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    AI model identifies certain breast tumor stages likely to progress to invasive cancer

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    Ductal carcinoma in situ (DCIS) is a type of preinvasive tumor that sometimes progresses to a highly deadly form of breast cancer. It accounts for about 25 percent of all breast cancer diagnoses.Because it is difficult for clinicians to determine the type and stage of DCIS, patients with DCIS are often overtreated. To address this, an interdisciplinary team of researchers from MIT and ETH Zurich developed an AI model that can identify the different stages of DCIS from a cheap and easy-to-obtain breast tissue image. Their model shows that both the state and arrangement of cells in a tissue sample are important for determining the stage of DCIS.Because such tissue images are so easy to obtain, the researchers were able to build one of the largest datasets of its kind, which they used to train and test their model. When they compared its predictions to conclusions of a pathologist, they found clear agreement in many instances.In the future, the model could be used as a tool to help clinicians streamline the diagnosis of simpler cases without the need for labor-intensive tests, giving them more time to evaluate cases where it is less clear if DCIS will become invasive.“We took the first step in understanding that we should be looking at the spatial organization of cells when diagnosing DCIS, and now we have developed a technique that is scalable. From here, we really need a prospective study. Working with a hospital and getting this all the way to the clinic will be an important step forward,” says Caroline Uhler, a professor in the Department of Electrical Engineering and Computer Science (EECS) and the Institute for Data, Systems, and Society (IDSS), who is also director of the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard and a researcher at MIT’s Laboratory for Information and Decision Systems (LIDS).Uhler, co-corresponding author of a paper on this research, is joined by lead author Xinyi Zhang, a graduate student in EECS and the Eric and Wendy Schmidt Center; co-corresponding author GV Shivashankar, professor of mechogenomics at ETH Zurich jointly with the Paul Scherrer Institute; and others at MIT, ETH Zurich, and the University of Palermo in Italy. The open-access research was published July 20 in Nature Communications.Combining imaging with AI   Between 30 and 50 percent of patients with DCIS develop a highly invasive stage of cancer, but researchers don’t know the biomarkers that could tell a clinician which tumors will progress.Researchers can use techniques like multiplexed staining or single-cell RNA sequencing to determine the stage of DCIS in tissue samples. However, these tests are too expensive to be performed widely, Shivashankar explains.In previous work, these researchers showed that a cheap imagining technique known as chromatin staining could be as informative as the much costlier single-cell RNA sequencing.For this research, they hypothesized that combining this single stain with a carefully designed machine-learning model could provide the same information about cancer stage as costlier techniques.First, they created a dataset containing 560 tissue sample images from 122 patients at three different stages of disease. They used this dataset to train an AI model that learns a representation of the state of each cell in a tissue sample image, which it uses to infer the stage of a patient’s cancer.However, not every cell is indicative of cancer, so the researchers had to aggregate them in a meaningful way.They designed the model to create clusters of cells in similar states, identifying eight states that are important markers of DCIS. Some cell states are more indicative of invasive cancer than others. The model determines the proportion of cells in each state in a tissue sample.Organization matters“But in cancer, the organization of cells also changes. We found that just having the proportions of cells in every state is not enough. You also need to understand how the cells are organized,” says Shivashankar.With this insight, they designed the model to consider proportion and arrangement of cell states, which significantly boosted its accuracy.“The interesting thing for us was seeing how much spatial organization matters. Previous studies had shown that cells which are close to the breast duct are important. But it is also important to consider which cells are close to which other cells,” says Zhang.When they compared the results of their model with samples evaluated by a pathologist, it had clear agreement in many instances. In cases that were not as clear-cut, the model could provide information about features in a tissue sample, like the organization of cells, that a pathologist could use in decision-making.This versatile model could also be adapted for use in other types of cancer, or even neurodegenerative conditions, which is one area the researchers are also currently exploring.“We have shown that, with the right AI techniques, this simple stain can be very powerful. There is still much more research to do, but we need to take the organization of cells into account in more of our studies,” Uhler says.This research was funded, in part, by the Eric and Wendy Schmidt Center at the Broad Institute, ETH Zurich, the Paul Scherrer Institute, the Swiss National Science Foundation, the U.S. National Institutes of Health, the U.S. Office of Naval Research, the MIT Jameel Clinic for Machine Learning and Health, the MIT-IBM Watson AI Lab, and a Simons Investigator Award. More

