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Projects for students Biomedical Engineering / Physics / Electronics / Informatics Department of Biomedical Engineering, Thoraxcenter, Erasmus MC Rotterdam September 2006 These are some examples of graduation/practical work projects currently available for students at our department. For more information, you can contact the persons mentioned on each project description, or: J.G. Bosch Ph.D., tel. 010-4638088 [email protected] Regular updates and more projects will be posted on our website: http://www.erasmusmc.nl/ThoraxcenterBME/ 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. Measuring the radius of vibrating contrast bubbles in high-speed camera optical images Design of a transducer driver circuit for a handheld ultrasound system The effect of an acoustic lens on the acoustic field transmitted by an unfocussed axisymmetric single element transducer Tracking of the mitral valve ring in three-dimensional ultrasound images Medical bubbles in the tube Posttrigger for the Brandaris Camera 4D interpolation of sparse, irregularly sampled ultrasound image data 3D image reconstruction for a fast-rotating transesophageal echo transducer Tissue tracking on tendons in the hand using high-frequency ultrasound imaging Locating the salient structures of the heart in 3D ultrasound images Balloon-based Optical Coherence Elastography for detection of vulnerable plaques Model-based estimation of the outflow conditions of coronary arteries for patient specific shear stress computations Registration of multislice computer tomography and histological cross sections of human atherosclerotic plaques Analysis of temperature distribution over atherosclerotic plaques Implementation of time-dependent, MRI based in- and outflow boundary conditions for carotid arteries for shear stress calculations Patient specific wall stress computations: application to predict aortic root dilatation Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 1 of 17 Measuring the radius of vibrating contrast bubbles in high-speed camera optical images Master’s project assignment Our group has developed a special high-speed microscopic camera (the “Brandaris”) for studying the behavior of contrast bubbles in an ultrasound pressure field. The vibrations of such bubbles (typically at several MHz) are visualized at 25 million frames per second, which allows sub-micron variations in bubble size to be determined. The studies require the accurate automatic measurement of the radius of selected bubbles as a function of the applied ultrasound pressures. Currently, a semiautomatic contour detection approach is used that does not supply an optimal detection and is liable to some artifacts in the images. The current analysis software is based on Dynamic Programming (Minimum Cost Analysis) and developed mainly in Matlab. Purpose of this project: improve the accuracy of the measurement of the bubble’s radius over the complete 128-frame movie. This can be done by improvements to the current detection method (based on dynamic programming), by improvements to image preprocessing (intensity normalizations, background corrections, optical corrections) or by applying a different approach to radius determination, e.g. scaling and matching a 2D template. In this project, we would like to investigate a number of such possibilities. Fig. 1. Three consecutive frames from a Brandaris movie of some contrast bubbles. An interesting bubble is marked by an arrow. Short outline of the project (6-9 months) - literature study and study of previous work - optimization of current detection method - implementation of improved method(s) - optimization of preprocessing - developments in Matlab and/or C - evaluation of new method(s) against old. Requirements: - knowledge of image processing techniques - programming experience in MatLab and/or C For more information, please contact: Prof. N. de Jong PhD [email protected] J.G. Bosch PhD [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 2 of 17 Design of a transducer driver circuit for a handheld ultrasound system Master’s project assignment Background: In several clinical situations, i.e. the intensive care, the recovery room, and the urology department, it is often necessary to know the bladder filling. Catheterisation is the golden standard for bladder volume assessment due to its accuracy and reliability. However, it has major disadvantages. Besides the fact that catheterisation is not comfortable for the patient, it is invasive and might produce infections and traumas. In an attempt to reduce the number of catheterisations, thus reducing the chance of infections, alternative measurement techniques are addressed. One possibility is the use of ultrasound. A device called “Bladderscan™” by the company Diagnostic Ultrasound Corp. (DxU) is specifically developed for bladder volume assessment with ultrasound. It is non-invasive and is claimed to be as accurate as catheterisation. Although the BladderScan™ is extremely useful within the clinic, it is less suitable for personal use due to complex handling and device cost. To make bladder volume assessment suitable for personal use, new ultrasound techniques are being investigated at the Experimental Echocardiography department from the ErasmusMC in Rotterdam. Fig. 1. The Bladderscan. Main graduation activities: For this project, the student is asked to design and implement a functional prototype for a new ultrasound bladder volume assessment technique. The focus will be on the transducer front-end, i.e. the transducer driver circuitry. The new measurement technique is based on non-linear propagation of ultrasound waves. To have significant non-linear propagation, relatively high acoustic pressures have to be transmitted by the transducer. The generation of very high pressures is directly related to the application of high voltages on the transmitting transducer. This is currently done with the use of a linear power amplifier (1000 Watts). This amplifier amplifies a predefined waveburst, which is generated by