges ”frontline” position som leverantör av testade och validerade lösningar, vårdmodeller och produkter riktade mot hela tillämpningsområdet. Grundläggande i Metis är en "Öppen Innovation/Open Innovation" influerad aktiv samverkan mellan näringsliv, vårdgivare och akademi, och ett signifikant antal aktörer från dessa parter är också representerade i projektet. I modellen ingår bl.a. en samverkansarena benämnd Metis Forum, inkl. websida www.metis.nu, samt en handbok/handledning, Metis Handbok. Den senare är ett ”levande” dokument som innehåller råd, rekommendationer och information att beakta och ta ställning till då man t.ex. önskar utnyttja någon av de testbäddar Metis har tillgång till. Exempel på innehåll är juridik/legala frågor, IT-miljö och krav, tekniska förutsättningar, sjukvårdsorganisation och prövningsmetoder. Metis tar inledningsvis sin utgångspunkt regionalt, men ambitionen är nationell och på sikt internationell. Resultat Metis har nu slutfört sin första projektfas. I denna har Metis Forum etablerats, dess tänkta samarbetsformer och ”programförklaring” fastställts och dokumenterats, samt en första version av Metis Handbok producerats. I presentationen kommer projektet Metis, aktuellt läge, erfarenheter och resultat, samt planer för framtiden att redovisas. 68 Sammanfattningar Modellering Session 2G 69 69 2G1 THE HEART AS A DISPLACEMENT PUMP: A NOVEL CARDIAC MODEL Elira Maksuti1, Jonas Johnson1, Anna Bjällmark1,2, Michael Broomé1,3 Department of Medical Engineering, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden 2 Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 3 ECMO Department, Karolinska University Hospital, Stockholm, Sweden 1 1. Introduction A common approach to cardiac mechanics is to consider the heart as a squeezing pump emptying its content with a considerable change in outer volume. In more recent studies [1], it was suggested that the heart can be described as a displacement pump with the atrioventricular (AV)–plane acting like a piston unit. This theory was supported by cardiac imaging and provides a better explanation of ventricular pumping action in healthy individuals [2]. Simulation models are useful tools for understanding complex systems such as the heart. The widely used time-varying elastance function in cardiac simulation models is based on a reverse engineering approach, where experimental observations have been used to create clinical relevant pressure and volume changes in the cardiac chambers. These models are mainly descriptive and have a limited connection to physical reality. We therefore propose a novel model of the left heart based on physical modelling of the AV-plane displacement in a fixed outer volume providing a better understanding of cardiac mechanics. 2. Methods The left heart model (Figure 1a) is composed of an upper chamber (the atrium) and a lower chamber (the ventricle). One-way valves are located between the two chambers (mitral valve) and between the ventricle and the artery model (aortic valve). The piston has different areas in the upper and lower crown and it is pushed downwards by an external force during the contraction phase (ventricular systole). This causes the opening of the outlet valve, while the inlet valve is closed. During the relaxation phase (ventricular diastole) the external force ceases, the outlet valve closes, the inlet valve opens and the piston goes back to its initial position by an hydraulic return due to the differential area between the two crowns of the piston. This pump model is then connected in a closed loop to a vascular model mimicking resistive and elastic properties of the vascular tree. The only input to the model is a trapezoidal function force during the contraction phase and this force is set to zero during the relaxation phase. Parameter selection is done using values from literature or by calculating the parameters through physical laws. The domain-independent bond graph formalism (Figure 1b) is chosen in this work and the model was implemented in the software platform Dymola (Dassault Systèmes, France) based on the object-oriented programming language Modelica. 3. Results The results of the simulations show a realistic dynamic behaviour of the model in relation both to ventricular filling and contraction. Pressure and flow profiles matches the ones shown in standard physiology textbooks and the piston velocity curve follows a Tissue Doppler Imaging profile measured in proximity to the AV-plane (Figure 1c). 4. Discussion and Conclusion Model output is realistic despite the use of a simulation method not previously published. Future development of the model includes the consideration of the atrial contraction and the non-linear valve resistance, and also to test how the model adapts to changes in preload (filling) and afterload (vascular impedance) in clinical scenarios. Moreover, a sensitivity analysis could reveal which parameters in the model play crucial roles. To summarize, the suggested model shows physiological dynamics, which could be interpreted as a further proof of the concept that the heart behaves as a displacement pump. References [1] S. Lundbäck, “Cardiac Pumping and Function of the ventricular Septum”, Acta Physiologica Scandinavica Supplementum, vol. 550, pp. 69-73 (1986). [2] Carlsson M., Cain P., Holmqvist C., Stahlberg F., Lundbäck S. and Arheden H. (2004) Total heart volume variation throughout the cardiac cycle in humans. American Journal of Physiology Heart and Circulatory Physiology 287, H243-H250. (a) (c) (b) Figure 1: (a) Physical modelling of the heart; (b) equivalent bond graphs model; (c) simulation results. 70 2G2 Dielectric characterization of osteosarcoma cells in the 2-50 GHz range for microwave hyperthermia 1 Robin Augustine1*, Dragos Dancila1, Marjam Ott2 and Anders Rydberg1 Microwave Group, Division of Solid State Electronics, Department of Engineering Sciences, Uppsala University,Sweden 2 Division of Applied Materials Science, Department of Engineering Sciences, Uppsala University, Sweden 1. Introduction This work aims at characterization osteosarcoma cells for finding out frequencies which could be used for treatment of bone cancer. The power dissipated in a dielectric medium in a (time-varying) electromagnetic field is dependent on the dielectric permittivity of the medium. Therefore, when examining the potential effects of microwave radiation on cells, it can be useful to know the permittivity of the cells. In this experiment, the dielectric permittivity of various cell types was measured using a coaxial probe, connected to a vector network analyzer. The Agilent coaxial probe measures the reflection coefficient of guided electromagnetic (EM) waves at its tip and the associated 85070E software then calculates the dielectric permittivity of the medium. 2. Materials and Method The cells are modeled as small spheres and the culture medium is homogeneous, the dielectric permittivity of the cells can be calculated from measurements of pure culture medium and cell suspension permittivities using Maxwell’s mixture equation [1].The permittivity measurements were performed using a 200 mm coaxial probe (Agilent 85070E Dielectric Probe Kit) connected to a vector network analyzer (Agilent E8364B PNA series) via a semi-rigid coaxial cable (Wiltron V120-12). The material under test (MUT) was raised up to the probe so that the tip was immersed (at least 5 mm) into the suspension. The coaxial probe can only be used for liquid samples or soft semi-solids, since the tip has to be inserted into the sample. Therefore, measurements were performed on suspensions of cells in culture medium [2]. The permittivity of the cells was calculated from the difference in permittivity between culture medium and cell suspension using Maxwell's mixture equation. A concentration of 2700000/ml Osteosarcoma (Soas-2) cell line was used to make the cell suspension. The experiments were carried out at room temperature, 22°C. 3. Results and Discussion Figures 1(a) and 1(b) show the arithmetic means of the measurements (solid curves) and 95% confidence interval (dashed curves) of Osteosarcoma cells and pure culture medium respectively. Figure 1(c) shows the arithmetic mean of the differences in measured permittivity between cell suspension and culture medium, and the associated 95% confidence intervals. For frequency samples where the value 0 is located inside the confidence interval, there is no statistically significant difference. For cancerous bone cells with a concentration of 2700000/ml, only the imaginary part showed significance, and only for frequencies below 15 GHz. All measurements show an increase in the arithmetic mean of the permittivity difference at low frequencies. As a result, it could be inferred that any difference in permittivity between cells and culture medium should primarily be sought at the low end of the spectrum. 4. Conclusion We measured the dielectric properties of osteosarcoma cell lines in the range of 2-50 GHz. The results show significant difference in imaginary part of complex permittivity with respect to culture medium. The obtained results could be crucial for our future development of microwave based treatment of bone cancer. SciLife platform is acknowledged for providing us with cell lines. References [1] S. Takashima, Electrical Properties of Biopolymers and Membranes. Adam Hilger, Bristol and Philadelphia 1989. [2] Zhadobov et al., Complex Permittivity of Representative Biological Solutions in the 2-67 GHz range.Bioelectromagnetics 33(4):346-355, 2012. (a) (b) (c) Figure 1. Arithmetic means of the measurements (solid curves) and 95% confidence interval (dashed curves). (a) Soas-2 cell line, (b) Culture medium and (c) difference. 71 71 2G3 VARIATION IN HIP CONTACT FORCE DURING GAIT DUE TO NECK SHAFT ANGLE AND FEMORAL ANTEVERSION Priti Yadav1, M.Tech. , Eva Pontén2, MD, PhD, and Elena M Gutierrez-Farewik 1, 2, PhD 1 Department of Mechanics, Royal Institute of Technology, Stockholm, Sweden. 2 Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden 1. Introduction Children with CP often have normal skeletons at birth [1] but lower limb skeletal deformities often develop thereafter. Coxa valga (increased femoral neck shaft angle) and torsional deformities (femoral anteversion) are frequently observed in children with CP and can lead to hip dislocation [2]. The femoral neck shaft angle (NSA) and femoral anteversion (FA) angles change during development in typically-developing (TD) children, and are commonly 20˚ to 50˚ greater in children with CP [3]. The hip contact force and muscle forces play a crucial role in the development of these deformities during skeletal growth. Our hypothesis is that the forces on the femur during walking can influence growth and deformity development. The aim of this study is to evaluate how varying neck shaft angle and femoral anteversion affect hip contact forces during gait in TD children. 2. Method The subjects considered in this study were 10 TD children between 5 and 17 years of age. For this abstract, results from only one 10-year old girl are illustrated and discussed. Gait analysis was performed using an 8-camera motion analysis system (Vicon MX40) with 2 force platforms (Kistler). From the experimental data, a generic musculoskeletal model (SIMM, Musculographics Inc.) was scaled to each subject. The hip joint was defined as a ball and socket joint. A deform tool was used at the proximal femur to allow variation of NSA and FA. The ranges considered in the analysis for NSA and FA are 125°-150° and 15°-60° respectively. The expected muscle activation patterns for normal walking were determined by performing inverse dynamic analysis and static optimization in SIMM. The computed muscle activations together with external forces were used as input for a second inverse dynamic analysis to compute the hip contact force. The peak hip contact force as well as computed muscle forces at this instance were analysed. 3. Results The peak hip contact force on the femur and its variation with NSA and FA are shown in Figure 1. The peak hip contact force was observed at contralateral toe-off position, which is approximately 20% of the gait cycle. The inferior and posterior components of peak hip contact force increase with increasing NSA and FA, while the medial-lateral component remains almost unchanged with increase in NSA and FA. Results also show that peak hip contact force acts posteriorly and laterally for the considered range of NSA and FA. 4. Discussion and Conclusion Muscles lines and points of action change with varying NSA and FA, thereby changing muscle forces. These changes in muscle forces cause the computed increase in peak hip contact force with increasing NSA and FA. Future studies can be performed to investigate whether this increase in peak hip contact force may inhibit the endochondral growth by reducing the effect of tensile stress on the femoral neck in a growing child References [1]Lundy et al, Journal of Pediatric Orthopedics. 18: 528–34, 1998. [2]Gage, Schwartz, Koop, Novacheck, The Identification and Treatment of Gait Problems in Cerebral Palsy, MacKeith Press 2009. [3]Davids et al, The Journal of Bone and Joint Surgery Am, 85: 481-488, 2003. Figure 1: Peak hip contact force on the femur (at contralateral toe-off) in all directions as a function of neck shaft angle and femoral anteversion. 72 2G4 The information contained in a mechanistic model yields improved biomarkers compared to existing methods when diagnosing diffuse liver disease Markus Karlsson1, Mikael Forsgren1,3,4,5, Olof Dahlqvist Leinhard3,4, Örjan Smedby3,4, Peter Lundberg3,4, Gunnar Cedersund1,2 1 Dpt of Biomedical Engineering, Linköping university, Linköping, Sweden. 2 Dpt of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden,3Dpt of Medicine and Health, Linköping University, Linköping, Sweden,4 Center for Medical Image Science and Visualization, Linköping University, Sweden,5Wolfram MathCore AB, Linköping, Sweden 1. Background Liver diseases are a growing problem in the westernized world, and it is typically hard to evaluate the pathology in the early stages. The current gold standard is a liver biopsy, but this method has many problems, such as risks, and its regional assessment. A promising alternative and complement is Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCEMRI), which provides 3D time-series of the contrast agent (CA) uptake. However, current methods only analyze this information from a purely data-driven point of view. Such an analysis thus disregards the fact that uptake processes are possible to model mathematically, and that the addition of such knowledge may improve the diagnosis. We here show that such an improvement is indeed possible. 2. Method and Results Using data from healthy human subjects [1] and a standard clinical MRI protocol, we developed an identifiable mechanistic model, based on a few compartments described by ordinary differential equations and standard kinetic expressions [2]. The model was validated on independent validation data, using several-fold higher CA concentrations measured in blood samples [2], see Figure 1. We then showed that the model can describe also diseased patients, and that the estimations are significantly and crucially improved by the use of nonlinear mixed-effect modelling [3]. We then finally showed that the estimated parameters allows for a more clearcut separation between different patient groups compared to what other previously developed methods [4] could obtain. This was demonstrated using various statistical measures, which all pointed to the same conclusion [3], see Table 1. 3. Summary and significance In summary, we have showed that the information contained in our mechanistic model does improve the patient-specific diagnosis that can be done based on MRI data, compared to methods that does not use such information. This mechanistic model therefore opens the door to the development of a link between the multi-level models developed for instance in the virtual liver network and even more refined clinical end-usage, such as spatially resolved models to be used in surgical planning for cancer patients. References [1] O Dahlqvist-Leinhard et al, Eur. Radiol. 2012:22(3);642-53 [2] M Forsgren et al, submitted [3] M Karlsson et al, submitted [4] Norén et al, Eur Radiol. 2013;23(1):174-81 Table 1: Examples of tests showing that the new model parameters (kph and khp) serve as superior diagnostic biomarkers (in bold) compared to existing biomarkers (khep, LSC_N10 and LSC_N20). In particular, our twodimensional approach, combining the two model parameters are the most superior, also compared to combinations of existing biomarkers. More tests than these have been applied, including ROC-curve analysis. Figure 1: Agreement with independent validatation data (red) and the model (green). In this case, the model has not been fitted to this data, and the measurements have been done in an new way. 73 73 2G5 FLOW CHARACTERISTICS IN THE AORTIC ARCH 1 1 1 2 3 3 L. Prahl Wittberg , S. Van Wyk , L. Fuchs , E. Gutmark , I. Gutmark-Little , P. Backeljauw 1 2 3 KTH Mechanics, Stockholm, Sweden. University of Cincinnati, Ohio, USA, Cincinnati Children’s Hospital, Ohio, USA 1. Introduction The blood flow in the human aortic arch and how it is affected by geometrical anomalies is the focus of this study. The underlying reason for this is that hemodynamics is believed to play an important role in localizing vascular diseases. Anatomic cardiovascular defects can be characterized by changes in the shape of the arch geometry, including widening or narrowing of the aortic diameter, as well as lengthening of parts of the arch. Malformations as mentioned above may lead to undesired changes in blood pattern directly affecting the fluid mechanical forces acting on the vessel wall. Moreover, the transport of Red Blood Cells (RBC) may be altered as it depends on the flow itself, also influencing the wall shear stresses. Since cardiovascular anomalies are often found in patients having the genetic disorder Turners Syndrome (TS), the flow in the aortic arch in this patient population will be investigated. The main objective is to assess the differences in flow phenomena occurring in the different geometries studied and how these changes affect the local blood distribution as well as wall shear stresses. 