AVMs are a relatively small but important cause of stroke from spontaneous intracranial hemorrhage (ICH) that is potentially treatable. Because the primary reason to intervene in the natural course of the disease is prophylaxis from spontaneous ICH, the decision to treat should be based on hemorrhagic risk. However, insufficient information is available on the mechanisms and natural history of AVM hemorrhage. This interdisciplinary project will bring together a group of clinical neuroscientists, applied mathematicians and engineers in an effort to theoretically model the risk of spontaneous ICH. We will test the primary hypothesis that weighting structural factors (intranidal vessel wall thickness-to-radius ratio in what we will call """"""""structural- weighted"""""""" risk estimate) is more important than weighting hemodynamic factors (intranidal transmural pressure in what we will call """"""""hemodynamic-weighted"""""""" risk estimate) in determining the relative risk of spontaneous ICH. Theoretical predictions of risk (Riskmodel) will be compared to experimentally-derived estimates (Riskexp). (Spec.
Aim 1) We will collect data from 90 consecutive AVM patients (30/yr). A patient-specific computational model of the cerebral circulation will be constructed for all cases based on (a) detailed angiographic and MR data, (b) cerebral arterial pressures measured during superselective angiography and (c) histopathologic examinations of surgically-excised AVM specimens. The two model risk estimates (Riskmodel), """"""""structural- weighted"""""""" and """"""""hemodynamic-weighted,"""""""" will be compared to the risk of spontaneous ICH risk determined by experimental observations (Riskexp). Riskexp is calculated using a previously-described statistical method for determining the relative risk of having initially presented with AVM hemorrhage. (Spec.
Aim II) To partially validate each patient-specific computational model, we will measure changes in cerebral arterial pressure during nitroprusside-induced systemic hypotension and compare this to the patient-specific model's predictions. Use of modeling will allow delineation of pathomechanisms and risk factors for spontaneous ICH, to be used as a means of risk stratification in the design of future clinical trials. Such an approach is important because of the low incidence of AVMs. Overall, interdisciplinary modeling studies of the cerebral circulation can be an important adjunct to experimental studies to increase knowledge of cerebral pathophysiology and to devise treatment strategies by either the screening of proposed theories or the testing of existing ones.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS037921-02
Application #
6224179
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Marler, John R
Project Start
1999-04-01
Project End
2002-03-31
Budget Start
2000-02-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
073133571
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