an Arbitrary Waveform Generator (AWG). The student will be challenged to implement a transmit circuit that is capable of generating the high-voltage transmit bursts to drive the transducer, bearing in mind that this should be done in a handheld device. One possible solution to this problem is that the driving circuit should be specifically designed for the transducer used, avoiding the need of a bulky power-consuming linear amplifier. As the volume measurement technique, as well as the complete system, is fully experimental and completely new, the design should be transparent to allow for adjustments. This means the effects of changes in transducer specifications and waveform characteristics (e.g. transmit frequency) on the performance of the circuit should be easily interpreted and should allow for quick redesign. Since a first functional prototype is almost operational and clinical experiments are pending, the driving circuit is of great importance to the project. Hence, implementation and testing of the design is an important part of this project. During this project the student will gain knowledge of medical ultrasound applications and perform several acoustic measurements. Requirements: - discipline: Microelectronics For more information, please contact: Ir. E. Merks [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands Phone 010-4089358 Dr.ir. Wouter A. Serdijn [email protected] Microelectronics Department, Delft University of Technology, Delft Phone: +31 (0)15-2781715 Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 3 of 17 The effect of an acoustic lens on the acoustic field transmitted by an unfocussed axisymmetric single element transducer Master’s project assignment Background: In several clinical situations, i.e. the intensive care, the recovery room, and the urology department, it is often necessary to know the bladder filling. Catheterisation is the golden standard for bladder volume assessment due to its accuracy and reliability. However, it has major disadvantages. Besides the fact that catheterisation is not comfortable for the patient, it is invasive and might produce infections and traumas. In an attempt to reduce the number of catheterisations, thus reducing the chance of infections, alternative measurement techniques are addressed. One possibility is the use of ultrasound. A device called “Bladderscan™” by the company Diagnostic Ultrasound Corp. (DxU) is specifically developed for bladder volume assessment with ultrasound. It is non-invasive and is claimed to be as accurate as catheterisation. Although the BladderScan™ is extremely useful within the clinic, it is less suitable for personal use due to complex handling and device cost. To make bladder volume assessment suitable for personal use, new ultrasound techniques are being investigated at the Experimental Echocardiography department from the ErasmusMC in Rotterdam. Fig. 1. The Bladderscan. A new bladder volume measurement technique is under development, which instantaneously measures the bladder volume on the basis of non-linear wave propagation. Using spectral analysis on the received echoes, the bladder volume can be obtained. This technique requires a transducer that is able to generate a diverging acoustic beam that instantly captures the complete or a large part of the bladder. This can be achieved by using an unfocussed or flat transducer equipped with an acoustic lens to diverge the ultrasound wave. Main graduation activities: For this project the student is asked to investigate the effect the additional acoustic lens has on the characteristics of the transducer and to simulate the transmitted diverging acoustic field using existing simulation schemes. Several simulation schemes are available that can simulate the acoustic field. However, the characteristics of the unfocussed transducer are influenced by the addition of the lens. This results in a different transducer behaviour, and thus in a different transmitted sound field. Multiple reflections within the lens are also a problem. These so-called reverberations also alter the emitted sound field. Extension to this project: Depending on the progress made, the student is also asked to determine how well the bladder is covered by the generated acoustic field. The acoustic field or beamprofile split in several parts depending on the magnitude of the generated pressures. For example, when we are only looking at the pressures with maximum magnitudes (0dB) till half the maximum magnitude (–6 dB), the beamprofile will be less diverging than when we are looking at pressures as low as one tenth (-20 dB) of the maximum. So, which part of the bladder is covered by pressures from 0 to –6 dB, which part is covered by pressures from –6dB to –12dB, and so on? This, of course depends on the size of the bladder and the location. Requirements: - discipline: Physics or electronics - Programming experience in Matlab and /or C++ For more information, please contact: Ir. E. Merks [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands Phone 010-4089358 Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 4 of 17 Tracking of the mitral valve ring in three-dimensional ultrasound images. Master’s project assignment Our group is working on automatic contour detection techniques for 3-dimensional ultrasound images of the heart (3D echocardiograms). In these images, the beating heart is visible. The images show the contracting left heart chamber, together with the mitral valve which is opening and closing (see fig. 1). Echocardiograms are normally used primarily for visual assessment of the functioning of a patient’s heart, but with an automated contour detection technique, they can also be used for measurement of the left ventricular volume, detection of wall motion abnormalities etc. Manual segmentation of such 3D images is extremely time consuming and is not very reproducible. We have developed a semiautomatic contour detection technique for such images, which supplies good volume estimates. However, the accuracy of the results could be considerably improved