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      New hope for early pancreatic cancer intervention via AI-based risk prediction

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      The first documented case of pancreatic cancer dates back to the 18th century. Since then, researchers have undertaken a protracted and challenging odyssey to understand the elusive and deadly disease. To date, there is no better cancer treatment than early intervention. Unfortunately, the pancreas, nestled deep within the abdomen, is particularly elusive for early detection. 

      MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) scientists, alongside Limor Appelbaum, a staff scientist in the Department of Radiation Oncology at Beth Israel Deaconess Medical Center (BIDMC), were eager to better identify potential high-risk patients. They set out to develop two machine-learning models for early detection of pancreatic ductal adenocarcinoma (PDAC), the most common form of the cancer. To access a broad and diverse database, the team synced up with a federated network company, using electronic health record data from various institutions across the United States. This vast pool of data helped ensure the models’ reliability and generalizability, making them applicable across a wide range of populations, geographical locations, and demographic groups.

      The two models — the “PRISM” neural network, and the logistic regression model (a statistical technique for probability), outperformed current methods. The team’s comparison showed that while standard screening criteria identify about 10 percent of PDAC cases using a five-times higher relative risk threshold, Prism can detect 35 percent of PDAC cases at this same threshold. 

      Using AI to detect cancer risk is not a new phenomena — algorithms analyze mammograms, CT scans for lung cancer, and assist in the analysis of Pap smear tests and HPV testing, to name a few applications. “The PRISM models stand out for their development and validation on an extensive database of over 5 million patients, surpassing the scale of most prior research in the field,” says Kai Jia, an MIT PhD student in electrical engineering and computer science (EECS), MIT CSAIL affiliate, and first author on an open-access paper in eBioMedicine outlining the new work. “The model uses routine clinical and lab data to make its predictions, and the diversity of the U.S. population is a significant advancement over other PDAC models, which are usually confined to specific geographic regions, like a few health-care centers in the U.S. Additionally, using a unique regularization technique in the training process enhanced the models’ generalizability and interpretability.” 

      “This report outlines a powerful approach to use big data and artificial intelligence algorithms to refine our approach to identifying risk profiles for cancer,” says David Avigan, a Harvard Medical School professor and the cancer center director and chief of hematology and hematologic malignancies at BIDMC, who was not involved in the study. “This approach may lead to novel strategies to identify patients with high risk for malignancy that may benefit from focused screening with the potential for early intervention.” 

      Prismatic perspectives

      The journey toward the development of PRISM began over six years ago, fueled by firsthand experiences with the limitations of current diagnostic practices. “Approximately 80-85 percent of pancreatic cancer patients are diagnosed at advanced stages, where cure is no longer an option,” says senior author Appelbaum, who is also a Harvard Medical School instructor as well as radiation oncologist. “This clinical frustration sparked the idea to delve into the wealth of data available in electronic health records (EHRs).”The CSAIL group’s close collaboration with Appelbaum made it possible to understand the combined medical and machine learning aspects of the problem better, eventually leading to a much more accurate and transparent model. “The hypothesis was that these records contained hidden clues — subtle signs and symptoms that could act as early warning signals of pancreatic cancer,” she adds. “This guided our use of federated EHR networks in developing these models, for a scalable approach for deploying risk prediction tools in health care.”Both PrismNN and PrismLR models analyze EHR data, including patient demographics, diagnoses, medications, and lab results, to assess PDAC risk. PrismNN uses artificial neural networks to detect intricate patterns in data features like age, medical history, and lab results, yielding a risk score for PDAC likelihood. PrismLR uses logistic regression for a simpler analysis, generating a probability score of PDAC based on these features. Together, the models offer a thorough evaluation of different approaches in predicting PDAC risk from the same EHR data.

