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

图像引导脑转移认知保留放射外科手术：避免白质和海马区域

• 批准号: 9920106
• 负责人: Jona A Hattangadi-Gluth
• 金额: $ 25.77万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920106
• 关键词: 3-Dimensional; Adult; Affect; Aftercare; Anatomy; Anisotropy; Area; Attention; Brain; Brain Neoplasms; Brain region; Cancer Patient; Clinical Trials; Cognitive; Computer software; Data; Deterioration; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Dose; Enrollment; Expressive Aphasia; Hippocampus (Brain); Image; Imaging Techniques; Imaging technology; Impaired cognition; Injury; Intervention; Language; Linear Regressions; Location; Longitudinal trends; Magnetic Resonance Imaging; Manuals; Measures; Memory; Metastatic malignant neoplasm to brain; Modality; Modernization; Neurocognition; Neurocognitive; Outcome; Pathway interactions; Patient Care; Patients; Predisposition; Publishing; Radiation; Radiation Dose Unit; Radiation therapy; Radiosurgery; Research Design; Speech; Statistical Models; Structure; Techniques; Testing; Time; automated segmentation; brain tissue; cognitive performance; cognitive testing; cohort; executive function; experience; hippocampal atrophy; image guided; image processing; imaging biomarker; imaging modality; imaging study; improved; in vivo; innovation; knowledge base; melanoma; neurocognitive test; new technology; novel imaging technique; novel strategies; prospective; prospective test; standard of care; tractography; tumor; white matter; white matter damage

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.

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）是有限脑转移患者的标准治疗方法。然而大多数 鉴于高剂量的潜在可能，患者将经历治疗后认知能力下降 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来识别关键 使用先进的扩散张量成像 (DTI) 和 体积成像。这些新颖的成像技术还使我们能够直接、非侵入性地 测量体内关键脑结构放疗后的微观结构变化。我们将使用这些 先进成像技术在认知保留脑 SRS 前瞻性试验中的应用 转移患者。具体目标： 1：评估雄辩白是否相对保守 物质束（对于记忆、语言、注意力和执行功能至关重要）和 大脑 SRS 期间高剂量的海马可改善 SRS 后 3 个月的认知能力 与具有 1 至 3 个脑转移的患者的历史对照相比的表现。 2：到 测量白质损伤（使用 DTI）和海马萎缩的纵向趋势 （使用体积变化）接受认知保留大脑 SRS 的患者并将其关联起来 这些具有特定领域认知结果的成像生物标志物。研究设计：我们会 前瞻性招募 60 名患有 1-3 个脑转移且符合脑 SRS 资格的成年患者 和核磁共振成像。患者将在基线时接受 MRI、DTI 和 3D 体积成像（SRS 前） 以及之后的1个月、3个月和6个月。白质和海马分割 将执行并将关键区域整合到认知保留大脑 SRS 规划中 基于知识的自动化优化。认知保留剂量限制源自 之前的数据。一套完善的、经过验证的神经认知测试将在 基线和 SRS 后 3 个月。将比较不同群体之间的认知恶化率 当前试验和历史对照以及线性回归用于分析患者、肿瘤和 认知能力下降的治疗相关预测因素。统计模型将用于分析 成像生物标志物随时间和辐射剂量的变化而变化，这些变化将 进行与特定领域认知测试的关联测试。对 RT 剂量的空间敏感性 将分析整个白质束。