Project to use computer modeling to study nonremovable blood clots

A team of Penn State and U.S. Food and Drug Administration researchers studying why certain stroke-causing blood clots cannot be removed benefited from an early investment by Penn State Clinical and Translational Science Institute. National Institutes of Health recently awarded a $2.49 million grant for the research project.

“If we can understand more about these clots and the surrounding environment, we hope to find ways to remove them safely,” Keefe B. Manning, PhD, associate dean of Penn State Schreyer Honors College, professor of biomedical engineering and co-principal investigator of the study, said.

Strokes occur when the blood supply to the brain is interrupted or reduced. Leaking or bursting blood vessels cause hemorrhagic strokes, and a blockage or narrowing in a blood vessel causes ischemic strokes. Dislodged blood clots that move with the blood flow are a common blockage.

While the use of stents to reopen blocked blood vessels is improving, more than 15% of the clots cannot be cleared. In addition, another 17% of patients die within 90 days despite the successful restoration of blood flow.

“Understanding the exact nature of the blood clots that are very hard to remove is a challenge since we cannot get to them,” Manning said. “We rely on a lot of peripheral data — from patient imaging to the patient’s blood biochemistry to testing patient clots that have been removed.”

To address this problem, researchers will use computer modeling to simulate clot formation, movement and removal.

This approach mimics how computer models are used to forecast weather and design rockets and aircraft, according to Francesco Costanzo, PhD, co-principal investigator, associate head of engineering science and mechanics and professor of engineering science and mechanics, mathematics, mechanical engineering and biomedical engineering.

“A great deal of aircraft performance design is now done on a computer rather than in the shop,” Costanzo said. “We are striving to achieve the same goal in medicine. We want to be able to monitor the health of a patient, predict when something might go wrong and prepare for optimal interventions when some problem does indeed occur. All of this effort requires the acquisition and processing of an enormous amount of information, and computational technology is a key factor in achieving our goal.”

Penn State Clinical and Translational Science Institute funded an earlier project by Costanzo through its Bridges to Translation Pilot Grant Program, which laid the groundwork for the current work.

“The Bridges to Translation pilot grant was an essential element of the progress we have already made and the new work that we are starting right now,” Costanzo said. “Seed grants are often the key to the generation of preliminary data for a follow-up grant. In our case, the Clinical and Translational Science Institute grant provided an opportunity to bring together researchers who had not worked together previously. The grant gave us the freedom to brainstorm and to become a research team.”

The institute funded “Computational Modeling of Clot Fracture Mechanics for the Surgical Therapy of Acute Stroke” in 2014. The project started as a collaboration between Scott Simon, MD, associate professor of neurosurgery, Penn State College of Medicine, and Sulin Zhang, PhD, professor of engineering science and mechanics, Penn State University Park.

The motivation for the project was the idea a new technique could improve clot retrieval.

“As ‘trial and error’ is not a viable approach for developments involving human subjects in life-threatening situations, we realized that this type of project was a perfect opportunity for the use of computer simulations to improve surgical techniques,” Costanzo said. “The pilot grant was instrumental in allowing our team to learn about what modeling can do to advance surgical techniques.”

During this work, Costanzo said the team realized it needed a specific research component focused on blood clotting and clot blockages. The team added Keefe, an expert in the modeling of clot formation in cardiovascular devices, which provided crucial experience and credibility.

“The scope of the Clinical and Translational Science grant was limited to the study of the interface between artery and clot,” Costanzo said. “With Dr. Manning’s experience, we were able to propose a model and a new experimental approach that led to a publication, the latter providing the foundation for the new NIH grant. “

The new research may lead to better outcomes for stroke victims and other types of patients.

“We may be able to apply any technology developed from the grant to other blood clots that get stuck in other areas,” Manning said.

The research is an example of beneficial collaboration and translational science within the Penn State system, according to Simon, co-principal investigator of the study.

“With regard to designing better stroke devices, we do not have the computational expertise or resources here in Hershey, and the University Park campus doesn’t have the clinical expertise or the patients to impact this disease process effectively,” Simon said. ”Together, we can bring impressive reservoirs of knowledge and skills from many perspectives to solve pressing clinical problems.”

Penn State Clinical and Translational Science Institute awarded six rounds of its Bridges to Translation pilot grants. The institute invested $3.5 million into novel research at Penn State through the program, which has led to $40.8 million in external funding to continue the projects.

This story was adapted from a Penn State News story by Jamie Oberdick.

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