if the movement of the mitral valve could be tracked over time. We have successfully worked on valve tracking in 2D ultrasound sequences using a 2D block matching approach combined with novel multidimensional dynamic programming (MDP). This was investigated at our lab by Shelly Nevo (MSc student Biomedical Engineering, TU Delft) with very promising results. We want to extend this technique towards a full 3D analysis. Purpose of this project: track the 3D motion of the mitral valve ring (as defined in the first images) over the cardiac cycle. We propose to use the described 2D block matching over rotation angle and time in combination with a multidimensional dynamic programming approach, but this is open to be investigated within the project. To track the 3D motion of the valve, several alternative image processing approaches may be applied: block matching in 3D; Kalman filters; detection of features of the valve leaflets and attachment points; temporal filtering to detect the fast motion of the valve leaflets; model-driven detection based on template books. This can be done in temporal sequences of 2D or 3D images. Fig. 1. Two-dimensional ultrasound images of the left heart chamber with the mitral valve (arrows), taken from a 3D set. Left: end diastole (largest volume); Mid: end systole (smallest volume); Right: cross section at another rotation angle. Short outline of the project (6-9 months) - literature study of valve detection/tracking techniques, and study of the previous work - comparison of methods - experimentation using Matlab and/or C++ developments - evaluation of method on a database of 3D patient images. Requirements: - knowledge of image processing techniques - programming experience in MatLab and/or C++ For more information, please contact: Fig. 2. Rendering of 3D dataset and detected endocardial surface J.G. Bosch PhD [email protected] Assistant Professor, Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 5 of 17 Medical Bubbles in the tube Graduation project assignment Researchers: - H.J. Vos (Contact, PhD student EMC Rotterdam, [email protected]) - B. Dollet (postdoc UTwente) - D. Goertz (postdoc EMC Rotterdam) - N. de Jong / A.F.W. van der Steen (professors EMC Rotterdam / UTwente) Introduction: Ultrasound Contrast Agents consist of micrometer sized gas bubbles with a human friendly shell, inserted into the bloodstream. These bubbles vibrate in the ultrasound field generated for ultrasound imaging, and will thus act as a secondary sound source, enhancing the signal to noise ratio. This facilitates the imaging of small vessels in heart and tumors, but it is seen in preliminary experiments that the size of such small tubes damps the spherical oscillations of the bubbles. The disadvantage of this reduction of signal might be transformed into new detection techniques with further research. Subject: A small amount of literature describes the behavior of bubbles in a inhomogeneous medium, but the models have to be redefined for the geometry at hand. The Brandaris fast framing camera will be used for optical verification of the model of a bubble in a small tube (12 micron diameter). The results could be used to for optimizing current detection techniques or develop new strategies, and could be tested in-vitro or in-vivo. ------------------------Medische bellen in ‘t vat Onderzoekers: - H.J. Vos (Contactpersoon, PhD student EMC Rotterdam, [email protected]) - B. Dollet (postdoc UTwente) - D. Goertz (postdoc EMC Rotterdam) - N. de Jong / A.F.W. van der Steen (professoren EMC Rotterdam / UTwente) Inleiding: Ultrageluid contrast middelen bestaan uit micrometer-kleine gasbellen met een lichaamsvriendelijke schil, die in de bloedbaan worden gespoten. Deze bellen gaan trillen als gevolg van het ultrageluid waarmee gekeken wordt in het lichaam, en worden zo een secundaire geluidsbron die relatief eenvoudig te detecteren is. Dit opent de deur naar het afbeelden van de kleine bloedvaten in het hart, maar ook naar bijvoorbeeld de vaatstructuur van tumoren. Echter, in zulke kleine vaten zal een bel geremd worden in zijn trilling ten opzichte van een trilling in een vat met een diameter veel groter dan z’n eigen diameter. Deze reductie kan nadelige signaal effecten hebben, maar zou ook omgezet kunnen worden in nieuwe detectietechnieken. Opdracht: Er is beperkte literatuur beschikbaar die het gedrag van bellen in een niet-homogeen medium beschrijven, maar deze modellen zullen moeten worden omgeschreven naar de huidige geometrie. De Brandaris snelle camera zal gebruikt worden voor optische verificatie van het model van een bel in een kleine buis (12 micron diameter). Aan de hand van de resultaten zullen bestaande detectietechnieken verbeterd kunnen worden en misschien zelfs nieuwe technieken bedacht en getest kunnen worden in-vitro of in-vivo. Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 6 of 17 Posttrigger for the Brandaris Camera Master-task In the default mode, the 128 CCD cameras of the Brandaris (see below) work in slave mode. The rotating turbine, as a master, generates pulses which are used by the master controller to start the experiment (e.g. by generating ultrasound, light etc.), followed by one or more control signals to store the image. So the trigger precedes the experiment. In this project, we want to develop posttrigger capability of the camera. So the experiment is preceding the trigger. (e.g., a waterdrop falling on a table causes a sound at the moment it hits the table. This sound is used as the trigger. The interesting part is the moment just before it reaches the table, so you have to record the instant before the trigger arrives). The project: Images should be continuously stored and refreshed on the on-board memory inside the Brandaris. Possible approaches: - Change the firmware in the FPGA - Adapt the master controller software Or a combination of these 2. Another aspect should also be included. The firmware of each board is stored in an on-board eprom, which is read at startup. Recently, all the boards have a serial connection (beside a usb2). Can