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      Teaching AI to ask clinical questions

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      Physicians often query a patient’s electronic health record for information that helps them make treatment decisions, but the cumbersome nature of these records hampers the process. Research has shown that even when a doctor has been trained to use an electronic health record (EHR), finding an answer to just one question can take, on average, more than eight minutes.

      The more time physicians must spend navigating an oftentimes clunky EHR interface, the less time they have to interact with patients and provide treatment.

      Researchers have begun developing machine-learning models that can streamline the process by automatically finding information physicians need in an EHR. However, training effective models requires huge datasets of relevant medical questions, which are often hard to come by due to privacy restrictions. Existing models struggle to generate authentic questions — those that would be asked by a human doctor — and are often unable to successfully find correct answers.

      To overcome this data shortage, researchers at MIT partnered with medical experts to study the questions physicians ask when reviewing EHRs. Then, they built a publicly available dataset of more than 2,000 clinically relevant questions written by these medical experts.

      When they used their dataset to train a machine-learning model to generate clinical questions, they found that the model asked high-quality and authentic questions, as compared to real questions from medical experts, more than 60 percent of the time.

      With this dataset, they plan to generate vast numbers of authentic medical questions and then use those questions to train a machine-learning model which would help doctors find sought-after information in a patient’s record more efficiently.

      “Two thousand questions may sound like a lot, but when you look at machine-learning models being trained nowadays, they have so much data, maybe billions of data points. When you train machine-learning models to work in health care settings, you have to be really creative because there is such a lack of data,” says lead author Eric Lehman, a graduate student in the Computer Science and Artificial Intelligence Laboratory (CSAIL).

      The senior author is Peter Szolovits, a professor in the Department of Electrical Engineering and Computer Science (EECS) who heads the Clinical Decision-Making Group in CSAIL and is also a member of the MIT-IBM Watson AI Lab. The research paper, a collaboration between co-authors at MIT, the MIT-IBM Watson AI Lab, IBM Research, and the doctors and medical experts who helped create questions and participated in the study, will be presented at the annual conference of the North American Chapter of the Association for Computational Linguistics.

      “Realistic data is critical for training models that are relevant to the task yet difficult to find or create,” Szolovits says. “The value of this work is in carefully collecting questions asked by clinicians about patient cases, from which we are able to develop methods that use these data and general language models to ask further plausible questions.”

      Data deficiency

      The few large datasets of clinical questions the researchers were able to find had a host of issues, Lehman explains. Some were composed of medical questions asked by patients on web forums, which are a far cry from physician questions. Other datasets contained questions produced from templates, so they are mostly identical in structure, making many questions unrealistic.

      “Collecting high-quality data is really important for doing machine-learning tasks, especially in a health care context, and we’ve shown that it can be done,” Lehman says.

      To build their dataset, the MIT researchers worked with practicing physicians and medical students in their last year of training. They gave these medical experts more than 100 EHR discharge summaries and told them to read through a summary and ask any questions they might have. The researchers didn’t put any restrictions on question types or structures in an effort to gather natural questions. They also asked the medical experts to identify the “trigger text” in the EHR that led them to ask each question.

      For instance, a medical expert might read a note in the EHR that says a patient’s past medical history is significant for prostate cancer and hypothyroidism. The trigger text “prostate cancer” could lead the expert to ask questions like “date of diagnosis?” or “any interventions done?”

      They found that most questions focused on symptoms, treatments, or the patient’s test results. While these findings weren’t unexpected, quantifying the number of questions about each broad topic will help them build an effective dataset for use in a real, clinical setting, says Lehman.

      Once they had compiled their dataset of questions and accompanying trigger text, they used it to train machine-learning models to ask new questions based on the trigger text.

      Then the medical experts determined whether those questions were “good” using four metrics: understandability (Does the question make sense to a human physician?), triviality (Is the question too easily answerable from the trigger text?), medical relevance (Does it makes sense to ask this question based on the context?), and relevancy to the trigger (Is the trigger related to the question?).

      Cause for concern

      The researchers found that when a model was given trigger text, it was able to generate a good question 63 percent of the time, whereas a human physician would ask a good question 80 percent of the time.

      They also trained models to recover answers to clinical questions using the publicly available datasets they had found at the outset of this project. Then they tested these trained models to see if they could find answers to “good” questions asked by human medical experts.

      The models were only able to recover about 25 percent of answers to physician-generated questions.

      “That result is really concerning. What people thought were good-performing models were, in practice, just awful because the evaluation questions they were testing on were not good to begin with,” Lehman says.

      The team is now applying this work toward their initial goal: building a model that can automatically answer physicians’ questions in an EHR. For the next step, they will use their dataset to train a machine-learning model that can automatically generate thousands or millions of good clinical questions, which can then be used to train a new model for automatic question answering.

      While there is still much work to do before that model could be a reality, Lehman is encouraged by the strong initial results the team demonstrated with this dataset.