      One paramount point for gaining the trust of physicians, the team notes, is better understanding how the models work, known in the field as interpretability. The scientists pointed out that while logistic regression models are inherently easier to interpret, recent advancements have made deep neural networks somewhat more transparent. This helped the team to refine the thousands of potentially predictive features derived from EHR of a single patient to approximately 85 critical indicators. These indicators, which include patient age, diabetes diagnosis, and an increased frequency of visits to physicians, are automatically discovered by the model but match physicians’ understanding of risk factors associated with pancreatic cancer. 

      The path forward

      Despite the promise of the PRISM models, as with all research, some parts are still a work in progress. U.S. data alone are the current diet for the models, necessitating testing and adaptation for global use. The path forward, the team notes, includes expanding the model’s applicability to international datasets and integrating additional biomarkers for more refined risk assessment.

      “A subsequent aim for us is to facilitate the models’ implementation in routine health care settings. The vision is to have these models function seamlessly in the background of health care systems, automatically analyzing patient data and alerting physicians to high-risk cases without adding to their workload,” says Jia. “A machine-learning model integrated with the EHR system could empower physicians with early alerts for high-risk patients, potentially enabling interventions well before symptoms manifest. We are eager to deploy our techniques in the real world to help all individuals enjoy longer, healthier lives.” 

      Jia wrote the paper alongside Applebaum and MIT EECS Professor and CSAIL Principal Investigator Martin Rinard, who are both senior authors of the paper. Researchers on the paper were supported during their time at MIT CSAIL, in part, by the Defense Advanced Research Projects Agency, Boeing, the National Science Foundation, and Aarno Labs. TriNetX provided resources for the project, and the Prevent Cancer Foundation also supported the team. More

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      Emma Gibson: Optimizing health care logistics in Africa

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      Growing up in South Africa at the turn of the century, Emma Gibson saw the rise of the HIV/AIDS epidemic and its devastating impact on her home country, where many people lacked life-saving health care. At the time, Gibson was too young to understand what a sexually transmitted infection was, but she knew that HIV was infecting millions of South Africans and AIDS was taking hundreds of thousands of lives. “As a child, I was terrified by this monster that was HIV and felt so powerless to do anything about it,” she says.

      Now, as an adult, her childhood fear of the HIV epidemic has evolved into a desire to fight it. Gibson seeks to improve health care for HIV and other diseases in regions with limited resources, including South Africa. She wants to help health care facilities in these areas to use their resources more effectively so that patients can more easily obtain care.

      To help reach her goal, Gibson sought mathematics and logistics training through higher education in South Africa. She first earned her bachelor’s degree in mathematical sciences at the University of the Witwatersrand, and then her master’s degree in operations research at Stellenbosch University. There, she learned to tackle complex decision-making problems using math, statistics, and computer simulations.

      During her master’s, Gibson studied the operational challenges faced in rural South African health care facilities by working with staff at Zithulele Hospital in the Eastern Cape, one of the country’s poorest provinces. Her research focused on ways to reduce hours-long wait times for patients seeking same-day care. In the end, she developed a software tool to model patient congestion throughout the day and optimize staff schedules accordingly, enabling the hospital to care for its patients more efficiently.

      After completing her master’s, Gibson wanted to further her education outside of South Africa and left to pursue a PhD in operations research at MIT. Upon arrival, she branched out in her research and worked on a project to improve breast cancer treatment in U.S. health care, a very different environment from what she was used to.

      Two years later, Gibson had the opportunity to return to researching health care in resource-limited settings and began working with Jónas Jónasson, an associate professor at the MIT Sloan School of Management, on a new project to improve diagnostic services in sub-Saharan Africa. For the past four years, she has been working diligently on this project in collaboration with researchers at the Indian School of Business and Northwestern University. “My love language is time,” she says. “If I’m investing a lot of time in something, I really value it.”