2. Method Data from Cardiac Magnetc Resonance Imaging (CMR) have been used in order to reconstruct the geometries of the aortic arch from four patients having TS. The four geometries studied are one normal aortic arch (TS normal), an arch having a dilated ascending aorta (TS dilated), an arch characterized by a constriction found in the descending aorta (TS constriction) and an aortic arch with an elongated transverse aorta (TS ETA). To fully resolve the flow field in time and space, the Navier-Stokes equations of an incompressible fluid, where the fluid in this case is represented by a mixture of RBC and blood plasma, are solved using OpenFOAM-1.6. The mixture density is considered as a function of the RBC and plasma densities. To model the evolution of the RBC mixture, a mass transport equation is solved, where the RBC are acting as an active scalar that is coupled to the blood viscosity, modeled by the Quemada rheological model [1]. The inflow into the ascending aorta is pulsatile, representing a heart pulsation cycle representing a volume flow of 5 L/min at 60 BPM (Beats Per Minute). At the outlets, i.e. the brachiocephalic branch, the left common carotide, the left subclavian branch and the descending aorta, a pressure condition is set that allows for a temporal evolution of the pressure. The walls of the aortic arch are assume to be rigid, and the distribution of RBCs at the inlet are corresponding to what has been observed in experimental studies of large arterial scaled tubes [2], where the bulk RBC volume fraction is set to 45%. 3. Result & Discussion The results show a clear geometry effect, depict for TS dilated and TS constricted in Fig. 1 displaying the normal velocity, and the in-plane velocity components. Common for all aortas is that recirculation zones are formed at approximately the same time in the cardiac cycle. However, the occurrence of recirculation zones is increased in TS constricted and TS ETA, in which three recirculation zones are formed (marked by the red rings in Fig. 1). The recirculation zones are found to coincide with areas displaying low time averaged wall shear stress and highly fluctuating behavior of the wall shear stress. The interest in understanding the locations of recirculation zones combined with the wall shear stress behavior is for example connected to identifying sites prone to develop atherosclerosis. As indicated above, the presentation of this work regarding the flow and corresponding forces occurring in different aortic archs will reveal a clear geometry effect. Also, the distribution of the RBCs along with the feature that the blood is found to leave though the branches on the arch to a greater extent for TS constricted and TS ETA as compared to TS normal and TS dilated are other topics that will be discussed within the scope of this work. References [1] D. Quemada, Rheologica Acta, 17(6), 632-642 (1978). [2] R. M. Tiggelaar, T. T. Veenstra, R. G. P. Sanders, J. G. E. Gardeniers, M. C. Elwenspoek, and A. van den Berg, Talanta, 56, 331-339 (2002). 74 Figure 1: Snapshots of the normal velocity component taken at a point in time of the cardiac cycle corresponding to t/T=0.254 for TS dilated (top) and TS constriction (bottom). For two additional cross sections, represented by E and H in the figure, the normal and the in-plane velocity components are displayed. Sammanfattningar Medicinsk bild- och signalbehandling Session 3G 75 75 3G1 ADVANCED PROSTHETIC CONTROL THROUGH AN OSSEOINTEGRATED BIDIRECTIONAL INTERFACE 1,2 1 1 2 Max Ortiz-Catalan , Bo Håkansson , and Rickard Brånemark 2 Chalmers University of Technology, Gothenburg, Sweden, Sahlgrenska University Hospital, Gothenburg, Sweden. 1. Introduction Although myoelectric prostheses have been clinically implemented since the 1960’s, they are still far from the functionality of their biological counterpart. It is a widely known fact that the lack and instability of physiologically appropriate control signals are the bottleneck of the field. Implantable neuromuscular interfaces could provide enough and long-term stable signals [1], however, the permanent communication with implanted devices is a major constraint that has hindered this solution for decades. In order to overcome this problem, we have developed a permanent bidirectional interface into the human body, the Osseointegrated Human-Machine Gateway (OHMG). 2. Method The OHMG is an enhancement of the OPRA Implant System [2], which has been used to treat over 200 patients worldwide (Figure 1). The OHMG’s modular design allows customization of the neuromuscular interfaces according to the patient’s anatomy and prosthetic needs. It initially comprises epimysial and cuff electrodes combinations which account for up to 12 contacts. The recording features of the cuff electrodes have been optimized in a frog sciatic nerve model [3]. Furthermore, analog electronics and an advanced control system based in pattern recognition have been developed (BioPatRec) [4]. Figure 1: The Osseointegrated Human-Machine Gateway (OHMG), an enhancement of the OPRA Implant system [2]. Animation to illustrate the concept at: http://youtu.be/w8hlziytLkM 3. Results 20 non-amputees and 5 amputees, with and without OPRA, have shown successful real-time control of multifunctional prostheses using BioPatRec [4]. Furthermore, simultaneous control has also been achieved with superior real-time performance over individual control [5]. A new semi-discrete tripolar configuration was found to increase the signal to noise ratio in neural recordings, but more importantly, it provides additional channels for neural information [3]. Finally, The OHMG has been successfully implanted in the first patient and preliminary tests are currently ongoing. This is the first time that neuromuscular electrodes have been permanently implanted in amputee patient in order to interface limb prostheses. 4. Discussion Preliminary clinical results show that the OHMG has the potential to allow permanent access to implanted electrodes, and once validated, it will open new possibilities for more advanced and natural prosthetic control. Long-term clinical studies are required to prove the benefits of implantable interfaces in prosthetic control. The early clinical results from the OHMG study will be reported. References [1] M. Ortiz-Catalan, R. Brånemark, B. Håkansson, and J. Delbeke, “On the viability of implantable electrodes for the natural control of artificial limbs: Review and discussion.,” Biomed Eng Online, vol. 11, p. 33, Jun. 2012. [2] K. Hagberg and R. Brånemark, “One hundred patients treated with osseointegrated transfemoral amputation prostheses—rehabilitation perspective,” J Rehabil Res Dev, vol. 46, no. 3, pp. 331–344, 2009. [3] M. Ortiz-Catalan, J. Marin-Millan, J. Delbeke, B. Håkansson, and R. Brånemark, “Effect on signal-to-noise ratio of splitting the continuous contacts of cuff electrodes into smaller recording areas,” J Neuroengineering Rehabil, vol. 10, no. 22, 2013. [4] M. Ortiz-Catalan, R. Brånemark, and B. Håkansson, “BioPatRec: A modular research platform for the control of artificial limbs based on pattern recognition algorithms,” Source Code Biol Med, vol. 8, p. 11, 2013. [5] M. Ortiz-Catalan, B. Håkansson, and R. Brånemark, “Real-time classification of simultaneous hand and wrist motions using Artificial Neural Networks with variable threshold outputs,” in Proceedings of the XXXIV International Conference on Artificial Neural Networks (ICANN), Amsterdam, May 15-16, 2013. 76 3G2 QT INTERVALS AND HEART RATE VARIABILITY FROM HOLTER-ECG:S IN CHILDREN WITH LONG QT SYNDROME 1 1 1 2 1 Anna Lundström , Marcus Karlsson , Gabriel Granåsen , Håkan Eliasson , Annika Rydberg , Urban Wiklund 1 2 Norrlands universitetssjukhus, Umeå, Sweden, Astrid Lindgrens barnsjukhus, Stockholm, Sweden 1 1. Introduction Congenital long QT syndrome (LQTS) is an inherited autosomal dominant disease that affects the cardiac ion channels, leading to a prolonged ventricular repolarisation with risk for torsade de pointes and sudden cardiac death. The characteristic findings on the electrocardiogram (ECG) are a prolonged corrected QT interval (QTc) and T wave abnormalities. The purpose of this study was to longitudinally evaluate QTc, heart rate variability (HRV) and the influence of prophylactic medication, in two-channel Holter-ECG recordings from children/adolescents with LQTS. 2. Methods Included in this retrospective study were genetically verified LQT1, LQT2 or LQT3 patients that during the age of 0-18 years underwent at least one 24-hour ECG (Holter) recording. In total, we analysed 364 Holter recordings from of 79 patients (42 female, 53%). The patients were followed longitudinally for a median of 3 years (0-10) and the average amount of Holter recordings per patient were 4,5 (1-17). A control group consisting of 39 healthy children and youths, with a median age of 10.6 (1-18) years underwent echocardiography and presented Holter-ECG:s with normal findings. The LQTS patients were all managed at the Department of Pediatric Cardiology at Norrland´s University Hospital or Astrid Lindgren Children´s Hospital, Karolinska – Solna. Since a large part of the Holter recordings had been performed with a system that did not include any QT-analysis, we have developed software for automatic beat-to-beat analysis of QT and RR intervals. All QT values were filtered using an algorithm that eliminated inaccurate measured values. The validity of the software has previously been proven through comparison against >14000 manually on-screen measurements of heartbeats from 10 children with LQTS and 10 healthy children. In this study, all analyses were based on 24-hour averages of QTc and indices from power spectrum analysis of HRV. Non-parametric statistical methods were used for all comparisons. 3. Results The LQTS patients were, as expected, found to have a significantly longer mean QTc interval and a longer RR interval during the 24-hour recording when compared to the control group. When the QTc values were plotted out in relation to age, a majority of the patients (n=53, 68%) had a QTc over 460 ms, 20 patients had a borderline value between 440-460 ms and four had a QTc under 440. The LQTS patients showed a decrease in low-frequency (LF) variability when compared to the control group. Fifteen LQTS patients had undergone a Holter recording before the start of medication and later underwent a recording while on Beta-blocker therapy. When comparing the QTc and HRV parameters for these 15 patients before medication and on medication, a significantly longer RR interval and lower PLF/PHF ratio were found. 4. Discussion To our knowledge, there are few (if any) previous studies that have analysed QT intervals and HRV from Holter-ECG recordings in children with LQTS. However, our results regarding QTc and mean RR interval are in agreement with previous studies based on short ECG recordings. The reduced PLF/PHF after betablockade could be an indicator of reduced sympathetic activity, acting as a protection against arrhythmias. Our on-going research is based on this database of nearly 400 recordings, and our current analyses aims to determine whether HRV can be used for risk assessment in LQTS. 77 77 3G3 Multivariate Classification of Cardiac Autonomic Function and Echocardiographic Abnormalities 1 1 Gabriel Granåsen , Ole B Suhr , Urban Wiklund 1 Umeå University Hospital, Umeå, Sweden. 1 1. Aims: Abnormalities in the function, physiology and the regulation of the heart can be diagnosed using echocardiography (ECHO) and analysis of heart rate variability (HRV). Patients with transthyretin amyloidosis often present cardiac hypertrophy and/or autonomic dysfunction. We used a novel approach to analyse the relationship between these findings, using a combination of dimension reduction techniques and model based clustering. The aim of this work was to develop a model for future predictions of the current state of the disease in context of HRV and ECHO abnormalities 2. Methods Data were obtained from 39 adult patients and 62 healthy controls. HRV indices were calculated as 24-hour averages: the mean RR interval; the power of the very low-frequency, low-frequency and high-frequency components. From ECHO we used: posterior wall thickness, septal thickness, left ventricular end diastolic dimension, isovolumetric relaxation time and deceleration time. Principal component analysis was performed to model the within modality variability of each group of variables. The hierarchical Gaussian mixture modelling method, Mclust[1], was used to find clusters of subjects in the resulting component scores. Models were validated using bootstrap resampling techniques. 3. Results For each modality, subjects were classified into three groups. The cluster that mainly consisted of controls was denoted as Normal. The most diverging cluster was denoted Abnormal. The middle cluster was denoted Borderline. All controls were classified as normal in ECHO, and as normal (young and middle-aged subjects) or borderline (middle-aged and old) in HRV, reflecting the well-known successive decrease in HRV with age in healthy subjects. For patients, the classification was related to the progress of disease: 36% had normal or borderline HRV and normal ECHO; 18% had abnormal HRV and normal ECHO; while 46% were classified as borderline or abnormal in both examinations. 4. Conclustions The analysis successfully separated between patients with regulatory involvement but only minor structural abnormalities, and those with both structural abnormalities and severe autonomic dysfunction. Clinically, the model can be used to predict how subgroups of ATTR patients are classified with respect to the training material, for example for examining abnormality patterns for patients with arrhythmia, or for quantification of progression of cardiac and autonomic complications after liver transplantation. The presented method can also be extended to model patterns in other diseases with cardiac and autonomic involvement. HRV 0 PC2 1 2 3 Control HN Control HB Patient HN Patient HB Patient HA -4 -2 0 2 PC1 4 6 -3 -3 -2 Control EN Control EB Patient EN Patient EB Patient EA -2 -1 0 -1 PC2 1 2 3 ECHO -4 -2 0 2 4 6 PC1 Figure 1: Results after dimensional reduction and mixed gaussian clustering. For each modality two significant principal componetns were found with three clusters each. The clusters were named after progress of disease and relation to controls as Normal, Borderline and Abnormal. 95% confidence ellipses for controls are marked with dashed lines and cluster centroids with solid lines. References [1] C. Fraley and A. E. Raftery, “MCLUST version 3 for R: Normal mixture modeling and model-based clustering,” 2006. 78 3G4 ECHOCARDIOVARIABILITY – LOW AND HIGH FREQUENCY BEAT-TO-BEAT VARIABILITY IN ECHOCARDIOGRAPHIC SIGNALS Amanda Albano1, Sandra Gustavsson2, Per Lindqvist2, Michael Henein2, Urban Wiklund1, Christer Grönlund1 1 Medicinsk teknik – FoU, Strålningsvetenskaper, Umeå universitet, Umeå, Sverige. 2 Hjärtcentrum, Folkhälsa och klinisk medicin, Umeå Universitet, Umeå, Sverige 1. Introduction The cardiovascular system comprises several oscillating components, e.g. respiration (~0.3Hz, HF), Meyer waves (~0.1Hz, LF). Since echocardiographic variables are known to be load and respiration dependent, the guidelines say that images should be taken at end-expiration. However, this does not account for low frequency variations. This work aims at assessing this low and high frequency beat-beat variability in healthy and diseased subjects. 2. Methods Five young and two older healthy subjects (20-35y and 50-60y), and two patients with amyloid cardiac disease (50-70y), participated in this pilot study. A two-minute B/CDI-mode echocardiographic exam was performed with acquisition of ECG, respiration and blood pressure (BP) signals. Simultaneous blood flow velocity and myocardial motion echo-variables, and systolic BP were extracted per heart-beat off-line. Variability of the unfiltered, LF (bandpassed BP), and the HF signals was calculated using the coefficient of variation (CV). Coupling strength to Meyer waves and respiration signals was quantified by the coherence power index (CPI). Analysed signals included: early and late peak diastolic flow velocity (E, A), peak myocardial velocity (E’), E/E’, and E/A. 3. Results Figure 1 illustrates the variability in the E/E’ index over a 90 second period for one healhy young and one older subject, and one patient. In general, the echovariables had wider band spectra than BP, respiration and RR signals. Variability of unfiltered signals was 10-30% and was lower in patients and old compared to healthy subjects. The variability in the LF and HF bands were similar (~10%) except for the A and E/A (higher in HF band). The coupling strength (CPI) between echovariables and respiration was overall stronger (20-80%) than coupling to Meyer waves 10-50%, and was lower in patients than in healthy subjects. E/E’ 4. Discussion This work introduces and illustrates the concept echocardio-variability (ECV). The magnitude of the high and low-frequency variations was similar and may influence clinical assessment. This approach seems promising for the development of novel diagnostic indices. Figure 1: 90 seconds E/E’ variations for a young and old healthy subject, and a patient with amyloid cardiac disease (FAP). End-inspiration and expiration is indicated by dots and asterix. 