      This research was supported, in part, by the MIT-IBM Watson AI Lab. Additional co-authors include Leo Anthony Celi of the MIT Institute for Medical Engineering and Science; Preethi Raghavan and Jennifer J. Liang of the MIT-IBM Watson AI Lab; Dana Moukheiber of the University of Buffalo; Vladislav Lialin and Anna Rumshisky of the University of Massachusetts at Lowell; Katelyn Legaspi, Nicole Rose I. Alberto, Richard Raymund R. Ragasa, Corinna Victoria M. Puyat, Isabelle Rose I. Alberto, and Pia Gabrielle I. Alfonso of the University of the Philippines; Anne Janelle R. Sy and Patricia Therese S. Pile of the University of the East Ramon Magsaysay Memorial Medical Center; Marianne Taliño of the Ateneo de Manila University School of Medicine and Public Health; and Byron C. Wallace of Northeastern University. More

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      Exploring emerging topics in artificial intelligence policy

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      Members of the public sector, private sector, and academia convened for the second AI Policy Forum Symposium last month to explore critical directions and questions posed by artificial intelligence in our economies and societies.

      The virtual event, hosted by the AI Policy Forum (AIPF) — an undertaking by the MIT Schwarzman College of Computing to bridge high-level principles of AI policy with the practices and trade-offs of governing — brought together an array of distinguished panelists to delve into four cross-cutting topics: law, auditing, health care, and mobility.

      In the last year there have been substantial changes in the regulatory and policy landscape around AI in several countries — most notably in Europe with the development of the European Union Artificial Intelligence Act, the first attempt by a major regulator to propose a law on artificial intelligence. In the United States, the National AI Initiative Act of 2020, which became law in January 2021, is providing a coordinated program across federal government to accelerate AI research and application for economic prosperity and security gains. Finally, China recently advanced several new regulations of its own.

      Each of these developments represents a different approach to legislating AI, but what makes a good AI law? And when should AI legislation be based on binding rules with penalties versus establishing voluntary guidelines?

      Jonathan Zittrain, professor of international law at Harvard Law School and director of the Berkman Klein Center for Internet and Society, says the self-regulatory approach taken during the expansion of the internet had its limitations with companies struggling to balance their interests with those of their industry and the public.

      “One lesson might be that actually having representative government take an active role early on is a good idea,” he says. “It’s just that they’re challenged by the fact that there appears to be two phases in this environment of regulation. One, too early to tell, and two, too late to do anything about it. In AI I think a lot of people would say we’re still in the ‘too early to tell’ stage but given that there’s no middle zone before it’s too late, it might still call for some regulation.”

      A theme that came up repeatedly throughout the first panel on AI laws — a conversation moderated by Dan Huttenlocher, dean of the MIT Schwarzman College of Computing and chair of the AI Policy Forum — was the notion of trust. “If you told me the truth consistently, I would say you are an honest person. If AI could provide something similar, something that I can say is consistent and is the same, then I would say it’s trusted AI,” says Bitange Ndemo, professor of entrepreneurship at the University of Nairobi and the former permanent secretary of Kenya’s Ministry of Information and Communication.

      Eva Kaili, vice president of the European Parliament, adds that “In Europe, whenever you use something, like any medication, you know that it has been checked. You know you can trust it. You know the controls are there. We have to achieve the same with AI.” Kalli further stresses that building trust in AI systems will not only lead to people using more applications in a safe manner, but that AI itself will reap benefits as greater amounts of data will be generated as a result.

      The rapidly increasing applicability of AI across fields has prompted the need to address both the opportunities and challenges of emerging technologies and the impact they have on social and ethical issues such as privacy, fairness, bias, transparency, and accountability. In health care, for example, new techniques in machine learning have shown enormous promise for improving quality and efficiency, but questions of equity, data access and privacy, safety and reliability, and immunology and global health surveillance remain at large.

      MIT’s Marzyeh Ghassemi, an assistant professor in the Department of Electrical Engineering and Computer Science and the Institute for Medical Engineering and Science, and David Sontag, an associate professor of electrical engineering and computer science, collaborated with Ziad Obermeyer, an associate professor of health policy and management at the University of California Berkeley School of Public Health, to organize AIPF Health Wide Reach, a series of sessions to discuss issues of data sharing and privacy in clinical AI. The organizers assembled experts devoted to AI, policy, and health from around the world with the goal of understanding what can be done to decrease barriers to access to high-quality health data to advance more innovative, robust, and inclusive research results while being respectful of patient privacy.

      Over the course of the series, members of the group presented on a topic of expertise and were tasked with proposing concrete policy approaches to the challenge discussed. Drawing on these wide-ranging conversations, participants unveiled their findings during the symposium, covering nonprofit and government success stories and limited access models; upside demonstrations; legal frameworks, regulation, and funding; technical approaches to privacy; and infrastructure and data sharing. The group then discussed some of their recommendations that are summarized in a report that will be released soon.

