Neurobehavioral Core

项目摘要：神经行为核心3 我们建议建立一个研究项目，名为“提高脑瘤的治疗指数”。 通过创新的闪光放射治疗(闪光-RT)，重点是转化一种新的照射 医疗模式迅速进入临床。要检验的总体假设是，辐射是否在超高辐射下传递 剂量率(与当前临床实践中使用的低得多的剂量率相比)可以显著地 改善正常组织并发症，同时保持可接受的肿瘤控制，如果不是改善的话。为了测试这一点 假设，该计划将部署一系列全面的临床前研究，这些研究将对 闪光放射治疗后肿瘤控制、神经认知结果和由此导致的脑辐射损伤 常规剂量率照射。总的来说，这些研究将产生所需的数据集 将新型闪光照射平台快速转化为临床方案。小鼠的临床前研究 评估原位肿瘤控制、认知、神经元和血管结构可塑性、免疫调节 辐射损伤的氧依赖机制与对GBM犬患者的临床试验相结合 告知肿瘤学家这种潜在的范式转换技术的潜在好处。目标 本方案项目的执行将由剂量学/物理学核心(核心2)开展的活动提供便利 神经行为核心(核心3)。 核心3的主要功能将是提供一个统一的行为测试平台，在其中动物 在其他表演地点(CHUV、斯坦福、印第安纳州)辐射的产品将运往UCI并在其进行测试。这个 UCI的神经行为核心能够适应动物所需的神经认知测试目标 接受单次、多次闪光和常规剂量率照射方案 在项目1、2和4中描述。这将通过统一的神经行为测试来完成 平台，旨在确定特定的照射方案如何影响敏感的学习范例， 记忆和情绪，多方面的终点对治疗结果至关重要。 三号核心将由著名的分析多种辐射类型影响的专家查雷斯·利莫利博士领导， 范例和癌症治疗方案对认知的影响，由神经生物学家Munjal Acharya和 放射生物学家珍妮特·鲍尔奇。该团队拥有超过12年的行为测试经验，并已 被公认为识别了一些基于干细胞、外显体、药理学和遗传学的策略 解决癌症治疗引起的认知功能障碍。总而言之，核心3将成为一个综合枢纽，以 确保项目1、2和4的实验一致性。更广泛地说，Core 3将为以下项目提供主要服务 通过促进获取和传播与辐射肿瘤学研究有关的数据 放射肿瘤学和癌症治疗的潜在变革性分支。

PROJECT SUMMARY: NEUROBEHAVIORAL CORE 3 We are proposing the creation of a research program entitled, “Increasing the therapeutic index of brain tumor treatment through innovative FLASH radiotherapy (FLASH-RT), focused on translating a novel irradiation modality rapidly into the clinic. The overall hypothesis to be tested is whether radiation delivered at ultra high dose rates (compared to the much lower dose rates used in current clinical practice) can significantly ameliorate normal tissue complications while maintaining acceptable if not improved tumor control. To test this hypothesis, the program will deploy a comprehensive series of preclinical studies that will critically evaluate tumor control, neurocognitive outcomes and resultant radiation injury to the brain following FLASH-RT and conventional dose rate irradiation. Collectively, these studies will generate the requisite data sets required for the rapid translation of the novel FLASH irradiation platform to the clinical scenario. Preclinical studies in mice assessing orthotopic tumor control, cognition, neuronal and vascular structural plasticity, immune-modulation and oxygen dependent mechanisms of radiation injury are coupled with a clinical trial in GBM dog patients to inform the oncologists of the potential benefits of this potentially paradigm shifting technology. The objectives of this program project will be facilitated by the activities conducted by the dosimetry/physics core (Core 2) and the Neurobehavioral Core (Core 3). The primary function of Core 3 will be to provide a uniform behavioral testing platform in which animals irradiated at the other performance sites (CHUV, Stanford, Indiana) will be shipped to and tested at UCI. The neurobehavioral core at UCI is able to accommodate the neurocognitive testing objectives required for animals subjected to single fraction, and multifraction FLASH and conventional dose rate irradiation protocols as described in Projects 1, 2 and 4. This will be accomplished through a unifying neurobehavioral testing platform, designed to determine how specified irradiation protocols impact sensitive paradigms of learning, memory and mood, multifaceted endpoints critical to therapeutic outcome. Core 3 will be led by Dr. Chares Limoli, renowned expert in analyzing the impact of multiple radiation types, paradigms and cancer treatment regimens on cognition, and operated by neurobiologist Munjal Acharya and radiobiologist Janet Baulch. This team has more than 12 years of behavioral testing experience and has been recognized for identifying some of the first stem cell, exosome, pharmacologic and genetic based strategies for resolving cancer treatment-induced cognitive dysfunction. In sum, Core 3 will serve as an integrative hub to ensure experimental consistency across Projects 1, 2 & 4. More broadly, Core 3 will provide a major service to the radiation oncology research field by promoting the acquisition and dissemination of data relevant to a potentially transformative branch of radiation oncology and cancer treatment in general.