79 79 3G5 A COMPARISON OF SHEAR WAVE ELASTOGRAPHY PUSHING SEQUENCES 1 Tim Nordenfur1, Elira Maksuti1, Erik Widman1, Anna Bjällmark1,2, Matilda Larsson1,2 Department of Medical Engineering, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden 2 Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 1. Introduction Changes in stiffness of soft tissue are a sign of abnormalities. Therefore, techniques capable of estimating elasticity of tissue can contribute in the assessment of various diseases. Shear wave elastography (SWE) is an ultrasound-based technique where a pushing beam induces shear waves (SW) characterized by lower wave speed than longitudinal waves and that travel orthogonally to the pushing beam direction. Tissue elasticity can then be estimated from measuring the local SW velocity. There are multiple ways of generating SW using acoustic radiation force impulses. The purpose of this study was therefore to compare the performance of four different pushing sequences with a commercial device and in an experimental setup. 2. Methods A programmable ultrasound system (Verasonics Inc, Redmond, WA, USA) with a 128-element linear transducer (Philips L74) was used to induce SW in a homogeneous PVA phantom (10% PVA, 3% graphite, 2 freeze cycles) and to measure the SW propagation. 180V p-p voltage and 5 MHz centre frequency were used for each transmission. Four pushing sequences were investigated: 1) focused push, focusing at a single point for 96 μs, 2) unfocused push, where the 12 central elements were excited for 198 μs to generate an unfocused plane wave, 3) unfocused comb-push [1], where four simultaneous and unfocused pulses, equally spaced in the lateral direction, were emitted, and 4) line-push [2], where three pushes were focused along a line at progressively deeper focal points. The focused pushes were spaced 0.7 mm axially with a 0.2 ms delay between pushes. SW propagation was imaged with plane wave pulses at a frame rate of 10 kHz and 5 MHz centre frequency. The average of three angled plane waves (-8º, 0º, 8º) was used to construct each frame. Axial particle velocity was estimated at each pixel and frame using Loupas’ 2D autocorrelator [3] setting a 5-sample range gate length across 5 frames. The result was directionally filtered to reduce noise and artefacts. By cross-correlating the time-dependent axial velocity of two pixels, 2 mm apart laterally, the local SW speed was estimated (Figure 1). Due to the absence of SW in the pushing region, all implemented sequences, apart from the comb-push, exhibit blind areas, in which SW speed cannot be estimated. The width of this area was also measured. Finally, our implementations were compared with the commercial SW system Aixplorer (Supersonic Imagine, France). Figure 1: Directionally filtered axial velocity of SW generated by the four pushing sequences, at one depth. 3. Results Table 1 summarizes the measured SW velocity and blind area width for each implementation. As can be seen, SW velocity mean values are close to each other and to those obtained with the commercial system. The line-push resulted in the widest blind area, while the comb-push had none. Table 1: Measurement results for different pushing sequences. SW velocity Width of blind area Unfocused 4.39 ± 0.18 m/s 2.3 mm Comb-push 4.40 ± 0.21 m/s 0 mm Focused 4.65 ± 0.29 m/s 2.5 mm Line push 4.57 ± 0.30 m/s 3.0 mm Aixplorer 4.5 ± 1.5 m/s - 4. Conclusions To summarize, all the pushing sequences implemented in this study performed similarly concerning the SW speed estimation, with values close to the ones obtained with the commercial SW system. The comb-push, however, had the advantage of not leading to any blind areas. Further investigations should include quality measures relevant to specific clinical applications. References [1] Zhao, Heng, Pengfei Song, Matthew W Urban, James F Greenleaf, and Shigao Chen. “Shear Wave Speed Measurement Using an Unfocused Ultrasound Beam.” Ultrasound in Medicine & Biology 38, no. 9 (September 2012): 1646–1655. [2] Bercoff, J., M. Tanter, and M. Fink. “Supersonic Shear Imaging: a New Technique for Soft Tissue Elasticity Mapping.” IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control 51, no. 4 (April 2004): 396 –409. [3] Loupas, T., J.T. Powers, and R.W. Gill. “An Axial Velocity Estimator for Ultrasound Blood Flow Imaging, Based on a Full Evaluation of the Doppler Equation by Means of a Two-dimensional Autocorrelation Approach.” IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control 42, no. 4 (July 1995): 672–688 80 3G6 AN INTELLIGENT PHONOCARDIOGRAM FOR AORTIC STENOSIS DIAGNOSIS Arash Ghare Baghi1, Birgitta Janerot-Sjoberg2, Peter Hult, Per Ask1 Physiological measurement, Department of biomedical engineering, Linköping University, Linköping, Sweden 2 Departments of Clinical Science, Intervention and Technology, Karolinska Institutet & Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden 1 1. Introduction “Cardiovascular diseases” is still the main factor of human mortality. A large percentage (as many as 70%) of the paediatric referrals to the hospital for cardiac examinations, have normal hearts while to a lesser extent a number of pathological patients are neglected by the screening procedures in primary healthcare centres [1]. The intelligent phonocardiogram is a non-invasive, powerful and inexpensive approach which can serve as a screening tool in hands of the practitioners or nurses in primary healthcare centres to select appropriate patients to undergo echocardiography which is by far a more expensive approach. Studies showed that a computer assisted phonocardiography will substantially improve the screening accuracy [2]. Heart has a rhythmic mechanical action by which blood is pumped through the circulatory system. The mechanical action constituted from the heart muscle movements and thereby opening and closure of heart valves. Phonocardiogram is an acoustical recording of the heart sounds associated with the mechanical action. Auscultation of these sounds is still the main technique for screening heart disease in the primary healthcare centres. However, the accuracy of this technique is influenced by physiological restrictions exist in the human auditory system as well as other psychological and environmental effects. Intelligent phonocardiogram is indeed a computer based stethoscope, supported by the intelligent algorithms to analyse heart sound signal in order to detect pathological symptoms of the heart sound. As the aforementioned negative effects are efficiently attenuated thanks to the rapid progresses in electronics systems and artificial intelligence, the undesirable factors would be decreased in favour of the intelligent stethoscope. This device helps the practitioners or nurses in the primary healthcare centres as a decision support or even as a screening tool. The powerful algorithms could be incorporated into smart phones or tablets for automatic diagnosis to be used as a home healthcare system. 2. Method Phonocardiogram signals were collected from the patients diagnoses as normal patients (30 cases) and the patients with aortic stenosis (30 cases) according to the echocardiography. An electronic stethoscope which is commercially available was utilized for signal recording. Data recording was done according to the guidelines of the corresponding hospitals which were in compliance with the declaration of Helsinki. Patients gave their informed consents prior to the data recording. The study was approved by the corresponding local committees. In this study, signal processing techniques in conjunction with our innovative pattern recognition methods are employed to screen and diagnose Aortic stenosis in children and elderly people, respectively. In order to evaluate the screening performance, random repeated sub sampling (RRSS) method is applied to estimate an expected value for the three performance measures; classification rate, sensitivity and specificity. 3. Results Balanced RRSS with 50%/50% of training/testing data is employed to evaluate the performance of the system. The average values for accuracy, sensitivity and specificity after 50 iterations are estimated as 88%, 86% and 89% respectively. Regression analysis confirmed the significance of the diagnosis with R>0.81. 4. Discussion Results showed that the proposed system can act as an efficient tool for screening and diagnosis of aortic stenosis. It is evidenced by the previous studies that the screening accuracy of a specialized cardiologist who relies on auscultation is about 80% [2], while the corresponding value of the intelligent phonocardiogram described is 88%. As a consequence, the performance of the system in screening is at least as good as a specialized cardiologist and may, when tuned to a larger database including greater variety of different heart conditions, it has potential to further improve frugal performance availability e.g. in smartphones. References [1] C. G. DeGroff, S. Bhatikar, J. Hertzberg, R. Shandas, L. Valdes-Cruz and R. L. Mahajan, "Artificial neural networkbased methods of screening heart murmurs in children," Circulation, vol. 103, pp. 2711-2716, 2001. [2] R. L. Watrous, R. W. Thompson and S. J. Ackeman, "The Impact of Computer-assisted Auscultation on Physician Referrals Asymptomatic Patients with Heart Murmurs," Clinical Cardiology, vol. 31, pp. 79-83, 2008. 81 81 3G7 ULTRASOUND CONTRAST AGENT LOADED WITH NITRIC OXIDE AS A THERANOSTIC MICRODEVISE FOR MYOCARDIAL ISCHEMIA. Grishenkov D.1, Gonon A.2, Paradossi G.3, Janerot-Sjoberg B.1,2 Karolinska Institutet, Department of Clinical Science, Intervention and Technology: Medical Imaging and Technology, Stockholm, Sweden. 2 Karolinska University Hospital: Department of Clinical Physiology, Stockholm, Sweden 3 Università di Roma Tor Vergata, Diapartimento di Chimica, Rome, Italy 1 Introduction Cardiovascular disease (CVD) accounts for 1/3 of total global deaths worldwide. The most widespread CVD is ischemic heart disease. It is the leading cause of death in both genders, equally diagnosed in developed and developing countries with mortality exponentially increasing with age. Efforts of healthcare system should be primary focused on prevention, timely detection, efficient differentiation and instant treatment of the disease. Method Current project introduces a new class of microdevices providing integrated diagnostic and therapeutic applications, i.e. theranostics, of ischemic heart disease using novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO). We use a gas filled MBs with an average diameter of 3 µm stabilized by a biocompatible poly-vinyl-alcohol (PVA) shell (see Figure 1). A gas core makes MBs an efficient ultrasound contrast agent. Substituting the core gas with a therapeutic gas, in our case NO, opens new possibilities for local, specific drug delivery triggered by ultrasound. Results and Discussion A fabrication protocol of air-filled polymer shelled contrast agent has been developed. Polymer shelled MBs can be obtained with different average sizes, and shell thicknesses depending on the pH and temperature of the master solution. The external mean diameter changed from 2.0 ± 0.3 µm to 4.4 ± 1.1 µm, when the temperature was increased from 4 °C to 37 C°. Shell thickness increased from 0.4 ± 0.1 µm to 0.6 ± 0.1 µm when pH was decreased from 5 to 2. Polydispersity and size distribution can be further controlled by sizing the homogenizer’s tips. Particles' dimension should be not larger than the capillary lumen, i.e. about 5 µm, and not smaller than hundreds of nanometres in order to avoid nanospecific effects such as potential immune effects. MBs with narrow size distribution, i.e. monodisperse suspension, have unique resonance frequency of oscillation. Acoustic insonation at a frequency close to the resonance generate strong nonlinear harmonic response, which can be specifically discriminated in the received echo. In vitro ultrasound tests showed an enhancement of the backscattered power (25±1 dB), comparable to the soft tissue attenuation coefficients (0.8±0.04 dB/cm MHz) and phase velocities (1519±2 m/s). Assessment of the pressure threshold, Pthr, at which the MBs shell fractures suggests that fatigue, i.e. accumulation of damage within the shell, is a physical mechanism responsible for the fracturing process. A decrease of Pthr from 1.2±0.09 MPa to 0.9±0.05 MPa is obtained when the number of cycles in the pulse increases from 6 to 12. Worth noting that below Pthr MBs can be imaged non-destructively using second or super harmonic techniques and above Pthr destruction/replenishment algorithm offers the possibility to study tissue perfusion and delivery therapeutic payload. The cell viability tests performed so far indicate that polymer MBs are biocompatible but that there is an apparent immune system response after 8 hours after accumulation especially in macrophages.. A preliminary protocol for NO loading of MBs has been developed. NO-gas, can be incorporated in the MBs by exposing freeze-dried MBs to NO atmosphere in a pressure chamber. The re-dispersed MBs release NO during about 2 hours. In vitro studies have shown that these NO loaded MBs are able to stop the clot formation. Ex vivo tests reveal that cardioprotection mediation via NO is plausible and depends on intact NO-syntase. Potentially e.g. unstable plaques and reperfusion injuries due to NO-syntase depletion can be treated with local NO delivery, thereby avoiding hazardous systemic effects. Conclusion We describe a polymer-shelled gas-core MBs that can be manufactured according to clinical requirements of controlled size below 5 µm and narrow size distribution. They are chemically and mechanically stable, provide adequate acoustic enhancement and can be loaded with NO for local and specific therapy. The plain MBs are biocompatible but alert immune system response after 8 hours which has to be verified after NO-loading. A single injection of the proposed multifunctional contrast agent together with ultrasound exposure has the potential to combine initial diagnostics, with treatment and terapeutic monitoring. Figure 1. Left: Schematic representation of PVA MB. Right: Electron micrograph of freeze-fractured MB showing a shell thickness of about 200 nm with a microstructure of PVA microfibrils 82 Sammanfattningar POSTERS P1-P25 Moderator: Göran Salerud 83 P1 Quantitative Analysis of Aortic 4D Flow MRI: Reproducibility and Correlation with Growth 1 Petter Dyverfeldt1,2, Michael D. Hope2, Monica Sigovan2,3, Jarrett Wrenn2, David Saloner2 2 3 Linköping University, Linköping, Sweden. University of California San Francisco, CA, United States. University of Lyon, Lyon, France Introduction 3D cine phase-contrast magnetic resonance imaging (“4D Flow MRI”) permits quantitative assessment of anomalous alterations of aortic blood flow. Two hemodynamic parameters that have been used for this purpose is the wall shear stress (WSS), which is known to regulate endothelial cell function, and the normalized flow displacement from the vessel center, which was recently shown to correlate with increased growth rates of ascending aortic dilation [1,2]. Analysis of these hemodynamic parameters requires that a user 1) positions a 2D plane of interest in the volumetric dataset and 2) delineates the contour of the vascular lumen in this 2D plane. We set out to assess the reproducibility of 4D Flow MRI-based estimation of WSS and normalized flow displacement at these two critical levels of user-interaction. Furthermore, we assessed which of the parameters correlate best with aortic growth. Materials and Methods 25 patients previously studied with 4D Flow imaging were included. Previously reported data on interval aortic growth was available for each subject [2]. CMR velocity data from a plane perpendicular to the ascending aorta just distal to the sinotubular junction was collected independently by two blinded reviewers, and then separately segmented by two blinded observers (see Figure 1). Subsequently, the following parameters were calculated: normalized flow displacement, maximum peak-systolic WSS, maximum of systoleaveraged WSS, mean peak-systolic WSS, minimal peak-systolic WSS. Normalized flow displacement, which estimates the degree of flow eccentricity, was calculated as in ref [1]. WSS calculation was performed with propriety software (Flow Tool) [4]. Reproducibility analysis and correlation with interval aortic growth were performed. Figure 1: Example case demonstrating the reproducibility analysis performed in the present study. An isosurface of the thoracic aorta is provided on the left to show the location of the planes selected independently by two observers (one in red, the other in yellow). Each plane was then independently segmented by two separate observers for quantification of CMR hemodynamics parameters (one contour in purple, the other in green). Normalized flow displacement from the vessel center (blue circle) is depicted for each of the planes. Results Inter-observer correlations with regards to plane selection and contour delineation are reported in Table 1. For the contour delineation, correlation coefficients were 0.97-0.98 for normalized displacement and 0.78-0.96 for the WSS parameters. For the plane positioning, these correlation coefficients were 0.91-0.93 for normalized displacement and 0.47-0.85 for the WSS parameters. Flow displacement best correlated with interval aortic growth (r = 0.65). The range of WSS parameters did not correlate well with growth (r < 0.15). Table1. Reproducibility analysis: inter-observer correlations Observerplanes#1 versus Observerplanes#2 Mean peaksystolic WSS Max peaksystolic WSS Min peaksystolic WSS Max systoleaveraged WSS Min systoleaveraged WSS Normalized Flow Displacement Contours #1 0.71 0.67 0.47 0.74 0.71 0.91 Contours #2 0.82 0.85 0.51 0.85 0.70 0.93 0.93 0.87 0.84 0.87 0.88 0.98 0.96 0.91 0.81 0.90 0.78 0.97 Observercontours#1 Planes #1 versus Observercontours#2 Planes #2 Discussion Normalized flow displacement is a reproducible hemodynamic marker that shows good correlation with interval aortic growth. Reproducibility of contour delineation for WSS analysis was good and in line with previous reports [3]. However, markedly lower reproducibility was found for the plane-positioning step of the WSS analysis. Normalized flow displacement should be considered in future work aimed at identifying and risk-stratifying patients who are likely to develop clinically significant aortic dilation based on MR-estimated hemodynamic parameters. References: [1] Sigovan M, et al. JMRI 2011;34:1226-30. [2] Hope MD, et al. JACC 2012;60:356-7. [3] Markl M, et al. JMRI 2011;33:988-94. [4] Stalder A, et al. MRM 2008;60:1218-31. 