new firmware also be uploaded via the serial connection? Requirements: Discipline: electronics or physics Experience in FPGA programming and controller systems programming Supervisors: Jerome Borsboom Frits Mastik Nico de Jong [email protected] 010-4088037 The Brandaris 128 - fast framing camera Ultrasound is the most widely used medical imaging modality. The majority of ultrasound systems operate at frequencies in the 1-5 MHz range and form images using a hand-held transducer that is external to the body. It is capable of providing real-time information about tissue structure and blood flow in the heart and larger vessels. Unfortunately, in smaller vessels and capillaries blood detection is not possible due to low signal strengths from blood, tissue motion effects, and limited resolution (~0.5-1 mm). Ultrasound contrast agents (UCA, consisting of small (encapsulated) gas bubbles), will increase the reflection of ultrasound by the blood pool, after intravenous administration, and by that make it possible to provide perfusion images. Besides using UCA for measuring perfusion there is a growing interest in the use of coated microbubbles for therapeutic applications. In this case the microbubbles can act as transport carriers for drug delivery or when targetted, to image the targeted site acoustically, referred as molecular imaging. A third application for therapy is known as sonoporation. Here, the oscillation of ultrasound-driven microbubbles in close contact with a cell lead to an increased permeability of the cell to macromolecules, hence to an increased uptake of drugs or genes in close vicinity to the cell. To study the dynamics of the bubble upon insonification optically, e.g. under a microscope, it is necessary to use a high-speed camera. We have constructed (together with the university of Twente) a digital ultra high-speed camera operating at up to 25 The Brandaris (blue case) with optical microscope million frames per second based on the principle of a rotating mirror camera to study contrast agent behavior upon insonification down to a 40 nanosecond timescale. This camera, which measures 1.5 x 1.5 x 0.3 meter, weight 150 kg and has costed about 700 k€ (grant from FOM), is unique in the world. The results collected from these interesting experiments have already revealed the complicated interaction between cells and bubbles and have given more insight in the complex vibration of the bubbles for diagnostic use. (see figure). Cracking of a contrast microbubble under diagnostic ultrasound. The gas escapes, leading to a free gas bubble with an increased ultrasound echogenicity. Size of the image is 5x5 micrometer. The ultra high-speed camera is called Brandaris because it makes use of an optical principle similar to that of a light house. Research with the camera is performed in two labs in the Netherlands. See for the Brandaris: Chin CT, Lancee L, Borsboom J, Mastik F, Frijlink ME, de Jong N. Brandaris 128: A digital 25 million frames per second camera with 128 highly sensitive frames. Review of Scientific Instruments 2003;74:5026-5034. Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 7 of 17 Master’s project assignment 4D interpolation of sparse, irregularly sampled ultrasound image data Our group is working on automatic contour detection techniques for 3-dimensional ultrasound images of the heart (3D echocardiograms). In these images, the beating heart is visible. These images are recorded with a special transducer developed in Rotterdam: the Fast Rotating Ultrasound (FRU) transducer. This transducer rotates around its image axis at high speed (4-8 rotations per second), while acquiring two-dimensional images (figure 1). A cone-shaped volume is scanned continuously over several seconds, and from the data a set of 3D volumes covering the full heart cycle can be constructed. Since there is no synchronization between the heart rate and the continuous rotation, the data is irregularly distributed over cardiac phase and angle. For visualization and segmentation, voxel sets for a number of time instances (cardiac phases) should be constructed from this irregularly distributed data (fig.2). At the moment, such images are constructed by temporal binning of the samples and trilinear interpolation. Due to the neglection of the temporal differences between samples and the sparseness, considerable interpolation artifacts can occur. We have developed a 4-dimensional Normalized Convolution interpolation approach that gives better results (fig.3), but improvements can still be achieved. Issues involved: - Theoretical comparison of our approach to other possibilities. - size and shape of the convolution kernels (currently Gaussian) in temporal and spatial dimensions - multi-scale approach to better bridge gaps in the data - better handling of motion artifacts Fig. 1. Seven consecutive twodimensional ultrasound images of the FRU transducer positioned in 3D Purpose of this project: develop a suitable interpolation technique for this data Short outline of the project (6-9 months) - literature study of sparse data interpolation techniques, and study of previous work - theoretical comparison of methods for this specific problem - implementation of improvements and/or alternatives - C++ developments, experimentation partly in Matlab - evaluation of method on a number of patient images. Requirements: - knowledge of image processing techniques - programming experience in C++ Fig. 2 Multi-beat fusion. Left: example of sparse sampling of time-volume space for one interval (1/12) of a cardiac cycle. Right: same for multi beat fusion. For more information, please contact: J.G. Bosch PhD [email protected] Laboratory for Experimental Echocardiography Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 www.erasmusmc.nl/ThoraxcenterBME Fig 3. Interpolation results. Left: temporal binning and trilinear interpolation. Notice the jagged edges. Right: interpolation with normalized convolution. Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 8 of 17 Master’s project assignment 3D image reconstruction for a fast-rotating transesophageal echo transducer In cooperation with Oldelft Ultrasound, we are investigating the possibilities of 3D imaging with a mechanically fast rotating transesophageal echo (TEE) transducer (fig. 1). The shaft of this probe (fig. 2) is brought into the esophagus through the mouth. The tip of the probe is positioned close to the heart, and can make high-resolution 2D images (fig. 3). By rotating the transducer plane, we can construct 3D images of the heart. Fig. 1. TEE probe. Fig. 2. Patient with TEE probe Fig. 3. 2D TEE image Fig. 4. Images of 7 angles in 3D The principle of the fast rotating 3D image construction is als follows. We rotate the image plane at a high speed by an external motor and record the images over multiple heart cycles, together with the patient’s ECG (electrical signal of the heart). The heart cycle is divided into multiple phases and a 3D image is constructed per phase by composing images of different rotation angles within the phase (fig. 4). Since there is no synchronization possible between the rotation speed and the heart rate, distribution of image angles is irregular; because of the fast rotation, image planes are curved. Therefore, image reconstruction is quite complicated, but we gain in image quality and speed with respect to other approaches. We have experience in constructing such 3D images from a transthoracic fast rotating ultrasound (FRU) transducer; the image reconstruction techniques developed for the FRU transducer can be applied here as well. The differences for the TEE approach are the alternating rotation (-90 Æ +90 Æ -90 degrees) at 5 cycles per second and the rotation angle measurement. Purpose of this project: realize a 3D imaging setup with the novel fast rotating TEE probe. Short outline of the project (6-9 months) - study literature and previous hardware setups - study image reconstruction of FRU transducer - set up acquisition hardware for rotation angle and ECG in combination with ultrasound machine and rotation controller - acquire and reconstruct images of phantoms and tissue specimens - acquire and reconstruct images of animals or volunteers Requirements: - background in biomedical/electrical engineering, physics or medical informatics - knowledge of image processing techniques - programming experience in Matlab and/or C/C++ For more information, please contact: Prof. N. de Jong PhD [email protected] J.G. Bosch PhD [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 www.erasmusmc.nl/ThoraxcenterBME Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 9 of 17 Master’s project assignment Tissue tracking on tendons in the hand using high-frequency ultrasound imaging Function of the hand is to a large extent determined by the long flexor and extensor tendons of the hand, originating proximally from the wrist and extending to the top of the fingers and thumb. Within a complex system of ligaments, pulleys and tendon sheets, the appropriate moment arm of the tendon at the different joints of the hand is maintained while the tendons can move highly independent from its surrounding tissues over relatively large distances. While highly efficient in healthy subjects, the function of the tendon can be severely impaired in a number of pathologies. For example, in hand trauma, tendons are often ruptured and need to be surgically repaired, frequently leading to adhesion formation and poor outcome. In sports injuries (e.g., rock climbing), tendons, ligaments or pulleys may rupture, changing the moment arm of the muscle relative to the joint and therefore the functional properties of the muscle tendon system. Measurement of tendon dynamics would provide important insight into the (dys)function of tendons in the hand. New high-resolution ultrasound imaging techniques show potential; some pilot studies conducted in our lab have shown some promising results with Bmode and RF mode 2D tissue tracking. In this project, we would like to further investigate these possibilities. Purpose of this project: investigate 2D tracking techniques for high-resolution images of human tendons. Fig. 1. Ultrasound image of a tendon in the wrist (left) with a one-dimensional velocity trace (right) The project will be performed in close cooperation with R.W. Selles, PhD, [email protected], dept. Revalidation / Plastic Surgery, Erasmus MC. Short outline of the project (6-9 months) - Study of literature (speckle tracking) and previous work (pilot studies performed by our group) - Set up acquisition hardware for RF analysis with Vevo 770 ultrasound machine - Acquire and analyze images of phantoms, volunteers and patients - Development of two-dimensional tracking in B-mode images and RF data - Testing and clinical validation Requirements: - background in biomedical/electrical engineering, physics or medical informatics - knowledge of image processing techniques - programming experience in Matlab and/or C/C++ For more information, please contact: J.G. Bosch PhD [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 www.erasmusmc.nl/ThoraxcenterBME Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 10 of 17 Master’s project assignment Locating the salient structures of the heart in 3D ultrasound images Purpose of this project: devise a robust method for locating the position and orientation of the heart’s main structures in 3D ultrasound. We are working on automated contour detection and registration techniques for 3D echocardiography. The automated techniques developed so far (based on Active Appearance Models) require an initialization which is sufficiently close to the actual situation. This initialization (in terms of 3D position, scale, and 3D rotation should preferably be in the order of 1cm precise. The structure is generally only partly visible in the 3D set. Therefore, a very robust technique is required for analyzing the coarse structure of the image. At the high resolution level, the image is heavily contaminated by speckle, noise and artifacts. At the lower resolution, mostly the lateral wall suffers from severe dropout; the septal