      One of the findings calls for the need to make more data available for research use. Recommendations that stem from this finding include updating regulations to promote data sharing to enable easier access to safe harbors such as the Health Insurance Portability and Accountability Act (HIPAA) has for de-identification, as well as expanding funding for private health institutions to curate datasets, amongst others. Another finding, to remove barriers to data for researchers, supports a recommendation to decrease obstacles to research and development on federally created health data. “If this is data that should be accessible because it’s funded by some federal entity, we should easily establish the steps that are going to be part of gaining access to that so that it’s a more inclusive and equitable set of research opportunities for all,” says Ghassemi. The group also recommends taking a careful look at the ethical principles that govern data sharing. While there are already many principles proposed around this, Ghassemi says that “obviously you can’t satisfy all levers or buttons at once, but we think that this is a trade-off that’s very important to think through intelligently.”

      In addition to law and health care, other facets of AI policy explored during the event included auditing and monitoring AI systems at scale, and the role AI plays in mobility and the range of technical, business, and policy challenges for autonomous vehicles in particular.

      The AI Policy Forum Symposium was an effort to bring together communities of practice with the shared aim of designing the next chapter of AI. In his closing remarks, Aleksander Madry, the Cadence Designs Systems Professor of Computing at MIT and faculty co-lead of the AI Policy Forum, emphasized the importance of collaboration and the need for different communities to communicate with each other in order to truly make an impact in the AI policy space.

      “The dream here is that we all can meet together — researchers, industry, policymakers, and other stakeholders — and really talk to each other, understand each other’s concerns, and think together about solutions,” Madry said. “This is the mission of the AI Policy Forum and this is what we want to enable.” More

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      Emery Brown wins a share of 2022 Gruber Neuroscience Prize

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      The Gruber Foundation announced on May 17 that Emery N. Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT, has won the 2022 Gruber Neuroscience Prize along with neurophysicists Laurence Abbott of Columbia University, Terrence Sejnowski of the Salk Institute for Biological Studies, and Haim Sompolinsky of the Hebrew University of Jerusalem.

      The foundation says it honored the four recipients for their influential contributions to the fields of computational and theoretical neuroscience. As datasets have grown ever larger and more complex, these fields have increasingly helped scientists unravel the mysteries of how the brain functions in both health and disease. The prize, which includes a total $500,000 award, will be presented in San Diego, California, on Nov. 13 at the annual meeting of the Society for Neuroscience.

      “These four remarkable scientists have applied their expertise in mathematical and statistical analysis, physics, and machine learning to create theories, mathematical models, and tools that have greatly advanced how we study and understand the brain,” says Joshua Sanes, professor of molecular and cellular biology and founding director of the Center for Brain Science at Harvard University and member of the selection advisory board to the prize. “Their insights and research have not only transformed how experimental neuroscientists do their research, but also are leading to promising new ways of providing clinical care.”

      Brown, who is an investigator in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT, an anesthesiologist at Massachusetts General Hospital, and a professor at Harvard Medical School, says: “It is a pleasant surprise and tremendous honor to be named a co-recipient of the 2022 Gruber Prize in Neuroscience. I am especially honored to share this award with three luminaries in computational and theoretical neuroscience.”

      Brown’s early groundbreaking findings in neuroscience included a novel algorithm that decodes the position of an animal by observing the activity of a small group of place cells in the animal’s brain, a discovery he made while working with fellow Picower Institute investigator Matt Wilson in the 1990s. The resulting state-space algorithm for point processes not only offered much better decoding with fewer neurons than previous approaches, but it also established a new framework for specifying dynamically the relationship between the spike trains (the timing sequence of firing neurons) in the brain and factors from the outside world.

      “One of the basic questions at the time was whether an animal holds a representation of where it is in its mind — in the hippocampus,” Brown says. “We were able to show that it did, and we could show that with only 30 neurons.”

      After introducing this state-space paradigm to neuroscience, Brown went on to refine the original idea and apply it to other dynamic situations — to simultaneously track neural activity and learning, for example, and to define with precision anesthesia-induced loss of consciousness, as well as its subsequent recovery. In the early 2000s, Brown put together a team to specifically study anesthesia’s effects on the brain.

      Through experimental research and mathematical modeling, Brown and his team showed that the altered arousal states produced by the main classes of anesthesia medications can be characterized by analyzing the oscillatory patterns observed in the EEG along with the locations of their molecular targets, and the anatomy and physiology of the neural circuits that connect those locations. He has established, including in recent papers with Picower Professor Earl K. Miller, that a principal way in which anesthetics produce unconsciousness is by producing oscillations that impair how different brain regions communicate with each other.

      The result of Brown’s research has been a new paradigm for brain monitoring during general anesthesia for surgery, one that allows an anesthesiologist to dose the patient based on EEG readouts (neural oscillations) of the patient’s anesthetic state rather than purely on vital sign responses. This pioneering approach promises to revolutionize how anesthesia medications are delivered to patients, and also shed light on other altered states of arousal such as sleep and coma.

