RADIOSURGERY OF ARTERIOVENOUS MALFORMATION MODELS

动静脉畸形模型的放射外科治疗

• 批准号: 2823453
• 负责人: FERNANDO VINUELA
• 金额: $ 35.6万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2823453
• 关键词: cerebroangiography; cerebrovascular disorders; cerebrovascular surgery; congenital cardiovascular disorder; cytokine; disease /disorder model; hemodynamics; histopathology; image processing; immunocytochemistry; model design /development; nonhuman therapy evaluation; radiation therapy; radiobiology; radiowave radiation; stereotaxic techniques; swine; therapeutic blood vessel occlusion

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.

尽管立体定向放射外科的作用不断扩大，但有关放射外科消除脑动静脉畸形（AVM）的基本放射生物学和组织病理学机制的许多关键问题仍未得到解答。 放射外科剂量选择在很大程度上仍然是经验性的，并且可能决定剂量依赖性放射外科闭塞的 AVM 特征（体积、血流动力学、血管口径）尚未得到充分研究。该项目的长期目标是通过提高立体定向放射外科的疗效和安全性来改善脑动静脉畸形患者的整体临床管理。这可以通过对适当的实验模型的研究获得的基本放射生物学原理的更彻底的理解来实现。该项目的直接目标是使用我们实验室开发的可靠的实验性 AVM 体内模型进行放射外科研究：1）研究可能影响其对放射外科反应的 AVM 特征。 我们将特别研究 AVM 血流动力学作为改变病变对放射外科反应的变量的作用。 2) 对放射外科效应进行详细的组织病理学研究，并研究这如何导致血管闭塞。 3) 阐明放射外科手术后 AVM 中观察到的形态变化的分子因素。特别是对辐照组织进行免疫组织化学分析，寻找可能在此过程中发挥作用的细胞因子的存在。通过这些努力，我们希望提高脑动静脉畸形患者立体定向放射外科手术的成功率和安全性。