wall and the posterior onset of the right ventricular wall are generally best visualized. We propose an approach based on the well-known Hough transform, capable of finding circular/elliptical structures. It will need to be combined with a preprocessing step to enhance the structure and suppress noise. The aim is to locate the left ventricular long axis in the images, with the rotation of the right ventricle, and an estimate of the apex and the valve plane. Alternative/additional approaches may encompass temporal analyses such as factor analysis and fourier filtering, scale-space techniques for detecting ridges and corners, etc. The work can be performed mostly in Matlab and/or other toolboxes, but likely some non-standard processing will need to be implemented. Fig. 1. different cross sections from a 3D dataset. Left: four-chamber view. Right: short-axis view. Short outline of the project (6-9 months) - Study of literature and previous work (pilot studies performed by our group) - Comparison of preprocessing approaches - Evaluate Hough transform and/or alternative feature detection - Testing and clinical validation on a dataset of patients Requirements: - background in biomedical/electrical engineering, physics or medical informatics - knowledge of image processing techniques - programming experience in Matlab and/or C/C++ For more information, please contact: J.G. Bosch PhD [email protected] Laboratory for Experimental Echocardiography, Department of Biomedical Technology Room Ee23.02, Thoraxcenter, Erasmus MC P.O.Box 1738, 3000 DR Rotterdam, The Netherlands 010-4638088 / 4088037 www.erasmusmc.nl/ThoraxcenterBME Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 11 of 17 Master’s project assignment Balloon-based Optical Coherence Elastography for detection of vulnerable plaques Most heart attacks are preceded by the rupture of a so-called vulnerable atherosclerotic plaque in the coronary artery wall. These vulnerable plaques (VPs) consist of a necrotic core, containing lipid material and cellular debris, covered by a thin fibrous cap which is weakened by inflammation. Rupture of the cap releases the necrotic material into the bloodstream, causing a thrombus to form, that may block the artery. One method of VP detection is intravascular elastography: imaging the strain in vascular tissue in response to an applied stress. In elastography, two or more images at different pressure are compared using a registration algorithm, to find the tissue displacement field, from which the strain can be derived. Soft plaques exhibit a characteristic strain pattern that provides an estimate of their vulnerability. Intravascular ultrasound (IVUS) elastography has proven very successful in mapping such strain patterns. Strain 1% Figure 1: (left) IVUS image of a human coronary in vivo, showing an atherosclerotic plaque. (right) Corresponding strain elastogram. 0% Optical coherence tomography (OCT) provides high resolution (≈ 10 µm) real time imaging of tissue using infrared light and interferometric detection. Recently, the technique has become commercially available for intravascular application. In collaboration with LightLab Imaging, Inc., we aim to extend OCT to in vivo intracoronary elastography, augmenting the tissue structure imagery with information on the arterial wall’s mechanical properties. In this project, we investigate the use of a semi-compliant balloon catheter to apply a precisely defined pressure to the vessel wall. The displacements in the images will be tracked using (semi-automated) OCT image segmentation and registration. The research will be a combination of experimental work and image processing, concentrating on the following issues: • optimal imaging/pressure sequence • segmentation method (for feature tracking) • image feature registration algorithm Requirements: • knowledge of image processing techniques • programming experience in MatLab and/or C • basic hands-on lab experience Figure 2: OCT image of a human coronary in vivo. Note the fine details in the complex structure of the vessel wall. For more information, please contact: Gijs van Soest [email protected] Department of Biomedical Engineering Thoraxcenter, Erasmus MC 010-4089363 Graduation projects Thoraxcenter Biomedical Engineering, Erasmus MC, Rotterdam, sept 2006 Page 12 of 17 Model-based estimation of the outflow conditions of coronary arteries for patient specific shear stress computations Graduation project for a master student of Biomedical Engineering, Physics, Mechanical Engineering or Aerospace Technology with proven interest in fluid dynamics, modeling and/or finite element applications ErasmusMC Biomedical Engineering Hemodynamics Laboratory Contact Ir. A.G. (Alina) van der Giessen [email protected] Dr. ir. F.J. (Frank) Gijsen [email protected] Tel. 010-408 8039 Aim of the project To obtain a model-based estimation of the outflow conditions at coronary artery branches, such that implementation in finite element calculations will result in realistic values for flow and shear stress. Background The coronary arteries provide the heart with blood. With aging and in the presence of risk factors, such as smoking, obesity and diabetes, atherosclerotic plaques tend to develop in the vessel wall of these arteries, see the upper figure. In an advanced stage of atherosclerosis these plaques start to narrow the artery. This eventually can result in a heart attack, which is a major cause of death in the Western World. The atherosclerotic plaques originate at specific locations in the coronary arteries. Parts of the vessel wall that sense a low shear stress are more prone to develop plaques than parts sensing a high shear stress. Also in an advanced stage of the disease, shear stress plays an important role in the progression and the composition of the plaques. Therefore shear stress is an important parameter to study in atherosclerotic research. Shear stress is the friction force of the blood along the vessel wall. This parameter depends on the blood-flow through the artery, the diameter of the artery and the