Project Details
Description
PROJECT SUMMARY
This competitive renewal application focuses on advancing the field of intracranial flow diversion (FDs), that
currently constitutes approximately one-third of the treatment of unruptured intracranial aneurysms. There
remain key gaps in the knowledge that hinder expansion of the clinical application of these transformational
devices, which to date are limited in scope to unruptured, proximal aneurysms along the internal carotid artery.
We envision that, with our proposed discovery system, we will facilitate application of novel, next-generation
devices in ruptured aneurysms and in aneurysms distal to the Circle of Willis, and will allow customization of
approaches to minimize thromboembolic risk in individual patients. We will break down these barriers to
expanded utility by 1) understanding of key aspects of aneurysm occlusion, such as the role of acute and
appropriate fibrin deposition across the aneurysm neck, 2) unraveling the mechanisms underlying side branch
occlusion (i.e. the impact of hemodynamic, or neointimal growth and endothelizalization across the side branch
ostia, or both), and 3) identifying the potential risk factors that cause elevated risk of thromboembolic
complications, such as hemodynamical variable, device malapposition, platelet function, and untoward fibrin
deposition beyond the neck of the aneurysm, among others. We propose to employ innovative approaches in
in vivo intravascular fibrin molecular imaging, computational fluid dynamics modeling, and improved animal
modeling, and finally biomarker discovery in clinical studies. These approaches can improve the outcome of
not only FD, but other devices in treating aneurysms by better understanding of the mechanisms of both
aneurysm healing and complications. Our robust and reproducible methods of statistical evaluations will
directly assess 1) the role of fibrin deposition rapidity in the device at the neck of the aneurysm aids robust
aneurysm, 2) the suitability and validity of the superior mesenteric artery branches to simulate the patency of
the small perforating vessels covered by FDs, and 3) correlate biological and imaging data with delayed
ischemic events following FD therapy.The discoveries from this hypothesis-driven, multidisciplinary,
multimodality, clinical-translational research will provide a robust understanding of not only the mechanism of
action of FDs in aneurysm healing, but also the development of device-related complications. These
discoveries can provide guidance to clinicians using current technologies to optimize outcomes and minimize
complications, as well as investigators and engineers to develop improved devices. Ultimately, this information
will allow neurointerventionalists to make better informed decisions on device choice, leading to improved
patient care.
Status | Finished |
---|---|
Effective start/end date | 9/20/11 → 11/30/23 |
Funding
- National Institute of Neurological Disorders and Stroke: $509,078.00
- National Institute of Neurological Disorders and Stroke: $526,105.00
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