BME Alum Guides Iliac Vein Fluid Dynamics Research He Began as an Undergraduate

A team of researchers working with C. Alberto Figueroa, the Edward B. Diethrich Professor of Vascular Surgery, Professor, Biomedical Engineering, discovered that patients with iliac vein compression syndrome (IVCS) have elevated shear rates, which may explain why they have a higher risk of experiencing venous blood clots. The U-M research findings were published in recent issues of Frontiers in Bioengineering and Biotechnology and the Journal of Vascular Surgery Venous and Lymphatics Disorders.

More than 20 percent of the population has IVCS, which is associated with left leg pain, swelling and clotting. Dr. Figueroa noted that IVCS originates as an anatomical abnormality, when one of the veins, specifically the left common iliac, is more compressed than normal. This extra compression combines with additional risk factors to increase the likelihood that a patient may experience recurring episodes of blood clots.

To build and validate patient-specific computational fluid dynamics models of the iliac veins, the U-M team used computed tomography and ultrasound data. Based on their results, the researchers propose that non-invasive measurement of shear rate may help with risk stratification of patients with moderate compression in which current treatment is highly variable. More investigation is needed to determine the prognostic value of shear rate as a clinical metric and to understand the mechanisms of clot formation in IVCS patients.

The first author of this report is BME alum Ismael Assi (BSE, ‘22), who has researched this topic for more than three years, beginning as an undergraduate. Assi and Dr. Figueroa recently discussed the backstory of how the study came together.

“The very origin of this project came from the PhD work of BME student Sabrina Lynch, who developed methods to simulate flow on the venous system, where properties of blood are different from those that we see on the arterial side,” Dr. Figueroa said. “At the time, Ismael was a sophomore. He started closely working with Sabrina and eventually took over this project, looking specifically at patients with iliac vein compression syndrome, his own.”

Dr. Figueroa continued: “Ismael made it into a very clinically oriented study and demonstrated tremendous initiative. He started working with vascular surgeons, interventional radiologists, and also with nurses and other staff in the diagnostic vascular unit (DVU). He basically developed a prospective study entirely by himself–including securing an IRB (Institutional Review Board) approval.” Dr. Figueroa noted that Assi worked in tandem with clinicians and was engaged in all aspects of the study, including patient recruitment.

“It was very much a team effort,” Assi said. We collaborated with nurses, sonographers, interventional radiologists, surgeons and engineers. You had everyone from mechanical engineering to clinical researchers involved, and I think that’s what really helped to bring the project together.”

Assi noted that his work with a diverse group of professionals taught him how to organize his thoughts, improve his writing skills and interact with journal reviewers. He was especially thankful for all the mentorship he received from Drs. Figueroa, Lynch, Obi, Wakefield, Williams, and all the sonographers at the diagnostic vascular unit.

“You learn so much by doing a research project,” Assi said. “Especially when it’s a longitudinal one over several years. I look back at the mistakes I made, and they’re very valuable because I was learning how to communicate with people from different backgrounds and skill sets, how to acquire data and how to organize meetings. These are all valuable skills that I learned in research that I wouldn’t have learned in other avenues. I would definitely encourage students to seek out research to explore their interests. There’s nothing like it.”

Assi added that he was inspired by hearing the stories of patients and what they went through when they had blood clots. “Hopefully, I will be able to make a difference in the treatment of these patients,” he said. “Many people have this compression, so the medical community is working to gain a better understanding of when it is indicated to treat patients. Do you only treat symptomatic patients with anticoagulation? When do you stent patients? When do you not treat patients? There are a lot of questions that are unanswered.”

This study consisted of a group of four patients with venous compression and four control patients with no compression. “The goal was to look for a metric that could stratify patients,” Assi said. “How can you measure the severity of a patient’s disease? That question requires further clinical validation. Right now, we found that shear rate, which is a surrogate index for the activation of platelets, can be used to differentiate healthy patients versus patients who have compressed iliac veins.”

“The results are quite statistically strong,” added Dr. Figueroa, “in the sense that these parameters or these biomarkers of the shear rate showed a very strong significance between patients with normal iliac vein anatomy and patients who have compression syndrome. Even for the iliac vein compression syndrome examples, there was a very substantial difference between the contralateral vein, which is the vein on the other side. There’s an ongoing study where measurements are being taken for both diameters and ultrasound-derived velocities to look at a much larger group of patients. One of the things that we are trying to do is integrate something into the clinical workflow that you can almost get a quick answer for without having to go through all the sequence of steps in the computational analysis that we do, which is quite time consuming.”

BME alum Assi knew about the breadth of professional options available to biomedical engineering majors, but his research experience ultimately inspired him to attend medical school. “I think one of the big reasons I chose medical school was a patient who was a former nurse who had a blood clot in her leg,” Assi said. “Because she was a nurse, she knew exactly what was going on, so she went right to the emergency room. She told me her whole story, but I think another aspect that was very important was that her daughter had had a blood clot in her carotid artery, which is in the neck. The patients’ dad had also passed away from a blood clot. When I heard about how her entire family was unfortunately afflicted by blood clotting, it was very motivating. My interest in the project just increased that much more because I really wanted to make a difference in the lives of patients like her.”