density of blood. In a straight tube, shear stress can be calculated analytically, however for a patient specific geometry of coronary artery and for time-varying flow, this is not possible. Therefore finite element calculations are used to calculate shear stress. This computational method requires the geometry of the arteries and in, - and outflow conditions. The geometry of the arteries is obtained from computed tomography (CT) images. The artery divides in several branches, which results in several locations where the blood can exit the geometry, see bottom figure. The amount of blood directed to each of these locations in the calculation depends on the described outflow conditions. Usually stress-free outlet boundary conditions are applied, but that would result in unrealistic flow ratios, because most of the blood will exit via the larger first side-branch To prescribe outflow boundary conditions, we would like to measure parameters, which are related to flow, in the patient. However this is not possible with an image modality as CT. Thus, we need an alternative method to obtain realistic flow and shear stress distribution in the coronary bifurcation. The proposed approach is to develop a model that gives a description of the vasculature behind the outflow locations, which will enable us to prescribe parameters, such as pressure, resistance or flow at these locations. Registration of multislice computer tomography and histological cross sections of human atherosclerotic plaques ErasmusMC Biomedical Engineering Hemodynamics Laboratory Head Dr. ir. J.J. Wentzel [email protected] Tel. 010-408 8044 Fax. 010-408 9445 Contact Ir. H.C. Groen [email protected] 010-4638166 Technical background Mathematics Physics Image processing In the presence of risk factors, such as smoking, diabetes, obesity, atherosclerotic plaques tend to develop at specific sites in the arterial system: close to side branches and in innercurves of arteries. A subgroup of these plaques develop into a plaque with a high risk to rupture, the so called vulnerable plaque. The vulnerable plaque is characterized by its large lipid pool covered by a thin fibrous cap and large macrophage infiltration. Rupture of these vulnerable plaques in the carotid arteries, ie. the main blood supply to the brain, will cause stroke resulting in life-long disability or death. Remarkedly, plaque rupture is often observed at the upstream side of the plaque. At this site the shear stress of the blood is supposed to be high. It is known that rupture of tissues depends on the imposed mechanical load and its material properties. The mechanical load working on these plaques can be mainly attributed to the blood pressure, which is orders of magnitude higher than the blood flow induced shear stress. The material properties of a vulnerable plaque are well characterized, however not much is known about the spatial distribution of the different components. Therefore the question was raised whether the tissue composition at the upstream side of the plaque differs from the down stream side and whether shear stress has influenced that process. Projects conducted at the hemodynamics laboratory investigate the relationship between shear stress and plaque composition. Therefore, both the shear stress and the tissue composition need to be determined. The best way to study the plaque composition is by investigating histological cross section of the tissue. For that reason, plaque tissue removed from the carotid arteries during invasive surgery, is collected and investigated. To obtain the shear stress of the blood at the vessel wall we will apply computational fluid dynamics. This technique requires a 3D geometry of the vessel under study. Therefore, prior to surgery, the patient is subjected to multislice computer tomography imaging, which allows for assessment of the 3D lumen and wall geometry. Before the relationship between shear stress and plaque composition can be studied, the histological cross sections need to be registered on the CT images. High accuracy of this matching procedure is crucial for the final outcome of the study. Aim of the project Develop and apply methods to ensure highest possible accuracy for registration of histological cross sections and MSCT of the carotid arteries. This project will be performed in close collaboration with the Biomedical Imaging Group Rotterdam of the Radiology Department. ErasmusMC Biomedical Engineering Hemodynamics Laboratory Analysis of temperature distribution over atherosclerotic plaques Background Contact Dr. ir. F.J.H. Gijsen [email protected] Tel 010-408 8039 Acute coronary syndromes, including myocardial infarction and sudden death, are often caused by the rupture of a so called vulnerable plaque. The vulnerable plaque is a specific stage of atherosclerosis. This type of plaque is characterized by a lipid pool, covered by a thin fibrous cap, and an abundance of inflammatory cells, the macrophages. These macrophages are believed to be metabolically active, and cause higher temperatures in the plaque, much like fever. This increased temperature could be detected with intravascular thermographic devices, making the detection of vulnerable plaques possible. However, no detailed studies on the relationship between macrophages and heat production are available. We performed an animal study, using atherosclerotic mice to investigate this topic. Excised aortic arches, showing advanced atherosclerotic plaques, were studied with an infrared camera to measure the temperature distribution. Macrophage and lipid content of these aortas were obtained with histological staining, and these were matched to the observed temperature distributions. The results showed no clear, unambiguous relationship between macrophages and temperature increase. The reason for this discrepancy might be the presence of inactive macrophages not producing a temperature increase. Objectives and methods Aortic arch of a mouse: A) staining for lipid B) detection of lipid in histological cross section C) full aortic arch In this project we will combine the experimental mice data with numerical methods to establish a relationship between measured temperature distribution, the macrophages , their activity and lipid distribution in atherosclerotic plaques (see figure). 