84 P2 ULTRASOUND SPECKLE TRACKING FOR ARTERIAL STRAIN IMAGING – A VALIDATION STUDY IN-SILICO, IN-VITRO AND IN-VIVO 1,2 1 2 1 2 Matilda Larsson , Brecht Heyde , Lars-Åke Brodin , Jan D’hooge KTH-Royal Institute of Technology, School of Technology and Health, Stockholm, Sweden. 2 Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium 1. Introduction Ultrasound-based speckle tracking for estimation of arterial wall strain has potential to be used for assessment of arterial stiffness to improve cardiovascular risk stratification. However, most speckle tracking algorithms have been developed and validated for cardiac applications, whereas strain assessment in the artery wall is more challenging due to lower strain amplitudes combined with poor spatial resolution. This project aimed to develop and test an ultrasound-based speckle tracking algorithm for strain estimation of the artery wall in simulated data sets, in an experimental setup and in an animal model. 2. Method A speckle tracking algorithm tuned for the vascular setting was developed in Matlab (normalized cross-correlation for 2D motion estimation across frames, kernel size: 5λ×2λ, axial and lateral kernel overlap: 40% and spline interpolation for subsample motion detection). Accumulation of the displacement maps throughout the cardiac cycle was performed and longitudinal and radial strains were then obtained by linear regression after averaging in one direction of the selected region of interest (radially for longitudinal strain and vice versa). The strain curves were then drift compensated and low-pass filtered. The speckle tracking algorithm was validated in three steps: in-silico, in-vitro and in-vivo. First, it was applied on simulated ultrasound images from a kinematic cylindrical model of the carotid artery with realistic dimensions and movement pattern. The ultrasound images were simulated using a generalized convolution model (COLE) with realistic image properties and the estimated strain was then compared with the ground truth from the model. In the experimental validation, the algorithm was applied on ultrasound images from polyvinyl alcohol phantoms mimicking the carotid artery. The phantoms were connected to a pulsatile pump, programmed to generate carotid flow profiles. Sonomicrometry crystals were glued on the phantom walls and used to acquire reference values of strain. In the in-vivo validation, the algorithm was applied on ultrasound images obtained in a sheep model. The left carotid arteries of 3 sheep were exposed during isofluran anesthesia and two sonomicrometry crystals were sutured onto the artery wall to obtain reference values of longitudinal strain. The wound was closed and filled with ultrasound gel followed by ultrasound imaging at baseline and stress. 3. Results An overall good agreement was found between the strain estimated with the speckle tracking algorithm and the reference strain in the three validation setups. In-silico, the peak systolic radial strain was estimated to be -13.15 ± 0.99% (ground truth 13.89%) while longitudinal strain was 5.25 ± 1.20% (ground truth 5.30%). The correlation between estimated mean peak strain values and reference peak strain values was r = 0.92 (p < 0.001) for radial strain and r = 0.72 (p = 0.006) for longitudinal strain in the experimental setup. The results from the in-vivo validation are shown in Fig. 1. 4. Discussion This study shows the feasibility of estimating radial and longitudinal strain in the carotid artery using ultrasound speckle tracking. However, the step from in-silico and in-vitro to in-vivo estimation is challenging and the surgical exposure in the in-vivo validation may have affected the artery wall properties since lower strain values than previously observed in-vivo were obtained. Moreover, further studies are needed to test the algorithm on human in-vivo data and to investigate the potential of the method to estimate arterial stiffness and detect cardiovascular diseases at an early stage. 85 85 P3 Bioclearance of a novel polymer-shelled multimodal contrast agent Malin Larsson1, Johan Härmark1, Anton Razuvajev 2, Kenneth Caidahl2, Anna Bjällmark1,2 1 Kungliga tekniska högskolan - STH, Stockholm, Sweden. 2 Karolinska institutet, Solna, Sweden 1. Introduction Multimodal imaging is a promising approach in the diagnosis of various diseases. To increase the sensitivity and specificity of modality fusion, contrast agents (CA) consisting of encapsulated microbubbles (MBs) supporting multimodality imaging approaches would be of great value. A novel polymer-shelled CA with multimodality potential is currently under development. This CA has physical properties which differ significantly from the presently used lipidic CAs such as a high mechanical and chemical stability, facilitating a possible use of these MBs as carriers for different substances. Despite all possible improvements, the bioclearance of the novel CA needs be investigated. The aim of this study was therefore to investigate the blood circulation time and the elimination pathway of three different types of the novel CAs in a rat model using ultrasound imaging and transmission electron microcopy (TEM). 2. Methods Three types of the novel polymer-shelled CA were employed in the study; a plain polymer- shelled CA (Plain) useful solely with ultrasound (US) imaging and two types with modified shell or shell surface, both containing superparamagnetic iron oxide nanoparticles (SPIONs) for combined ultrasound and magnetic resonance imaging [1-2]. In one of the modified CA (Type A), the SPIONs were covalently linked to the shell surface through chitosan molecules, whereas in the other modified CA (Type B), the SPIONs were embedded in the shell. Moreover, SonoVue® was used as reference in the US experiments. A bolus of 0.4 ml of the CAs listed in Table 1 was injected through the jugular vein. For animals analyzed with US, image sequences of the carotid artery were acquired using a Vevo2100 system (f=18MHz, 15 frames/s) (FUJIFILM VisualSonics Inc., Canada) in the nonlinear contrast mode. After completed experiments, the image sequences were exported to a workstation for further analysis. A region of interest (ROI) was manually placed in the middle of the vessel lumen and the mean intensity over time, within the ROI from each image sequences, was analyzed in Matlab (MathWorks, United States). Before further processing, the obtained data was filtered using a convolution filter (1x8). In order to evaluate the wash-outtimes for the different CAs, normalized curves were approximated using the nonlinear last square method. In the other animal group, tissue samples from liver, lung, spleen and kidney were collected at different time points and analyzed using TEM. Table 1. The contrast agents and the number of animals included in the study. Contrast agent Histological analysis Plain [7.5 x 107MBs/ml] Type A [7.5 x 107MBs/ml] Type B [7.5 x 107MBs/ml] Plain [6.6 x 108MBs/ml] Type A [6.6 x 108MBs/ml] Type B [6.6 x 108MBs/ml] SonoVue® [2-5 x 108MBs/ml] *Two repeated injections 10 min 1 1 1 - 3. Results A 50 % decrease in the peak enhancement was observed for all CAs during the first 30-60 seconds, see Figure 1. Compared with SonoVue®, the novel CAs had longer detectable circulation time in the blood, where the longest circulation time was observed for the Plain CA. An uptake of MBs in the macrophages was observed in all tissue types for all CAs investigated, see Figure 2. None of the CAs were located outside the blood vessels, indicating no uptake in parenchymal or endothelial cells for any types of tissues investigated. Fragments of CAs were observed all every tissue sections, regardless of time point and CA type. 40 min 1 1 1 - Ultrasound 24 h 1 1 1 - 4* 4* 4* 4* Figure 1: Wash-outtime-curve obtained for SonoVue® blue curve, Plain red curve, Type A black curve and Type B green curve. 4. Conclusions The blood elimination time, determined when using ultrasound imaging, indicated a longer elimination times for the novel CAs compared with the commercially available CA SonoVue®. The macrophages were suggested to be responsible for the elimination processes. Figure 2: Electron micrographs of Type A microbubbles found (A) internalized in a rat liver Kupffer cell and (B) inside a rat lung capillary, both obtained 10 min after injection. References [1] Brismar TB, et al., Magnetite Nanoparticles Can Be Coupled with Microbubbles to Support Multimodal Imaging. Biomacromolecules 2012;13 (5):1390-9. [2] Paradossi G, et al., Tailoring of physical and chemical properties of macro- and microhydrogels based on telechelic PVA. Biomacromolecules 2002;3:1255-62. 86 P4 THE CARDIAC STATE DIAGRAM AS A NOVEL APPROACH FOR EVALUATION OF CARDIAC TIME INTERVALS IN ACS PATIENTS. 1 1 2 Jonas Johnson , Carl Westholm 2 Department of Medical Engineering, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden. Department of Cardiology, Karolinska University Hospital, Huddinge, Sweden. ABSTRACT The CSD method is based on a new model for how the heart performs its pump and regulatory functions [1,2]. This model states that the heart pumps and auto-regulates the flow of blood according to the DAPP technology, which is a new type of pump technology with very efficient pump characteristics. The DAPP technology and therefore also the heart performs its functions optimally based on a dynamic process in the hearts inflow, outflow and internal flow. Therefore the starting and end point of the different cardiac events and changes in dynamic and static energy generated by the heart’s AV-plane (piston) movements transferred to pressure and flow into, inside and out of the heart. This definition of cardiac phases is novel and does not coincide with the previously described phases since the DAPP-technology has not previously been known. 1. Objective To investigate cardiac time intervals using Tissue velocity imaging (TVI) echocardiography and generate a state diagram that provides easily accessible overview of the cardiac state regarding timing events on the segmental level. We intended to interrogate whether state diagram could differentiate ACS patients from healthy individuals. 2. Method The study consisted of 197 consecutive ACS patients and a control group of 42 healthy individuals. TVI measurements were done at the basal segment of the LV in the 3 apical planes. All analyses were performed off-line using EchoPac workstation. All cardiac state diagrams were generated with the analysing software, GHLab. Statistical analysis was done with SPSS. 3. Results The majority of the cardiac time intervals between events under investigation differ between healthy and non-healthy individuals. The transition phases i.e. the pre- and post-ejection intervals were significantly prolonged in the ACS group (p<0.001), using independent t-test. 4. Conclusion Cardiac time intervals assessed by cardiac state diagrams (CSD) can differentiate ACS patients from healthy individuals. The novel approach is feasible and may provide robust information for the differentiation between ACS and healthy individuals. References [1] Lundbäck, Stig, “Cardiac Pumping and Function of the ventricular Septum”, Acta Physiologica Scandinavica Supplementum, 1986 [2] Lundbäck, Stig, Heart Cluster State Machine Simulating the Heart US patent application 20080154142 (2005) 87 87 P5 THE CARDIAC STATE DIAGRAM AS A NOVEL APPROACH FOR EVALUATION OF PRE- AND POST EJECTION PHASES OF THE CARDIAC CYCLE IN ASPHYXIATED FETAL LAMBS 1 2 1 3 3 2 2 Elle Wågström , Jonas Johnson , Kjerstin Ferm-Widlund , Nina Elmstedt , Karina Liuba , Britta Lind , Lars-Åke Brodin , Stig 4 1 Lundbäck , Magnus Westgren 1 2 Department of Obstetrics and Gynecology, Center of Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden. Department of 3 Medical Engineering, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden. Department of Obstetrics and 4 Gynecology, Skåne University Hospital, Sweden. Gripping Heart AB, Stockholm, Sweden. ABSTRACT The CSD method is based on a new model for how the heart performs its pump and regulatory functions [1,2]. This model states that the heart pumps and auto-regulates the flow of blood according to the DAPP technology, which is a new type of pump technology with very efficient pump characteristics. The DAPP technology and therefore also the heart performs its functions optimally based on a dynamic process in the hearts inflow, outflow and internal flow. Therefore the starting and end point of the different cardiac events and changes in dynamic and static energy generated by the heart’s AV-plane (piston) movements transferred to pressure and flow into, inside and out of the heart. This definition of cardiac phases is novel and does not coincide with the previously described phases since the DAPP-technology has not previously been known. 1. Objective To investigate myocardial wall motion, using echocardiography and colour-coded tissue velocity imaging and generate Cardiac State Diagram according to a recently new developed program for evaluation of the duration of the Pre- and Post Ejection phases, in the cardiac cycle in asphyxiated fetal lambs. 2. Method Six near term lambs were partly exteriorized and monitored using echocardiography and colour-coded tissue velocity imaging while brought through asphyxia to cardiac arrest. Arterial blood sampling for lactate and blood gas measurements were simultaneously performed, the first sample taken before cord occlusion and then every 5 min until cardiac arrest. The heart’s mechanical function of the fetal lamb was evaluated in newly developed software GHLab based on the assumption that the heart’s pumping and regulating functions acts according to a new pump-principle today recognized as the Dynamic Adaptive Piston Pump principle. The results from the software are displayed in an easy to interpret Cardiac State Diagram. 3. Results All fetal lambs showed a prolongation of the Pre- and Post Ejection phases at the same time when the most pronounced change in lactate and pH occurred. The percentage change of the duration of the Pre- and Post Ejection phases were significantly longer in all fetal lambs, 49% (p<0.001) and 38% (p<0.049) respectively. The heart’s mechanical function was interpreted and visualized in a Cardiac State Diagram where the cardiac events are detected and displayed. 4. Conclusion As asphyxia progresses in fetal lambs, the duration of the Pre- and Post Ejection phases increased and the Cardiac State Diagram has the potential of being a comprehensible tool for detecting fetal asphyxia. References [1] Lundbäck, Stig, “Cardiac Pumping and Function of the ventricular Septum”, Acta Physiologica Scandinavica Supplementum, 1986 [2] Lundbäck, Stig, Heart Cluster State Machine Simulating the Heart US patent application 20080154142 (2005) 88 P6 NON-INVASIVE INTERVENTION PLANNING OF STENOTIC FLOWS USING SCALE-RESOLVED IMAGE-BASED COMPUTATIONAL FLUID DYNAMICS 1 2 Magnus Andersson , Jonas Lantz , Matts Karlsson 1 1 2 Department of Management and Engineering, Linköping University, Sweden. Department of Sciences and Technology (ITN), and Center for Medical Image Science and Visualization (CMIV), Linköping University, Sweden. 1. Introduction Subject-specific hemodynamic is often associated with laminar flow characteristics, which favour turbulent blood flow as a fruitful indicator for prediction of potential cardiovascular events. A typical example of this is the turbulent flow triggered by an aortic coarctation, which if left untreated could result in a fatal outcome. The energy associated with this flow, the turbulence kinetic energy (TKE), will feed on the main flow and consequently increase the heart workload in order to maintain the peripheral blood flow. Today, the severity of these coarctations is typically estimated based on the pressure gradient over the narrowed region using invasive catheters pre- and post-intervention, which could be time consuming, expensive and/or handling dependent. Instead we propose here a first step toward and non-invasive intervention planning framework guided by scale-resolved image-based computational fluid dynamics (CFD) to get estimates of these severities. The motivation is to provide a TKE map for both the coarctation as well as a variety of possible post-intervention configuration at different cardiac output (CO) as the body will respond to the geometrical change. The advantages using TKE is that it can be measured using MRI [1] and also proven to have a good relation versus simulated data [2]. Thus, this framework is not only predictable using simulation but can also be validated through post-intervention TKE measurement. Stenotic area increase 11% 17% 45% Figure 1: Left: Patient specific aortic coarctation model, Right: Three different simulated balloon dilatations at 11%, 17% and 45% area increase. 