Powerful Learning Technique May Expand Artificial Intelligence Medical Applications

Supervised deep learning models for image-based medical diagnostics are usually trained with large and expertly annotated datasets collected using high resolution imaging systems at one clinical center. These models can perform with high accuracy during testing but fail when applied to a dataset collected using a different imaging system at a different clinical setting. This problem is critical in medical image analysis tasks since it could affect clinical decision making and reliability across different centers and practices.

Investigators from the Brigham have developed a new approach for AI-based medical image processing that can be adapted across imaging systems and used for images of varying quality including medical images recorded with low-cost, portable smartphone-based optical settings. The team evaluated their approach using three diverse clinical models: the evaluation of human embryos, the quantification of human sperm morphology, and the diagnosis of malarial infections in blood.

“We have tackled one of the major challenges in AI-based medical image processing approaches where image data from different distributions with different image qualities are analyzed,” said corresponding author Hadi Shafiee, PhD, a faculty member at the Division of Engineering in Medicine and Renal Division of Medicine at the Brigham and Harvard Medical School. “We have developed novel approaches that are generalizable with different medical image data distributions and have tested our frameworks with three different clinical models in infectious diseases and infertility.”

Read more in Nature Biomedical Engineering

 

Microneedle Patches Could Offer Local, Painless Drug Delivery

Microneedles delivering immune modularity molecules and sampling tissue state. Credit: Ella Maru

Investigators from the Brigham and MIT have developed a microneedle platform that can simultaneously deliver therapeutics and monitor changes in tissue inflammatory states. The team designed a highly swellable microneedle platform composed of hyaluronic acid that is able to locally release therapeutics and to sample the interstitial fluid in the skin.

“Applying the microneedles to the skin is not only painless, but also allows us to locally release molecules that modulate the immune system while avoiding the side effects associated with systemic delivery. The patch was engineered to enable noninvasive interstitial fluid sampling to diagnose the response to the therapy,” said co-senior author Natalie Artzi, PhD, a bioengineer in the Division of Engineering in Medicine and a principal research scientist at MIT.

In a newly published study, the team demonstrated for the first time that this patch, when applied on top of skin allografts — patches of skin that can be transplanted — can deliver immunomodulatory drugs to suppress transplant rejection.

“We used this technology to release compounds that reeducate the immune system to stop attacking the skin. This platform technology could be critical for novel targeted therapies for skin immune-mediated diseases — such as psoriasis, alopecia areata and atopic dermatitis — and we are working on next steps to translate this technology to the clinic,” said co-senior author Jamil R. Azzi, MD, associate director of the Kidney Transplant Division and physician scientist at the Transplantation Research Center.

Read more in Advanced Functional Materials.

Sleep Difficulty and Disturbance Linked to Increase Risk of Dementia, All-Cause Mortality in Older Adults

A new study from the Brigham’s Division of Sleep and Circadian Disorders demonstrates the relationship between sleep difficulties and the risk of incident dementia and all-cause mortality. The team used data collected over an eight-year follow-up period from the National Health and Aging Trends Study (NHATS), which is representative of more than 32 million adults over the age of 65 living in the United States. The specific sleep difficulties studied were difficulty initiating sleep and nighttime awakenings. The research team found that sleep duration and latency were associated with incident dementia. Furthermore, difficulty maintaining alertness, napping, sleep quality and very short sleep duration were linked to all-cause mortality.

“Our study is novel in that it explores specific sleep difficulties and incident dementia,” said corresponding author Rebecca Robbins, PhD, of the Division of Sleep and Circadian Disorders at the Brigham. “Each sleep difficulty has unique challenges and treatment recommendations, and difficulties are reported at varying intensities across the population of older adults, lending support for exploring each difficulty distinctly.”

Read more in the Journal of Sleep Research.

Study Finds Women with Osteoporosis and Low Bone Density Are at Increased Risk of Hearing Loss

Studies of people with hearing loss have uncovered higher prevalence of osteoporosis — a disease in which the bones become weak and brittle — and low bone density (LBD). But research on whether these conditions may influence risk of hearing loss over time is scarce. It is also unknown whether hearing loss can be avoided by taking bisphosphonates, the primary medication used to prevent fractures in people with reduced bone density. As part of the Conservation of Hearing Study (CHEARS),Brigham researchers analyzed data from nearly 144,000 women who were followed for up to 34 years. They found that risk of subsequent moderate or worse hearing loss was up to 40 percent higher in study participants with osteoporosis or LBD. Bisphosphonates did not alter risk of hearing loss.

