RADIOSURGERY OF ARTERIOVENOUS MALFORMATION MODELS

尽管立体定向放射外科的作用日益扩大，但关于导致脑动静脉畸形(AVM)放射外科闭塞的基本放射生物学和组织病理学机制，仍有许多关键问题尚未得到解答。放射外科剂量选择在很大程度上仍然是经验性的，而可能决定剂量依赖的放射外科闭塞的AVM特征(体积、血流动力学、血管口径)还没有得到充分的研究。该项目的长期目标是通过提高立体定向放射外科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。这可以通过更彻底地理解潜在的放射生物学原理来实现，这是通过在适当的实验模型中进行调查而获得的。该项目的近期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的特征。特别是，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外科治疗的反应中的作用。2)对放射外科效应进行详细的组织病理学研究，并调查这是如何导致血管闭塞的。3)阐明动静脉动静脉畸形放射外科治疗后形态改变的分子因素。特别是，将对受照射的组织进行免疫组织化学分析，以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，我们希望提高脑动静脉畸形患者立体定向放射外科治疗的成功率和安全性。

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.