Quantifying Radiation-Therapy Brain Injury With 1H-MRS

描述（由申请人提供）：50- 80%的患者存在脑转移 小细胞肺癌（SCLC）幸存者在两年内。减少这种 风险和改善他们的结果，颅放射治疗（PCI）现在是 即使在没有明显可见的大脑的情况下， 病理虽然神经毒性一直是一个关注的大脑 放射治疗（RT），目前还没有直接的方法来量化其 对中枢神经系统（CNS）的损害。这种知识对于（a） 风险/益处评估;和（B）剂量确定。目前，这种损害可能 只能通过神经认知测试间接评估。可惜 此类测试的结果往往会受到语言等其他因素的混淆 障碍，患者的精神状态和/或他们的疲劳，恐惧和 萧条显然，一个目标，即，最好是仪器性的非侵入性的 最重要的是，定量RT神经毒性的敏感方法是 必要 我们建议量化传递给大脑的神经元1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）。以来 据信NAA仅存在于神经元细胞中，其量为 与其数量和/或完整性成比例。因此，我们将获得 40例患者术前、术后即刻（2-3 全脑放射治疗（WBRT）后6个月。以来 我们将评估整个大脑中NAA的含量， 信噪比（SNR）将是优秀的，有利于短，< 15分钟。 考试它也不会受到配准错误的影响， 目前困扰着系列研究，也不会对局部瞬态敏感， 水肿在WBRT中常见。WBNAA测量将通过当前的 用于评估CNS损伤的工具-简易精神状态检查（MMSE） 进行对比和比较。我们将使用这些观察结果来测试 假设H1- H3： H1：WBRT诱导的神经元损伤可以用WBNAA定量， 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是短暂的，部分，可以解决 在WBRT之后的几个月内。

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.