Functional Imaging as a Biomaker for Neurotoxicity After Brain Irradiation

描述（由申请人提供）： 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。临床症状可在脑照射后急性和亚急性发生，但大多数破坏性神经毒性表现为晚期神经系统后遗症，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，必须开发生物标志物，包括从体内功能和分子成像中获得的生物标志物，以便早期评估个人对辐射的敏感性和预测晚期神经毒性。放射性脑组织损伤是一个复杂的动态过程，涉及多个组织分区。脑血管损伤，这一直被认为是至关重要的脑组织毒性的发展，发生在照射后早期。白色物质变性，包括脱髓鞘和坏死，在脑照射后随着时间的推移而进行。在这项研究中，使用在体内动态对比增强磁共振成像和扩散张量成像，我们的目的是检测脑血管和白色物质组织的早期变化的患者有低级别胶质瘤或良性肿瘤，并接受分割部分脑RT。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，对脑血管和白色物质的变化。我们的目的是评估患者从放疗前到放疗后2年的神经认知功能，并确定早期脑血管损伤和早期延迟性白色退化与晚期神经认知功能障碍的相关性。我们假设，早期监测脑微血管的变化和组织变性对分次RT的反应将使我们能够预测晚期神经认知功能障碍。公共卫生相关性：放射治疗是脑肿瘤的主要治疗方式。然而，放射治疗后可能会产生神经系统并发症。本研究旨在通过功能成像识别并发症的早期体征，从而通过先进的放射技术和/或治疗干预来减少放射并发症。

DESCRIPTION (provided by applicant): 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 neurocognitive 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 neurocognitive 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 t fractionated RT would allow us to predict late neurocognitive deficits. PUBLIC HEALTH RELEVANCE: Radiation therapy is a major treatment modality for brain tumor. However, radiation can generate neurological complications after treatment. This study aims to identify early signs of complications using functional imaging, thereby to reduce radiation complications by advanced radiation technologies and/or therapeutic intervention.