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Eliot Siegel, MD, FSIIM, FACR Professor of Radiology University of Maryland School of Medicine Chief Imaging Services, VA Maryland Healthcare System Dwyer AI Session Outline • Tanveer F. Syeda-Mahmood, PhD – Chief Scientist, Medical Sieve Radiology Grand Challenge – IBM Almaden Research Center • Panel Discussion – Rasu B. Shrestha, MD, MBA, Chief Innovation Officer, University of Pittsburgh Medical Center, Executive Vice President, UPMC Enterprises; – Khan M. Siddiqui, MD, Co-Founder, Chief Technical Officer, higi, CoDirector, Center for Biomedical & Imaging Informatics, Visiting Associate Professor Radiology, Johns Hopkins University Disclaimer – ACR – Fuji – Philips – AGFA – Galileo – RADLogics – Amalga – Herman Miller – Radsite – Anatomic Travelogue – IBM – Redrick/Evolve – Anthro – Intel – RSNA – Applied Radiology – Kodak – Siemens – ATL – NIBIB – SIIM – Barco – NIST – Sonare – Bracco – NLM – Steelcase – Brightfield – NCI – TeraRecon – Carestream – Life images – Topoderm – Cydar – McCoy – Toshiba – Dejarnette – McKesson – Virtual Radiology – Dell – Medrad – Vital Images – Diagnostic Imaging – Medscape – Xybix – Digital Art Forms – Merge – YYESIT – Dynamic Imaging – Microsoft – Zebra – Eizo – Montage – Fovia – GE Samuel J. Dwyer, III, PhD, FSIIM (1932–2008) • On May 4, 2002 Sam became the ninth SCAR member to be inducted into the SCAR College of Fellows. • Dr. Dwyer received his PhD in Electrical Engineering at the University of Texas-Austin specializing in systems and signal processing • Dr. Dwyer at the time of his retirement was a Professor of Radiology at the University of Virginia Health Sciences System Steve Horii, M.D. • I knew him to be always ready with a smile or infectious laugh and with a perpetual gleam in his eye that spoke of his friendly manner • There are some who would claim the title of “PACS Man”, but it is Sam Dwyer who led the revolution in PACS • Sam Dwyer was a major pioneer who brought many of the important advances in technology to us and helped move concepts from the realm of engineering to that of healthcare • I will miss Sam very much, but the strong memory of him is never further than the PACS workstation I use every day R. Gilbert Jost, MD Past President RSNA and RISC • If one were to identify a “father of PACS”, unquestionably it would be Sam Dwyer… • He is truly a pioneer who has changed the specialty of radiology for the better in innumerable ways Continued Relationship with Sam • Sam was very reassuring when we became the world’s first filmless hospital that our problems would not be insurmountable and that the time was right to go filmless • As this “kid” right out of residency aspiring to the first filmless hospital, I think I amused Sam • In subsequent years we got together frequently at RSNA and he often scribbled messages and drawings on napkins and handed them to me • Kept in contact by phone and e-mails and always enjoyed talking with him • Makes me wonder what Sam would have thought about “Artificial Intelligence” and its potential in diagnostic imaging Where Are We in 2016 in AI in Diagnostic Imaging? • Sam would be surprised that CAD hasn’t made more progress in diagnostic imaging • 10’s of thousands of machine learning algorithms but almost no connection between the research and clinical application of these • Relatively small incremental improvements in fairly narrowly defined image analysis algorithms, e.g. mammography CAD, lung nodule detection, vascular stenosis analysis Where Are We in 2016? • Is there a generalized learning algorithm/program for imaging that could create a jumpstart to a major advance in diagnostic imaging? • Amazing advances in ML and AI in many domains high publicity • Lots of companies lately are claiming to have made that jump • How much is reality and how much is hype? Dedication: to João Louro 11 12 The Economist and Others Are Talking about the 4th Industrial Revolution Based on Cyber-Physical Systems The substitution of machinery for machine labour” may “render the population redundant The discovery of this mighty power” has come “before we knew how to employ it rightly” the Debate in early 1800s about industrial revolution in England Easy to Replace?! • Andrew Ng, renowned Stanford Professor and expert on machine learning was quoted in The Economist this week as saying “a highly trained and specialized radiologist may now be in greater danger of being replaced by a machine than his own executive assistant: She does so many different things that I don’t see a machine being able to automate everything she does any time soon.” Ezekiel Emanuel, PhD, MD, MSc • Gave keynote presentation at ACR 2016 – Faculty member at the Wharton School and School of Medicine at University of Pennsylvania – Founding chair of the Clinical Center of the National Institutes of Health – Former special advisor on health policy for the Office of Management and Budget. Ezekiel Emanuel, PhD, MD, MSc Keynote ACR 2016 Five Megatrends • • • • Decline in the use of hospitals More outpatient care More care in patients’ homes Fewer medical tests • Machine learning – “While all of these factors will shape the future landscape, machine learning will be the most pressing for radiology – Emanuel called the machine learning “the real threat to radiology.” • “The biggest barrier will not be technical but human willingness to accept machine based diagnoses.” Major “Inspiration”/”Motivation” for This Year’s 2016 Sam Dwyer Lecture • Visiting Professor at Hospital of University of Pennsylvania • CEO of well funded and well known start-up company in medical imaging space related that he wanted to (paraphrased) “get rid of the wasted protoplasm sitting in front of the workstation that was the radiologist and replace it with a much better and reliable and consistent alternative in the next few months” Stephen Hawking on AI • “Success in creating AI would be the biggest event in human history,” wrote Stephen Hawking in an op-ed, which appeared in The Independent in 2014. • “Unfortunately, it might also be the last, unless we learn how to avoid the risks. In the near term, world militaries are considering autonomous-weapon systems that can choose and eliminate targets.” Professor Hawking added in a 2014 interview with BBC, “humans, limited by slow biological evolution, couldn’t compete and would be superseded by A.I.” • Hawking told the BBC: “The primitive forms of artificial intelligence we already have, have proved very useful. But I think the development of full artificial intelligence could spell the end