      To advance that vision, Brown recently discussed how he is working to develop a new research center at MIT and MGH to further integrate anesthesiology with neuroscience research. The Brain Arousal State Control Innovation Center, he said, would not only advance anesthesiology care but also harness insights gained from anesthesiology research to improve other aspects of clinical neuroscience.

      “By demonstrating that physics and mathematics can make an enormous contribution to neuroscience, doctors Abbott, Brown, Sejnowski, and Sompolinsky have inspired an entire new generation of physicists and other quantitative scientists to follow in their footsteps,” says Frances Jensen, professor and chair of the Department of Neurology and co-director of the Penn Medicine Translational Neuroscience Center within the Perelman School of Medicine at the University of Pennsylvania, and chair of the Selection Advisory Board to the prize. “The ramifications for neuroscience have been broad and profound. It is a great pleasure to be honoring each of them with this prestigious award.”

      This report was adapted from materials provided by the Gruber Foundation. More

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      Artificial intelligence predicts patients’ race from their medical images

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      The miseducation of algorithms is a critical problem; when artificial intelligence mirrors unconscious thoughts, racism, and biases of the humans who generated these algorithms, it can lead to serious harm. Computer programs, for example, have wrongly flagged Black defendants as twice as likely to reoffend as someone who’s white. When an AI used cost as a proxy for health needs, it falsely named Black patients as healthier than equally sick white ones, as less money was spent on them. Even AI used to write a play relied on using harmful stereotypes for casting. 

      Removing sensitive features from the data seems like a viable tweak. But what happens when it’s not enough? 

      Examples of bias in natural language processing are boundless — but MIT scientists have investigated another important, largely underexplored modality: medical images. Using both private and public datasets, the team found that AI can accurately predict self-reported race of patients from medical images alone. Using imaging data of chest X-rays, limb X-rays, chest CT scans, and mammograms, the team trained a deep learning model to identify race as white, Black, or Asian — even though the images themselves contained no explicit mention of the patient’s race. This is a feat even the most seasoned physicians cannot do, and it’s not clear how the model was able to do this. 

      In an attempt to tease out and make sense of the enigmatic “how” of it all, the researchers ran a slew of experiments. To investigate possible mechanisms of race detection, they looked at variables like differences in anatomy, bone density, resolution of images — and many more, and the models still prevailed with high ability to detect race from chest X-rays. “These results were initially confusing, because the members of our research team could not come anywhere close to identifying a good proxy for this task,” says paper co-author Marzyeh Ghassemi, an assistant professor in the MIT Department of Electrical Engineering and Computer Science and the Institute for Medical Engineering and Science (IMES), who is an affiliate of the Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the MIT Jameel Clinic. “Even when you filter medical images past where the images are recognizable as medical images at all, deep models maintain a very high performance. That is concerning because superhuman capacities are generally much more difficult to control, regulate, and prevent from harming people.”

      In a clinical setting, algorithms can help tell us whether a patient is a candidate for chemotherapy, dictate the triage of patients, or decide if a movement to the ICU is necessary. “We think that the algorithms are only looking at vital signs or laboratory tests, but it’s possible they’re also looking at your race, ethnicity, sex, whether you’re incarcerated or not — even if all of that information is hidden,” says paper co-author Leo Anthony Celi, principal research scientist in IMES at MIT and associate professor of medicine at Harvard Medical School. “Just because you have representation of different groups in your algorithms, that doesn’t guarantee it won’t perpetuate or magnify existing disparities and inequities. Feeding the algorithms with more data with representation is not a panacea. This paper should make us pause and truly reconsider whether we are ready to bring AI to the bedside.” 

      The study, “AI recognition of patient race in medical imaging: a modeling study,” was published in Lancet Digital Health on May 11. Celi and Ghassemi wrote the paper alongside 20 other authors in four countries.

      To set up the tests, the scientists first showed that the models were able to predict race across multiple imaging modalities, various datasets, and diverse clinical tasks, as well as across a range of academic centers and patient populations in the United States. They used three large chest X-ray datasets, and tested the model on an unseen subset of the dataset used to train the model and a completely different one. Next, they trained the racial identity detection models for non-chest X-ray images from multiple body locations, including digital radiography, mammography, lateral cervical spine radiographs, and chest CTs to see whether the model’s performance was limited to chest X-rays. 

      The team covered many bases in an attempt to explain the model’s behavior: differences in physical characteristics between different racial groups (body habitus, breast density), disease distribution (previous studies have shown that Black patients have a higher incidence for health issues like cardiac disease), location-specific or tissue specific differences, effects of societal bias and environmental stress, the ability of deep learning systems to detect race when multiple demographic and patient factors were combined, and if specific image regions contributed to recognizing race. 

      What emerged was truly staggering: The ability of the models to predict race from diagnostic labels alone was much lower than the chest X-ray image-based models. 

