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Jiménez Works on International Team of Researchers Receiving Nearly $1-million Grant to Study the Pathobiology of Cerebrovascular Diseases

Juan Jiménez

Juan Jiménez

Assistant Professor Juan Jiménez of the Mechanical and Industrial Engineering (MIE) Department is a co-principal investigator with Dr. Kristian Valen-Sendstad from the Simula Research Laboratory of Oslo, Norway, on a $937,848 grant from the Research Council of Norway to study a critical question: “Are Computer Simulations Misleading Us About the Pathobiology of Cerebrovascular Diseases?”

The group headed by Dr. Valen-Sendstad will develop numerical methods to accurately resolve the flow field in the human cerebral vasculature. In an in vitro flow chamber, Dr. Jiménez’s group will expose endothelial cells that make up the inner layer of blood vessels to the flow fields present in the cerebral vasculature and that were identified in the numerical simulations. The in vitro experiments will help identify genes that play a role in the development of cerebral aneurysms.

The Jiménez Research Group studies the interaction between fluid flow and biology by integrating fluid dynamic engineering with cellular and molecular biology.

As Jiménez explains about his MIE research team, “Body fluids or biofluids, such as blood, lymph, and cerebrospinal fluid, continuously interact with cells in the body eliciting biochemical and physical responses. Our research seeks to elucidate the fluid flow characteristics and fluid flow-dependent biomolecular pathways relevant in medicine.”

The grant proposal states that “Cardiovascular diseases are burdening the healthcare systems, and the costs are expected to rise in the years to come. Acute stroke is alone estimated to cost the European countries an overwhelming 40 billion Euros.”

The team goes on to explain that medical image-based computational fluid dynamics (CFD) has been extensively used to study ‘patient-specific’ abnormal forces in search for a mechanistic biological link to the initiation of cerebrovascular diseases. Commercial CFD solvers offer black-box solution strategies and have dominated the aneurysm literature.

“However,” as the proposal explains, “while robust, the default settings in most commercial codes trade accuracy for speed, and are generally not capable of handling transition from a laminar regime into more complex flows, an intricacy generally overlooked by users not being CFD experts.”

Research has previously shown that such tools as CFD can be misleading about the nature of blood flow in the cardiovascular system by overlooking a flow phenotype colloquially called “turbulence.” This project funded by the Research Council of Norway is meant to answer fundamental questions in vascular biology critical for the understanding of cerebrovascular disease initiation and progression.

“If we can understand disease initiation,” exclaim the investigators, “we can possibly prevent or even reverse disease. The majority of the work will be related to the development of new sophisticated numerical models needed to test hypotheses in biomechanics, and the numerical simulation results will be used to guide in vitro cell experiments.”

The proposal adds that “More specifically, the goal is to investigate whether endothelial cells can sense, distinguish, and finally respond (adversely) to the different hemodynamic stimuli and frequencies we observe from highly accurate and resolved CFD simulations.”

The research team will also test this hypothesis in vivo by looking at differences in flow phenotype in patients with aneurysms and hence shed light on fundamental biology. The proposal concludes that “the proposed project…can potentially have a profound impact on vascular biology, cardiovascular disease understanding, and potentially clinical practice.”

The complex nature of the problem is reflected by the multidisciplinary character of the team, consisting of both national and international collaborators from highly renowned research and clinical groups such as that of Jiménez. (May 2016)