of the human race.” 19 Elon Musk • Elon Musk has spoken out against artificial intelligence (AI), declaring it the most serious threat to the survival of the human race to students from Massachusetts Institute of Technology (MIT) • “I think we should be very careful about artificial intelligence. If I had to guess at what our biggest existential threat is, it’s probably that. So we need to be very careful,” said Musk • “I’m increasingly inclined to think that there should be some regulatory oversight, maybe at the national and international level, just to make sure that we don’t do something very foolish.” Bill Gates • Microsoft co-founder Bill Gates has also expressed concerns about Artificial Intelligence • During a Q&A session on Reddit in January 2015, Mr. Gates said, “I am in the camp that is concerned about super intelligence. First the machines will do a lot of jobs for us and not be super intelligent. That should be positive if we manage it well • A few decades after that though the intelligence is strong enough to be a concern • I agree with Elon Musk and some others on this and don’t understand why some people are not concerned.” More Dangerous Than Nuclear Weapons? • Mr. Hawking recently joined Elon Musk, Steve Wozniak, and hundreds of others in issuing a letter unveiled at the International Joint Conference in Buenos Aires, Argentina • The letter warns that artificial intelligence can potentially be more dangerous than nuclear weapons. 22 Who Is Investing All Those Dollars in Artificial Intelligence? Investment in Artificial Intelligence • Ironically, given Elon Musk and Sam Altman’s concern that artificial intelligence will take over the world, the two entrepreneurs are putting more than a billion dollars into a not-for-profit company that will maximize the power of AI— and then share it with anyone who wants it • In an interview with Steven Levy of Backchannel about Open AI, Altman said they expect this decades-long project to surpass human intelligence • But they believe that any risks will be mitigated because the technology will be “usable by everyone instead of usable by, say, just Google.” Many Many AIs and Dr. Evil • They were asked whether their plan to freely share this technology would actually empower bad actors, if they would end up giving state-of-the-art AI to the Dr. Evils of the world. But they played down this risk • They feel that the power of the many will outweigh the power of the few. “Just like humans protect against Dr. Evil by the fact that most humans are good, and the collective force of humanity can contain the bad elements,” said Altman, “we think its far more likely that many, many AIs, will work to stop the occasional bad actors.” 25 AI/Machine Learning Basic Terms Deep Learning Falls Within Machine Learning Within AI Artificial Intelligence • Basically an umbrella term for a variety of applications and techniques • Artificial intelligence refers to "a broad set of methods, algorithms and technologies that make software 'smart' in a way that may seem humanlike to an outside observer” » Lynne Parker, director of the division of Information and Intelligent Systems for the National Science Foundation • John McCarthy, who coined the term “Artificial Intelligence” in 1956, complained that “as soon as it works, no one calls it AI anymore.” Artificial Intelligence • Machine learning, computer vision, natural language processing, robotics and related topics are all part of A.I. • Also referred to as “machine intelligence” or “computational intelligence” • Can distinguish different types of AI • When will AI Arrive? – It’s here already!!! Is There A General Equation for Winning at AI? • The action-value function is the maximum sum of rewards rt discounted by γ at time step t, achievable by a behavior policy Π=P(a|s), after making an observation (s) and taking an action (a) • Can be optimized using a Deep convolutional neural network • Key to winning at Atari Video games • Key to “happiness”? • Key to LIFE? Where is AI? Everywhere. My Monday Morning Diary • Wake up by iphone, One Dance/Drake • Arrive at work at VA Hospital • Check indoor temperature on Nest • Big stack of papers on desk to be signed-rummage through drawers to • Amazon Echo checks out weather and find pen and move papers from one traffic on the way to work and turns on side of the desk to the other the lights • Take 10 minutes to sign into EMR to • Google Now says flying to Portland check consults after waiting about tomorrow with itinerary • Take another 8 minutes to sign into • Set temperature in the Car on iphone PACS • Get read for work while Siri plays latest • Take 10 minutes to play messages on unread messages and e-mails phone machine • Car displays today’s schedule from • Grab stack of paper requisitions to Google calendar and goes on autopilot protocol and does 95% of driving to work autonomously Artificial Intelligence (Narrow) • Also referred to as Weak AI • AI that specializes in one area • There’s AI that can beat the world chess champion in chess, but that’s the only thing it does – Speech recognition – Translation – Self-driving cars – Siri, Alexa, Cortana, Google Now Artificial General Intelligence • Sometimes referred to as Strong AI, or Human-Level AI • Computer that is as smart as a human across the board—a machine that can perform any intellectual task that a human being can • Creating AGI is a much harder task than creating ANI, and we are nowhere near close to it Artificial General Intelligence (AGI) • Professor Linda Gottfredson describes intelligence as “a very general mental capability that, among other things, involves the ability to: – Reason – Plan – Solve problems – Think abstractly – Comprehend complex ideas – Learn quickly – Learn from experience” When Will AGI Arrive? • A study, conducted recently by author James Barrat at Ben Goertzel’s annual AGI Conference asked when participants thought AGI would be achieved—by 2030, by 2050, by 2100, after 2100, or never. The results: • By 2030: 42% of respondents • By 2050: 25% • By 2100: 20% • After 2100: 10% • Never: 2% Artificial Superintelligence • Oxford philosopher and leading AI thinker and author Nick Bostrom defines super-intelligence as “an intellect that is much smarter than the best human brains in practically every field, including scientific creativity, general wisdom and social skills.” Machine Learning • Also blanket term that covers multiple technologies • Doesn’t necessarily have to actually “learn” as we think of it and doesn’t necessarily provide feedback over time just refers to a class of statistical