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 放射外科手术（SRS）是有限脑转移患者的标准治疗。然而大多数 患者将经历治疗后认知能力下降，因为高剂量可能导致 明显的白色物质和海马体。目标/假设：我们的团队开发了 创新、强大的成像方法和自动分割技术， 白质束和海马使用先进的扩散张量成像（DTI）， 容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RT后体内关键脑结构的微结构变化。我们将会用这些 先进的成像技术在认知保留脑SRS的前瞻性试验中用于脑 转移患者。具体目的：1：评价是否有相对保留的口才白色 物质束（对记忆、语言、注意力和执行功能至关重要）， 脑SRS期间高剂量的西吡格雷可改善SRS后3个月的认知功能 在1 - 3处脑转移患者中相对于历史对照的性能。2：向 测量白色物质损伤（使用DTI）和海马萎缩的纵向趋势 （使用体积变化）在接受认知保留脑SRS的患者中， 这些成像生物标志物与特定领域的认知结果。研究设计：我们将 前瞻性入组60例有1-3处脑转移且符合脑SRS条件的成人患者 和MRI。患者将在基线（SRS前）接受MRI和DTI和3D体积成像 以及1个月、3个月和6个月后。白色物质和海马分割 将进行关键区域整合到认知保留脑SRS计划中， 基于知识的自动优化。认知保留剂量约束来自于 以前的数据。将在以下时间进行一组成熟、经验证的神经认知测试： 基线和SRS后3个月。将比较两组患者的认知恶化率， 当前试验和历史对照以及用于分析患者、肿瘤和 认知功能下降的治疗相关预测因素。统计建模将用于分析 作为时间和辐射剂量的函数的成像生物标志物的变化，并且这些变化将 与特定领域认知测试进行关联测试。对RT剂量的空间敏感性 将分析穿过白色物质束的图像。

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.