Researchers Use Machine Learning to Improve Breast Cancer Screening Techniques

Imagine enduring a painful, expensive and scar-inducing surgery—only to find out afterwards that it wasn’t necessary.

This is the situation for many women with high-risk breast lesions—areas of tissue that appear suspicious on a mammogram and have abnormal but not cancerous cells when tested by needle biopsy. Following surgical removal, 90% of these lesions end up being benign.

A change in the standard of care could be on the horizon thanks to researchers at Massachusetts General Hospital and MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) who have found a more precise and less invasive way to separate harmful lesions from benign ones.

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From left: Manisha Bahl, director of the Massachusetts General Hospital Breast Imaging Fellowship Program; MIT Professor Regina Barzilay; and Constance Lehman, chief of the Breast Imaging Division at MGH’s Department of Radiology. Photo courtesy of MIT News

“The decision about whether or not to proceed to surgery is challenging, and the tendency is to aggressively treat these lesions [and remove them],” said Manisha Bahl, MD, Director of the Breast Imaging Fellowship Program at Mass General, in a recent interview.

Bahl, along with a team of researchers, have harnessed the power of artificial intelligence (AI) to develop a more accurate and less invasive screening method for high-risk lesions. When tested, the machine correctly diagnosed 97 percent of 335 high-risk breast lesions as malignant and reduced the number of benign surgeries by more than 30 percent compared to existing approaches. These results were recently published in Radiology.

The team developed an AI system that uses machine learning to distinguish between high-risk lesions that need to be surgically removed from those that should just be watched over time. They created this model by feeding it data on over 600 high-risk lesions, including information on the patient’s demographics and pathology reports, and then tasked it to identify patterns among the different data elements.

Through a process called deep learning, the machine uses the data to create an algorithm that can be used to predict which high-risk lesions should be surgically removed. This process differs from traditional software programming in that the researchers did not give the machine the formula for diagnosis, but rather let it analyze the data and identify patterns on its own.

“To our knowledge, this is the first study to apply machine learning to the task of distinguishing high-risk lesions that need surgery from those that don’t,” said collaborator Constance Lehman, MD, PhD, chief of the Breast Imaging Division at Mass General’s Department of Radiology, in a recent interview. “We believe this could support women to make more informed decisions about their treatment and that we could provide more targeted approaches to health care in general.”

Lehman says Mass General radiologists will begin incorporating the model into their clinical practice over the next year.

Pocket-Sized Device Provides Food Allergy Sufferers with Life-Saving Tableside Lab Results

If you’re among the 50 million Americans with a severe allergy to foods like gluten or nuts, every meal at a restaurant can feel like a potential land mine. Even if the restaurant has made an effort to provide dishes that are allergen-free, worries of cross-contamination and a subsequent severe or potentially life threatening reaction can still put a damper on your dinner plans.

To help ease concerns and keep food allergy sufferers safe, a team at Massachusetts General Hospital has developed a new device small enough to fit on a keyring that costs only $40 and can quickly and accurately test for food allergens.

While advances have been made in the packaged food industry, where new federal regulations require the manufacturer to disclose whether the product is made in a facility that also processes common allergens, these disclosures are not always accurate and there are no similar regulations for the restaurant industry.

Rather than force diners to completely avoid foods that have the chance of containing an allergen, or eat something only to regret it later, Mass General researchers created integrated exogenous antigen testing (iEAT), a pocket-sized device that can accurately analyze food for the presences of allergens in less than 10 minutes. Specifically, the device can screen for peanuts, hazelnuts, wheat, milk and eggs.

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The iEAT system

Developed by co-senior team leaders Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology (CSB) at Mass General and Hakho Lee, PhD, Hostetter MGH Research Scholar and Director of the Biomedical Engineering Program at the CSB, the device consists of three components:

  1. A small plastic test tube that the user can put a small sample of food into. The tube contains a solution that dissolves the sample and adds magnetic beads to the solution. The beads are designed to bind to the food allergen of interest.
  2. The user can then drop the solution onto an electrode chip, which is inserted into the keychain sized reader.
  3. The reader analyzes the sample and indicates on a small display whether the allergen is present, and if so, in what concentration.

Testing performed by the research team showed that measurements of the concentration of the allergen is extremely accurate. In fact, the device could detect levels of gluten that were 200 times lower than the federal standard. Accuracy is key because everyone’s sensitivity varies — some individuals could experience a reaction after consuming a miniscule trace of an allergen.