techniques to characterize, discover, classify data • Vast majority of these have been around for many years/decades Machine Learning • As a part of A.I., machine learning refers to a wide variety of algorithms and methodologies that can also enable software to improve its performance over time as it obtains more data • "Fundamentally, all of machine learning is about recognizing trends from data or recognizing the categories that the data fit in so that when the software is presented with new data, it can make proper predictions," (Parker) Neural Networks • Neural networks are a type of machine learning, and deep learning refers to one particular kind • Neural networks -- also known as "artificial" neural networks -- are one type of machine learning that's loosely based on how neurons work in the brain, though "the actual similarity is very minor” Neural Networks • There are many kinds of neural networks, but in general they consist of systems of nodes with weighted interconnections among them • Nodes, also known as "neurons," are arranged in multiple layers, including an input layer where the data is fed into the system; an output layer where the answer is given; and one or more hidden layers, which is where the learning takes place • Typically, neural networks learn by updating the weights of their interconnections Examples Neural Network Types Types of Neural Networks: Autoencoder • Autoencoder is a simple 3-layer neural network where output units are directly connected back to input units. • Relatively simple and intuitive Restricted Boltzman Machine • Intuition behind RBMs is that there are some visible random variables (e.g. film reviews from different users) and some hidden variables (like film genres or other internal features), and the task of training is to find out how these two sets of variables are actually connected to each other Convolutional Neural Networks • Like Autoencoders and RBMs- translate many low-level features (e.g. user reviews or image pixels) to a compressed high-level representation (e.g. film genres or edges) - but now weights are learned only from neurons that are spatially close to each other. • CNNs are very specifically optimal for image recognition. Most of the top-level algorithms in image recognition are somehow based on CNNs today Purpose of These Neural Networks is Dimensionality Reduction • Autoencoders and RBMs both take a vector in nndimensional space they translate it into an mmdimensional one, trying to keep as much important information as possible and, at the same time, remove noise • If training of autoencoder/RBM was successful, each element of resulting vector (i.e. each hidden unit) represents something important about the object - shape of an eyebrow in an image, genre of a film, field of study in scientific article, etc. • You take lots of noisy data as an input and produce much less data in a much more efficient representation Neural Networks Used for Pretraining then Other Classifier Used • None of models mentioned here work as classification algorithms per se • Instead, they are used for pre-training learning transformations from low-level and hard-to-consume representation (like pixels) to a high-level one • Once deep (or maybe not that deep) network is pretrained, input vectors are transformed to a better representation and resulting vectors are finally passed to real classifier (such as SVM or logistic regression) Deep Learning Neural Networks Deep Learning • Deep learning refers to what's sometimes called a "deep neural network," or one that includes a large system of neurons arranged in several hidden layers – A "shallow" neural network, by contrast, will typically have just one or two hidden layers. • The idea behind deep learning is not new, but it has been popularized more recently because we now have lots of data and fast processors that can achieve successful results on hard problems Commonly Used Machine Learning Techniques • Regression techniques • Neural networks • Support vector machines • Decision trees • Bayesian belief networks • k-nearest neighbors • Self-organizing maps • Case-based reasoning • Instance-based learning Machine Learning Vs. Data Mining • Machine learning focuses on prediction, based on known properties learned from the training data. • Data mining focuses on the discovery of (previously) unknown properties in the data Machine Learning vs. Optimization •Optimization algorithms can minimize the loss on a training set •Machine learning is concerned with minimizing the loss on unseen samples Machine Learning and Statistics and “Statistical Learning” • Machine learning and statistics are closely related fields and machine learning can be considered a statistical technique • Leo Breiman distinguished two statistical modeling paradigms: data model and algorithmic model, wherein 'algorithmic model' means more or less the machine learning algorithms like Random forest • Some statisticians have adopted methods from machine learning, leading to a combined field that they call statistical learning What is Deep Learning? • DL consists of multiple hidden layers in an artificial neural network • This approach tries to model the way the human brain processes light and sound into vision and hearing • Two very successful applications of deep learning are computer vision and speech recognition • Falling hardware prices and the development of GPUs for personal use in the last few years have contributed to the development of the concept of Deep Learning (DL) Deep Learning vs. Machine Learning 56 ImageNet Large Scale Image Recognition Challenge Started in 2010 • Computers have always had trouble identifying objects in real images so it is not hard to believe that the winners of these competitions have always performed poorly compared to humans. • But all that changed in 2012 when a team from the University of Toronto in Canada entered an algorithm called SuperVision, which wiped the floor with the opposition. SuperVision • SuperVision, for example, consists of some 650,000 neurons arranged in five convolutional layers • It has around 60 million parameters that must be finetuned during the learning process to recognize objects in particular categories. 