Brain Metabolic Imaging in Amyotrophic Lateral Sclerosis

描述（由申请人提供）：肌萎缩性侧索硬化症（ALS）是一种进行性运动神经元神经退行性疾病，影响上运动神经元（UMN）（运动皮质和皮质脊髓束（CST））和下运动神经元（LMN）（脑干和脊髓）。肌电图和肌肉测试可以客观地确定LMN在ALS中的参与程度；然而，影像学上确定UMN是否累及ALS患者是耗时的，通常使用神经影像学方法来消除类似ALS的其他疾病/障碍的存在。此外，对ALS特异性的敏感生化标记物尚未确定。因此，目前UMN ALS的诊断完全基于主观临床评估。本研究的目的是利用非侵入性和非破坏性的全脑磁共振技术，即质子磁共振光谱成像（MRSI）和扩散张量成像（DTI），并评估它们在量化ALS患者神经化学和微观结构变化方面的有用性。通过结合全脑神经化学和结构变化数据，本研究将提高识别诊断UMN功能状态的潜在标志物的能力，可能具有更高的特异性和敏感性。本研究拟检验的具体假设为：1)运动皮质和CST中特异性神经化学物质、n -乙酰天冬氨酸和胆碱的浓度发生变化，且这种变化与临床评估的UMN评分、疾病严重程度和病程中至少一项相关；2) CST轴突有微结构变化，这些变化与神经化学变化与临床UMN评估密切相关。此外，利用现有的全脑数据，将评估非运动脑区的代谢物和结构变化。观察到的代谢物和非运动区域的结构变化，特别是额叶和颞叶区域，将与神经心理学评分相关联，以确定它们参与ALS发病机制的最新发现。通过在ALS患者中验证这些假设，这项脑成像研究将进一步表征ALS患者的脑代谢和结构变化，并可能找到合适的代谢生物标志物来客观地检测这种致命的进行性运动神经元疾病。本研究的长期目标是确定ALS疾病检测、诊断和评估新药疗效的敏感脑代谢生物标志物。公共卫生相关性：肌萎缩性侧索硬化症（ALS）是一种运动神经元的进行性神经退行性疾病，其病因尚不确定。由于目前还没有明确的生化或放射检测方法，检测渐冻症很复杂。该项目旨在确定潜在的检测ALS的生化和成像标记。

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, affecting both upper motor neurons (UMN) (the motor cortex and corticospinal tracts (CST)) and lower motor neurons (LMN) (the brain stem and spinal cord). LMN involvement in ALS can be determined objectively using electromyography and muscle testing; however, radiologically determining UMN involvement in ALS patients is time-consuming and usually neuroimaging methods are used for eliminating the presence of other diseases/disorders that mimic ALS. In addition, sensitive biochemical markers that are specific to ALS are yet to be identified. So, currently UMN ALS is diagnosed solely based on subjective clinical assessments. The objective of this study is to use noninvasive and nondestructive whole-brain magnetic resonance techniques, namely, proton magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI), and evaluate their usefulness in quantifying neurochemical and microstructural changes in subjects with ALS. By combining whole-brain neurochemical and structural changes data, this study will improve the ability to identify potential markers for diagnosing UMN functional status with possibly higher specificity and sensitivity. The specific hypotheses to be tested in this study are: 1) there are changes in the concentration of specific neurochemicals, N-acetyl aspartate, and choline in the motor cortex and CST, and the changes associate with at least one of the clinically assessed UMN scores, disease severity and disease duration; 2) there are microstructural changes in the axons of the CST and these changes together with neurochemical alterations correlate strongly with clinical UMN assessments. In addition, using the available whole- brain data, metabolite and structural changes in non-motor cerebral areas will be evaluated. The observed metabolite and structural changes from the non-motor areas, specifically, the frontal and temporal regions, will be associated with neuropsychological scores to ascertain the recent findings of their involvement in ALS pathogenesis. By testing these hypotheses in subjects with ALS, this brain- imaging study will further characterize cerebral metabolic and structural changes in ALS, and may lead to finding suitable metabolic biomarkers to detect this fatal progressive motor neuron disease objectively. The long-term goal of this study is to identify sensitive cerebral metabolic biomarkers specific to ALS in disease detection, diagnosis and assess efficacy of new drugs. PUBLIC HEALTH RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, and its cause is undetermined. Detecting ALS is complicated by the fact that currently there is no definitive biochemical or radiological test available. This project seeks to identify potential biochemical and imaging markers for detecting ALS.