13 Mice were imaged with an infrared camera after excision of the aortic arch. Infrared imaging was repeated after provocation of the macrophages with a substance, such that only the ‘active’ macrophages would reach a higher metabolic state. The infrared data after provocation will be combined with the data before the provocation to investigate which macrophages were active. Both the activity and the position, especially with respect to the lipid, of the macrophages will be fed into a finite element analysis to compute the resulting temperature distribution along the luminal surface. These computations will be compared to the measured temperature distribution to investigate the relationship between macrophages and temperature. Technical background: (bio)mechanical engineering, physics ErasmusMC Biomedical Engineering Hemodynamics Laboratory Contact Ir. H.C. Groen [email protected] 010-4638166 Dr. ir. J.J. Wentzel [email protected] 010-408 8044 Dr. ir. F.J.H. Gijsen [email protected] 010-4088039 Implementation of time-dependent, MRI based in- and outflow boundary conditions for carotid arteries for shear stress calculations Background Atherosclerosis is a progressive disease of the blood vessel wall, which development/presence is influenced by certain riskfactors (age, gender, smoking, obesity) affecting the whole vasculature. However, the disease is always located at or near bifurcations and inner curves of the blood vessels. These locations are characterized by their relative low and/or oscillatory wall shear stress (dragging force of the blood) patterns. Under these conditions an atherosclerotic plaque can grow which can eventually rupture, resulting in a brain- or heart infarction depending on the location of this ruptured plaque. This type of rupture-prone plaque is called a vulnerable plaque. During the late stage of plaque growth, the blood vessel gets narrowed which results in a change in the wall shear stress patterns. Our hypothesis is that this change has a negative influence, through biological mechanisms, on the stability of the vulnerable plaque. To test this hypothesis we link the plaque composition (histology) with the shear stress. Therefore we need accurate and patient specific wall shear stress values, which can be calculated by using computational fluid dynamics (CFD). Aim of this project Implement time-dependent, patient specific boundaries conditions for 3D carotid artery flow simulation for optimal shear stress calculations. Methods This project is divided into a number of subprojects that will have to be carried out. First the (time-dependent) MRI flow information has to be extracted from MRI data, filtered and converted into a format usable for SEPRAN (CFD software package). The second step is to simulate blood flow through patient specific geometries (meshed with GAMBIT) using the obtained (time-dependent) inflow information. The last step is to prescribe the measured outflow conditions which, altogether, results in the optimal simulation conditions for shear stress calculations. Technical background : (bio)mechanical engineering, physics Patient specific wall stress computations: application to predict aortic root dilatation ErasmusMC Biomedical Engineering Hemodynamics Laboratory Contact Dr. ir. F.J.H. Gijsen [email protected] 010-408 8039 Dr. ir. J.J. Wentzel [email protected] 010-408 8044 Background Patients with congenital defects can develop heart valve abnormalities, which often are accompanied by aorta root dilatation and aneurysm formation. Whenever such a dilated aorta or aneurysm ruptures, patients are at great risk to die. Replacement of the aortic root however is an operation which carries a great risk, and is therefore avoided whenever possible. Cardiologists have to decide when to proceed to intervene by replacing the diseased ascending aorta. Currently, the decision to intervene is based on the diameter of the aortic root, which is much like the decision procedure in operating abdominal aortic aneurysms (AAA). Recently, wall stress was investigated as an additional predictive parameter to help clinicians to decide when to operate an AAA. It turned out that a measure of peak wall stress can serve as an independent predictive parameter. The current project serves as a pilot to develop a method to determine wall stresses in the wall of the ascending aorta including the aortic root and to investigate if wall stress can be used to predict growth of the aortic root . Objectives and methods Wall stress distribution in aortic aneurysms obtained by the Hemodyn software package The objective of this project is 1) the development of a method to determine wall stress distribution in a patient derived geometry of the aortic root, and 2) the development of a relevant wall stress parameters to be related to aortic root dilation. 1) In a previous research project, a software environment, Hemodyn, was developed to determine wall stress distribution in human abdominal aortic aneurysms. Since this software is not used for aortic root aneurysms before, we will test the applicability of this software for aortic root aneurysms and we will adapt it where needed. Furthermore, to obtain accurate patient specific wall stress distributions by means of finite element analysis accurate boundary conditions, loading conditions and relevant material models need to be defined and if possible assessed for the individual patient. All these patient specific parameters will be fed into the software package. 2) The second part of this research project deals with the conversion of this patient derived wall stress distribution to a clinically relevant parameter that contains a measure of the peak stress such that this parameter can be used in prediction trials. Technical background : informatics, (bio)mechanical engineering, physics dilated aortic root