Weissleder and Lee have also developed a smartphone app to complement iEAT. With the app, users can compile and store the data they collect as they test different foods for various allergens at different restaurants and even in packaged foods. The app is set up to share this information online so others with the app will be able to find restaurants with foods that consistently have no or low levels that are below the individual’s triggering concentration.

cell phone app

Consumers may be able to purchase the $40 iEAT device and corresponding app in the near future — the research team has granted a license to a local start-up company to make the system commercially available. Weissleder and Lee also report that they could apply this technology to detect other substances in food such as MSG or even pesticides.

This research was recently highlighted in an NIH article and published in ACS Nano.

It was also recently featured in a news story on CBS Boston.

Partners Healthcare to Introduce New Platform for Recording Patients Data

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Partners Healthcare is launching a new online system, Connected Health Integration Pathway (CHIP), to make workflow easier for clinicians as well as to provide an easy platform for patients to securely record and share their medical information with their care team. CHIP will be used to integrate patient-generated health data into Epic Hyperspace, which is Partners’ electronic health record system.

For instance, if a clinician wants a patient to record their blood pressure for the next 10 days, instead of maintaining a journal the patient can record and submit their readings directly to the system through their sphygmomanometer (blood pressure machine). Through CHIP, the data will be stored as a part of the patients’ medical history.

How does CHIP work for clinicians?

This system would work only if the provider invites their patients to record their medical readings. The invitation process happens within Epic, then the provider chooses what data they wish to see (weight, glucose, blood pressure, etc.)

How does CHIP work for patients?

Patients will receive invite and instructions through the existing Partners Patient Gateway (PPG). After accepting the terms and conditions, the patient will be directed to the Device Marketplace.

Through the Marketplace, patients can send data only from the listed available manufacturers and devices. The data collection begins when a patient authorizes the data pull.

It is important to note that a device can only be used by one patient and cannot be shared by multiple patients. But patients can use multiple devices from different manufacturers at any time.

Also, patients and providers can choose to stop data sharing any time.

CHIP is currently in the pilot mode, and is expected to be live in 2018.

The Partners Connected Health team creates and deploys mobile technologies in a number of patient populations and care settings, and is conducting innovative clinical studies to test the effectiveness of mobile health technologies in various clinical applications, including medication adherence, care coordination, chronic disease management, prevention and wellness. Visit www.partners.org/connectedhealth for more information.

Lady Gaga’s Diagnosis Helps Shed Light on a Perplexing Chronic Pain Disorder

Despite her celebrity status, Lady Gaga has been remarkably honest and open about her struggles with fibromyalgia, a chronic pain disorder. The star announced her diagnosis on social media earlier this month, and just recently canceled tour dates due to disorder-related complications.

Fibromyalgia has traditionally been a challenge to diagnose and treat, because there is no test for it. Doctors make the diagnosis based on patient reported symptoms. Researchers at Mass General are hoping to change that by using imaging techniques to demonstrate brain changes in fibromyalgia patients and investigating potential causes for the disease.

What is fibromyalgia and what are the symptoms?

Fibromyalgia is a common chronic pain disorder that can be extremely debilitating. The disorder is characterized by widespread pain, accompanied with un-refreshing sleep, fatigue, memory and cognitive problems, sensitivity to temperatures, light, and sound, and headaches. It can also co-exist with other conditions including depression, anxiety and irritable bowel syndrome.

These symptoms severely impact the 5-10 million Americans living with this disorder. The pain and fatigue of fibromyalgia can make it difficult to maintain work and social obligations. Symptoms also come in waves at seemingly random intervals, which can blindside individuals.

What causes fibromyalgia?

It’s thought that disturbances in the central nervous system affect the way the brain processes pain signals, which amplifies the painful sensations that fibromyalgia patients experience. But why these disturbances occur remains a mystery.

Experts suggest that the disorder could be driven by several factors, including physical or emotional trauma, prior illness or infection, and genetics. Women are also more likely to develop fibromyalgia than are men, though researchers don’t know why.

In an effort to find answers to these questions, Marco Loggia, PhD, Associate Director of the Center for Integrative Pain NeuroImaging and a researcher in the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, studies the brain mechanisms of pain in patients with fibromyalgia. His research suggests that some degree of brain inflammation may be at play, given that brain inflammation is common among chronic back pain sufferers and most fibromyalgia patients suffer from chronic back pain.

