Multifunctional VAD Technology for High-Risk Pediatric Patients

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PROJECT SUMMARY This Diversity Supplement application promotes the qualified candidate’s development and transition to a high-ranking M.D./Ph.D. program toward a long-term career as a clinician and academic researcher. Research in this proposal will focus on the investigating the impact of non-pulsatile blood flow on cerebrospinal fluid (CSF) dynamics in patients who receive mechanical circulatory support (MCS). Her experienced mentor is Amy Throckmorton, PhD (MCS biomedical engineer) at Drexel University. She has assembled an Advisory Committee that is comprised of renowned researchers in cardiovascular physiology, computational modeling, cerebral hemodynamics, cerebrospinal fluid (CSF) dynamics, neurosurgery, and MCS; thus, she will develop and refine her expertise in these fields. She will also gain skills and knowledge in networking, technical writing, multi physics modeling, research ethics, pediatrics, and cardiothoracic surgery. The candidate is supported by outstanding institutional resources at Drexel University, Thomas Jefferson University, and Univ. of Delaware. There is limited understanding of the interchange between continuous-flow (CF) MCS and cerebrospinal fluid (CSF) dynamics. Studies have demonstrated clinical benefits from CF-MCS, but there are also challenges, such as thromboembolic (stroke) events. Research efforts to-date have concentrated on mitigating stroke risk, and the impact of CF-MCS on the CSF flow physics has not been investigated. Flow disturbances in the CSF are recognized to contribute to neurologic pathophysiology. The field of MCS is also now pivoting toward the use of more compact, less thrombogenic, non-pulsatile CF devices. These aspects emphasize the unmet clinical need of exploring the neurologic risk beyond stroke and examining the physiologic consequences of CF-MCS on CSF dynamics and the amplified risk of neurologic impairment. The long-term goal of this research is to build our understanding of the pathophysiologic consequences of CF-MCS on CSF dynamics. Strong prior work demonstrates evidence of abnormal CSF dynamics during CF-MCS. Thus, our central hypothesis is that CF in a patient with CF-MCS leads to a diminished or absent pulse pressure, which produces decreased pulsatile CSF flow. This hypothesis will be further tested in these Aims: 1) establish a computational framework of cardiovascular, cerebral and CSF fluid dynamics; and 2) characterize the impact of CF-MCS on the CSF physics. This research will advance our understanding of CF-MCS and enable us to devise new innovative solutions to mitigate the risk of neurologic complications during CF-MCS. The candidate intends to continue focusing her efforts on the improvement of cardiovascular therapeutic solutions both during her pursuit of an M.D./Ph.D. and throughout her clinical research. The experience and skills gained from the training in this proposal will allow the candidate to successfully continue these efforts, bolstering her ability make significant contributions towards advancing the field of medicine.