Functional Imaging as a Biomaker for Neurotoxicity After Brain Irradiation

放射治疗（RT）是原发性和转移性脑肿瘤的主要治疗方式。 放射诱导的神经毒性是脑RT的限制因素。临床症状可急性发生 和亚急性脑照射后，但大多数破坏性的神经毒性表现为晚期神经毒性， 后遗症，包括神经认知功能障碍和白色物质变性和坏死。鉴于 神经毒性的延迟性，重要的是要开发生物标志物，包括衍生的 从体内功能和分子成像，用于早期评估个体对 辐射和晚期神经毒性的预测。 放射性脑组织损伤是一个复杂的动态过程，涉及多个环节， 组织隔室。脑血管损伤，一直被认为是至关重要的 对于脑组织毒性的发展，在照射后早期发生。白色物质 包括脱髓鞘和坏死的变性在脑照射后随时间推移而进行。在 本研究使用活体动态对比增强磁共振成像和扩散张量 我们的目标是检测脑血管和脑内白色组织的早期变化， 患有低级别胶质瘤或良性肿瘤并接受分次部分脑RT的患者。此外， 我们的目的是确定生物剂量学效应，包括总剂量和剂量体积，对改变 脑血管和白色物质的组织我们的目的是评估患者的神经认知功能， RT前至RT后2年，并确定早期脑血管病变的相关关系， 损伤和早期延迟性白色物质退化，伴有晚期神经认知功能障碍。我们 假设早期监测脑微血管变化和组织变性 将使我们能够预测晚期神经认知缺陷。

Radiation therapy (RT) is a major treatment modality for primary and metastatic brain neoplasms. Radiation-induced neurotoxicity is a limiting factor for brain RT. Clinical symptoms can occur acutely and subacutely after brain irradiation, but most devastated neurotoxicity manifests of late neurological sequelae, including neurocognitve dysfunction, and white matter degeneration and necrosis. Given the delayed nature of neurotoxicity, it would be important to develop biomarkers, including derived from in vivo functional and molecular imaging, for early assessment of individual sensitivity to radiation and prediction of late neurotoxicity. Radiation-induced cerebral tissue injury is a complex and dynamic process, and involves in multiple tissue compartments. Cerebral vascular injury, which has been long considered to be crucial important for the development of cerebral tissue toxicity, occurs early after irradiation. White matter degeneration, including demyelination and necrosis, is progressive over time after brain irradiation. In this study, using in vivo dynamic-contrast-enhanced magnetic resonance imaging and diffusion tensor imaging, we aim to detect early alternations in cerebral vasculature and white matter tissue in the patients who have low-grade glioma or benign tumors and undergo fractionated partial brain RT. Also, we aim to determine the bio-dosimetric effects, including total dose and dose-volume, on the alterations of cerebral vasculature and white matter. We aim to assess neurocognitve function in the patients from pre RT up to 2 years post RT, and to determine correlative relationships of early cerebral vascular injury and early delayed white matter degradation with late neurocognitive dysfunction. We hypothesize that early monitoring of changes in cerebral microvessels and tissue degeneration in response to fractionated RT would allow us to predict late neurocognitive deficits.