How is it treated?

There is no cure for fibromyalgia. As a result, the focus of treatment is on managing pain and improving quality of life for patients. However, patients often struggle to find the right combination of treatments to manage their condition.

Clinicians often recommend medications including pain relievers, anti-depressants, and anti-seizure drugs to reduce pain and improve sleep. Some patients also utilize therapies such as physical therapy or counseling and alternative treatments like massage therapy, yoga or acupuncture.

Is there stigma associated with fibromyalgia?

Because there are no lab tests to diagnose fibromyalgia, patients are frequently met with skepticism, even by their own primary care team. The pain they report is often dismissed as being “all in their head.”

In a recent interview with HealthDay News, Loggia said, “Many studies—and particularly those using brain imaging techniques such as functional magnetic resonance imaging—have now provided substantial support to the notion that the excessive sensitivity to pain that these patients demonstrate is genuine. I think that it is time to stop dismissing these patients.”

With celebrities like Lady Gaga raising awareness of this disease and researchers like Loggia investigating its causes and progression, could individuals suffering from fibromyalgia soon see advances in treatment and care—as well as more public understanding of this debilitating disorder?

To read more on this topic:

Research Awards and Honors: September 2017

Massachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

Aguirre

Aaron Aguirre, MD, PhD, of the Cardiology Division and the Center for Systems Biology, has received a 2017 Physician/Scientist Development Award for “Morphology and Dynamic Functions of Pericytes in the Heart.” Aguirre’s project will use state-of-the-art microscopy techniques to better understand the role of pericytes—unique cells that line the outer walls of the smallest blood vessels in the heart. Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research along with the Center for Diversity and Inclusion.

“I am grateful for the research support provided by the MGH Physician Scientist Development Award. It will allow me to expand my current research into a new direction and to generate critical preliminary data necessary for future grant applications.”

 

Chung

David Chung, MD, PhD, attending neurointensivist in the Neurology Department, has been awarded the Timothy P. Susco Chair of Research and the Andrew David Heitman Foundation Chair of Research from The Brain Aneurysm Foundation for his work, “Impact of Spreading Depolarizations and Subarachnoid Hemorrhage on Brain Connectivity.” He is one of 14 awardees, given to those whose work is impacting a disease that affects one in 50 people in the United States, often leading to death or lifelong disability.

My immediate reaction to receiving this award was gratitude towards my mentors in the Department of Neurology at MGH: Cenk Ayata, Jonathan Rosand, Guy Rordorf, and Leigh Hochberg. Without their support, this work would not be possible. A major question in Neurocritical Care is how to prevent poor outcome after a ruptured brain aneurysm. Even when we successfully repair the aneurysm, many patients will develop a syndrome of progressive brain damage for unknown reasons. This award will enable us to examine unexplored causes of brain damage and poor outcome with the goal of improving quality of life in survivors of the disease.”

 

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Julie Levison, MD, MPhil, MPH, of the Division of General Internal Medicine, has received a CFAR ADELANTE Award from the National Institutes of Health, the Office of AIDS Research and the NIH-funded Centers for AIDS Research to support new  investigators working on HIV research in Latinos. Hispanic/Latino populations in the U.S. currently bear a disproportionate burden of the HIV/AIDS epidemic. The ADELANTE team is composed of Dr. Levison (principle investigator), Dr. Margarita Alegría, chief MGH Disparities Research Unit, and Carmen Rios, Respite Case Manager at the Barbara McGinnis House.

“The ADELANTE award is a special type of research award because it recognizes the value of community-academic collaborations in overcoming disparities in HIV outcomes in Latino populations. In this study, we will use qualitative research to solicit the needs and priorities of HIV-infected Latino migrants with substance use disorders or who report male-to-male sex and we will use that feedback to tailor and evaluate a community-based intervention we have developed for HIV-infected Latinos with inconsistent HIV primary care attendance.”

 

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Fatima Cody Stanford, MD, MPH, MPA, adult and pediatric obesity medicine physician of the MGH Weight Center, Department of Medicine-Gastroenterology and Department of Pediatrics-Endocrinology, has received a 2017 Physician-Scientist Development Award from the MGH Center for Diversity and Inclusion for “Exploring Referral Patterns and Shared Decision Making Regarding Weight Loss Surgery in Adolescents and Young Adults with Moderate to Severe Obesity.” Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research in conjunction with the Center for Diversity and Inclusion. Stanford also has been selected to the inaugural class of Emory University Alumni Association’s “40 Under Forty,” a selected group of outstanding young alumni with impressive track records who are “go-to” leaders.