61 Speech Recognition Deep Learning Breakthrough Human Vision: The Hardest Task for Computers? Introduced by Alan Turing in his 1950 paper “Computing Machinery and Intelligence” Opens with the words “I propose to consider the question, ‘Can machines think?” Asks whether a computer could fool a human being in another room into thinking it was a human being Modified Dr. Watson Turing Test might ask: Can a computer fool a human being into thinking it was a doctor? What’s Wrong with this Picture? Ultimate Challenge: Medical Imaging Scientific American June 2011 Testing for Consciousness Alternative to Turning Test Highlights for Kids “What’s Wrong with this Picture?” Christof Koch and Giulio Tononi Imaging May Be Ultimate/Future Frontier For “AI” Software Machine Learning Algorithms: Like Standards, So Many to Choose From! Can We Apply Those Incredible Advances in Object Recognition to Diagnostic Radiology? • These image challenges have used 24 big “RGB” color images with no experience with gray scale imaging in medicine • They can identify a chair but can’t tell if it’s – – – – – – Broken Something is missing Something extra is there Comfortable Beautiful or ugly Dirty or clean • Black box – Can’t explain why something is identified as abnormal • Adrenal challenge 5th Grader– Need to know anatomy “Magic” Aspect of Deep Learning • One major challenge is that we don’t understand what’s inside black box of deep learning when it solves a visual recognition challenge • Don’t need deep learning for Tic Tac Toe or Checkers or even chess because we can use combination of brute force to look at every possible move (chess out to 20 to 30 or more moves and further at the end game) • But game like Go or playing video games, can’t do brute force but can learn by trial and error even though black box without understanding of why, like magic • No general purpose learning system for diagnostic imaging like we train our residents • Our eyes and brains have evolved to detect patterns and our knowledge of medicine, physiology, a priori likelihood of disease and recognition of trends evolved over millions of years Challenges for Machine Learning Algorithms • Which to choose from? • How do evaluate different machine learning algorithms and determine which is most efficient for a particular problem? • Black box? • How to optimize parameters? – Practical Beyesian Optimization Machine Learning • Computational Time • Very specific MLA’s do a good job at different tasks which makes it difficult to select a single one as a generalized deep AI approach for image analysis or for data analysis • Problems with High Dimensional Datasets like electronic medical record requires different approach Applications of “Machine Learning” in Medical Imaging These Machine Learning Techniques Have Been Utilized in Imaging for Decades With Tens of Thousands of Published Papers 10,000s of Narrow Machine Learning Applications in Medicine Challenge is Binding these together and can one develop general learning theory? • Fracture detection • Brain hemorrhage • Mammography • MS diagnosis and quantification • Bone age determination • Lung nodule detection • Liver mass determination • Meniscal tear • Brain segmentation and diagnosis • Bone mineral density on CT • Carotid stenosis evaluation • Coronary Artery stenosis evaluation • Cardiac function evaluation Eliot Siegel, M.D. Prof. and Vice Chair University of Maryland Chief Imaging VA Maryland Healthcare System Black Box of CAD • The “black box” nature of CAD is seen as a substantial issue by many radiologists • If my residents and fellows told me they thought this right upper nodule was cancer and I asked why and they wouldn’t say why or how confident they were, I’d: – Be less confident – Be suspicious about their analysis – Be frustrated What Made You Circle the Lesion? • Lesion size • Lesion morphology (shape: smooth, spiculated) • Density distribution (solid, ground glass, partially calcified) • Location (subpleural, which lobe) • Connectedness (is it connected to vessels or other structures?) Level of Confidence and Quality of Evidence • What was your level of confidence in the magic box formula of the above that made you circle it? – Did it have to meet size, morphology, density and connectedness or even location characteristics – What database did you use to determine level of suspicious of cancer and how many cases were in it or was it based on expert opinion? • 10 • 100 • 1000 • 10,000 • More? Left Upper Lobe Lung Nodule CAD is Pretty Sure It’s There CAD is Not So Confident Where Are We Today With Clinical Use of CADe? • Mammography is far and away the most utilized application • But what do radiologists really think of Mammography CAD? Is CAD gaining momentum in clinical practice? – It seems to be happening too slowly, more slowly so than most of us had anticipated – In cases (unlike mammography) where there is no reimbursement for CAD, the radiologists and practices are feeling that their margins are low enough and there is major pressure related to decreased reimbursement and the impression that reimbursement will continue to drop • Difficult to make business case for added expenditure for CAD to radiologists Is CAD Gaining Momentum In Clinical Practice? – There is much skepticism among my colleagues about the added value of CAD and many only use it for mammography because of the reimbursement model – Colleagues will not pay any significant amount for say, CAD lung nodule detection for chest radiography even with a hypothetical scenario of a 10 or even 20% increase in sensitivity – I believe that they would pay more for something that increased their efficiency and productivity than their accuracy MATERIALS AND METHODS: • Separate links to an online survey were posted on the website of the Society of Breast Imaging and circulated to subscribers of Diagnostic Imaging.com, in order to evaluate opinions regarding CAD use and its underlying legal issues RESULTS: Use and Reliance on CAD? • 89% indicated they always use CAD when reading screening mammograms • 4% indicated that they rarely or never use CAD Use and Reliance on CAD and Reimbursement • However the extent to which clinicians are relying on CAD to provide an accurate diagnosis is split – 2% indicated that they always rely on CAD to provide an accurate diagnosis – 49% indicated they sometimes rely on CAD – 49% clinicians rarely or never rely on CAD – It is likely that the mismatch between use of and reliance on CAD relates to the reimbursements ($12, or $1000 per approximately 83 cases or $2,400 per day for 200 screening mammograms) radiologists receive when using CAD RESULTS: Use and Reliance on CAD? § Most radiologists have not changed a read based on the results of CAD § Only 2% indicated they alters their opinion after CAD § 36% sometimes change interpretation based on CAD § 61.7% rarely or ever change their interpretation based on CAD Use and Reliance on CAD • 15% found that CAD was often