2. Method The patient-specific data was acquired from a 1.5 T Philips Achieva MRI scanner, followed by a 3D level set segmentation technique in order to obtain the geometry of the central vessels surrounding the coarctation, see the left configuration in Figure 1. Flow boundary conditions were obtained using 2D through-plane phase-contrast MRI at the ascending and descending aorta. The balloon dilatation, which is typically used in the intervention procedure, was mimicked using an inflation simulation in ANSYS Mechanical. By altering a local transmural pressure profile and supports over the lumen surface a wide range of different deformation outcomes where obtained, Figure 1 shows three examples where 11%, 17% and 45% stenotic area was achieved. A scale-resolving turbulence model, large eddy simulation (LES), was utilized in order to resolve the significant turbulence scales and also to be able to capture the laminar-to-turbulent transition of the flow sufficiently. The measured ascending flow data was applied as an inlet boundary condition whereas the neck distribution used a power-law relation of the diameter and flow. The body will respond to this area increase and provide more flow through the coarctation. To get more insight of this flow adaption influence on the TKE levels a physiological upper limit of CO after intervention was simulated for each case. In this case we choose a 20% increase from the baseline CO. 3. Results and Discussion Evaluating the result over a specific control volume indicated a highly non-linear relationship between each dilatation and the amount of TKE. For the baseline flow some cases showed approximately the same amount of total TKE despite having a substantial difference in cross-sectional area. For the flow adaption scenario some cases ended up above the baseline TKE, which is not desirable. Moreover, increasing the dilatation further seems to converge the total TKE to a plateau. Thus, there should exist an optimum where the degree of dilatation meets the lowest possible decrease of total TKE, further balloon intervention may only induce unnecessary high stresses onto the vessel wall. References [1] P. Dyverfeldt, J. Kvitting, A. Sigfridsson, J. Engvall, A. Bolger and T. Ebbers, Assessment of fluctuating velocities in disturbed cardiovascular blood flow: In vivo feasibility of generalized phase-contrast mri, JMRI 28, 655-663 (2008). [2] J. Lantz, T. Ebbers, J. Engvall and M. Karlsson, Numerical and Experimental Assessment of Turbulent Kinetic Energy in an Aortic Coarctation, In press (2013). 89 P7 ENKEL DIAGNOSTISK UTRUSTNING FÖR TELEMEDICIN APPLIKATION I U-LÄNDER Sharin Ahmed1, Maurico Gatica1, Poorang Soleimani1, Armin Saljunovic1, Gunnar Nihlen2, Mannan Mridha2 1 Studenter, 2handledar, Skolan för Teknik och Hälsa, Kungliga Tekniska Högskolan, Stockholm, Sweden 1. Introduktion En stor del av världens befolkning saknar tillgång till basic hälso- och sjukvård pga. brist på läkare/vårdpersonal och tekniska resurser. Drygt 40 procent av sjukvårdsutrustningen i utvecklingsländerna fungerar inte tillfredställande. Det kan bero på att utrustnigen är för avancerad och personalen får inte adekvat utbildning och det saknas välfungerande underhållsystem [ 1]. .Det är nödvändigt att utveckla lämpliga och kostnadseffektiva diagnostiska utrustningar och satsa på att öka användarnas tekniska kompetens. Sedan många år har STH-KTH angagerat sig att utveckla telemedicin system för u-lands applikationer där ingår: a) att ta fram robusta, batteridrivna och säkra diagnostiska utrustningar b) utveckla kommunikation mellan patient/vårdpersonal och läkare via tillgänglig internetsystemet, c) att producera lämpliga utbildningsmaterial för empowerment av vårdpersonal och patienter och på så sätt förbättra hälsovården och öka patientsäkerheten [ 2]. 2. Metod I det här arbetet, har en prototyp konstruerats för att på ett non-invasivt sätt övervaka vitala signaler från patient genom användning av smarta sensorer. Den är lätthanterlig för användaren efter att denne har fått en kortare utbildning. Prototypen används tillsammans med ett USB-oscilloskop och dator för att registrera, dokumentera, observera och kommunicera patientdata till specialist läkare för behandlingsråd. 3. Resultat En prototyp som registrerar EKG-signaler, det arteriella blodtrycket, blodflödet och andningen har tagits fram. Dessa signaler kan registreras och sändas för fjärrdiagnostik. Sensorsystemet visar att det är möjligt att konstruera en pålitlig, och kostnadseffektiv medicinteknisk apparat för registrering av patientdata som kan användas i ”low resource settings”. Figur 1 Illustrationen visar hur prototypen ska användas. Patientdata överförs via ett USB-oscilloskop till en dator för att överföra till en kvalificerad läkare för diagnostik och behandlingsråd. Materialkostnaden för denna prototyp ligger väl under 1000. Jämförbara kommersiella utrustningar kostar cirka 8000 ke 4. Diskussion Läkarna som har bedömt användbarhet har varit positiva och har gett förbättringsförslag. Komponentkostaderna kan sänkas ytterligare. Den arteriella pulsregistreringen kan göras stabilare och EKG-registreringen kan förses med en kalibrerad baslinje. Nya patient data presentationssystem kommer att presenteras på tex. Läsplatta. Figur 2. En del av prototypens kretsschema. Ovan visas kretsschema över pulsregistrering Figur 3. Insidan av prototypen Figur 4. Utsidan av prototypen 5. Referenser [1] Peter Howitt, Donated medical equipment going unused in developing countries, http://www.radioaustralia.net.au/international/radio/program/connect-asia/donated-medical-equipment-going-unused-indeveloping-countries/991886 14 maj 2013 [2] Mridha M.,Pehrson Björn (2004) To develop a telemedicine system to improve remote diagnoses and to deliver cost effective, better quality specialist services in developing countries, International conference on Wide Open Access, Stockholm 2004 90 P8 Preliminary Results of Studying Bone Growth Using NaF-18 in Patients with a Taylor Spatial Frame Henrik Lundblad1, Marilyn E. Noz2,Gerald Q. Maguire Jr.3, Cathrine Jonsson4, Hans Jacossson5, Anders Sundin1 Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 2Department of Radiology, New York University, New York, NY 3School of Information and Computer Technology, KTH Royal Institute of Technology, Stockholm, Sweden 4Department of Medical Physics Karolinska University Hospital, Stockholm, Sweden 5Department of Radiology, Karolinska University Hospital, Stockholm, Sweden 1 1. Introduction The aim of this study is to assess bone growth in patients who are undergoing treatment of the tibia by surgical application of an Ilizarov derived Taylor Spatial Frame (TSF) (see Figure 1). This device is capable of simultaneously correcting displacements of angulation, rotation, and translation. Use of this apparatus may be indicated due to prior bone disease resulting in deformation, the need to lengthen one leg to match the other, or severe or malhealed fracture. We used a sodium fluoride F-18 (NaF-18) PET/CT bone scan to detect actively growing bone[1]. Although a CT scan by itself can indicate changes in bone, it cannot give an estimate of bone growth. Before beginning this study, we did a literature search to determine the optimal amount of radioactive material to administer to the patient. Additionally, we investigated the impact of the metallic reduction algorithm on the quantification of the PET scans by performing a phantom study in which a TSF was affixed to a plastic tibia, both of which were partially submerged in a bath of 217 Mbq NaF-18. The results were presented at the World Molecular Imaging Conference, Dublin, in September 2012. Proper positioning of the patient on the scanning couch has also been studied and these results will be presented at the Society of Nuclear Medicine annual meeting in Vancouver, Canada, June 2013. This study was approved by the Karolinska Hospital Ethics Committee North. 2. Method Since September 2012, every tibia patient undergoing this TSF procedure was invited to join to the study. Thus far a total of six (out of seven) patients have been studied. The study patients underwent a PET/CT scan (64 slice Siemens Biograph TruePoint TrueV) at approximately six weeks and then again at three months after the application of the TSF. One scan bed position was used (22 cm length). Administered activity was 2 Mbq per kilogram of body weight. A list mode acquisition was done for 45 minutes and a five minute static scan was acquired after 60 minutes. Additionally, two patients who were very close to having the TSF removed agreed to have a clinical PET/CT scan for comparison with the initial bone growth patients and to help determine if the state of their bone permitted removal of the device. We evaluated bone activity by using the standard uptake value (SUV). We matched the CT scans from the longitudinal studies in order to ensure that we evaluated the SUV at the same position in the bone for both studies. For this registration, we used a software tool that has been previously described and validated [2-4]. 3. Results In one patient, we detected that the fibula had an SUV max of 65 while the tibia had an SUV max of 8, thus indicating that the fibula was growing much faster than the tibia as illustrated in Figure 2. The surgeon had to intervene, and re-break the fibula. Three months after this, both bones were growing at approximately the same rate (with an SUV max of 35). One patient moved one leg between the CT scan and PET scan (see Figure 3), and thus image registration had to be performed to do the evaluation. We have obtained SUV values for all the studied patients, but no statistically valid estimate can be made from this preliminary data. 4. Discussion This study leads to a number of clinical questions that could be usefully answered. One question is: When has the bone healed well enough that the TSF can be removed without a high probability of the bone re-breaking? Another question is if there is some correlation with a non-imaging modality - especially for the clinical decision to remove the TSF; e,g., could a NaI probe over an area be used or some other naturally occurring tracer be evaluated. Further, could a provocation technique using a piezo-electric transducer be used as an external pressure transducer for external load to (a) assess bone growth and (b) encourage bone growth as part of the therapy. We hope to answer some of these questions as our study progresses. References [1] F.D. Grant, F.H. Fahey, A.B. Packard, R.T. Davis, A. Alavi,S.T. Treves, J Nucl. Med 49, 68-78 (2008). [2] M.E. Noz, G.Q. Maguire Jr, M.P. Zeleznik, E.L. Kramer, F. Mahmoud, J. Craford J. J Med Syst 25, 297–307 (2001). [3] L. Olivecrona, J. Crafoord, H. Olivecrona, M.E. Noz, G.Q. Maguire Jr, M.P. Zeleznik, L. Svensson, L. Weidenhielm Acta Radiol 43, 517–27 (202). [4] R.J.T. Gorniak, E.L. Kramer, G. Q. Maguire Jr, M.E. Noz, C.J. Schettino, M.P. Zeleznik, J Med Syst 27, 141–56 (2003). Figure 1: Taylor Spatial Frame 91 Figure 2: Accelerated Bone Growth Figure 3: Mismatched PET/CT P9 ON THE FULLY AUTOMATIC CONSTRUCTION OF A REALISTIC HEAD MODEL FOR EEG SOURCE LOCALIZATION Qaiser Mahmood,1 Yazdan Shirvany,1 Andrew Mehnert,1 Artur Chodorowski,1 Johanna Gellermann,2 Fredrik Edelvik,3 Anders Hedström,4 Mikael Persson1 1 Department of Signals and Systems, Chalmers University of Technology and MedTech West Center, Göteborg, Sweden, 2Universitätsklinik für Radioonkologie, Tübingen, Germany, 3 Fraunhofer-Chalmers Research Center, Chalmers Science Park, Göteborg, Sweden, 4Sahlgrenska Academy, Göteborg, Sweden. 1. Introduction Accurate multi-tissue segmentation of magnetic resonance (MR) images is an essential first step in the construction of a realistic finite element head conductivity model for electroencephalography (EEG) source localization. All of the segmentation approaches proposed to date for this purpose require manual intervention or correction and are thus laborious, time-consuming, and subjective. 2. Method We propose and evaluate a fully automatic method based on a hierarchical segmentation approach (HSA) incorporating Bayesian-based adaptive mean-shift segmentation (BAMS). 3. Results An evaluation of HSA-BAMS, as well as reference method HSA-HMRF-EM, in terms of both segmentation accuracy and the source localization accuracy of the resulting finite element head conductivity model is also presented. The evaluation was performed using real 3D T1-weighted MRI head data and real EEG data (with expert determined source localization). Tissue HSA-BAMS HSA-HMRF-EM WM GM CSF 0.885 0.848 0.523 0.879 0.836 0.517 Skin Skull/ Bone 0.868 0.697 0.822 0.588 Methods 21.0mm 25.0mm TABLE III. LOCALIZATION ERROR 0.35 HSA-HMRF-EM 0.42 Ground truth 0.23 Table II. RELATIVE ERROR FOR EACH METHOD Table I. Dice Index Values for Each Method and Each Tissue Methods HSA-BAMS HSA-HMRF-EM HSA-BAMS 22.0o 24.0o AND ORIENTATION ERROR 4. Discussion The results demonstrate the efficacy and accuracy of the method, that it outperforms the reference method, and suggest that it can be used as a surrogate for manual segmentation for the construction of a realistic finite element head conductivity model for EEG source localization. References [1] M. Rullmann , A. Anwander, M. Dannhauer, S. K. Warfield, F. H. Duffy, C. H. Wolters, “Source EEG source analysis of epileptiform activity using a 1 mm anisotropic hexahedra finite element head model,’’ Neuroimage, 44, 399-410 ( 2009). [2] C. H. Wolters, A. Anwander, X. Tricoche, D. Weinstein, M. A. Koch, R. S. MacLeod “Influence of tissue conductivity anisotropy on EEG/MEG field and return current computation in a realistic head model: a simulation and visualization study using high-resolution finite element modeling,” Neuroimage, 30, 813-26 (2006). [3] A. Mayer, H. Greenspan, “An adaptive mean-shift framework for MRI brain segmentation,” IEEE Trans. Med. Imag., 28, 1238–1249 (2009). 92 P10 Invitro toxicity testing utilizing microfluidic affinity biosensors Invitro toxicity testing utilizing cell lineages such as hepatic cells, cardiac cells and neuronal cells is an important tool for drug toxicity evaluation in the pharmaceutical industry. Micro-culture systems have the benefit of reducing both quantity of cells and pharmaceutical candidate needed for testing. A micro-culture system must be combined with a rapid and sensitive assay method capable of analysing small amounts of sample. Detection of the toxicity response is often carried out by affinity methods like SPR and ELISA, colorimetric assays using imaging systems or electrochemical methods. New findings will be pre presented on the above mentioned systems. We present a strategy for toxicity testing in a microfluidic culturing system where affinity biosensing and colorimetry are used as endpoint assays. 93 P11 HEART RATE VARIABILITY (HRV) IN PATIENTS WITH CHRONIC KIDNEY DISASES Farhad Abtahi1, Marie Hilderman2, Fernando Seoane1, 4, Annette Bruchfeld 2 and Kaj Lindecrantz1, 3 School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden, 2 Renal Medicine, CLINTEC, Karolinska Institute, Stockholm, Sweden, 3Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden. 4 School of Engineering, University of Borås, Borås, Sweden 1 1. Introduction Loss of renal function is a disorder that can strike acutely or develop progressively. The most common causes of slowly developing chronic kidney disease (CKD) are diabetes mellitus, chronic glomerulonephritis and hypertension. Advanced CKD often involves a number of complications such as disturbances in the autonomic nervous system and inflammation. The inflammation is often associated with autonomous nervous dysfunction quite common in these patients, since the central nervous system partly controls the immune system through the cholinergic anti-inflammatory pathway (CAP) [1]. This pathway functions as a nerve-mediated reflex that in case if injury, inflammation or infection send signals to the brain via the vagus nerve. Since HRV analysis is a common tool for assessment of autonomic nervous system, this study wishes to monitor autonomic dysfunction in patients with kidney diseases through HRV and respiratory measurements and try to find a potential correlation with inflammation markers in blood. 2. Method Twelve patients; seven in chronic haemodialysis (four male, three female; age range 26-84), five in peritonealdialysis (3 male, 2 female; age 47-84) and eight healthy control subjects (five male, three female; age 31-52) are included in this study. Electrocardiogram (ECG) and tetrapolar thoracic bioimpedance are measured using custom made instrument designed by ZHealth Technologies AB during 20 minutes. Subjects are assessed during morning hours at department of renal medicine in Karolinska Hospital (Huddinge) in a lying down position. C-reactive protein (CRP) levels and other blood markers were also measured to evaluate presence of inflammation. The RR interval variability (RRV) is automatically calculated based on traditional derivate-based algorithm, introduced by Jiapu Pan [6]. Artifacts and ectopic beats are detected visually and are removed. Frequency and time domain parameters such as LF, HF, LF/HF-ratio, SDNN, RMSSD, and pNN50 were extracted and compared between different groups of study population. Thoracic bioimpedance measurements are used to calculate respiration rate and check for effect of rhythmic heart rate variability (sinus arrhythmia) in calculated frequency domain parameters. HRV analysis had done according to European Tack Force for HRV measurements [3]. 3. Results The preliminary result of spectral analysis of HRV is depicted in Figure 1 by HF and LF parameters. It is obvious that there is a general reduction in both LF and HF power of HRV of patients compare to controls. The only patient with very high HRV can be considered as outlier and exclude from results. 4. Conclusion The preliminary results suggest that dialysis patients despite autonomic dysfunction which can cause systematic inflammation as well. Further analysis of recordings is now undergoing to see possible correlation between blood markers such as CPR with HRV parameters. References [1] Oke, Stacey L., and Kevin J. Tracey. "From CNI-1493 to the immunological homunculus: physiology of the inflammatory reflex." Journal of leukocyte biology 83.3 (2008): 512-517. [2] J. Pan, W. Tompkins, A real-time qrs detection algorithm, Biomedical Engineering, IEEE Transactions on (3) (1985) 230–236. [3] Camm, A. John, et al. "Heart rate variability: standards of measurement, physiological interpretation and clinical use, Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology." Circulation 93.5 (1996): 1043-1065. Figure 1: Example of frequency domain analysis of HRV for controls and patient groups are illustrated by using HF (Y axis) vs. LF (X axis). 