      For example, the bone density test used images where the thicker part of the bone appeared white, and the thinner part appeared more gray or translucent. Scientists assumed that since Black people generally have higher bone mineral density, the color differences helped the AI models to detect race. To cut that off, they clipped the images with a filter, so the model couldn’t color differences. It turned out that cutting off the color supply didn’t faze the model — it still could accurately predict races. (The “Area Under the Curve” value, meaning the measure of the accuracy of a quantitative diagnostic test, was 0.94–0.96). As such, the learned features of the model appeared to rely on all regions of the image, meaning that controlling this type of algorithmic behavior presents a messy, challenging problem. 

      The scientists acknowledge limited availability of racial identity labels, which caused them to focus on Asian, Black, and white populations, and that their ground truth was a self-reported detail. Other forthcoming work will include potentially looking at isolating different signals before image reconstruction, because, as with bone density experiments, they couldn’t account for residual bone tissue that was on the images. 

      Notably, other work by Ghassemi and Celi led by MIT student Hammaad Adam has found that models can also identify patient self-reported race from clinical notes even when those notes are stripped of explicit indicators of race. Just as in this work, human experts are not able to accurately predict patient race from the same redacted clinical notes.

      “We need to bring social scientists into the picture. Domain experts, which are usually the clinicians, public health practitioners, computer scientists, and engineers are not enough. Health care is a social-cultural problem just as much as it’s a medical problem. We need another group of experts to weigh in and to provide input and feedback on how we design, develop, deploy, and evaluate these algorithms,” says Celi. “We need to also ask the data scientists, before any exploration of the data, are there disparities? Which patient groups are marginalized? What are the drivers of those disparities? Is it access to care? Is it from the subjectivity of the care providers? If we don’t understand that, we won’t have a chance of being able to identify the unintended consequences of the algorithms, and there’s no way we’ll be able to safeguard the algorithms from perpetuating biases.”

      “The fact that algorithms ‘see’ race, as the authors convincingly document, can be dangerous. But an important and related fact is that, when used carefully, algorithms can also work to counter bias,” says Ziad Obermeyer, associate professor at the University of California at Berkeley, whose research focuses on AI applied to health. “In our own work, led by computer scientist Emma Pierson at Cornell, we show that algorithms that learn from patients’ pain experiences can find new sources of knee pain in X-rays that disproportionately affect Black patients — and are disproportionately missed by radiologists. So just like any tool, algorithms can be a force for evil or a force for good — which one depends on us, and the choices we make when we build algorithms.”

      The work is supported, in part, by the National Institutes of Health. More

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      Emery Brown earns American Institute for Medical and Biological Engineering Pierre Galletti Award

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      The American Institute for Medical and Biological Engineering has awarded its highest honor this year to Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Health Sciences and Technology in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT.

      Brown, who is also an anesthesiologist at Massachusetts General Hospital and the Warren M. Zapol Professor at Harvard Medical School, received the 2022 Pierre M. Galletti Award during the national organization’s Annual Event held on March 25.

      For decades, Brown’s lab has uniquely unified three fields: neuroscience, statistics, and anesthesiology. He is renowned for the development of statistical methods and signal-processing algorithms to enable and improve analysis of neural activity measurements. The work has had numerous applications including studies of learning and memory, brain-computer interfaces, and systems neuroscience. He has also pioneered investigations of how general anesthetic drugs work in the brain to induce and maintain simultaneous but reversible states of unconsciousness, amnesia, immobility, and analgesia. Building on these improvements in fundamental understanding, his lab engineers systems to improve monitoring of patient state and anesthetic dosing during surgery. Optimizing doses of general anesthetic drugs can improve patient care in many ways, including by minimizing side effects such as post-operative delirium and by improving post-operative pain management.

      AIMBE said Brown earned the award in recognition of his “significant contributions to neuroscience data analysis and for characterizing the neurophysiology of anesthesia-induced unconsciousness and demonstrating how it can be reliably monitored in real time using electroencephalogram recordings.”

      Brown, who is also a faculty member in MIT’s Department of Brain and Cognitive Sciences, is now working to develop a research center at MIT dedicated to taking neuroscience-based approaches to advance anesthesiology.

      “I am extremely honored and grateful to the AIMBE for choosing me to receive the 2022 Galletti Award in recognition of my research deciphering the neuroscience of how anesthetics work,” he says. “I would like to express my gratitude to my collaborators, post-doctoral fellows, students, research assistants, and clinical coordinators who have made this possible.” More

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      Deep-learning technique predicts clinical treatment outcomes

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      When it comes to treatment strategies for critically ill patients, clinicians want to be able to consider all their options and timing of administration, and make the optimal decision for their patients. While clinician experience and study has helped them to be successful in this effort, not all patients are the same, and treatment decisions at this crucial time could mean the difference between patient improvement and quick deterioration. Therefore, it would be helpful for doctors to be able to take a patient’s previous known health status and received treatments and use that to predict that patient’s health outcome under different treatment scenarios, in order to pick the best path.