“I am delighted to be the recipient of the MGH Physician Scientist Development award in partnership with the MGH Center for Diversity and Inclusion and ECOR. I believe that we are just at the beginning of discerning issues associated with addressing obesity in the pediatric and adult populations. This award allows me to ascertain information about shared decision making in adolescents and young adults with moderate to severe obesity in which weight loss surgery might be utilized to help them achieve a healthy weight. To our knowledge, no one has investigated the use of shared decision making regarding weight loss surgery in young people. This awards allows us to do just that.”

 

Temel GreerJennifer Temel, MD, director of the Cancer Outcomes Research Program and Hostetter MGH Research Scholar, along with Joseph Greer, PhD, program director of the Center for Psychiatric Oncology & Behavioral Sciences, have received a research funding award from the Patient-Centered Outcomes Research Institute (PCORI) for their research “Comparative Effectiveness of Early Integrated Telehealth Versus In-Person Palliative Care for Patients with Advanced Lung Cancer.” The new awards were given to those whose work specifically focuses on community-based palliative care delivery. The goal of this project is to determine if telehealth is an effective, patient-centered, and accessible delivery modality for early palliative care.

“We are overjoyed to receive this research award from PCORI. By testing novel models of care using telemedicine, we hope to demonstrate that greater numbers of patients with advanced cancer and their families can access and benefit from essential palliative care services closer to the time of diagnosis.”

 

Whetstine.jpgJohnathan Whetstine, PhD, of the MGH Cancer Center and Tepper Family MGH Research Scholar, has received a Lung Cancer Discovery Award from the American Lung Association. This award supports investigators at any level of research experience focusing on novel treatments or a cure for lung cancer. His goal is to use studies about histone modifiers to provide insights into tumor heterogeneity and emerging drug resistance so that better molecular diagnostics, epigenetic therapeutic molecules, or use of novel therapeutic combinations can be achieved in cancer treatment.

“We are very excited to receive this award from the ALA.  This support allows my group to continue to expand our lung cancer research program in the area of tumor heterogeneity and drug resistance. Most importantly, these resources allow us the opportunity to explore novel regulatory pathways driving heterogeneity and copy gains of regions affiliated with resistant lung cancer, which provides insights into novel diagnostics and therapeutic opportunities in this hard-to-treat cancer.”

 

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Alik Widge, MD, PhD, director of the Translational NeuroEngineering Laboratory, Division of Neurotherapeutics, has received the 2017 One Mind/Janssen Rising Star Translational Research Award from the One Mind Institute and Janssen Research & Development, LLC. This award identifies and funds pivotal, innovative research on the causes of and cures for brain disorders. Toward boosting the recovery of patients with illnesses such as schizophrenia, major depression or obsessive-compulsive disorder, Widge proposes to identify precisely the brain circuits that govern the inflexibility of thinking common among patients with such illnesses, and to test whether neurostimulation of these circuits could improve mental flexibility.

“I was very excited about the Rising Star award, for two reasons. First, it brings much-needed seed funding to our lab for an unconventional but possibly high-yield project. We have found that electrical brain stimulation in humans can improve mental flexibility — the ability to “take the road less traveled by” and explore new behavior strategies. That ability is impaired in many mental illnesses. Our problem is that we don’t yet know how the electrical stimulation improves flexibility. The Rising Star award will let us set up animal experiments to identify the circuit basis of the effect, findings we could then translate back into humans. 

Second, this is a really important award in psychiatric research. It’s brought our lab’s other work into the spotlight, which will help those projects progress. I’m grateful both to the OneMind Institute for the award and to the MGH team that helped me get the preliminary data that made it possible.”

Could an App Ease the Stress of Managing Heart Failure?

A heart failure diagnosis can be an unsettling experience. Add in a deluge of new medication regimens and lifestyle changes to implement, and the entire episode can begin to feel very overwhelming for a heart failure patient.

A new smartphone app from Jana Care, called Heart Habits, was created in the hopes of streamlining cardiac care management. Now a team at Massachusetts General Hospital wants to test out the app with patients.

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Screen shots of the Heart Habits app (photo courtesy of Jana Care)

“Heart failure patients are pretty complex,” Nasrien Ibrahim, MD, a cardiologist at Mass General and one of the lead investigators, said in a recent interview with MobiHealthNews. “We’re always looking for ways to improve patient care, reduce morbidity and mortality, to keep these patients out of the hospital or the emergency department, and just improve their overall quality of life.”

