Four Stanford Medicine researchers have been awarded Advanced Research Projects Agency for Health contracts.
ARPA-H, an agency within the U.S. Department of Health and Human Services, was established by U.S. Congress and President Joe Biden in 2022 to increase investments in breakthrough solutions with the potential to transform critical aspects of medicine and health that cannot readily be accomplished through traditional research or commercial activity.
Andreas Loening, MD, PhD, associate professor of radiology, is heading a team to make imaging of the lymphatic system more accessible. David Rehkopf, ScD, professor of epidemiology and population health and director of the Stanford Center for Population Health Sciences, and his colleagues are building a database to determine causes of and prevention of disease. A group led by Stanley Rockson, MD, a professor of cardiovascular medicine and the Allan and Tina Neill Professor in Lymphatic Research and Medicine, is developing a device to prevent lymphedema after cancer treatment. Michael Snyder, PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics, is leading a group to develop a measurement of age-related decline.
A more accessible imaging tool
For patients who need imaging of their lymphatic system, magnetic resonance lymphangiography can be a critical diagnostic tool. It offers a whole-body field of view; is able to penetrate deep into tissue at imaging resolutions permitting identification of individual lymphatic channels; provides an assessment of lymphatic flow; and visualizes secondary manifestations of lymphatic blockages such as fluid buildup, fibrosis and increased fat deposition.
But MRL in its present form has its limitations: Patients need to be injected with a contrast agent to evaluate lymphatic flow and areas of blockage, current MRI contrast agents are not designed for evaluating the lymphatic system, the examinations take over an hour to perform, and studies require a specially trained radiologist to administer the examination.
A team at Stanford Medicine collaborating with researchers at the University of California, Berkeley, and Imperial College London, led by Loening, has been awarded up to $3.9 million to make MRL faster and easier to perform by developing new contrast agents specifically for lymphatic evaluation, improving the resolution of the imaging exams and developing ways of evaluating lymphatic flow without the use of contrast. The goal is that more patients will be able to receive comfortable, high-quality scans closer to home and receive an earlier, more accurate diagnosis.
“Lymphatic diseases are often overlooked and surprisingly under-researched given their prevalence in the human population,” Loening said. “This award has given our team a unique opportunity to direct appreciable research effort at improving the state of the art in MR lymphangiography.”
Preventing chronic disease
Electronic health records tell important stories about the health struggles and successes of patients. A team at Stanford Medicine is using that data to determine what can cause — and what can prevent — chronic disease.
The team, led by Rehkopf, was awarded up to $6.4 million to create a national primary care data resource that will guide effective strategies for preventing disease.
Most electronic health record data used for research comes from large urban medical centers. But the researchers decided to use the PRIME registry — the largest registry of primary care practices in the U.S. with information from more than 8 million patients — because it includes many patients living in rural areas, creating a more inclusive dataset.
The researchers will look at individual and environmental elements in determining the risk of developing disease.
“As part of thinking broadly about preventing disease, we want to bring in information on all of the factors that impact people’s health and make it easier for them to be healthy. We will integrate factors like housing stability, food access and neighborhood air quality — things that may reveal not only why people are sick but also what might prevent the illness in the first place,” Rehkopf said.
The project team, concerned about patient privacy, is working on technical solutions to solve this, including leveraging generative artificial intelligence to create synthetic datasets, mirroring the real data.
Preventing lymphedema after cancer treatment
Cancer treatment frequently damages a patient’s lymphatic system, which can result in lymphedema, a condition marked by swelling of the limbs. Lymphedema can cause immobility, skin infections and pain. Despite major advances in cancer care, an estimated 15% to 40% of cancer patients, including nearly 1 in 3 breast cancer survivors, develop lymphedema.
Researchers, led by Rockson, were awarded up to $12.9 million to create a small implantable device that can be paired with medication to encourage the regeneration of lymphatic vessels, preventing chronic lymphedema. The implant, measuring approximately a half centimeter, can be placed at the site of lymphatic injury during cancer surgery. Several of these devices could be inserted in a single patient.
Unlike current preventive options, which often rely on complex microsurgical procedures requiring highly specialized teams, the new device will be usable by virtually any surgeon performing cancer surgery.
“This work represents an exciting opportunity to implement effective lymphedema prevention,” Rockson said. “By enabling the regeneration of lymphatic vessels at the time of surgery, we hope to prevent this life-altering and common complication of otherwise successful cancer treatment.”
The project will involve researchers from Imperial College London, Harvard University, Yale University, Rutgers University and the Lymphatic Education and Research Network.
Assessing how to PROSPR
Despite our aging population, there is no standardized, easily accessible or affordable way to determine a person’s age-related decline in intrinsic capacity, an aggregate measure of mental and physical capabilities.
A team of researchers, led by Snyder, hope to change that by developing an assessment that can score a person’s resilience and intrinsic capacity. The team received up to $34 million to develop this assessment, which will result in a score, called a PROSPR intrinsic capacity score. (PROSPR program stands for proactive solutions for prolonging resilience.)
The researchers aim to create the assessment using health data from hundreds of thousands of patients.
“We plan to develop and test a biomarker panel that predicts health outcomes for the next 20 years of a person’s life,” Snyder said.
Once the PROSPR IC score is developed, researchers will use an at-home assessment kit that can read biomarkers, via blood samples and health data from wearable technology, to enable patient monitoring. The researchers will also test whether certain interventions can improve a person’s PROSPR IC score as well as see if a person’s score declines as they age.
A standardized measure of a person’s health could empower individuals and their clinicians to personalize their health care and expedite preventive medicine, all while significantly reducing health care expenses, Snyder said.
The team includes researchers from Brigham and Women’s Hospital, the Buck Institute for Research on Aging, the Methuselah Foundation and the California Institute for Stress and Resilience.