      Now, a deep-learning technique, called G-Net, from researchers at MIT and IBM provides a window into causal counterfactual prediction, affording physicians the opportunity to explore how a patient might fare under different treatment plans. The foundation of G-Net is the g-computation algorithm, a causal inference method that estimates the effect of dynamic exposures in the presence of measured confounding variables — ones that may influence both treatments and outcomes. Unlike previous implementations of the g-computation framework, which have used linear modeling approaches, G-Net uses recurrent neural networks (RNN), which have node connections that allow them to better model temporal sequences with complex and nonlinear dynamics, like those found in the physiological and clinical time series data. In this way, physicians can develop alternative plans based on patient history and test them before making a decision.

      “Our ultimate goal is to develop a machine learning technique that would allow doctors to explore various ‘What if’ scenarios and treatment options,” says Li-wei Lehman, MIT research scientist in the MIT Institute for Medical Engineering and Science and an MIT-IBM Watson AI Lab project lead. “A lot of work has been done in terms of deep learning for counterfactual prediction but [it’s] been focusing on a point exposure setting,” or a static, time-varying treatment strategy, which doesn’t allow for adjustment of treatments as patient history changes. However, her team’s new prediction approach provides for treatment plan flexibility and chances for treatment alteration over time as patient covariate history and past treatments change. “G-Net is the first deep-learning approach based on g-computation that can predict both the population-level and individual-level treatment effects under dynamic and time varying treatment strategies.”

      The research, which was recently published in the Proceedings of Machine Learning Research, was co-authored by Rui Li MEng ’20, Stephanie Hu MEng ’21, former MIT postdoc Mingyu Lu MD, graduate student Yuria Utsumi, IBM research staff member Prithwish Chakraborty, IBM Research director of Hybrid Cloud Services Daby Sow, IBM data scientist Piyush Madan, IBM research scientist Mohamed Ghalwash, and IBM research scientist Zach Shahn.

      Tracking disease progression

      To build, validate, and test G-Net’s predictive abilities, the researchers considered the circulatory system in septic patients in the ICU. During critical care, doctors need to make trade-offs and judgement calls, such as ensuring the organs are receiving adequate blood supply without overworking the heart. For this, they could give intravenous fluids to patients to increase blood pressure; however, too much can cause edema. Alternatively, physicians can administer vasopressors, which act to contract blood vessels and raise blood pressure.

      In order to mimic this and demonstrate G-Net’s proof-of-concept, the team used CVSim, a mechanistic model of a human cardiovascular system that’s governed by 28 input variables characterizing the system’s current state, such as arterial pressure, central venous pressure, total blood volume, and total peripheral resistance, and modified it to simulate various disease processes (e.g., sepsis or blood loss) and effects of interventions (e.g., fluids and vasopressors). The researchers used CVSim to generate observational patient data for training and for “ground truth” comparison against counterfactual prediction. In their G-Net architecture, the researchers ran two RNNs to handle and predict variables that are continuous, meaning they can take on a range of values, like blood pressure, and categorical variables, which have discrete values, like the presence or absence of pulmonary edema. The researchers simulated the health trajectories of thousands of “patients” exhibiting symptoms under one treatment regime, let’s say A, for 66 timesteps, and used them to train and validate their model.

      Testing G-Net’s prediction capability, the team generated two counterfactual datasets. Each contained roughly 1,000 known patient health trajectories, which were created from CVSim using the same “patient” condition as the starting point under treatment A. Then at timestep 33, treatment changed to plan B or C, depending on the dataset. The team then performed 100 prediction trajectories for each of these 1,000 patients, whose treatment and medical history was known up until timestep 33 when a new treatment was administered. In these cases, the prediction agreed well with the “ground-truth” observations for individual patients and averaged population-level trajectories.

      A cut above the rest

      Since the g-computation framework is flexible, the researchers wanted to examine G-Net’s prediction using different nonlinear models — in this case, long short-term memory (LSTM) models, which are a type of RNN that can learn from previous data patterns or sequences — against the more classical linear models and a multilayer perception model (MLP), a type of neural network that can make predictions using a nonlinear approach. Following a similar setup as before, the team found that the error between the known and predicted cases was smallest in the LSTM models compared to the others. Since G-Net is able to model the temporal patterns of the patient’s ICU history and past treatment, whereas a linear model and MLP cannot, it was better able to predict the patient’s outcome.

      The team also compared G-Net’s prediction in a static, time-varying treatment setting against two state-of-the-art deep-learning based counterfactual prediction approaches, a recurrent marginal structural network (rMSN) and a counterfactual recurrent neural network (CRN), as well as a linear model and an MLP. For this, they investigated a model for tumor growth under no treatment, radiation, chemotherapy, and both radiation and chemotherapy scenarios. “Imagine a scenario where there’s a patient with cancer, and an example of a static regime would be if you only give a fixed dosage of chemotherapy, radiation, or any kind of drug, and wait until the end of your trajectory,” comments Lu. For these investigations, the researchers generated simulated observational data using tumor volume as the primary influence dictating treatment plans and demonstrated that G-Net outperformed the other models. One potential reason could be because g-computation is known to be more statistically efficient than rMSN and CRN, when models are correctly specified.