The Heart Habits app prompts patients to track their symptoms twice a week and provides alerts if any signs or symptoms, such as shortness of breath, suggest a problem that may require medical attention.

The app also provides information on and tracks other important factors including weight. Patients are prompted to record their weight on a daily basis. The data is then translated into graph form, which the patients’ care teams—who have access to the app—can easily view and interpret. The Heart Habits app also enables two-way communication with a messaging feature that allows patients to contact their physicians.

Ibrahim and her team want to investigate how patients respond to using the app and if its use improves patient symptoms. Their initial pilot will include 24 patients randomized to either the app or the standard of care—paper documents given to patients to take home—for six weeks.

“If the pilot study works, meaning the app is user-friendly, we see improvement in scores, that the patients like it, and that their symptoms have improved, a larger study would involve biomarker testing, outcome measures such as hospital readmissions and emergency department visits, and, essentially, cost as well,” Ibrahim said.

Shining a Light on MS-Related Fatigue

When the days are short and daylight is scant in the winter months, using special lamps that create artificial sunlight can help alleviate the symptoms of seasonal affective disorder — commonly referred to as the winter blues. But could light therapy serve a grander purpose and help treat the debilitating symptoms associated with neurological diseases?

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Farrah J. Mateen, MD, PhD

Farrah J. Mateen, MD, PhD, Associate Director of the MGH Multiple Sclerosis Clinic at Massachusetts General Hospital and Associate Professor of Harvard Medical School, is investigating the impact of light therapy on multiple sclerosis (MS), a degenerative condition of the central nervous system with no known cure.

In MS, damage to the protective sheath that covers nerve fibers causes communication problems between the brain, spinal cord and the rest of the body. The disease is primarily diagnosed in women in their 20s to 40s, and is a leading cause of non-traumatic disability in young adults. Celebrities including Jamie Lynn-Sigler, Ann Romney and Jack Osbourne have all publicly discussed their personal struggles with MS.

Signs and symptoms vary widely and usually come and go in a relapsing and remitting pattern. The most commonly reported symptom is fatigue — more than a quarter of people living with MS report fatigue as their most disabling symptom. MS-related fatigue is unique in that it can strike even after a restful night’s sleep, it can come on suddenly and severely, and it often occurs on a daily basis.

Given the substantial impact fatigue has on MS patients’ everyday life, Dr. Mateen has focused her efforts to determine whether light therapy could be a potential treatment option for the symptom. She hypothesizes that light therapy could improve fatigue by stimulating receptors in the frontal lobes of the brain, where fatigue is thought to be localized. It could also help set the circadian rhythm and aid with sleep.

“Light therapy has already had positive results in other diseases, such as Parkinson’s, where fatigue is a key symptom,” explains Mateen. She’s optimistic that, given the similarities between the two diseases, light therapy could also improve quality of life for patients with MS.

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Light therapy box

Her current study, funded by grants from the National MS Society and the Department of Neurology’s Spark Grant (with co-principal investigator, Aleksander Videnovic, MD, MSc, a Mass General-based sleep and neurodegenerative diseases expert), provides participants with a lightbox that can be placed on a desk or a table. Participants sit in front of either a dim red light or white light for an hour in the morning and an hour in the evening each day for four weeks and are asked to record their fatigue levels daily using a 10-point scale. Light therapy boxes can be used at home or work and participants can eat, watch TV, etc. during use.

Mateen and her team aim to enroll 50 participants, a number Mateen thinks they can easily meet.

“We have a backlog of people waiting to be in the study”, says Mateen. “An advantage of studying MS is the high number of dedicated patients who want to be part of research. Currently there’s really no good treatment for fatigue in MS. Of the few available medications, some are potentially habit-forming stimulants, which MS patients should be cautious of because it could interfere with other medications they’re already taking.”

Children with MS also have few medical options for treating their fatigue, and most trials for new treatments are deemed too risky to test on kids. Mateen’s future research interests are to also address MS-related fatigue in children, given how disabling the symptom can be for this population.

“Light therapy trials would provide an opportunity for kids to actually be part of a study that could help them, and help other kids. In my mind, it makes just as much sense to test light therapy on kids — if we see positive results, it could be a viable a treatment option for both kids and adults.”