This competitive renewal application focuses on advancing the rapidly-evolving field of intracranial flow diversion, which, over the span of less than 5 years, has grown to encompass up to one-third of intracranial aneurysm treatments in the US. We will address clinically-relevant, ongoing gaps in knowledge, including 1) what constitutes the primary mechanism of action of flow diverter efficacy, 2) what underlies the unusual, but devastating complications, including ipsilateral, intraparenchymal hemorrhage and spontaneous aneurysm rupture, and 3) what design features of these devices can be enhanced to optimize outcomes? Our translational, hypothesis-driven methodology traverses from computational/in vitro work (computational fluid dynamics and in vitro bioreactor studies) to in vivo experiments in a rabbit model and, finally, to clinical studies. Our statistically robust evaluations will directly address 1) the role of wall apposition in aneurysm healing and risk for complication, 2) downstream hemodynamic derangements caused by flow diverter implantation vis-- vis risk for spontaneous hemorrhage, and 3) the relative impact of diversion of flow versus other factors, including thrombus formation and endothelialization, in healing. The discoveries from this competitive renewal will be directly applicable to clinicians treating patients with currently-approved devices and managing patients following flow diversion treatment in order to optimize outcomes and minimize complications, as well as to engineers and scientists focused on developing idealized, future devices, even those with patient-specific, individualized features.

Public Health Relevance

This research proposal will substantially improve the tools available for studying new treatments for brain aneurysms, allowing individualized treatment plans to be devised and carried out for individual patients.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Koenig, James I
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Mayo Clinic, Rochester
United States
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Kolumam Parameswaran, Praveen; Dai, Daying; Ding, Yong-Hong et al. (2018) Assessment of endothelialization of aneurysm wall over time in a rabbit model through CD31 scoring. J Neurointerv Surg 10:888-891
Zhou, Geng; Li, Ming Hua; Tudor, Gabriel et al. (2018) Remote Ischemic Conditioning in Cerebral Diseases and Neurointerventional Procedures: Recent Research Progress. Front Neurol 9:339
Rouchaud, Aymeric; Brinjikji, Waleed; Dai, Daying et al. (2018) Autologous adipose-derived mesenchymal stem cells improve healing of coiled experimental saccular aneurysms: an angiographic and histopathological study. J Neurointerv Surg 10:60-65
Wang, Shunli; Dai, Daying; Kolumam Parameswaran, Praveen et al. (2018) Rabbit aneurysm models mimic histologic wall types identified in human intracranial aneurysms. J Neurointerv Surg 10:411-415
Brinjikji, Waleed; Ding, Yong H; Kallmes, David F et al. (2016) From bench to bedside: utility of the rabbit elastase aneurysm model in preclinical studies of intracranial aneurysm treatment. J Neurointerv Surg 8:521-5
Rouchaud, A; Ramana, C; Brinjikji, W et al. (2016) Wall Apposition Is a Key Factor for Aneurysm Occlusion after Flow Diversion: A Histologic Evaluation in 41 Rabbits. AJNR Am J Neuroradiol 37:2087-2091
Hodis, Simona; Ding, Yong-Hong; Dai, Daying et al. (2016) Relationship between aneurysm occlusion and flow diverting device oversizing in a rabbit model. J Neurointerv Surg 8:94-8
Dai, Daying; Ding, Yong-Hong; Kelly, Michael et al. (2016) Histopathological findings following pipeline embolization in a human cerebral aneurysm at the basilar tip. Interv Neuroradiol 22:153-7
Dai, Daying; Ding, Yong-Hong; Rezek, Issa et al. (2016) Characterizing patterns of endothelialization following coil embolization: a whole-mount, dual immunostaining approach. J Neurointerv Surg 8:402-6
Rouchaud, Aymeric; Brinjikji, Waleed; Lanzino, Giuseppe et al. (2016) Delayed hemorrhagic complications after flow diversion for intracranial aneurysms: a literature overview. Neuroradiology 58:171-7

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