RADIOSURGERY OF ARTERIOVENOUS MALFORMATION MODELS

动静脉畸形模型的放射外科治疗

• 批准号: 6394082
• 负责人: FERNANDO VINUELA
• 金额: $ 32.42万
• 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/6394082
• 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，但对于有助于脑动脉动脉畸形（AVMS）的放射外科闭塞的基本放射性生物学和组织病理学机制，许多关键问题仍未得到解决。 放射外剂量的选择仍然在很大程度上是经验的，并且尚未充分研究可能决定剂量依赖的放射外科闭塞的AVM特征（体积，血液动力学，血管口径）。该项目的长期目的是通过提高立体定向放射外科手术的功效和安全性来改善具有大脑AVM的患者的整体临床管理。这可以通过对通过适当的实验模型的研究获得的基本放射生物学原理有更透彻的理解来实现。该项目的直接目的是使用在我们的实验室中开发的可靠的实验AVM体内模型进行放射外科研究：1）研究AVM的特征，这可能会影响其对放射线的反应。 特别是，我们将研究AVM血液动力学作为改变病变对放射外科手术的反应的变量。 2）对放射外科效应进行详细的组织病理学研究，并研究如何导致血管闭塞。 3）阐明射线外科后AVM中观察到的形态变化的分子因子。特别是对辐照组织的免疫组织化学分析将进行，以寻找可能在此过程中起作用的细胞因子的存在。通过这些努力，我们希望增强对脑AVM患者的立体定向放射外科手术的成功和安全性。