Brain Metabolic Imaging in Amyotrophic Lateral Sclerosis

肌萎缩侧索硬化症的脑代谢成像

• 批准号: 7891265
• 负责人: Varan Govind
• 金额: $ 29.82万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7891265
• 关键词: Affect; Age; Amyotrophic Lateral Sclerosis; Anisotropy; Area; Axon; Biochemical; Biochemical Markers; Biological Markers; Brain; Brain Stem; Brain imaging; Brain region; Cerebrum; Chemicals; Choline; Clinical; Clinical Treatment; Clinical assessments; Computer software; Corticospinal Tracts; Creatine; Data; Dementia; Detection; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Electromyography; Goals; Image; Imaging Techniques; Individual; Lead; Location; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measures; Membrane; Metabolic; Methods; Motor; Motor Cortex; Motor Neuron Disease; Motor Neurons; Multiparametric Analysis; Muscle; N-acetylaspartate; Neurodegenerative Disorders; Neurons; Pathogenesis; Patients; Pharmaceutical Preparations; Protons; Sensitivity and Specificity; Severity of illness; Specificity; Spinal Cord; Techniques; Testing; Time; base; burden of illness; diffusion anisotropy; frontal lobe; functional status; illness length; imaging modality; improved; magnetic resonance spectroscopic imaging; motor neuron degeneration; motor neuron function; neurochemistry; neuroimaging; neuropsychological; public health relevance; tool; water diffusion; white matter

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.

描述（由申请人提供）：肌萎缩侧索硬化症（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）。ALS中的LMN参与可以使用肌电图和肌肉测试客观地确定;然而，在ALS患者中放射学确定UMN参与是耗时的，并且通常神经成像方法用于消除模拟ALS的其他疾病/病症的存在。此外，ALS特异性的敏感生化标志物尚未确定。因此，目前UMN ALS的诊断完全基于主观临床评估。本研究的目的是使用非侵入性和非破坏性的全脑磁共振技术，即质子磁共振波谱成像（MRSI）和扩散张量成像（DTI），并评估其在量化ALS受试者的神经化学和微观结构变化的有用性。通过结合全脑神经化学和结构变化的数据，这项研究将提高能力，以确定潜在的标志物诊断UMN功能状态可能更高的特异性和敏感性。本研究的具体假设是：1）运动皮层和CST中特定神经化学物质N-乙酰天冬氨酸和胆碱的浓度发生变化，并且这种变化与临床评估的UMN评分、疾病严重程度和疾病持续时间中的至少一种相关; 2）CST的轴突中存在微结构变化，这些变化与神经化学改变一起与临床UMN评估强烈相关。此外，将使用可用的全脑数据，评价非运动脑区的代谢物和结构变化。从非运动区，特别是额叶和颞区观察到的代谢物和结构变化将与神经心理学评分相关，以确定其参与ALS发病机制的最新发现。通过在ALS受试者中测试这些假设，这项脑成像研究将进一步表征ALS中的脑代谢和结构变化，并可能导致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特异性的敏感脑代谢生物标志物，用于疾病检测，诊断和评估新药的疗效。公共卫生相关性：肌萎缩侧索硬化症（amyotrophiclateralsclerosis，ALS）是一种进行性运动神经元退行性疾病，其病因尚未明确。检测ALS是复杂的事实，目前还没有明确的生化或放射性测试。该项目旨在确定用于检测ALS的潜在生化和成像标记物。