94 P12 CARENET: AN INFRASTRUCTURE FOR HOME-BASED HEALTHCARE SERVICES 1 1 1 1 1 1 2 2 Voravit Tanyingyong , M. Siraj Rathore , Markus Hidell , Peter Sjödin , Björn Pehrson , Sven Jonsson , Kristina Groth 2 KTH Royal Institute of Technology, Stockholm, Sweden. Utveckling och Innovation, Karolinska Universitetssjukhuset, Stockholm, Sweden 1. Introduction Healthcare services are usually high cost due to several factors such as the scarcity of high-skill medical practitioners, demanding logistics, and costly proprietary equipment and infrastructure. Home-based healthcare is an attractive alternative to reduce the cost. It also offers several advantages. For instance, it increases patient safety by enabling faster contact with caregivers and reduces the number of trips the patients need to get to the hospitals. Technologies can be used to extend the reach of healthcare services over the data network to virtually anywhere. Given the advancement in today's technologies, such healthcare services can be delivered competitively with open source solution on Commodity-Off-The-Shelf (COTS) hardware at a fraction of the cost. This work is carried out as a part of Carenet [1], a multi-stakeholder initiative to provide healthcare services to patients at their homes by allowing patients to interact and exchange medical data with doctors in realtime. Example use cases are elderly people and prematurely born babies who might require special care and attention in case of an abnormal event occurs. 2. Methods For the technical solution of the system, we propose Carenet architecture design based on open source solution on COTS hardware. The prototype architecture is developed using a residential gateway (RG) that enables healthcare extension from hospital to the patient's home in a robust, secure, and cost-effective manner. The design comprises of three parts; the RG hardware design suitable for home environment with low cost, noise, and power consumption, the services with security and guaranteed resources, and the resilient communication between home and hospital through multihoming to ISP. We consider three services in our work. These services include high definition video conferencing (HDVC), sensor monitoring, and patient records. The doctor can examine patients through HDVC and at the same time medical sensors such as heart rate sensor can be used to collect real time medical data. The third service is the patient records, a database that collects and provides medical history of a patient. The overview of the Carenet design is shown in Figure 1 (Left). To demonstrate our system, we focus on the prematurely born babies use case [2]. We develop different scenarios based on realistic situations derived from the home-care work flow process of the neonatal care unit in Karoliska university hospital in Huddinge. Each scenario triggers different usage patterns of the system. We have personnel from the neonatal care unit try out the system under different scenarios as shown in Figure 1 (Center) and (Right). After the trials, an individual interview is carried out using a questionnaire with 36 questions related to functionality, usability, and presentation of the system. 3. Results and Discussion According to the users’ feedback, the system is intuitive and easy to use. Although video conferencing can never replace all physical home visits, our system demonstrates good potential. It is especially useful when it comes to assisting parents under emergency situations as well as getting a second opinion from another medical practitioner. The results are promising and motivate us to continue with technical and clinical studies in collaboration with the patient and family in the home. Detail empirical studies on the technical solution are also carried out. Each of the three building blocks of our design is evaluated independently. Power consumption and performance evaluation for the low power RG with resilient power sources can be found in [3]. RG's isolation through Linux Containers is studied in [4]. Empirical results and analysis on resilient communication through multihoming can be found in [5]. References [1] Carenet-SE, http://www.carenet-se.se [2] S. Jonsson, K. Groth, M. Blennow and H. Teriö, CARENET POC – neonatalvård mellan sjukhus och hem, Nov. 2012. [3] A. Nungu, R. Olsson, and B. Pehrson, On the Design of Inclusive Ubiquitous Access, ICUFN 2011, pp. 288-293. [4] N. Roumpoutsos, Virtualization Isolation Report v.1.0, Dec. 2012. [5] V.Tanyingyong, M. S. Rathore, M. Hidell, and P. Sjödin, Resilient communication through multihoming for remote healthcare applications, manuscript under review, 2013. Figure 1: (Left) Carenet architecture design (Center) Trial scenarios – Hospital site (Right) Trial scenarios – Home site 95 P13 TEXTRODE BASED WEARABLE MEASURMENT SOLUTION FOR SKIN CONDUCTANCE AND TEMPERATURE MEASUREMENTS J Ferreira1,3, L Álvarez2, R Buendía1,2,3, D Ayllón2, C. Llerena2, R Gil-Pita2 and F Seoane1,3 1 School of Engineering, University of Borås, Sweden, 2 Department of Signal Theory and Communications, University of Alcala, Madrid, Spain, 3 School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden E-mail: [email protected] 1. Introduction In the frame of the project “Real Time Assessment of Mental Stress of Soldiers During Combat”, with acronym ATREC from its tittle in Spanish, several physiological signals were selected to find the most suitable way to detect stress in extreme situations. 2 of the signals selected were the skin temperature and the skin conductance also named Galvanic Skin Response (GSR). As GSR is the conductance measured between 2 points of the body, generally close to each other, it dramatically increases with sweat. That means if the GSR is measured in a part of the body where the sweat is due more to psychological stress than to physical effort, an increase in this signal might mean an increase in the stress of the subject. For that purpose 2 wearable measurement systems with smart textiles integrated for recording GSR in 2 different parts of the body were developed. Those 2 parts are the tips of the fingers and the triceps as both were pointed out as places with little sweat due to physical effort. Skin temperature measured in those 2 parts of the body might also be a stress indicator. 2. The wearable measurement system The reduced dimensions i.e. 50x35x15 mm, of the device to record GSR makes it suitable for its integration with the sensorized garments. For the measurements of GSR a Wheatstone bridge topology with constant voltage excitation of 0.5 V was used. The voltage is applied to the skin through a resistor of 2 kΩ that limits the maximum current. The Wheatstone bridge differential voltage is measured by an instrumentation amplifier that it is connected to an Analog-to-Digital Converter (ADC) input in the microcontroller in order to obtain the GSR value. The GSR is measured with a sampling frequency of 250 Hz. In addition it is battery operated with 900 mAh Lithium-Ion batteries, and is provided with an internal 4GB SD memory card to allow long-term recordings and off-line analysis. The first GSR measurement system consist of a glove with two textile electrodes integrated in the proximal phalanx of the index and middle fingers on the inside of the glove for measuring the GSR. Also a temperature sensor has been placed in the tip of the ring finger of the glove in order to sense the peripheral skin temperature, see Figure 1a for details. For the temperature measurements a 1-wire digital thermometer DS1825 manufactured by Maxim Integrated has been used. The second one is an upper arm strap with two textile electrodes integrated to sense the galvanic skin response in the skin surface between the electrodes. A DS1825 sensor is also integrated in the inner lining of the strap in order to contact the skin and this way measure the superficial skin temperature. � a) b) c) d) Figure 1: a) GSR and Temperature measurement places b) Glove for GSR and skin Temperature, b) representation of upper arm strap and c) measuring unit and strap worn on the upper arm. 3. Measurements Skin temperature and GSR were recorded in several subjects. While skin temperatures produced very stable measurements around 34 ºC with both garments producing flat recordings, GSR measurements exhibited larger variance, see Figure 2. Note that the GSR data has been filtered with a moving average window of 5 seconds as in [1]. Figure 2: Galvanic skin response measurements. a) Glove, b) Upper arm strap 4. Conclusion The proper functioning of the implemented garments and devices allows us to conclude that the system is ready for the next stage of this experimental phase: data recording in volunteers performing specifically design activities to cause stress. 5. [1] 96 References Shaomei, W.; Tao, L. In Exploring the use of physiology in adaptive game design, Consumer Electronics, Communications and Networks (CECNet), 2011 International Conference on, 16-18 April 201, pp 1280-1283. 96 P14 TEXTRODE BASED WEARABLE MEASURMENT SOLUTION FOR ECG AND THORACIC IMPEDANCE MEASUREMENTS J Ferreira1,3, L Álvarez2, R Buendía1,2,3, D Ayllón2, C. Llerena2, R Gil-Pita2 and F Seoane1,3 1 School of Engineering, University of Borås, Sweden, 2 Department of Signal Theory and Communications, University of Alcala, Madrid, Spain, 3 School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden E-mail: [email protected] 1. Introduction In the frame of the project “Real Time Assessment of Mental Stress of Soldiers During Combat”, with acronym ATREC from its title in Spanish, several physiological signals were selected to research the most suitable way to detect stress in extreme situations. 2 of them were Heart Rate (HR) and Respiration Rate (RR), which can be extracted from the physiological measurements ECG and Thoracic Electric Bioimpedance (TEB). For that purpose a wearable measurement system with smart textiles integrated which enable the measurement of ECG and TEB were developed. 2. The wearable measurement system The measurement device records both signals, ECG and TEB at a single frequency. The reduced dimensions of the device, 50x35x20 mm makes it suitable for its integration with the chest strap system. In addition it is battery operated with 900 mAh Lithium-Ion batteries, and is provided with an internal 4GB SD memory card to allow long-term recordings and off-line analysis. The intended use for this ECG/EBI device is to record cardiogenic biopotentials to compute the HR from the obtained ECG and measure the impedance change caused during breathing to extract the RR from the recorded TEB signal. The ECG signal is measured by a 1-lead instrumentation amplifier topology suggested by Merritt et al. in [1], the output voltage is connected to an ADC input in the microcontroller and recorded with a sampling frequency of 250 Hz. The TEB measurement is obtained using an excitation frequency of 50 kHz and a sampling frequency of 100 Hz. The impedance estimation core is based on the SOC AD5933 manufactured by Analog Devices, implementing an analog front-end customized for 4-electrode measurement [2]. A chest strap garment with repositionable textile electrodes to record 1-lead ECG from 2 textrodes and tetrapolar TEB measurements with other 4 textrodes has been developed. The possibility of placing the electrodes in any place along the horizontal and vertical straps enables the performance of different kinds of TEB measurements, see Figure 1. Depending on the placement of the textrodes around the surface of the thorax and abdomen the TEB measurement will have more or less cardiac and respiratory components allowing us to perform a multi-parametric signal recording if required. Figure 1: Chest straps system confectioned for placement of ECG and TEB electrodes. 3. Measurements Surface cardiac biopotentials were recorded in several subjects with the wearable measurement system presented in Figure 1. As shown in Figure 2 the recording is fair, allowing for a straight detection of the R complex for heart rate assessment. TEB recordings were obtained simultaneously to the ECG recording. The respiration activity is easily observable and thus the RR easily extracted from the TEB signal. Figure 2: (a) ECG recording. (b) Transthoracic Electrical Bioimpedance recording 4. Conclusion The proper functioning of the implemented garments and devices allows us to conclude that the system is ready for the next stage of this experimental phase: data recording in volunteers performing specifically design activities to cause stress. 5. [1] [2] 97 References Merritt, C. R.; Nagle, H. T.; Grant, E., Fabric-based active electrode design and fabrication for health monitoring clothing. IEEE Trans Inf Technol Biomed. 2009, 274-80. doi: 10.1109/TITB.2009.2012408. Epub 2009 Jan 23. Seoane, F.; Ferreira, J.; Sanchéz, J. J.; Bragós, R., Analog Front-End Enables Electrical Impedance Spectroscopy System On-Chip for Biomedical Applications. Physiol. Meas. 2008, 29 S267-S278. P15 E-health Dialysis: an Holistic Approach for a Telenephrology System 1 1 1 3 2 Fernando Seoane , Iván Pau , Javier Ferreira , Bodil Sjöberg Bengt Lindholm , School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden 2 Baxter Novum, Karolinska institute, Stockholm, Sweden 3 Kungsholmendialyskliniken karolinska university hospital, Stockholm, Sweden 1 1. Introduction One of the most resource requiring diseases is chronic kidney disease (CKD) with 10-12% of the population showing signs of different stages of this disease. As the disease progresses patients develop end-stage renal disease (ESRD) requiring lifesaving renal replacement therapy (RRT) with dialysis or renal transplantation. Due to a worldwide increase in the prevalence of obesity and DM, and the improved survival in patients with cardiovascular disease, the number of ESRD patients in the world increases rapidly, and now exceeds 2.5 million. In Sweden, almost 9,000 patients undergo RRT. About 80 % of the dialysis patients are being treated by hemodialysis (HD), which for the majority of patients is performed in specialized centers, usually located in a hospital or in a dialysis clinic, three times per week. A smaller number (< 5%) of the HD patients have self-care treatment at home (home HD, HHD) or at limited care or self-care centers. About 20% of all dialysis patients are being treated by peritoneal dialysis (PD) performed by the patients in their homes. Thus, home dialysis therapy by HHD or PD accounts for less than 25 % of all dialysis treatments despite considerable economic and medical advantages. In-center dialysis at the hospital or at specialized clinics produces a significant economic burden for society related not only with the direct costs for dialysis treatment itself, especially for health care personnel, disposables, and capital costs for buildings and equipment costs but also involves indirect costs associated with the management of patients such as and transportation of patients to and from dialysis facilities three times per week. The survival and quality of life of patients treated with dialysis at home is similar or better than center dialysis while the direct and indirect socioeconomic costs are substantially lower. Dialysis at home does not only reduce cost for example associated with less need of transportation but also improves the quality of life and well-being of patients. Thus increased use of home dialysis would allow considerable costs savings and free up resources that that could be used for example for management of other patients. Despite all the advantages associated with home dialysis, only 25% of the dialysis patients chose this modality. We believe that the number of patients with such therapy could increase initially to comprise maybe 40%, or more, of all dialysis patients. This could be done with existing technologies; however, such a transformation would be facilitated by improvements in specific areas such as in communication systems. 2. Objectives This work presents an on-going project project that intends to implement a full e-health system that will enable a complete paradigm shift in the care of CKD patient management thereby facilitating the intended increase of the number of patients choosing the available homecare options. Increasing the proportion of home dialysis would have an enormous impact in all aspects of point-of-care of these CKD patients. In order to achieve such ´tele-nephrology system´ the system should comply with several requirements: • The system should be user-centered from design to operation taking in to account the needs of the patients. • A videoconference system should be available for performing tele-consultations. • Dedicated home-monitoring equipment for blood pressure body fluid volume distribution assessment, including a bioimpedance spectrometer and sensorized garments with textile electrodes. • An efficient distribution system for the dialysis products and medications should ensure continuous functioning of the home therapy. • An IT platform integrating all the elements of the system ensuring, data collection, communication and visualization. 3. Current Status A VINNOVA challenge driven innovation - initiation project has been granted. The partners’ consortium involving patients, providers and clinicians is being built and at time of writing a fully functional existing prototype of a home monitoring system based on bioimpedance technology and sensorized garments is being customized to fulfil the users’ requirements. 98 98 P16 RELEVANSEN AV BREST SPECIFIC GAMMA IMAGING (BSGI) SOM KOMPLEMENT TILL RÖNTGENMAMMOGRAFI 1 1 Melker Hagelberg1, Victor Löf Kungliga Tekniska Högskolan, Stockholm, Sweden. 1. Introduktion I nuläget är Röntgenmammografi det första valet vid bröstcancerdiagnostik och har en genomgående sensitivitet på 78- 85 %. Vid avbildning av tätare bröstvävnad sjunker sensitiviteten och specificiteten för Röntgenmammografi och antalet falskt positiva resultat ökar, vilket leder till onödiga biopsier. Under 1990-talet utvecklades Breast Specific Gamma Imaging (BSGI) [1]. BSGI är en organspecifik gammakamera utvecklad för bröstavbildning. Tanken var att BSGI skulle komplettera Röntgenmammografi vid avbildning av tätare bröstvävnad. Studier från Palmedo et al. under 1990-talet visade att BSGI hade en sensitivitet och specificitet på 71 % respektive 69 %. Fler studier visade att BSGI endast kunde avbilda palperbara tumörer [2]. Avbildning av palperbara tumörer gav ingen diagnostiskt nytta och intresset för BSGI minskade. Detektorteknikerna för BSGI har utvecklas sedan 1990-talet och kommer att fortsätta utvecklas. Det är därför av intresse att utreda vilka krav som ställs på en detektor för att BSGI ska vara relevant som komplement till Röntgenmammografi. 