helpful • 49% considered it sometimes helpful 36% considered it rarely or never helpful What Do I Need from Next Generation CAD Clinically? • Improve efficiency/productivity • Increases my accuracy/reliability without compromising efficiency • Affordable • Increases my confidence • Allows me to measure things I couldn’t measure otherwise such as liver or pulmonary “texture” • Provide Imaging “Physical Exam” Next Generation of CAD • The next generation of CAD will reflect the trend toward big data and personalized medicine and shift away from the current second reader approach and toward one in which CAD algorithms increasingly serve as visualization and image measurement/annotation and quantification tools – Examples of probability maps rather than just binary yes and no and FDA requirements shaped the second reader – Tracking lesions over time – Highlighting certain types of findings to draw attention to the reader CAD Tools Requirements and Challenges • CAD applications must be able to be integrated into the image acquisition, display and interpretation workflow • They will not be adopted if they constrain the throughput of the radiologist • Need high level of accuracy in a single patient, need to more than just demonstrate efficacy in separating two groups • Commercialization and U.S. Food and Drug Administration (FDA) clearance is a big hurdle and needs to be revisited Next Generation CAD Apps Store for CAD Algorithms? • Want to be able to utilize all of these on a single platform, e.g. using API specified by DICOM working group 23 • Would like to see business ecosystem such as GRID that could allow users to have a payment model for these so you could download algorithm on the fly or send images up to a web service or could get consensus from multiple CAD programs Israeli StartUp • Platform to create and integrate a variety of algorithms to test against 12 million anonymized, indexed and catalogued imaging studies • Supports multiple coding languages and libraries, including Machine Learning Convolutional Network libraries such as Torch, Cafe and Theano, image processing libraries • All work is saved and projects can be collaborated on by several users • In addition, provide high end, dedicated GPUs and CPUs to run algorithms Second Start-up Company Creates Preliminary Report for Chest CT IBM Medical Sieve Recommendations for CAD • I believe the FDA has often limited the challenges to CAD as a second reader rather than as a tool that can be toggled on and off – Would like to see highlighted images like a spell checker that could also color code probability that a finding is real/confidence of the CAD algorithm – I’d like to see CAD to do image recognition before a study is reviewed as screening for things such as rib fractures, compression spine fractures, pneumothorax, etc. the equivalent of an imaging physical exam Applying Human Vision Research to CAD Adrenal Challenge • Challenge: –Can any CAD program find the adrenals as well as you could teach an 8 year old child in ten minutes? –I have never seen anyone successfully tackle the problem of finding the adrenals –This would have substantial value MACHINE LEARNING AND AI FOR LUNG NODULE SCREENING Eliot Siegel, MD, FACR Prof/Vice Chair IS Univ. Maryland Five Levels IT Decision Support for Lung Nodule Screening 1. Radiologist interprets nodule based on clinical experience and makes measurement and report 2. Radiologist interprets study based on LungRADS criteria and reports score after looking up information on paper or online 3. Radiologist has Lung-RADS criteria available and EMR/PACS automatically pulls up required information to make it easy and in one place Five Levels IT Decision Support for Lung Nodule Screening With Mr. Akami Example 4. PACS brings up lung rads criteria in the context of interpretation automatically with ACR Assist with data automatically classified according to template 5. Finally, Automatic click on nodule initiates search of database such as NLST which then finds similar patients, categorizes based on risk of a specific cohort based on detailed nodule and patient information, utilizes a priori probability based on PLCO and combines those for patient specific probability of disease and then also maps out to LungRads ACR Assist: Future Automated Reporting Using Template Directly to Report and Registry Standa rds Commi ttee Structured Content Structured Input Evidence-Based XML Encoding Algorithms Actionable ReportsCritical Test Results Mgmt Structured Output Integrating Workflow Registries Advanced Decision Support in Action: Your Next Door Neighbor Mr. Akami • Your next door neighbor and friend, • • • • Mr. Akami, a 62 year old native Hawaiian smoker with COPD who gets admitted for an elective Bunionectomy 7 mm spiculated soft tissue density left lower lobe nodule is discovered on “routine” pre-op exam and confirmed on CT with no other abnormalities What is the likelihood that it is malignant? How should this nodule be followed up? Do we have tools at the workstation while reporting to help apply the ACR LungRads criteria to help out the radiologist? National Lung Screening Trial Dataset and Decision Support Project Taking Personalization to the Next Level Beyond LungRads Reporting Tool • Can we personalize the ACR Lung Rads criteria • • • • • using data from the National Lung Screening Trial? Could the criteria for follow-up be refined and personalized more than high risk smoker vs. lower risk patient based on: Geographic location? Patient age/sex? Characteristics of nodule e.g. shape (spiculated or smoothly rounded), containing calcification? Presence of additional nodules? National Lung Screening Trial (NLST) 26,721 participants 32,289 nodules Searching By Cohort Match 5% of Nodules for Males 60 to 65 that were 5-7mm were Malignant N/A 0 <1 1, 2 % 13 2% 4A 515% >15% 4B Mr. Akami category 3 suggesting 1-2% prob. of malignancy with 6 6 0 2 9 5 4 8 1 Next Phases of NLST Analysis • Problem with cohort analysis is that cohorts get small very quickly with increasing number of variables • Linear regression analysis • Look up formula for linear regression from literature • More advanced multi-regression analysis would come closer to being the best fit • Bayesian Approach • Machine learning algorithm even better such as • Support Vector Machine • Many other machine learning possibilities • Deep Learning Now Add Nodule Shape Matching To Further Personalize and Refine Accuracy Next Step: Pixel Analysis NLST Images Statistics Features Shape Features 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 1. 2. 3. 4. 