RADIOSURGERY OF ARTERIOVENOUS MALFORMATION MODELS

尽管立体定向放射外科在脑动静脉畸形（avm）手术中的作用越来越大，但一些关于放射外科治疗脑动静脉畸形（avm）的基本放射生物学和组织病理学机制的关键问题仍未得到解答。放射手术剂量选择仍然主要是经验性的，AVM特征（体积、血流动力学、血管直径）可能决定剂量依赖的放射手术闭塞尚未得到充分研究。该项目的长期目标是通过提高立体定向放射手术的有效性和安全性来改善脑动静脉畸形患者的整体临床管理。通过在适当的实验模型中进行调查，可以更彻底地了解潜在的放射生物学原理，从而实现这一目标。本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AVM对放射外科反应的特性。特别地，我们将研究AVM血流动力学作为一个变量在改变病变对放射手术的反应中的作用。2)对放射手术效果进行详细的组织病理学研究，并探讨其如何导致血管闭塞。3)探讨引起AVM放射术后形态学改变的分子因素。特别是免疫组织化学分析辐照组织将进行寻找可能在这一过程中起作用的细胞因子的存在。通过这些努力，我们希望提高立体定向放射治疗脑动静脉畸形患者的成功率和安全性。

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.