The long term objective of this research program is to improve the care of patients harboring unruptured brain aneurysms. These aneurysms, present in approximately 2% of the population, may undergo spontaneous rupture with devastating consequences. Recent advances in minimally invasive treatments have allowed many patients to avoid open brain surgery. Unfortunately, these newer treatments often result in imperfect closure of the aneurysm, requiring additional treatments. A recently developed technique, called intraluminal flow diversion, has shown remarkable promise in treating even large or giant aneurysms, which are not well treated with any other technique. Notwithstanding promising results from small series of treated patients, many important questions about these new devices remain unanswered. First, practitioners have no concrete information on how to choose device size or number of devices in order to achieve aneurysm cure;addition of """"""""unnecessary"""""""" devices increases risk to patients and thus knowledge about the """"""""ideal"""""""" device for a given patient would be an important step forward. Second, the actual reasons behind why these flow diverters result in aneurysm cure remain unknown;advancing our knowledge of how they actually function would not only help individual patients but also speed development of improved devices. Third, a number of patients treated with these devices have suffered unexpected and usually fatal rupture of the aneurysm after treatment, which has convinced many practitioners either to avoid the use of flow diverters altogether or to use, at the same time, coil treatment in the aneurysm;adding the coil therapy increases both cost and risk, and thus understanding the reasons behind these rare but devastating ruptures would improve patient care. Finally, all patients treated with these devices require long term treatment with blood thinning medications;improvements in the device to avoid this need would decrease overall risk. The experiments outlined in this proposal include the latest advances in computer-based simulations of aneurysm flows, both before and after treatment, coupled with use of a widely-studied animal model. Study of these experimental systems will allow us to answer each of the important questions listed above, with the long term objective of safely and permanently curing brain aneurysms.

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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Special Emphasis Panel (ZRG1-SBIB-Q (80))
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Koenig, James I
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Mayo Clinic, Rochester
United States
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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
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
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
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
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 :
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; Johnson, C; Thielen, E et al. (2016) Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model. AJNR Am J Neuroradiol 37:1114-21
Puffer, Cole; Dai, Daying; Ding, Yong-Hong et al. (2015) Gene expression comparison of flow diversion and coiling in an experimental aneurysm model. J Neurointerv Surg 7:926-30
Brinjikji, W; Kallmes, D F; Kadirvel, R (2015) Mechanisms of Healing in Coiled Intracranial Aneurysms: A Review of the Literature. AJNR Am J Neuroradiol 36:1216-22
Holcomb, M; Ding, Y-H; Dai, D et al. (2015) RNA-Sequencing Analysis of Messenger RNA/MicroRNA in a Rabbit Aneurysm Model Identifies Pathways and Genes of Interest. AJNR Am J Neuroradiol 36:1710-5

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