5. Center Of Gravity Histogram Kurtosis Maximum Maximum Index Mean Median Minimum Minimum Index Skewness Standard Deviation Sum Variance Weighted Elongation Weighted Flatness Weighted Principal Axes Weighted Principal Moments 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Bounding Box Centroid Elongation Equivalent Ellipsoid Diameter Equivalent Spherical Perimeter Equivalent Spherical Radius Feret Diameter Flatness Number Of Pixels Number Of Pixels On Border Perimeter Perimeter On Border Perimeter On Border Ratio Physical Size Principal Axes Principal Moments Roundness Extract Nodules and Then Apply One of A Wide Variety of Machine Learning Algorithms Especially Convolutional Neural Network PLCO Dataset PLCO Dataset “Instant Research” Personalized Clinical Care 122 PLCO Participants Who Qualify for NLST 123 Creating Local/Regional Databases from Clinical Data • Would also like to be able to collect data at the University of Maryland, within the Department of Veterans Affairs Hospitals in Maryland and then nationally that could establish a similar database • Then could provide report that gave reference database such as NLST with likelihood of malignancy and also gave local reference to a specific population and then taking into account PLCO data NLST and PLCO Next Steps • Huge implications for screening, e.g. reduce cost from over $200,000 per life saved for smokers over 50 years old to a lower cost for a higher risk cohort for screening studies • PLCO use has major implications for Bayesian pretest probability data to assist in diagnosis • Working with multiple vendors, demonstrating ability to incorporate this into the workflow with ability to “click” on nodule and then have automated lesion characterization, lookup from EMR and then access reference database “service” to get information about likelihood of malignancy 126 • Would like to incorporate these data into routine applications such as CAD software that could take a priori probability of disease to help to CADx in addition to current CADe, e.g. if patient had prior breast cancer CAD should “realize” odds of another breast cancer higher and adjust accordingly • Would like to create on the fly statistical/machine learning models rather than just finding similar patients in databases such as NLST or PLCO 127 • IT is becoming increasingly critical to the success of today’s practice of radiology and is especially critical as we move to implement the complex process that is associated with Lung Cancer Screening • Clinical decision support tools are evolving from the current state of the art to next generation and beyond systems that will allow us to take care of patients such as Mr. Akami in an increasingly safe and effective manner • This will allow us to maximize the likelihood that our CT screening studies will save lives and reduce morbidity associated with lung cancer 128 129 130 Professor University of Maryland School of Medicine Chief Imaging VAMHCS Adjunct Professor Computer Science UMBC Board Scientific Counselors National Library of Medicine What is ORiGAMI ? An Artificial Intelligence Workflow for Discovering Novel Associations in Massive Medical Knowledge Graphs ORiGAMI under the hood ORiGAMI: Case “Patient as Art” This patient, like the artist who made her famous, was a “cripple and an outsider,” though she was not always so. She began life as a small, blond-haired girl with a “silver giggle,” who seemed no different from other children. However, by the time she reached the age of three, she was walking on the outside of her feet with an odd gait. Even so, she was a bright, fiercely determined child, who stomped around ignoring her disability as it gradually increased in severity. By the time she was 13, she stumbled and fell frequently, though with a mind so “bright, curious and hungry,” her teacher had hopes that she too would one day be a teacher. The patient, if not beautiful at age 19, was slim and handsome enough to attract a suitor, who claimed that during their brief courtship, she could do anything–“row a boat, climb a tree, harness a horse, and drive a carriage.” Her letters at that time, however, told a different story, one involving a series of “bad falls.” Her one and only suitor vanished from her life as suddenly as he had appeared. The patient’s balance soon worsened to the point that it was unsafe for her to look up without having a firm grip on something for steadiness. Although she was still able to walk, her crablike gait forced her to use the entire width of the road when ambulating. Her mother made her kneepads to wear under her skirt as protection against her many falls. Her hands, as yet unaffected, were capable of the intricate work of a talented seamstress. By the time she reached 26, the patient could walk only three or four steps without assistance, and her hands had become so misshaped and unsteady she had to her wrists, elbows, and knees to do those things formerly done with her hands. Offers of help were gently but firmly refused. By the end of her fifth decade, she had lost the ability to stand and resorted to crawling to get where she wanted to go. Her mind continued to be as sharp as ever. No neurological disorders are known to have affected other members of the patient’s family. Her father was a Swedish sailor with a disabling arthritis, who died at age 72 of unknown cause. Her mother developed kidney disease in her 40s and died edematous at age 68 of either renal failure or congestive heart failure. There were three brothers, one who died in his 80s of metastatic bone cancer. The medical histories of the other two are unknown. The patient was evaluated medically just once, when she was 26, at the Boston City Hospital. After a week of observation and tests failed to produce a diagnosis, she was told “to just go on living as [she] had always done. When the patient was 56, she developed a severe illness thought to have been pneumonia. One evening, while recuperating, she sat with one leg stretched out beneath a stove and fell asleep. When she awoke, the heat from the fire had seared the flesh from her withered leg. The third-degree burn healed slowly in response to repeated application of cod liver oil. At age 74, the patient finally consented to the use of a wheelchair and died shortly thereafter. ORiGAMI: Natural Language Processing This patient, like the artist who made her famous, was a “cripple and an outsider,” though she was not always so. She began life as a small, blond-haired girl with a “silver giggle,” who seemed no different from other children. However, by the time she reached the