Quantifying Radiation-Therapy Brain Injury With 1H-MRS

使用 1H-MRS 量化放射治疗脑损伤

• 批准号: 6468780
• 负责人: ODED GONEN
• 金额: $ 21.05万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-03 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6468780
• 关键词: adult human (21+); aspartate; brain; brain disorder diagnosis; brain injury; clinical research; disease /disorder prevention /control; human subject; hydrogen ions; longitudinal human study; metastasis; neoplasm /cancer radiation therapy; nervous system regeneration; neurons; neurotoxicology; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; patient oriented research; psychological tests; small cell lung cancer; therapy adverse effect

DESCRIPTION (provided by applicant): Brain metastases present in 50-80 percent of small-cell-lung-cancer (SCLC) survivors within two years. To reduce this risk and improve their outcome, prophylactic-cranial-irradiation (PCI) is now offered to certain SCLC patients even in the absence of distinct visible brain pathology. Although neurotoxicity is always a concern in brain radiation-therapy (RT), there is currently no direct method to quantify its damage to the central nervous system (CNS). Such knowledge is critical for (a) risk/benefit assessment; and (b) dose determination. Presently, such damage can only be assessed indirectly, using neurocognitive tests. Unfortunately, the results of such tests are often confounded by other factors such as language barriers, patients' state of mind and/or their level of fatigue, fear and depression. Clearly, an objective, i.e., preferably instrumental, non-invasive and, most importantly, sensitive method to quantify RT neurotoxicity is necessary. We propose to quantify the extent of neurona1 cell loss imparted to the brain by RT through the decline of the amino acid derivative N-acetylaspartate (NAA) using state-of-the-art proton magnetic resonance spectroscopy (1H-MRS). Since NAA is believed to be present in neuronal cells only, its amount is proportional to their number and/or integrity. Consequently, we will obtain the amount of whole-brain-NAA (WBNAA) in 40 patients pre, immediately post- (2-3 weeks later) and six months after whole-brain radiation-therapy (WBRT). Since we will evaluate the amount of NAA in the entire brain, its signal-to-noise-ratio (SNR) will be excellent, facilitating short, < 15 min. examinations. It will also not be susceptible to misregistration errors that currently beset serial studies, nor will it be sensitive to the local transient edema common in WBRT. The WBNAA measurements will be augmented by the current tool used to evaluate CNS injury - the mini-mental status examination (MMSE) for correlation and comparison. We will use these observations to test the following three hypotheses, H1- H3: H1: That WBRT induces neuronal injury quantifiable with WBNAA in these patients. H2: That WBNAA is more sensitive than MMSE to detect neuronal injury consequences of WBRT. H3: That this neuronal injury may be transient, in part, and could resolve within several months after WBRT.

描述（由申请人提供）： 50-80% 存在脑转移 两年内小细胞肺癌（SCLC）幸存者的数量。为了减少这种情况 风险并改善其结果，预防性颅脑照射 (PCI) 现在已成为 即使没有明显可见的大脑，某些 SCLC 患者也可以使用 病理。尽管神经毒性始终是大脑中一个令人担忧的问题 放射治疗（RT），目前没有直接的方法来量化其 损害中枢神经系统（CNS）。这些知识对于（a）至关重要 风险/效益评估； (b) 剂量确定。目前，此类损害可能 只能使用神经认知测试间接评估。不幸的是， 此类测试的结果常常会受到语言等其他因素的影响 障碍、患者的精神状态和/或疲劳、恐惧和 沮丧。显然，一个目标，即最好是工具性的、非侵入性的 最重要的是，量化 RT 神经毒性的敏感方法是 必要的。 我们建议量化传递给大脑的神经元细胞损失的程度 通过 RT 通过氨基酸衍生物 N-乙酰天冬氨酸 (NAA) 的下降 使用最先进的质子磁共振波谱 (1H-MRS)。自从 NAA被认为仅存在于神经元细胞中，其含量为 与其数量和/或完整性成正比。因此，我们将获得 40 名患者在治疗前、治疗后立即进行全脑 NAA (WBNAA) 量 (2-3 几周后）和全脑放射治疗（WBRT）后六个月。自从 我们将评估整个大脑中 NAA 的含量， 信噪比 (SNR) 将非常出色，有助于缩短 < 15 分钟的时间。 考试。它也不会容易出现注册错误错误， 目前困扰的是系列研究，也不会对局部瞬态敏感 WBRT 中常见水肿。 WBNAA 测量将通过当前的增强 用于评估中枢神经系统损伤的工具——简易精神状态检查（MMSE） 用于关联和比较。我们将使用这些观察结果来测试 以下三个假设，H1-H3： H1：在这些情况下，WBRT 诱导的神经元损伤可以用 WBNAA 量化 患者。 H2：WBNAA 比 MMSE 更敏感地检测神经元损伤 WBRT 的后果。 H3：这种神经元损伤可能部分是短暂的，并且可以解决 WBRT 后几个月内。