This project represents continuing collaboration between clinical and basic scientists to characterize the biophysical forces acting on arterial lesions. The modeling tools have been developed to the point where they can characterize the biophysical forces acting on giant cerebral fusiform aneurysms. Left untreated, giant aneurysms can continue to enlarge over the life of the patient. The risk of death or devastating morbidity approaches 85% over 5 years. To slow growth, the feeding artery is often occluded in the hope that it decreases hemodynamic stress. However, because local wall shear stress and pressure cannot be measured directly, quantitative data is lacking. We will test the primary hypothesis that treatments that decrease shear stress and pressure on the aneurysm wall slows the growth of giant aneurysms. Theoretical predictions of altered hemodynamics will be correlated to experimental values. The methods will include theoretical computational modeling, based on experimental characterization of the aneurysm by MRA, velocity encoded MRI, and CT. Computational patient-specific models will be developed from measured geometry and inlet flow. Data will be retrieved from 15 consecutive patients (5/year) to quantify vascular structure and hemodynamics. About half of the patients will be treated by proximal artery occlusion and half left untreated at the discretion of the surgeon, based on best clinical practices.
Aim I : Validating computational model assessment of velocity from MRI data: Aneurysm geometry and inlet flow derived from in vivo imaging prior to intervention will be reproduced in three representative physical models, and the velocity field will be measured and compared to simulations. We hypothesize that the velocity predicted by simulation will be in agreement with measurements in the physical model.
Aim II : Theoretical prediction of changes in shear stress and pressure due to treatment: To stimulate aneurysms that had undergone surgical treatment, patient- specific computational models will be modified by simulating occlusion in a proximal feeding artery. The predicted change in flow will be correlated to the change in flow measured by MRI.
Aim II : Associating aneurysms growth to biophysical forces: Shear stress and pressure estimated in untreated and treated aneurysms will be compared to measured aneurysm growth. We hypothesize that a change in aneurysm volume will be directly correlated with shear stress and pressure on the wall. The significance of the work is that patient-specific models can predict the result of surgical intervention, and provide clinicians with the ability evaluate emerging methods to treat aneurysms (e.g., stents, coiling).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037921-06
Application #
6623704
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Marler, John R
Project Start
1999-04-01
Project End
2005-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
6
Fiscal Year
2003
Total Cost
$215,532
Indirect Cost
Name
University of California San Francisco
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Hashimoto, Tomoki; Meng, Hui; Young, William L (2006) Intracranial aneurysms: links among inflammation, hemodynamics and vascular remodeling. Neurol Res 28:372-80
Acevedo-Bolton, Gabriel; Jou, Liang-Der; Dispensa, Bradley P et al. (2006) Estimating the hemodynamic impact of interventional treatments of aneurysms: numerical simulation with experimental validation: technical case report. Neurosurgery 59:E429-30; author reply E429-30
Jou, Liang-Der; Wong, Gregory; Dispensa, Brad et al. (2005) Correlation between lumenal geometry changes and hemodynamics in fusiform intracranial aneurysms. AJNR Am J Neuroradiol 26:2357-63
Quick, Christopher M; James, David J; Ning, Kelvin et al. (2002) Relationship of nidal vessel radius and wall thickness to brain arteriovenous malformation hemorrhage. Neurol Res 24:495-500
Quick, Christopher M; Leonard, Edward F; Young, William L (2002) Adaptation of cerebral circulation to brain arteriovenous malformations increases feeding artery pressure and decreases regional hypotension. Neurosurgery 50:167-73; discussion 173-5
Hashimoto, T; Mesa-Tejada, R; Quick, C M et al. (2001) Evidence of increased endothelial cell turnover in brain arteriovenous malformations. Neurosurgery 49:124-31; discussion 131-2
Joshi, S; Hashimoto, T; Ostapkovich, N et al. (2001) Effect of intracarotid papaverine on human cerebral blood flow and vascular resistance during acute hemispheric arterial hypotension. J Neurosurg Anesthesiol 13:146-51
Quick, C M; Hashimoto, T; Young, W L (2001) Lack of flow regulation may explain the development of arteriovenous malformations. Neurol Res 23:641-4
Quick, C M; Young, W L; Leonard, E F et al. (2000) Model of structural and functional adaptation of small conductance vessels to arterial hypotension. Am J Physiol Heart Circ Physiol 279:H1645-53
Hashimoto, T; Emala, C W; Joshi, S et al. (2000) Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations. Neurosurgery 47:910-8; discussion 918-9