One fourth of the deaths from cerebrovascular disease in the US arise from hemorrhagic stroke associated with rupture of intracranial aneurysms. Endovascular treatment for intracranial aneurysms has thus far focused on the intra-aneurysmal deposition of occlusive materials with little regard for the pathology of the disease. Our hypothesis is that the application of photothrombosis can establish a stable white thrombus, which is not subject to auto-lysis, inside the aneurysm within minutes of treatment. This method can, therefore, safely exclude aneurysms from the cerebral circulation even where coils fail. Concomitant treatment with a flow divertor prevents thrombus migration out of the aneurysm and provides a scaffold for parent artery/aneurysm remodeling, leading to a cure of the lesion. We have conducted extensive studies on different flow divertor designs and were able to identify the optimal range of device porosities for, and the effect of changes in filament diameter on, successful treatment. The next step in design improvement is to further reduce the profile of the flow divertor by decreasing filament size, while simultaneously increasing device flexibility and maneuverability. The hemodynamics in the parent artery/aneurysm complex can be favorably altered by the minimally invasive implantation of a flow divertor alone (without photothrombosis) in the parent vessel. When only a flow divertor is used, however, thrombus formation and subsequent remodeling of the aneurysm may take longer than expected, during which time the patient is exposed to risk of hemorrhage. Thus, deployment of a flow divertor alone may be restricted to aneurysms that have been discovered before rupture. To be able to treat ruptured aneurysms as well, photothrombosis treatment can be added, whereby the aneurysm sac is pre-treated before divertor implantation with photochemical therapy that leads to the production of an acute "white thrombus", primarily an aggregation of platelets, with only a few minutes of laser irradiation. Depositing a sac-filling thrombus inside an aneurysm during treatment immediately excludes it from the circulation, provides the interventionalist with definitive results while the patient is undergoing the procedure, and expedites aneurysm remodeling. The flow divertor prevents thrombus migration out of the aneurysm, re-establishes physiological flow conditions in the parent artery, and serves as a scaffold for parent artery remodeling. The aforementioned objectives will be achieved via the following specific aims. (a) Reduce the profile of the flow divertor such that it will fit on a 3.3 French delivery system and (b), investigate the performance of this device in vitro and in the in the elastase-induced aneurysm model in rabbit. (c) Develop an optical fiber that will safely generate the appropriate energy fluence within an aneurysm to induce requisite endothelial damage. (d) Optimize the parameters that will induce a thrombus in the aneurysm through photothrombosis for its accelerated exclusion from the circulation.

Public Health Relevance

Ten to fifteen million Americans are estimated to harbor intracranial aneurysms (abnormal bulges of blood vessels located in the brain) that can rupture and expel blood directly into the brain space outside of the arteries causing a stroke. A flow divertor is a refined tubular mesh-like device that is inserted through a small incision in the groin area (no need for open brain surgery) and navigated through a catheter into cerebral arteries to treat brain aneurysms. The permeability of the device is optimized such that it significantly reduces the blood flow in the aneurysm, while keeping small side branches of the artery open to supply critical brain tissue. Slowing down the blood in the aneurysm clots out the pathology and the biocompatible device elicits a healthy scar-response from the body that lines the inner metal surface of the device with biological tissue, thus restoring the diseased arterial segment to its normal state. Artificially depositing a clot inside completely occludes the aneurysm while the patient is undergoing the procedure and can significantly expedite the complete healing process

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS045753-09
Application #
8269679
Study Section
Special Emphasis Panel (ZRG1-BDCN-F (10))
Program Officer
Koenig, James I
Project Start
2003-04-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
9
Fiscal Year
2012
Total Cost
$336,569
Indirect Cost
$122,194
Name
State University New York Stony Brook
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Sadasivan, Chander; Fiorella, David J; Woo, Henry H et al. (2013) Physical factors effecting cerebral aneurysm pathophysiology. Ann Biomed Eng 41:1347-65
Sadasivan, Chander; Brownstein, Jeremy; Patel, Bhumika et al. (2013) IN VITRO QUANTIFICATION OF THE SIZE DISTRIBUTION OF INTRASACCULAR VOIDS LEFT AFTER ENDOVASCULAR COILING OF CEREBRAL ANEURYSMS. Cardiovasc Eng Technol 4:63-74
Lieber, Baruch B; Sadasivan, Chander (2010) Endoluminal scaffolds for vascular reconstruction and exclusion of aneurysms from the cerebral circulation. Stroke 41:S21-5
Lieber, Baruch B; Sadasivan, Chander; Hao, Qing et al. (2009) The mixability of angiographic contrast with arterial blood. Med Phys 36:5064-78
Sadasivan, Chander; Lieber, Baruch B (2009) Numerical Investigation of Coil Configurations That Provide Ultra-High Packing Density of Saccular Aneurysms. J Med Device 3:41005
Sadasivan, Chander; Cesar, Liliana; Seong, Jaehoon et al. (2009) Treatment of rabbit elastase-induced aneurysm models by flow diverters: development of quantifiable indexes of device performance using digital subtraction angiography. IEEE Trans Med Imaging 28:1117-25
Sadasivan, Chander; Cesar, Liliana; Seong, Jaehoon et al. (2009) An original flow diversion device for the treatment of intracranial aneurysms: evaluation in the rabbit elastase-induced model. Stroke 40:952-8
Trager, Asher L; Sadasivan, Chander; Seong, Jaehoon et al. (2009) Correlation between angiographic and particle image velocimetry quantifications of flow diverters in an in vitro model of elastase-induced rabbit aneurysms. J Biomech Eng 131:034506
Cesar, Liliana; Miskolczi, Laszlo; Lieber, Baruch et al. (2008) Neurological deficits associated with the elastase-induced aneurysm model in rabbits. Neurol Res :
Seong, Jaehoon; Wakhloo, Ajay K; Lieber, Baruch B (2007) In vitro evaluation of flow divertors in an elastase-induced saccular aneurysm model in rabbit. J Biomech Eng 129:863-72

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