2. Mål Studiens mål är att ta fram en metod för att studera kraven på en detektors spatiala upplösning och energiupplösning vid avbildning med BSGI för olika tumörstorlekar. 3. Metod Metoden grundas i Monte Carlo simuleringar av BSGI i programvaran GATE: Figur 1. Realistiska simuleringar, med avseende på aktiviteter, aktivitetsupptagsförhållande och detektoruppställning, framställs ifrån litteraturen inom området för BSGI. I simuleringarna generas bilder för tumörstorlekarna fem och tio millimeter. Genom att simulera kommer den spatiala upplösningen och energiupplösningen kunna varieras i efterhand. Resultatet från variationen av upplösningen i bilderna tolkas kvantitativt med Rose modellen. Den framtagna modellen kommer att kunna användas som en plattform för fortsatta studier inom BSGI. Resultatet presenterades grafisk för varje tumörstorlek med SNR som funktion av detektorernas spatiala upplösning och energiupplösning. Figur 1: Design i GATE 4. Slutsats Den framtagna metoden kan användas för att på ett realistiskt och pålitligt sätt utreda vilka krav som ställs på en detektors spatiala upplösning och energiupplösning vid avbildning av olika tumörstorlekar med BSGI. Vi har simulerat tumörer med storlekarna fem respektive tio millimeter. Båda tumörstorlekarna var synliga i det spatiala upplösningsintervallet 0.1 till 5 mm och energiupplösningsintervallet 1 till 10 %, enligt Rose modellen. Resultaten visar på en optimal spatial upplösning och energiupplösning för detektorn på två millimeter respektive 10 % för båda tumörstorlekarna: Figur 2. Figur 2. Resultat av variation av upplösning. 5. Referenser [1] Aktolun C, Bayhan H and Kir M, Clin Nucl Med, 17, 171-176 (1992). [2] Khalkhali I, Villanueva-Meyer J, Edell S. L, Connolly J. L, Schnitt S. J, Baum J. K, Houlihan M. J, Jenkins R. M and Haber S. B., Clin Nucl Med, 41, 1973-1980 (2001). 99 A PPB-LEVEL, MINIATURIZED AMPEROMETRIC NITRIC OXIDE SENSOR FOR ASTHMA MONITORING P17 Hithesh K Gatty1, S. Leijonmarck2, M. Antelius1, G. Stemme1 and N. Roxhed1 Microsystem Technology Lab, KTH Royal Institute of Technology, Stockholm, Sweden 2 Applied Electrochemistry, KTH Royal Institute of Technology, Stockholm, Sweden 1 This paper reports a novel miniaturized MEMS-based amperometric nitric oxide sensor that is suitable for a point of care testing device for asthma. The novelty lies in the combination of a high surface area microporous structured electrode, nanostructured Nafion that is coated on the side walls, and liquid electrolyte. This combination allows detection of very low concentration (parts-per-billion) gas, has high sensitivity of 0.130 nA/ppb/cm2 and has both response (t90) and recovery time of 6 s. The sensor is integrated with a PCB potentiostat to form a complete measuring module. Previous Work: Measurement of nitric oxide (NO) concentration in the range 0-100 ppb in exhaled breath is used as a method for detection of inflammation in the airways of asthma patients [1]. Conventional electrochemical sensors can detect 2-3 ppb gas concentration. However they suffer from long response time typically in the order of 60-100 s thus requiring complicated flow handling and buffered sampling of the gas. Most of the miniaturized NO sensors are realized using metal oxide as the sensing material, but have limited detection range of 1-100 ppm [2]. Amperometric detection techniques using only solid polymer electrolyte (SPE) like Nafion has been shown to detect NO [3-5] but the detection limit of 5 ppm is not useful for asthma detection. This Work: We report a novel miniaturized MEMS-based amperometric nitric oxide sensor that has the required performance for a portable asthma detector. The sensor is miniaturized with the surface area of only 0.27 cm2. It uses a combination of thin (approx. 500 nm) nanostructured Nafion together with liquid electrolyte. This combination gives it a response time of 6 s as opposed to conventional amperometric sensor, which has response time typically in the order of 60-100 s. The sensor presented in this work has a sensitivity of 0.130 nA/ppb/cm2. Experiments and Results: The working electrode of the NO sensor was fabricated according to the process scheme illustrated in Figure 1. The counter and reference electrodes are fabricated on a 2 mm thick polycarbonate sheet by evaporation of silver on one of the surfaces. The working electrode is glued with a spacer above the silver electrodes using silicone adhesive. This set-up is then connected to a PCB based potentiostat forming the NO sensing module as shown in Figures 2-4. The potential placed at the working electrode was +0.7 V vs. Ag/AgO2 reference electrode. At this potential the NO is oxidized, NO+2H2O → NO3- + 4H+ + 3e- . The sensitivity of the NO sensor was measured to be 0.130 nA/ppb/cm2 with a detection limit in the ppb-range. The thin diffusion layer of Nafion results in a response time of 6 s and makes the sensor potentially useful in breath analysis and point of care testing for asthma. This work demonstrates the potential for miniaturized MEMS-based electrochemical gas sensors with very high sensitivity and fast response time, enabling ubiquitous sensing in portable devices. [1] T. Hemmingsson et al, J.Clinical Monitoring and Computing, (2004) 18:379-387. [2] A. Afzal, et al, Sensors and Actuators B 171– 172 (2012) 25– 42 [3] P. Jacquinot, A.W. E. Hodgson, P. C. Hauser, Anal. Chim. Acta 2001, 443, 53. [4] F. Opekar, K. Stulik, Anal. Chim. Acta 1999, 385, 151. [5] F. Maseeh, M. J. Tierney, W. S. Chu, J. Joseph, H.-O. L. Kim,T. Otagawa, Transducers '91 Al2O3 Pt Counter Electrode Working Electrode Reference Electrode NAFION 1cm Si Fig 1: Cross-section of the porous grid structure with Pt deposition on the grid using atomic layer deposition (ALD). Fig 3: Image showing the NO sensor on polycarbonate substrate with electrolyte channel. Silver is evaporated on one of the surfaces and is milled to demarcate counter and reference electrode. Si Nafion Al2O3 , Pt Fig 2: SEM image showing close up of the cross section of 500nm thick nafion coated grid. 100 Fig 4: Plot of Nitric Oxide concentration vs. output current showing a linear relationship. Each point in the graph shows one measurement sample. 100 P18 NOVEL CHROMATIN TEXTURE FEATURES FOR THE CLASSIFICATION OF PAP SMEARS 1 1 2 3 3 1,4 Babak Ehteshami Bejnordi , Ramin Moshavegh , K. Sujathan , Patrik Malm , Ewert Bengtsson , Andrew Mehnert 1 2 Department of Signals and Systems, Chalmers University of Technology, Gothenburg, Sweden. Regional Cancer Centre, 3 4 Thiruvananthapuram, India. Centre for Image Analysis, Uppsala, Sweden. MedTech West, Gothenburg, Sweden. 1. Introduction The Papanicolaou or Pap test is the primary screening test for cervical cancer. One in every 10 to 20 positive cases is missed in routine screening because of inappropriate interpretation and sampling error. Automation using a computer and robotic microscope can address the first issue. Research suggests that malignancy-associated change (MAC) analysis can address the second. MACs are subtle sub-visual changes in the appearance of normal-looking cells on an abnormal Pap slide. The MACs features that have the most discriminatory power are those describing chromatin (stained DNA and associated proteins) texture in the cell nuclei. We have developed a novel structural approach to the quantitative analysis of chromatin texture [1,2,3]. 2. Theory/method Our approach is based on deriving features from an initial segmentation of the chromatin [2] in each nucleus into blob-like texture primitives (see Figure 1). Our structural texture features [1,2,3] in essence describe the attributes and arrangement of these resulting blobs. They fall into two broad categories: (i) statistics of morphometric features (size, shape, etc.) computed for the blobs, and (ii) contextual features. The latter can be further subdivided into the following classes of features: margination (blob distance to the nuclear boundary), clustering, blob features (e.g. proportion of nucleus occupied by dark blobs), discrete texture features, and features derived from the Voronoi diagram and its associated graphs. 3. Experiments The image data used originate from a set of 68 conventional Pap smear slides. Each was reviewed by a cytopathologist and assigned a cytological diagnosis according to the Bethesda system [4]. The cytopathologist subsequently acquired representative fields of view (FOVs) from each slide. In the case of abnormal smears this included FOVs with and without diagnostic cells. The cytopathologist also labelled individual cells in each FOV accordingly. The FOV images were acquired using a monochrome CCD camera mounted on a light microscope with a 40× objective lens. Each image has Figure 1. The proposed structural texture features are derived from an initial a grey-scale resolution of 8 bits per pixel segmentation of the chromatin into blob-like primitives and their spatial and is of size 1024×1344 pixels with characterisation in terms of neighbourhood graphs associated with the square pixels of size 0.25µm. To evaluate Voronoi diagram. the performance of the proposed chromatin structural texture features two experiments were performed [1]. The aim of the first was to determine the most discriminatory subset of features, from among the proposed features and a wide range of features drawn from the literature, for discriminating between normal (NILM [4]) and abnormal (LSIL or HSIL) Pap smear slides. The aim of the second experiment was to evaluate the performance of a variety of classifiers built using the features obtained in the first experiment to discriminate between the normal and abnormal slides on the basis of only normal-appearing cells (i.e. excluding diagnostic cells). 4. Results and discussion The results of experiment 1, based on 159 features, show that a combination of our structural features and conventional features yields a classification performance of 0.954 ± 0.019 (AUC ± SE) for the discrimination of normal (NILM) and abnormal (LSIL and HSIL) slides [1]. The results of experiment 2, which considered only normal appearing cells from both normal and abnormal slides, show (i) a classification performance of 0.822 ± 0.024, and (ii) that chromatin margination alone yields a classification performance of 0.815 ± 0.019 [1]. Overall the results demonstrate the efficacy of the proposed structural approach and that it is possible to detect MACs in Papanicolaou stain. References [1] B. E. Bejnordi, R. Moshavegh, K. Sujathan, P. Malm, E. Bengtsson and A. Mehnert, “Novel chromatin texture features for the classification of Pap smears”, Proc. SPIE 8676, Medical Imaging 2013: Digital Pathology, vol. 867608 (2013). [2] A. Mehnert, “Image analysis for the study of chromatin distribution in cell nuclei with application to cervical cancer screening,” PhD Thesis, School of ITEE, The University of Queensland (2004). [3] P. Jackway and A. Mehnert, “Chromatin segmentation”, United States Patent, no. 7574304 (11 August 2009). [4] S. Diane, N., Ritu, R. Kurman, D. Davey and D. Wilbur, The Bethesda System for reporting cervical cytology: Definitions, criteria, and explanatory notes, 2nd edition, New York, Springer (2004). 101 P19 ON-CHIP ACTUATION OF POLYMER SHELLED MICROBUBBLES Satya. V.V.N. Kothapalli1, Muhammad Asim Faridi 1, Martin Wiklund1, Dmitry Grishenkov1 1 Royal Institute of Technology, KTH, Stockholm, Sweden 1. Introduction Micro-sized gas bubbles (MBs) are used as a contrast agent for diagnostic ultrasound imaging as well as drug or gene transfection due to their stable oscillation under ultrasound exposure [1]. The acoustically driven microfluidic chip is utilized for cell/microparticle manipulations and cell-cell interactions [2]. The motion of thin protein/lipid shelled MBs are shown to be controlled by acoustic standing wave in a bulk situation [3]. However, drug loaded thin shelled MBs are mechanically unstable in the circulation. In contrast, having relatively stiff and thick shell polymer MBs offers increase stability both mechanical and chemical [4]. As a result we focus on the study the interaction of thick shelled MBs and cells under ultrasound exposure. The preliminary aim of this study is to observe the acoustical behaviour of thick polymer shelled MBs in a microfluidic chip. 2. Method A 4 cm long microfluidic chip (GeSim GmbH, Dresden, Germany) containing two rectangular and two oval sono-cages of varying geometries was utilized. A 4×7 mm PZT piezoceramic element was glued on one sided of microfluidc chip. The fundamental resonance frequency of the transducer was about 2.4 MHz. The chip contains one inlet and one outlet. Polymer shelled MBs with a concentration of 108 MBs/ml was diluted 1000 times and injected through inlet. The chip was placed under the transmission light microscope. The light transmitted through a 300×300×110 µm3 sized sono-cage was captured by CCD camera [5]. The chip was kept under stationary position for some time to avoid pressure gradient. The excitation voltage of the transducer was varied between 1 Vp-p to 10 Vp-p and the frequencies were changed within the range of 2.3 MHz to 2.8 MHz. 3. Results As shown in Figure (1a), there were no movements in MBs below 7 Vp-p and at 7 Vp-p the MBs started to actuate rapidly and trapped at pressure node as shown in Figure (1b). When the driving frequency was changed from 2.3 MHz to 2.8 MHz, the trajectories of MBs motions were varied. 4. Discussion and Conclusion Initial observation indicates that the polymer shelled MBs behave as polystyrene micro beads of size around 5µm and cells [2]. Therefore polymer MBs and cells could be trapped in close proximity if introduced simultaneously. This makes it possible to study one to one interaction between cell and MB that may provide an opportunity to study cavitations associated mechanism, for e.g., sonoporation, drug delivery mechanism and cell lysis. References [1] Postema, Michiel, and Odd H. Gilja. "Ultrasound-directed drug delivery."Current pharmaceutical biotechnology 8, no. 6 (2007): 355361. [2] Wiklund, Martin, and Björn Önfelt. "Ultrasonic manipulation of single cells." InSingle-Cell Analysis, pp. 177-196. Humana Press, 2012. [3] Wiklund, Martin, Roy Green, and Mathias Ohlin. "Acoustofluidics 14: Applications of acoustic streaming in microfluidic devices." Lab on a Chip 12, no. 14 (2012): 2438-2451. [4] Sirsi, Shashank R., and Mark A. Borden. "Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents." Theranostics 2, no. 12 (2012): 1208. [5] Wiklund, Martin, C. Günther, R. Lemor, M. Jäger, G. Fuhr, and Hans M. Hertz. "Ultrasonic standing wave manipulation technology integrated into a dielectrophoretic chip." Lab on a Chip 6, no. 12 (2006): 1537-1544. (a) (b) Figure.1 Micrographs of microfluidic chip filled with polymer shelled MBs (a) below 7 Vp-p (b) above 7 Vp-p 102 P20 Evaluation of a Portable SoC-based Bioimpedance System for Plethysmography Applications J Ferreira1,2, F Seoane1,2 and K. Lindecrantz2 1 School of Engineering, University of Borås, Sweden, 2 School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden E-mail: [email protected] 1. Introduction The application of Electrical Bioimpedance (EBI) technology for respiration function monitoring is one of the earliest noninvasive monitoring applications of EBI measurements and is commonly known as Impedance Pneumography (IP). Already in 1969, NASA used IP to monitor the breathing of the astronauts during the Apollo XI mission. Since then, EBI technology has improved to a great extent and it can accurately correlate with volume estimations obtained from spirometers. Respiratory volume and flow signal extracted from IP during tidal breathing contains pathological signs of Chronic Obstructive Pulmonary Disease (COPD), cystic fibrosis, or asthma among others. Few years ago, Analog Devices introduced the first System-on-Chip (SoC) solution that perform complex impedance measurements, named the AD5933, that in combination with a custom Analog-Front-End (4E-AFE) enabled the measurement of Bioimpedance using a tetrapolar configuration [2]. The AD5933 has been used successfully in EBI applications e.g. an implantable impedance spectroscopy [1] or Body Composition Assessment using Textile Electrodes [2]. In this work, the performance of the AD5933+4E-AFE for continuous impedance measurements was evaluated for the implementation of impedance plethysmography applications. 2. Materials and Methods The AD5933-Based Bioimpedance Meter (AD5933-EBIM) used in this work, shown in Figure 1, it is a battery operated portable tetrapolar spectrometer. It uses Bluetooth technology to transfers control messages and data between device and a PC station. The AD5933-EBIM dimensions are 50x90x15 mm, and 70 gr of weight including the battery and a plastic box. The maximum continuous impedance estimation frequency and system performance error were assessed over 2R1C electrical circuits for the excitation frequencies of 50, 100, 200, 300 and 400 kHz, recording a total of 30 seconds for each excitation frequency. Also the Transthoracic Electrical Bioimpedance (TEB) measurements were recorded in a subject that was in sitting position and relaxed, using a tetrapolar Lateral Spot Electrode Configuration and repositionable EKG Ag/AgCl 3M Electrodes. The obtained TEB signal was processed using MATLAB to obtain the respiration and cardiac signals (∆Z) and its first derivative signal (dZ/dt). 