      While G-Net has done well with simulated data, more needs to be done before it can be applied to real patients. Since neural networks can be thought of as “black boxes” for prediction results, the researchers are beginning to investigate the uncertainty in the model to help ensure safety. In contrast to these approaches that recommend an “optimal” treatment plan without any clinician involvement, “as a decision support tool, I believe that G-Net would be more interpretable, since the clinicians would input treatment strategies themselves,” says Lehman, and “G-Net will allow them to be able to explore different hypotheses.” Further, the team has moved on to using real data from ICU patients with sepsis, bringing it one step closer to implementation in hospitals.

      “I think it is pretty important and exciting for real-world applications,” says Hu. “It’d be helpful to have some way to predict whether or not a treatment might work or what the effects might be — a quicker iteration process for developing these hypotheses for what to try, before actually trying to implement them in in a years-long, potentially very involved and very invasive type of clinical trial.”

      This research was funded by the MIT-IBM Watson AI Lab. More

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      in Data Management & Statistics

      Professor Emery Brown has big plans for anesthesiology

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      Emery N. Brown — the Edward Hood Taplin Professor of Medical Engineering and of Computational Neuroscience at MIT, an MIT professor of health sciences and technology, an investigator with The Picower Institute for Learning and Memory at MIT, and the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School and Massachusetts General Hospital (MGH) — clearly excels at many roles. Renowned internationally for his anesthesia and neuroscience research, he embodies a unique blend of anesthesiologist, statistician, neuroscientist, educator, and mentor to both students and colleagues. Notably, Brown is one of the most decorated clinician-scientists in the country; he is one of only 25 people — and the first African-American, statistician, and anesthesiologist — to be elected to all three National Academies (Science, Engineering, and Medicine).

      Now, he is handing off one of his many key roles and responsibilities. After almost 10 years, Brown is stepping down as co-director of the Harvard-MIT Program in Health Sciences and Technology (HST). He will turn his energies toward working to develop a new joint center between MIT and MGH that uses the study of anesthesia to design novel approaches to controlling brain states. While a goal of the new center will be to improve anesthesia and intensive care unit management, according to Brown, it will also study related problems such as treating depression, insomnia, and epilepsy, as well as enhancing coma recovery.

      Founded in 1970, HST is one of the oldest interdisciplinary educational programs focused on training the next generation of clinician-scientists and engineers, who learn to translate science, engineering, and medical research into clinical practice, with the aim of improving human health. The MIT Institute for Medical Engineering and Science (IMES), where Brown is associate director, is HST’s home at MIT. Brown was the first HST co-director after the establishment of IMES in 2012; Wolfram Goessling is the Harvard University co-director of HST.

      “Emery has been an exemplary leader for HST during his tenure, and has helped it become a hub for the training of world-class scientists, engineers, and clinicians,” says Anantha Chandrakasan, dean of the MIT School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “I am deeply grateful for his many years of service and wish him well as he moves on to new endeavors.”

      Elazer R. Edelman, director of IMES, calls Brown “a phenom who has been dedicated to our programs for years.”

      “With his thoughtful leadership and understated style, Emery made many contributions to the HST community,” Edelman continues. “On a personal note, this is bittersweet for me, as Emery has been a partner and mentor in my role as IMES director. And while I know that he will always be there for me, as he has been for all of us at IMES and HST, I will miss our late-night calls and midday conferences on matters of import for MIT, IMES, and HST.”

      Brown says “it was an honor and a privilege to co-direct HST with Wolfram.”

      “The students, staff, and faculty are simply amazing,” Brown continues. “Although, now more than 50 years old, HST remains at the vanguard for training PhD and MD students to work at the intersection between engineering, science, and medicine.”

      Goessling also thanks Brown for his leadership: “I truly valued Emery’s partnership and friendship, working together to deepen ties between the MIT and Harvard sides of HST. I am particularly grateful for working with Emery on our combined diversity efforts, leading to the HST Diversity Ambassadors initiative that made HST a better and stronger program.”

      According to Edelman, Brown was instrumental in the transition to new paradigms and relationships with HMS in the context of IMES. In 2014, he led the establishment of clear criteria for HST faculty membership, thereby strengthening the community of faculty experts who train students and provide research opportunities. More recently, he provided guidance through the turmoil of the ongoing Covid-19 pandemic, including the transition to online instruction and the return to the classroom. And Brown has always been a strong supporter of student diversity efforts, serving as an advocate and advisor to HST students.

      Brown holds BA, MA, and PhD degrees from Harvard University, and an MD from Harvard Medical School. He has been recognized with many awards, including the 2020 Swartz Prize in Theoretical and Computational Neuroscience, the 2018 Dickson Prize in Science, and an NIH Director’s Pioneer Award. Brown also served on President Barack Obama’s BRAIN Initiative Working Group. Among his many accomplishments, he has been cited for developing neural signal processing algorithms to characterize how neural systems represent and transmit information, and for unlocking the neurophysiology of how anesthetics produce the states of general anesthesia.