“Adult onset hearing loss is typically irreversible; therefore, CHEARS focuses on identifying potentially modifiable risk factors that may contribute to hearing loss,” said study leader Sharon Curhan, MD, ScM, of the Channing Division of Network Medicine at the Brigham. “We wanted to investigate whether bisphosphonates alter risk of hearing loss in adults, in addition to whether there is a longitudinal association between osteoporosis or LBD and risk of subsequent hearing loss.”

Read more in the Journal of the American Geriatric Society and in a Brigham research brief.

Ultrasensitive Blood Test Detects Viral Protein, Confirms mRNA Vaccine Activates Robust Immune Response

A new study by Brigham investigators at used an ultrasensitive, single-molecule array (Simoa) assay to detect extremely low levels of molecules in the blood and measured how these levels change over the days and weeks following vaccination with the Moderna (mRNA-1273) vaccine. The team found evidence of circulating protein subunits of SARS-CoV-2, followed by evidence of the body mounting its immune response and then clearing the viral protein to below the level of single-molecule detection.

“Because of our ultra-sensitive method, we’re able to corroborate that the mRNA vaccine is operating as intended, stoking the body’s immune response,” said co-corresponding author David Walt, PhD, a member of the faculty in the Department of Pathology at the Brigham. Walt is also a member of the Wyss Institute and is a Howard Hughes Medical Institute Professor. “We were able to detect extremely low levels of viral protein and see that as soon as the body begins generating antibodies, those levels declined to undetectable.” Walt has a financial interest in Quanterix Corporation, the company that developed the ultra-sensitive digital immunoassay platform used in this work.

Read more in Clinical Infectious Diseases and in a Brigham research brief.

T Cells Offer Insights into TB Progression

Nearly a quarter of the world’s population is estimated to be infected with the pathogen that causes tuberculosis (TB), but less than 15 percent of infected individuals develop TB disease. A new study by investigators from the Brigham, Harvard Medical School and the Broad Institute offers insights into the immune system that may help identify risk factors for disease progression. In collaboration with Socios en Salud (a part of Partners in Health based in Peru), researchers looked at memory T cells from 259 individuals in a Peruvian tuberculosis (TB) progression cohort. The study leveraged high-dimensional single cell data with new computational techniques to define key cell states for TB progression. By integrating single-cell RNA and surface protein data from more than 500,000 memory T cells, researchers defined 31 cell states and identified a key T cell type that may be deficient in many individuals who progress to develop active TB. This study implicated Th17 function as a potential component of preventing TB progression.

“We are hopeful that the strategies used will help us in the future identify high-risk individuals for TB, and point the way to the kinds of vaccines and other immunomodulatories that might prevent TB,” said corresponding author Soumya Raychaudhuri, MD, PhD, a principal investigator in the Division of Rheumatology, Inflammation, and Immunity at Brigham. “This study is not only exciting because of the large-scale single cell genomic tools that we use, but also because it is one of the only studies of its kind in infectious disease.”

Read more in their paper in Nature Immunology.

Study Finds Potential Causality Between Blood Clot Factors and Migraine with Aura

Individuals who experience migraine with aura (MA) face a heightened risk of stroke and cardiovascular disease, although scientists continue to explore why this correlation exists. In a new study, Brigham researchers used a technique in genetic analysis termed Mendelian randomization to examine 12 coagulation measures, uncovering four that are associated with migraine susceptibility. Interestingly, scientists only observed these associations in individuals who experience MA and did not observe such associations among individuals who experience migraine without aura. Their research suggests that these hemostatic factors could potentially have a causal role in MA.

“We’ve always wanted to know why people with MA have this higher risk of stroke and other cardiovascular diseases,” said corresponding author Daniel Chasman, PhD, of the Division of Preventive Medicine at the Brigham. “This study offers promising leads specific to MA. Finding a possible cause for migraine with aura has been an outstanding question in the field for a long time.”

Read more in their paper in Neurology and a Brigham research brief.