age of three, she was walking on the outside of her feet with an odd gait. Even so, she was a bright, fiercely determined child, who stomped around ignoring her disability as it gradually increased in severity. By the time she was 13, she stumbled and fell frequently, though with a mind so “bright, curious and hungry,” her teacher had hopes that she too would one day be a teacher. The patient, if not beautiful at age 19, was slim and handsome enough to attract a suitor, who claimed that during their brief courtship, she could do anything–“row a boat, climb a tree, harness a horse, and drive a carriage.” Her letters at that time, however, told a different story, one involving a series of “bad falls.” Her one and only suitor vanished from her life as suddenly as he had appeared. The patient’s balance soon worsened to the point that it was unsafe for her to look up without having a firm grip on something for steadiness. Although she was still able to walk, her crablike gait forced her to use the entire width of the road when ambulating. Her mother made her kneepads to wear under her skirt as protection against her many falls. Her hands, as yet unaffected, were capable of the intricate work of a talented seamstress. By the time she reached 26, the patient could walk only three or four steps without assistance, and her hands had become so misshaped and unsteady she had to use her wrists, elbows, and knees to do those things formerly done with her hands. Offers of help were gently but firmly refused. By the end of her fifth decade, she had lost the ability to stand and resorted to crawling to get where she wanted to go. Her mind continued to be as sharp as ever. No neurological disorders are known to have affected other members of the patient’s family. Her father was a Swedish sailor with a disabling arthritis, who died at age 72 of unknown cause. Her mother developed kidney disease in her 40s and died edematous at age 68 of either renal failure or congestive heart failure. There were three brothers, one who died in his 80s of metastatic bone cancer. The medical histories of the other two are unknown. The patient was evaluated medically just once, when she was 26, at the Boston City Hospital. After a week of observation and tests failed to produce a diagnosis, she was told “to just go on living as [she] had always done. When the patient was 56, she developed a severe illness thought to have been pneumonia. One evening, while recuperating, she sat with one leg stretched out beneath a stove and fell asleep. When she awoke, the heat from the fire had seared the flesh from her withered leg. The third-degree burn healed slowly in response to repeated application of cod liver oil. At age 74, the patient finally consented to the use of a wheelchair and died shortly thereafter. Case: “Patient as Art” – Christina’s World No mental health issues Family history: Arthritis , Kidney Disease, Bone Cancer Swedish/Scandinavian Blonde Hair Odd Gait Misshaped hands Fell Frequently Crab-like Gait Third-degree burn Lost ability to stand Pneumonia Age Birth 3 13 19 26 50 56 74 Death Relevance Mapping and Disambiguation Case Re-annotation Patient ‘Is a’ Female. Patient ‘Has’ Blonde Hair Patient ‘became’ Crippled Patient ‘is’ Scandinavian . . Disease ‘Affects’ Patient Disease ‘Is a’ Degenerative Disorder Disease ‘Is a’ Neuromuscular Disease . . . . . Disease ‘Affects’ Child Disease ‘Affects’ Women Disease ‘Affects’ Gait Disease ‘Causes’ Standing Pain Disease ‘Co-exists with’ Distal Muscle Weakness Patient has normal childhood Google Search Step 1: Automatic Case-Context Generation Step 2: Reasoning with N-ary associations Neuromuscular disease - Distal muscle weakness Gait - Distal muscle weakness Gait abnormality - Falls frequently Step 3: Hypothesis from Random Walks Case vs. Control Random Walk Disease Symptom Hypothesis / Results – Charcot Marie Tooth Not Polio as in Art/History Books Hypothesis Probability Hereditary Motor and Sensory Neuropathies Category Charcot Marie Tooth Disease 1 Welander Distal Myopathy (common in Sweden) 2 Fasciitis Plantar Talocalcaneal coalition Cerebellar atrophy Friedreich Ataxia Hypolipoproteinemia Multi infarct state Neuroleptic Induced Parkinson Quadriplegic spastic cerebral palsy Subcortical vascular encephalopathy Base probability for random disease : 1e-6 Mining for potential causes and credibility Evaluating relevance to weak observations Blonde_hair CAUSES Tyrosinase_related COEXISTS (Rev) _protein_1 WITH SCANDINAVIAN PART OF (Rev) 9p21 PART_OF PER2_protei COEXIST n__mammali S WITH an (Rev) 11q22 CAUSES MTMR2 ASSOCIATED Charcot_Marie_Toot WITH h_Disease Charcot_Marie_Tooth_Disease Opening up previous year cases… Character Diagnosis (Expert) ORiGAMI Hypothesis 2014 – Oliver Cromwell Malaria, Typhoid, Salmonella infection Malaria, Sepsis, Urinary Tract Infection 2006 – Booker T. Washington Nephrosclerosis, Hypertensive cardiomyopathy Acute congestive heart failure, atrial flutter 2004 – Schliemann Temporal lobe abscess/ exostoses of the external auditory canal, Post-operative meningitis Actinomycotic brain abscess, Enterovirus Infection 2002 – Herod Uremia complicated by Fournier gangrene, Generalized atherosclerosis/hypertension Fournier Gangrene, Deep Vein Thrombosis, Pulmonary Edema 2001 - Claudius Congenital dystonia/Amanita mushroom poisoning, Atherosclerosis Sclerosing lipogranuloma, Acute toxic hepatitis 2000 – Mozart Acute rheumatic fever, poststreptococcus equiglomerulonephritis Fever disorder, Legionnaires disease 2003 – Florence Nightingale Bipolar disorder, PTSD, (Heart failure/old age) Vascular dementia, atrial flutter, high pressure neurological syndrome Top results listed…. Lessons Learned • Positive Bias in Literature – Not enough negations (elimination) in literature • Fusion of Data (Statistics) and Meta-Data (Text) – Quality of publication, size of control group, etc. • Disambiguation terminology and resolution with hierarchies in – Can be handled with advanced computing architectures • Mapping of Spoken-English to Medical-Speak – Solvable in the near future with “deep learning” techniques that translate languages today. Major Advances in Non-Medical Artificial Intelligence Nature February 2015 Groundbreaking Article Closest So Far to AI for Radiology? 