      Scheduling sample transport

      Diagnostic testing is an essential tool that allows medical professionals to identify new diagnoses in patients and monitor patients’ conditions as they undergo treatment. For example, people living with HIV require regular blood tests to ensure that their prescribed treatments are working effectively and provide an early warning of potential treatment failures.

      For Gibson’s current project, she’s trying to improve diagnostic services in Malawi, a landlocked country in southeast Africa. “We have the tools” to diagnose and treat diseases like HIV, she says. “But in resource-limited settings, we often lack the money, the staff, and the infrastructure to reach every patient that needs them.”

      When diagnostic testing is needed, clinicians collect samples from patients and send the samples to be tested at a laboratory, which then returns the results to the facility where the patient is treated. To move these items between facilities and laboratories, Malawi has developed a national sample transportation network. The transportation system plays an important role in linking remote, rural facilities to laboratory services and ensuring that patients in these areas can access diagnostic testing through community clinics. Samples collected at these clinics are first transported to nearby district hubs, and then forwarded to laboratories located in urban areas. Since most facilities do not have computers or communications infrastructure, laboratories print copies of test results and send them back to facilities through the same transportation process.

      The sample transportation cycle is onerous, but it’s a practical solution to a difficult problem. “During the Covid pandemic, we saw how hard it was to scale up diagnostic infrastructure,” Gibson says. Diagnostic services in sub-Saharan Africa face “similar challenges, but in a much poorer setting.”

      In Malawi, sample transportation is managed by a  nongovernment organization called Riders 4 Health. The organization has around 80 couriers on motorcycles who transport samples and test results between facilities. “When we started working with [Riders], the couriers operated on fixed weekly schedules, visiting each site once or twice a week,” Gibson says. But that led to “a lot of unnecessary trips and delays.”

      To make sample transportation more efficient, Gibson developed a dynamic scheduling system that adapts to the current demand for diagnostic testing. The system consists of two main parts: an information sharing platform that aggregates sample transportation data, and an algorithm that uses the data to generate optimized routes and schedules for sample transport couriers.

      In 2019, Gibson ran a four-month-long pilot test for this system in three out of the 27 districts in Malawi. During the pilot study, six couriers transported over 20,000 samples and results across 51 health care facilities, and 150 health care workers participated in data sharing.

      The pilot was a success. Gibson’s dynamic scheduling system eliminated about half the unnecessary trips and reduced transportation delays by 25 percent — a delay that used to be four days was reduced to three. Now, Riders 4 Health is developing their own version of Gibson’s system to operate nationally in Malawi. Throughout this project, “we focused on making sure this was something that could grow with the organization,” she says. “It’s gratifying to see that actually happening.”

      Leveraging patient data

      Gibson is completing her MIT degree this September but will continue working to improve health care in Africa. After graduation, she will join the technology and analytics health care practice of an established company in South Africa. Her initial focus will be on public health care institutions, including Chris Hani Baragwanath Academic Hospital in Johannesburg, the third-largest hospital in the world.

      In this role, Gibson will work to fill in gaps in African patient data for medical operational research and develop ways to use this data more effectively to improve health care in resource-limited areas. For example, better data systems can help to monitor the prevalence and impact of different diseases, guiding where health care workers and researchers put their efforts to help the most people. “You can’t make good decisions if you don’t have all the information,” Gibson says.

      To best leverage patient data for improving health care, Gibson plans to reevaluate how data systems are structured and used in the hospital. For ideas on upgrading the current system, she’ll look to existing data systems in other countries to see what works and what doesn’t, while also drawing upon her past research experience in U.S. health care. Ultimately, she’ll tailor the new hospital data system to South African needs to accurately inform future directions in health care.

      Gibson’s new job — her “dream job” — will be based in the United Kingdom, but she anticipates spending a significant amount of time in Johannesburg. “I have so many opportunities in the wider world, but the ones that appeal to me are always back in the place I came from,” she says. More