Despite an expanding role of stereotactic radiosurgery, a number of key questions remain unanswered regarding the fundamental radiobiological and histopathological mechanisms contributing to radiosurgical obliteration of brain arteriovenous malformations (AVMs). Radiosurgical dose selection remains largely empirical, and AVM characteristics (volume, hemodynamics, vessel caliber) that may dictate dose dependent radiosurgical occlusion have not been studied adequately. The long-term objective of this project is to improve the overall clinical management of patients harboring brain AVMs by increasing the efficacy and safety of stereotactic radiosurgery. This may be achieved by a more thorough understanding of the underlying radiobiological principles, obtained through investigations in an appropriate experimental model. The immediate objective of this project is to use a reliable in vivo model of experimental AVM developed in our laboratories for radiosurgical research: 1) To study characteristics of AVM that may affect its response to radiosurgey. In particular we will investigate the role of AVM hemodynamics as a variable in altering the response of the lesion to radiosurgery. 2) To perform detailed histopathological studies of radiosurgical effects and investigate how this leads to vessel occlusion. 3) To elucidate the molecular factors responsible for the morphological changes observed in an AVM following radiosurgery. In particular immunohistochemical analysis of irradiated tissue will be performed looking for the presence of cytokines that may have a role in this process. Through these efforts, we hope to enhance the success and safety of stereotactic radiosurgery for patients with brain AVMs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS038453-04
Application #
6540061
Study Section
Radiation Study Section (RAD)
Program Officer
Jacobs, Tom P
Project Start
1999-05-15
Project End
2004-03-31
Budget Start
2002-04-01
Budget End
2004-03-31
Support Year
4
Fiscal Year
2002
Total Cost
$330,569
Indirect Cost
Name
University of California Los Angeles
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Jahan, Reza; Solberg, Timothy D; Lee, Daniel et al. (2007) An arteriovenous malformation model for stereotactic radiosurgery research. Neurosurgery 61:152-9;discussion 159
Jahan, Reza; Solberg, Timothy D; Lee, Daniel et al. (2006) Stereotactic radiosurgery of the rete mirabile in swine: a longitudinal study of histopathological changes. Neurosurgery 58:551-8; discussion 551-8
Jahan, R; Murayama, Y; Gobin, Y P et al. (2001) Embolization of arteriovenous malformations with Onyx: clinicopathological experience in 23 patients. Neurosurgery 48:984-95; discussion 995-7