Image-Guided Cognitive-Sparing Radiosurgery for Brain Metastases: Avoidance of Eloquent White Matter and Hippocampal Regions

背景：脑转移影响三分之一的成年癌症患者。立体定向 放射外科(SRS)是有限脑转移瘤患者的标准治疗方案。然而，大多数 患者将经历治疗后认知能力的下降，因为大剂量可能会 雄辩的白质和海马体。目标/假设：我们的团队已经开发出 创新、强大的成像方法和自动分割技术，可识别关键的 应用高级弥散张量成像(DTI)和 体积成像。这些新的成像技术也使我们能够直接和非侵入性地 测量在体脑关键结构放射治疗后的微结构变化。我们将使用这些 先进的影像技术在认知保留脑SRS的前瞻性试验中的应用 转移病人。具体目标：1：评价雄辩的白色是否相对节俭 物质通道(对记忆、语言、注意力和执行功能至关重要)和 脑SRS期间大剂量的海马区可改善SRS后3个月的认知功能 有1到3个脑转移瘤的患者相对于历史对照的表现。2：至 测量白质损伤(使用DTI)和海马区萎缩的纵向趋势 (使用体积变化)接受认知保留脑SRS的患者及其相关性 这些成像生物标记物具有特定领域的认知结果。研究设计：我们将 前瞻性招募60例有1-3个脑转移瘤的符合脑SRS条件的成年患者 还有核磁共振。患者将在基线(Pre-SRS)时接受磁共振弥散张量成像(DTI)和3D体积成像 术后1个月、3个月、6个月。脑白质与海马区分割 将执行并将关键区域整合到认知保护的大脑SRS规划中 基于知识的自动化优化。认知节余剂量限制源自 以前的数据。一系列完善的、经过验证的神经认知测试将在 基线和SRS后3个月。认知衰退率将在两种情况下进行比较 当前试验和历史对照以及线性回归用于分析患者、肿瘤和 与治疗相关的认知功能下降的预测因素。将使用统计建模来分析 成像生物标志物随时间和辐射剂量的变化，这些变化将 接受特定领域认知测试的关联性测试。放射治疗剂量的空间敏感性 将对白质束进行分析。

Background: Brain metastases affect one third of adult cancer patients. Stereotactic radiosurgery (SRS) is standard of care for patients with limited brain metastases. Yet most patients will experience post-treatment cognitive decline given the potential for high doses to eloquent white matter and the hippocampus. Objective/Hypothesis: Our team has developed innovative, robust imaging methods and automated segmentation techniques to identify critical white-matter tracts and the hippocampus using advanced diffusion tensor imaging (DTI) and volumetric imaging. These novel imaging techniques also allow us to directly and non-invasively measure microstructural changes after RT to critical brain structures in vivo. We will use these advanced imaging technologies in a prospective trial of cognitive-sparing brain SRS for brain metastases patients. Specific Aims: 1: To evaluate whether relative sparing of eloquent white matter tracts (critical for memory, language, attention, and executive functioning) and hippocampi from high doses during brain SRS results in improved 3-month post-SRS cognitive performance relative to historical controls in patients with 1 to 3 brain metastases. 2: To measure longitudinal trends in white matter damage (using DTI) and hippocampal atrophy (using volumetric change) among patients receiving cognitive-sparing brain SRS and correlate these imaging biomarkers with domain-specific cognitive outcomes. Study Design: We will prospectively enroll 60 adult patients with 1-3 brain metastases who are eligible for brain SRS and MRI. Patients will undergo MRI with DTI and 3D volumetric imaging at baseline (pre-SRS) and 1 month, 3 months, and 6 months afterwards. White matter and hippocampal segmentation will be performed and critical regions integrated into cognitive-sparing brain SRS planning with automated knowledge-based optimization. Cognitive-sparing dose constraints are derived from previous data. A well-established, validated battery of neurocognitive tests will be performed at baseline and 3 months post-SRS. Cognitive deterioration rate will be compared between the current trial and historical controls and linear regression used to analyze patient, tumor, and treatment related predictors of cognitive decline. Statistical modeling will be used to analyze changes in imaging biomarkers as a function of time and radiation dose, and these changes will be tested for association with domain-specific cognitive tests. Spatial sensitivity to RT dose across white matter tracts will be analyzed.