150 The Atlantic March 28, 2016 “Go” Was Called the “Holy Grail” of AI Not Achievable for Another Decade How Google’s AlphaGo Beat Lee Sedol • Most major South Korean television networks are carrying the game. In China, 60 million people are tuning in • A few hundred members of the press are in adjacent rooms, watching the game alongside expert commentators • Potential board positions: • 208,168,199,381,979,984,699,478,633,344,862,770,2 86,522,453,884,530,548,425,639,456,820,927,419,61 2,738,015,378,525,648,451,698,519,643,907,259,916, 015,628,128,546,089,888,314,427,129,715,319,317,5 57,736,620,397,247,064,840,935 more than atoms in the Universe Go • Before the match, Lee claimed that the challenge wasn’t whether he would beat AlphaGo, but whether it would be 5-0 or 4-1 • Other Korean players stated that it was the easiest million dollars a top level player could make • Lee goes on to lose Game 1, resigning after 186 moves • In game 2 AlphaGo plays a move 37 after which Lee walks out of the room, he resigns after 211 moves • After losing game 3, Lee apologizes to the entire world, “I apologize for being able to satisfy a lot of people’s expectations” • Lee went on to win game 4 with a “hand of God” move at turn 78 and then lose game 5 using the same strategy Does Artificial Intelligence Just Emerge With Enough Speed and Memory? • When Mike was installed in Luna, he was pure thinkum, a flexible • logic--"High-Optional, Logical, Multi-Evaluating Supervisor, Mark IV, • Mod. L"--a HOLMES FOUR. He computed ballistics for pilotless freighters • and controlled their catapult. This kept him busy less than one percent • of time and Luna Authority never believed in idle hands. They kept • hooking hardware into him--decision-action boxes to let him boss other • computers, bank on bank of additional memories, more banks of • associational neural nets, another tubful of twelve-digit random numbers, • a greatly augmented temporary memory. Human brain has around ten-to-the tenth neurons. By third year Mike had better than one and a half times that number of neuristors. • And woke up. • He winked lights at me. "Hello, Man." • "What do you know?" • He hesitated. I know--machines don't hesitate. But remember, Mike was designed to operate on incomplete data. Lately he had reprogrammed himself to put emphasis on words; his hesitations were dramatic. Maybe he spent pauses stirring random numbers to see how they matched his • Memories. • "'In the beginning,'" Mike intoned, "God created the heaven and the earth. And the earth was without form, and void; and darkness was upon • the face of the deep. And--'" • "Hold it!" I said. "Cancel. Run everything back to zero.” Can We Really Trust Deep Learning Algorithms to Drive or Practice Medicine? How Do We Debug Them? But Could AI Ever Be Creative? If equal to human which human? Prehistoric Man Me? Tanveer, Khan, and Rasu? Wired Magazine Conclusion Reasons Why Radiologists Won’t be Replaced Any Time Soon • There are tens of thousands of algorithms that have been developed for image analysis and decision support over the past 30 years and for the most part none are in clinical practice • In order to replace a radiologist, someone would have to find the best of these and consolidate them into a package that could work independently (unsupervised) for image review but these are written in different “languages” with different assumptions about the images • Each of these algorithms is generally super narrow, so in order to replace a radiologist, one would have to have a general portfolio that did everything all specialists do currently • The work on computer vision recognizing water bottles in an image database is fundamentally different from diagnostic images including the fact that the images are 24 bit color (8 bit) and that there is no algorithm or methodology that is comparable for these image challenges for diagnostic radiology • Assuming you had all of these available and somehow integrated you would then have to start getting FDA approval which could take another 30 years for each and every one given resources and rate of approval of software • Let’s assume that you actually discovered/created a program so “smart” that it could read textbooks and journal articles and review prior images on PACS and reports in the EMR and that it actually was better than any subspecialty radiologist at all tasks (far fetched from today’s reality) • If so, then how would you test it to make sure it had knowledge in all of those areas satisfactorily Will Computers Replace Radiologists Soon? • How long would it take to complete those tests? Years? • • • • • Decades? We barely know how to test humans in these areas. How long would it take to get the datasets ready to train these How long would it take to get FDA approval for these What would be the medico-legal issues associated with implementation of these? How long would it take people to purchase these and what would they cost given the cost of development? Much more likely incremental changes that will be informed by machine learning Incredibly Exciting Potential for Machine Learning in Medicine and Diagnostic Imaging • Intelligent screening criteria for mammography, lung cancer, and other • • • • • • • • • • cancers including genomic/liquid biopsy data and other lab info Patients at risk for contrast Automatic protocoling of studies Smart PACS hanging protocols and synchronization protocols Smart transfer of findings from workstation to speech recognition Assessment of patients at high risk to have positive findings (or low risk) Communication and tracking of findings Multiparametric analysis across multiple modalities Improved departmental efficiency with decreased waiting times Dose optimization Quality improvement in scanning • So I’m here to tell all of the “worthless protoplasm” that are radiologists and the rest of you human beings that you can continue to ingest food, reproduce, and create waste products without fear of being replaced by computers, at least in radiology, any time soon! 170 And Finally, It’s Not Easy To Tweet Like a Human: Microsoft Bot 171 172 173 Conclusions: So João • Finish your residency • Lots of work to do before we have a general ML, DL, AI program that can learn radiology conceptually, rapidly, like radiology resident • Loads of low hanging fruit for machine learning techniques that we should be pursuing much more aggressively now Humans Have Been Around 1 minute 17 seconds - Computers closer to a Millisecond. Who Knows What Will Happen in the Next Microsecond?! Summer Reading? 176 Coming Events • SIIM AI Conference and potential role of SIIM with Dr. Brad Erickson • Debate at RSNA about whether radiologists will be replaced in 20 years also Dr. Bradley Erickson Eliot Siegel, MD, FSIIM, FACR Professor of Radiology University of Maryland School of Medicine Chief Imaging Services, VA Maryland Healthcare System