Cerebral aneurysms are sac-like expansions of arteries in the brain. If left untreated, some may rupture causing death or impairment. Endovascular coiling is a recent and increasingly popular method of treatment. Here the aneurysm sac is accessed by a catheter and filled with coils, which should induce formation of a clot inside the aneurysm. The coil-clot mass will disallow entry of blood and hence protect the aneurysm from rupture and bleeding. But in some patients, within months to years of the procedure, blood is noted to re-enter the sac, a complication called recurrence. Recurrence can occur in 10-30% of patients treated with coils. The causes of recurrence are poorly understood. It is important to understand what causes recurrence because that is the first step in addressing this challenge and reducing its incidence. It will also significantly impact intervention strategie for aneurysm patients. The overall goal of this project is to shed light on the mechanisms underlying recurrence. Conventional thinking holds that recurrence occurs because the coil mass compacts itself (i.e., reduces in size) inside the sac over time, making room for blood to re-enter it. Plausible as this may seem, preliminary studies performed by employing rigorous three-dimensional image analysis techniques with a pilot population suggest otherwise. The primary hypothesis of this study is that the mechanism for recurrence is the growth of the aneurysm sac itself, not necessarily coil compaction Specific aim #1 of the project is to test the hypothesis in a statistically powered population of 25 coil-embolized aneurysm patients presenting with recurrence. Three dimensional image processing and computational analysis tools will be leveraged for accurate reconstructions and estimations of the aneurysm sac and coil mass volumes from rotational angiography scans in order to assess whether sac growth exists in recurrence subjects. Further, it would be quite beneficial to identify if some measurable metrics of aneurysm morphology or treatment procedure ay serve as risk factors for recurrence. The applicants'group has developed computational morphometric tools for rigorously quantifying the three-dimensional morphology of patient- specific aneurysms into size and shape metrics.
Specific aim #2 is to compare metrics of morphology and procedure between the recurrence-prone population from aim #1 with a control population (i.e., coiled aneurysms that do not show recurrence) that is size and location-matched. The goal is to ascertain which, if any, of the patient-specific measurable metrics may serve as prognostic indicators of recurrence. Identifying risk factors of recurrence may help identify and avoid patients prone to this major complication from this otherwise safe and effective procedure. If the results in aim #1 are consistent with proposed hypothesis that recurrence is associated with sac growth, patients with growing aneurysms are not suitable candidates for this procedure. The proposed project therefore can significantly impact clinical management of aneurysm patients.

Public Health Relevance

Cerebral aneurysms are increasingly treated by placement of embolization coils that will block blood from entering them. One common complication is the re-entry of blood into the aneurysm, called recurrence. This project aims to understand the cause of recurrence and develop ways to predict which patients may be prone to it using three-dimensional computational analysis methods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
5R03NS079227-02
Application #
8420408
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Koenig, James I
Project Start
2012-02-15
Project End
2014-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
2
Fiscal Year
2013
Total Cost
$72,858
Indirect Cost
$24,608
Name
University of Iowa
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Starke, Robert M; Thompson, John W; Ali, Muhammad S et al. (2018) Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis. Arterioscler Thromb Vasc Biol 38:610-621
Chalouhi, Nohra; Starke, Robert M; Correa, Tatiana et al. (2016) Differential Sex Response to Aspirin in Decreasing Aneurysm Rupture in Humans and Mice. Hypertension 68:411-7
Starke, Robert M; Chalouhi, Nohra; Ding, Dale et al. (2015) Potential role of aspirin in the prevention of aneurysmal subarachnoid hemorrhage. Cerebrovasc Dis 39:332-42
Peña-Silva, Ricardo A; Chalouhi, Nohra; Wegman-Points, Lauren et al. (2015) Novel role for endogenous hepatocyte growth factor in the pathogenesis of intracranial aneurysms. Hypertension 65:587-93
Hoppe, Anna L; Raghavan, Madhavan L; Hasan, David M (2015) Comparison of the association of sac growth and coil compaction with recurrence in coil embolized cerebral aneurysms. PLoS One 10:e0123017
Hasan, David M; Hindman, Bradley J; Todd, Michael M (2015) Pressure changes within the sac of human cerebral aneurysms in response to artificially induced transient increases in systemic blood pressure. Hypertension 66:324-31
Hasan, David M; Starke, Robert M; Gu, He et al. (2015) Smooth Muscle Peroxisome Proliferator-Activated Receptor ? Plays a Critical Role in Formation and Rupture of Cerebral Aneurysms in Mice In Vivo. Hypertension 66:211-20
Peña Silva, Ricardo A; Kung, David K; Mitchell, Ian J et al. (2014) Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice. Hypertension 64:362-8
Starke, Robert M; Chalouhi, Nohra; Jabbour, Pascal M et al. (2014) Critical role of TNF-? in cerebral aneurysm formation and progression to rupture. J Neuroinflammation 11:77
Hudson, Joseph S; Hoyne, Danielle S; Hasan, David M (2013) Inflammation and human cerebral aneurysms: current and future treatment prospects. Future Neurol 8:

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