      Edelman says the process is underway to name a successor to Brown as co-director of HST at MIT. More

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      in Data Management & Statistics

      The downside of machine learning in health care

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      While working toward her dissertation in computer science at MIT, Marzyeh Ghassemi wrote several papers on how machine-learning techniques from artificial intelligence could be applied to clinical data in order to predict patient outcomes. “It wasn’t until the end of my PhD work that one of my committee members asked: ‘Did you ever check to see how well your model worked across different groups of people?’”

      That question was eye-opening for Ghassemi, who had previously assessed the performance of models in aggregate, across all patients. Upon a closer look, she saw that models often worked differently — specifically worse — for populations including Black women, a revelation that took her by surprise. “I hadn’t made the connection beforehand that health disparities would translate directly to model disparities,” she says. “And given that I am a visible minority woman-identifying computer scientist at MIT, I am reasonably certain that many others weren’t aware of this either.”

      In a paper published Jan. 14 in the journal Patterns, Ghassemi — who earned her doctorate in 2017 and is now an assistant professor in the Department of Electrical Engineering and Computer Science and the MIT Institute for Medical Engineering and Science (IMES) — and her coauthor, Elaine Okanyene Nsoesie of Boston University, offer a cautionary note about the prospects for AI in medicine. “If used carefully, this technology could improve performance in health care and potentially reduce inequities,” Ghassemi says. “But if we’re not actually careful, technology could worsen care.”

      It all comes down to data, given that the AI tools in question train themselves by processing and analyzing vast quantities of data. But the data they are given are produced by humans, who are fallible and whose judgments may be clouded by the fact that they interact differently with patients depending on their age, gender, and race, without even knowing it.

      Furthermore, there is still great uncertainty about medical conditions themselves. “Doctors trained at the same medical school for 10 years can, and often do, disagree about a patient’s diagnosis,” Ghassemi says. That’s different from the applications where existing machine-learning algorithms excel — like object-recognition tasks — because practically everyone in the world will agree that a dog is, in fact, a dog.

      Machine-learning algorithms have also fared well in mastering games like chess and Go, where both the rules and the “win conditions” are clearly defined. Physicians, however, don’t always concur on the rules for treating patients, and even the win condition of being “healthy” is not widely agreed upon. “Doctors know what it means to be sick,” Ghassemi explains, “and we have the most data for people when they are sickest. But we don’t get much data from people when they are healthy because they’re less likely to see doctors then.”

      Even mechanical devices can contribute to flawed data and disparities in treatment. Pulse oximeters, for example, which have been calibrated predominately on light-skinned individuals, do not accurately measure blood oxygen levels for people with darker skin. And these deficiencies are most acute when oxygen levels are low — precisely when accurate readings are most urgent. Similarly, women face increased risks during “metal-on-metal” hip replacements, Ghassemi and Nsoesie write, “due in part to anatomic differences that aren’t taken into account in implant design.” Facts like these could be buried within the data fed to computer models whose output will be undermined as a result.

      Coming from computers, the product of machine-learning algorithms offers “the sheen of objectivity,” according to Ghassemi. But that can be deceptive and dangerous, because it’s harder to ferret out the faulty data supplied en masse to a computer than it is to discount the recommendations of a single possibly inept (and maybe even racist) doctor. “The problem is not machine learning itself,” she insists. “It’s people. Human caregivers generate bad data sometimes because they are not perfect.”

      Nevertheless, she still believes that machine learning can offer benefits in health care in terms of more efficient and fairer recommendations and practices. One key to realizing the promise of machine learning in health care is to improve the quality of data, which is no easy task. “Imagine if we could take data from doctors that have the best performance and share that with other doctors that have less training and experience,” Ghassemi says. “We really need to collect this data and audit it.”

      The challenge here is that the collection of data is not incentivized or rewarded, she notes. “It’s not easy to get a grant for that, or ask students to spend time on it. And data providers might say, ‘Why should I give my data out for free when I can sell it to a company for millions?’ But researchers should be able to access data without having to deal with questions like: ‘What paper will I get my name on in exchange for giving you access to data that sits at my institution?’

      “The only way to get better health care is to get better data,” Ghassemi says, “and the only way to get better data is to incentivize its release.”

      It’s not only a question of collecting data. There’s also the matter of who will collect it and vet it. Ghassemi recommends assembling diverse groups of researchers — clinicians, statisticians, medical ethicists, and computer scientists — to first gather diverse patient data and then “focus on developing fair and equitable improvements in health care that can be deployed in not just one advanced medical setting, but in a wide range of medical settings.”

      The objective of the Patterns paper is not to discourage technologists from bringing their expertise in machine learning to the medical world, she says. “They just need to be cognizant of the gaps that appear in treatment and other complexities that ought to be considered before giving their stamp of approval to a particular computer model.” More