3. Results The experimental maximum impedance estimation time had an averaged value of 1.791 ms, therefore the maximum impedance estimation frequency is approximately 550 Hz. The maximum impedance magnitude error over the 2R1C circuit was 0.26% at 400 kHz with a maximum standard deviation of 0.04 Ω at 50 kHz. A 23 seconds recording of the TEB signal Zraw is shown in Figure 2 upper plot, were the cardiac and respiratory components could be observed, as well as high frequency content due to the AD5933 impedance estimation error. The filtered respiratory signal Zresp is also displayed in Figure 2 upper plot with a dashed line. The respiration interval appears to be approximately 3.5 seconds per cycle, giving an average respiration rate of 17 breaths per minute. In Figure 2 middle and lower plots the cardiac signal is displayed, the beatto-beat interval as extracted from the plots is approximately 0.91 seconds giving a heart rate of 66 beats per minute. Some parameters for Impedance Cardiography analysis can be extracted from such as the increment difference for ΔZ signal with a value of 0.17Ω, the peak value for dZ/dt which is 1.55 Ωs-1, or the baseline thoracic impedance Z0 value of 29.4 Ω. Figure 1. Portable AD5933 EBIM Figure 2 . TEB impedance and respiration, filtered impedance (ΔZ) and first derivative (dZ/dt) plots 4. Conclusion The first performance tests over a 2R1C circuit showed that the system could perform continuous impedance measurement for a maximum frequency of 550 Hz and with a magnitude error below 0.26%. In Figure 1.b, the obtained TEB signal exhibited a good performance before any signal processing, the cardiac and respiratory components could be observed. The obtained results suggest that this type of system could be used in plethysmography applications such as pulmonary flow or ICG assessment among others, also enabling the development of portable instrumentation that could be integrated into textile garments using textile electrodes. 5. [1] [2] 103 References P. Bogónez-Franco, A. Bayés-Genís, J. Rosell et al., “Performance of an implantable impedance spectroscopy monitor using ZigBee,” Journal of Physics: Conference Series, vol. 224, no. 1, pp. 012163, 2010. J. Ferreira, F. Seoane, and K. Lindecrantz, "AD5933-based electrical bioimpedance spectrometer. Towards textileenabled applications.", doi: 10.1109/IEMBS.2011.6090891, pp. 3282-5, 2011. 103 P21 INTEGRATION OF Bio-Patch AND iMedBox FOR IN-HOME HEALTHCARE AND SERVICES 1 1 1 1 1 Geng Yang ,Li Xie , Zhibo Pang1,2, Qiang Chen , Lirong Zheng 2 Royal Institute of Technology (KTH), Stockholm, Sweden. Corporate Research, ABB AB, Västerås, Sweden 1. Introduction Among many other countries, Sweden is undergoing hospital restructuring by reducing the number of hospital beds and increasing the proportion of home healthcare. By moving the routine medical check and other healthcare services from hospital to the home environment, the limited hospital resources can be released to the people with urgent needs. Especially in the background of global ageing and the prevalence of chronic diseases, in-home healthcare and services can drastically lower down the total expenditure on medical care/treatment, therefore, it is promising for ICT enabled healthcare industry in the near future. In this paper, we introduce a micro chip based Bio-Patch, and a tablet PC based intelligent medicine box (iMedBox). By combining the Bio-Patch and iMedBox together, the concept in-home healthcare system is presented. 2. Bio-Patch and iMedBox Based In-home Healthcare System An ultra-low power, tiny-sized application specific integrated circuit has been developed for bio-electrical sensing purpose. The developed microchip has successfully measured ECG, EEG, EOG, and EMG signal. A temperature sensor is on-chip integrated which can be used for body temperature measurement. Based on this microchip, we developed a patch-like sensor with design targets of sensor miniaturization and an improvement of user comfort. By simply applying the Bio-Patch on user’s chest, ECG signal and body temperature can be automatically detected and transmitted to the outside world via wireless link. Powered by silicon based integrated circuits, the implemented Bio-Patch achieves a long battery life, it can operates for several days with a coin battery. Several prototypes have been developed using different integration technologies. Features and corresponding results can be found in [1-3]. iMedBox has been developed based on high performance and open platform-based tablet PC. Wearable medical sensors (e.g. Bio-Patch), intelligent medicine packages, as well as the sensors/devices from the third parties can be connected to the iMedBox via various wireless technologies. The iMedBox can serve as a common in-home healthcare platform to deliver various services such as the health social network, telemedicine, emergency and medication management services. Detailed device and service integration architecture and hardware and software architecture are presented in [4]. 3. Discussion An application scenario of the proposed in-home healthcare system is illustrated in Figure 1. Although the performances of present hardware and network infrastructure are insufficient to entirely meet our expectation, the feasibility of the proposed architecture is confirmed. References [1] L. Xie, G. Yang, M. Ma:ntysalo, L. Zheng, F. Jonsson, L.-R. Zheng, "Heterogeneous Integration of Bio-Sensing Systemon-Chip and Printed Electronics," IEEE Journal on Emerging and Selected Topics in Circuits and Systems (JETCAS), vol.2, no.4, pp.672-682, Dec. 2012. [2] G. Yang, L. Xie, M. Ma:ntysalo, J. Chen, T. Hannu, and L.-R. Zheng "Bio-Patch Design and Implementation Based on a Low-Power System-on-Chip and Paper-based Inkjet Printing Technology" IEEE Transactions on Information Technology in Biomedicine (T-ITB), vol.16, no.6, pp.1043-1050, Nov. 2012. . [3] G. Yang, J. Chen, L. Xie, J. Mao, T. Hannu, and L.-R. Zheng "A Hybrid Low Power Bio-Patch for Body Surface Potential Measurement" IEEE Journal of Biomedical and Health Informatics (J-BHI), 2013 (accepted). [4] Zhibo Pang, Lirong Zheng, Junzhe Tian, Sharon Kao-Walter, Elena Dubrova , Qiang Chen. “Design of a Terminal Solution for Integration of In-home Healthcare Devices and Services towards the Internet-of-Things”, Enterprise Information Systems, April 2013 (accepted). Microchip Bio-Patch Wireless Link ECG Signal Body Temperature In-home healthcare station Intelligent pharmaceutical package Figure 1: Proposed Bio-Patch and iMedBox based in-home healthcare system. 104 Wearable biomedical devices P22 DEVELOPMENT OF A CLINICALLY-RELEVANT HIGH-Tc SQUID MAGNETOENCEPHALOGRAPHY SYSTEM Justin F. Schneiderman1,2, Fredrik Öisjöen3, Minshu Xie3, Maxim L. Chukharkin3, Alexei Kalabukhov3, Anders Hedström4, Mikael Elam1,2,4, and Dag Winkler3 1 MedTechWest. 2 The University of Gothenburg,Göteborg, Sweden. 3 Chalmers University of Technology, Göteborg, Sweden. 4 Sahlgrenska University Hospital, Göteborg, Sweden. 1. Introduction Commercially-available magnetoencephalography (MEG) systems are presently used for a variety of neuroscience studies of brain activity because of their high spatio-temporal resolution. However, MEG has yet to reach widespread clinical use because state-of-the-art systems suffer from low signal-to-noise ratios (SNRs) and high up-front and running costs. Both of these issues can be relieved with the introduction of high critical-temperature (high-Tc) superconducting quantum interference device (SQUID) technology. The elevated operating temperature of high-Tc SQUIDs compared to their conventional low critical-temperature (low-Tc) counterparts enables relaxed cooling requirements that both lowers cost and improves SNRs in MEG recordings. The gain in SNR is especially high for sources close to the scalp. We aim to develop a full-head high-Tc SQUID-based MEG system that may supplement or replace the commercially available MEG systems that presently rely on low-Tc SQUIDs. 2. Present Status We have recorded spontaneous brain activity with our 2-channel high-Tc MEG system depicted in Figure 1 [1]. These recordings constituted the first demonstration of a multi-channel high-Tc MEG system and served as a validation of the technology in recordings of low-frequency brain activity of interest. 3. Discussion Future challenges include development and validation of a 7-channel system. Open areas of interest are optimization of the size and geometrical distribution of the high-Tc SQUIDs in a full-head system, theoretical comparison of the information available to a high-Tc MEG system with respect to its low-Tc counterpart, benchmarking the technologies, and quantifying the selective and/or overall advantage a complete high-Tc MEG system may have when compared to commercially available MEG and other neuro-imaging systems. References [1] F. Öisjöen, J.F. Schneiderman, G.A. Figueras, M.L. Chukharkin, A. Kalabukhov, A. Hedström, M. Elam, and D. Winkler, Appl. Phys. Lett., 100(13), 132601 (2012). Figure 1: Our 2-channel high-Tc SQUID MEG system. A subject sits in the subject chair with his/her head fixed in the headsupport/stabilizer. Two high-Tc SQUIDs housed inside separate non-magnetic liquid nitrogen cryostats can be placed at nearly arbitrary locations on the subject’s head via articulated armatures (also non-magnetic). 105 105 P24 A TABLET APPLICATION FOR CLINICAL ETHICAL REFLECTION WITHIN PALLIATIVE CARE 1 1 2 3.4 Daniel Sjöström , Maria Rampou , Lars Sandman , Leif Sandsjö Signals and Systems, Chalmers University of Technology, Gothenburg, Sweden. 2 School of Health Sciences, University of Borås, Borås, Sweden. 3 4 School of Engineering, University of Borås, Borås, Sweden. MedTech West, Gothenburg, Sweden. 1 1. Introduction The personnel working in palliative care are often handling delicate and sometimes unruly situations based only on their experiences and intuition. In a recent project focusing on ethical issues experienced at the Palliative Care Unit of the Sahlgrenska University Hospital, a care philosophy was developed ranging from an overarching philosophy, with a number of central values and norms, to a concrete action level specifying what the philosophy could imply in a specific situation. The philosophy originated from focus groups made up of registered and assistant nurses discussing and documenting everyday situations from an ethical perspective, mainly concerning conflicting views on how to act in specific situations, in terms of patient integrity and security, and often regarding relatives or friends (i.e. “significant others” to the patient), and in relation to spontaneous meetings, feelings, culture, treatment, lack of communication and understanding. To enable a structured use of the resulting philosophy and enable an “organizational memory” in terms of documented strategies and knowledge about past cases or situations the gathered information should be made easy to use by organizing it in a database. This would enable easy documentation and retrieval of both old and new situations to facilitate ethical reflection in weekly follow-up meetings, to support the organizational memory, and to be used as a guide when introducing new personnel. From a biomedical engineering perspective the “database” asked for is identical to a decision support system (DSS), i.e. an interactive software system or tool that compiles information from various sources and presents the user with options according to application specific rules in order to support decision making in a specific situation. Decision support systems have successfully been applied in medicine for clinical decision making and have been found to improve both practitioner’s performance and patient outcome. Thus, the aim of this study was to develop and present a prototype decision support system for documentation and retrieval of situations of ethical concern to be used as guide and a means for ethical reflection in the everyday care practice at the palliative care unit. 2. Method A focus group of stakeholders and end users was set up to get input on the potential use of the intended application. Based on the recently developed care philosophy and ethical guidelines a number of use scenarios were presented using paper prototypes to get the focus group’s views on functionality, design and appearance. This was done in an iterative process where the input from each iteration and evaluation session was considered for the next round of paper prototypes and in the software implementation using the spiral lifecycle model. With respect to present and potential future demands for the application to be easily adaptable to various tablet devices the software development was conducted in a cross-platform environment. 3. Results Three main use cases were identified. The first is to provide the personnel at the PCU a way of reporting situations of ethical concern, the second is to retrieve the stored information about past situations to share experiences and enable ethical reflection among colleagues and allow the group to add comments, the third is a browsing function for individual repetition and/or introduction of new personnel, i.e. the “organisational memory”. Central to all three use cases is the situation where the ethical difficulty occurs. Thus the application is centred on a way to specify the situation in terms of present persons and their relations or roles (nurse, spouse, friend, etc) and the circumstance (food, visit, rest, etc) that, taken together, makes the situation ethically challenging. Thus, the key features being developed for the tablet application are: - Straightforward specification of the situation (persons and circumstances) with a dynamically updated list showing available guidelines and/or past cases relevant to the specified situation. - The possibility to retrieve guidelines and past cases from the list based on the specified situation. - The possibility to document a new case for later evaluation with colleagues if there is no applicable past case or guideline. - Supporting the process of later evaluation of each case and allowing new information to be added before either including it in the guideline/past cases or remove it from the database. These features are currently developed as an application/embedded relational database for an Android tablet device. 4. Discussion It is believed that the presented tablet application can be a useful tool at the palliative care unit as it contributes easy access to both guidelines and advice based on documented past cases. The tablet application’s stand out feature compared to a paper-based version is the immediacy of its operation making it attractive to use. This may support the use of existing guidelines, the development of everyday care practice and the organisational memory of the palliative care unit. 106 P25 BICEPS BRACHII ACTIVITY PATTERN DURING REPETITIVE ELBOW FLEXIONS USING ULTRASOUND – EFFECTS OF FATIGUE Frida Lindberg1, Mattias Hedlund2, Fredrik Öhberg3, Lars-Åke Brodin1, Andreas Holtermann4, Christer Grönlund3 1 School of Technology and Health, Royal Institute of Technology (KTH), Huddinge, Sweden Department of Community and Rehabilitation, Physiotherapy, Umeå University, Umeå, Sweden 3 Department of Biomedical Engineering – R&D, Radiation science, Umeå University, Umeå, Sweden 4 National Research Centre for the Working Environment, Copenhagen, Denmark 2 1. Introduction and purpose Active fiber strains during lengthening of the muscle have been proposed to predict muscle injury and the spatial distribution of the fiber strains may be valuable in the etiology of fiber damage [1-2]. In this study, ultrasound strain from Tissue Velocity Imaging (TVI) was used to describe the intramuscular activity during repetitive elbow flexions. The purpose was to study the effects of fatigue, pre and post exercise, and determine if the regional strain pattern can be used to capture the physiological changes. 2. Method Eight healthy subjects participated in this study and the activity patterns based on ultrasound strain was analyzed in isotonic contractions of the biceps brachii at 5% of maximum voluntary contraction (MVC) before and after fatiguing exercise. In order to access the intramuscular activity pattern over time motion-mode (M-mode) strain was used (see Figure 1). The effects of fatigue were quantified by the correlation of the strain values along one image lines at different time epochs and by analyzing the number of strain areas. 3. Results The results show a significant effect of fatigue (Z = -2.52, p < 0.05, r = 0.63) on the number of active strain areas and the positive correlation between the correlation values of image lines at different time epochs and the normalized force shows a stronger linear relationship pre fatigue (r = 0.85) compared to post fatigue (r = 0.71). See Figure 2. 4. Conclusion We suggest the results to be due to less active motor units when fatigued and that the force regulation was mainly controlled by the slow, fatigue resistant muscle fibers and conclude that ultrasound TVI may provide the possibility analyze the distribution of motor units and different fiber types. References [1] T.A. Butterfield, W. Herzog, Quantification of muscle fiber strain during in vivo repetitive stretch-shortening cycles. J Appl Physiol 99: 593-602 (2005) [2] R.L. Lieber, J. Friden, Muscle damage is not a function of muscle force but active muscle strain. J Appl Physiol 74: 520526 (1993) Figure 2: Mean correlation coefficients as a function of mean normalized force. The red lines demonstrate the linear regression and r is the corresponding correlation coefficient. Figure 1: Example of M-mode strain for one subject a) pre and b) post fatigue together with c) elbow joint angle. Comparing the M-mode images pre and post fatigue, the number of strain areas has been reduced in the fatigued state. The M-mode images show the relative strain from the first image line in the plot and the time zero indicates the start of the selected time interval. The red colour indicates positive strain in the axial direction and thus a contraction, while the blue colour indicates a negative strain in the axial direction. 107 107