1H MRSI OF AMYOTROPHIC LATERAL SCLEROSIS

肌萎缩侧索硬化症的 1H MRSI

• 批准号: 6394489
• 负责人: MICHAEL W WEINER
• 金额: $ 37.51万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-11 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394489
• 关键词: ammonia lyase; amyotrophic lateral sclerosis; bioimaging /biomedical imaging; biomarker; brain metabolism; cerebral cortex; cerebrospinal fluid; choline; clinical research; creatine; degenerative motor system disease; human subject; longitudinal human study; motor cortex; motor neurons; neural degeneration; nuclear magnetic resonance spectroscopy; prognosis; pyramidal tracts

The primary goal of this project is to establish an 1H MRSI measurement of N-acetylaspartate (NAA) as a surrogate marker for quantitative measurements of upper motor neuron (UMN) loss in amyotrophic lateral sclerosis (ALS), and to detect ALS in an early stage of the disease. This proposal uses a newly developed short TE multislice 1H MRSI method with high test retest reproducibility, which samples surface cerebral cortex with minimal lipid contamination and which provides atrophy corrected [NAA], [creatine(Cr)], (choline (Cho)], and [myo-inositol (mI)]. MRI segmentation quantifies the gray and white matter, and cerebrospinal fluid in each MRSI voxel. A pilot study showed significant decreases in NAA (-11.9%), Cre (-10.7%), and Cho (-19.5%) in motor cortex of ALS after 3 months of enrollment in our study. This technique will be used to study the following subject groups in a longitudinal fashion. Clinically definite or probable ALS (n=20) and clinically possible or suspected ALS (n=20) will have MRI/1H MRSI every 3 months. Age and sex matched controls will have one MRI/1H MRSI. Hypotheses: l) Regional metabolic changes: The greatest neuron loss (assessed from [NAA] loss) in ALS brain occur in the primary motor cortex and the corticospinal tract (CST), 2) NAA as a surrogate marker of UMN function: Neuron loss (assessed from [NAA] loss) in motor cortex and CST of ALS patients correlates with clinical measures of UMN dysfunction, 3) Prediction of course of ALS: The long term time course of motor cortex neuron loss (assessed from (NAA]) in an individual can be predicted from 2-3 measurements in 6-9 months, 4) Early detection of UMN impairment: UMN loss (assessed from (NAA] loss) occurs before clinical UMN dysfunction is apparent. In addition to these hypotheses, changes in metabolites other than NAA, especially mI, will be explored. The ability of arterial spin labeled perfusion MRI to detect changes in motor and other brain regions and a small pilot study to determine the effects of oral creatine supplementation will be explored. It is expected that this project will lead to the development of improved diagnostic techniques for assessment, screening of subjects at risk for, monitoring progression of, and quantifying treatment effects of ALS and other motor neuron disease.

该项目的主要目的是建立1H MRSI测量N-乙酰天冬氨酸（NAA），作为肌萎缩性侧面硬化症（ALS）的上运动神经元（UMN）损失的定量测量的替代标记物，并在早期疾病的早期阶段检测ALS。该提案使用具有高测试重复可重复性的新近开发的短TE多层MRSI方法，该方法采样表面脑皮质具有最小的脂质污染，并提供经萎缩的[NaA]，[creatine（cr）]，（croline（cr）]，（Choline（cho）），（choline（cho））和[myo inositol（myo inositol（myositol and north and grian and grian）。 MRSI体素研究显示，NAA（-11.9％），CRE（-10.7％）和CHO（-19.5％）在我们研究3个月后，ALS的运动皮层在我们的研究中进行了研究。 MRI/1H MRSI每3个月都会有一个MRI/1H MRSI假设：L）区域代谢变化：ALS大脑中最大的神经元损失（评估[NAA]损失）在原发性运动皮层中发生在运动皮层和ALS患者的CST中，与UMN功能障碍的临床度量相关，3）ALS过程的预测：运动皮层神经元丧失的长期时间过程（根据（NAA]评估（NAA））可以预测单个中的2-3个月的2-3个测量值，在6-9个月内，umn损失的早期损失：UMN（UMN）（UMN）（UMN）（UMN）（UMN）（UMN）（UMN）（UMN）（[]功能障碍是显而易见的。除了这些假设外，还将探讨除NAA以外的其他代谢产物（特别是MI）的变化。将探讨动脉自旋标记MRI检测运动和其他大脑区域变化的能力以及一项小型试点研究来确定补充口服肌酸的影响。预计该项目将导致改进的评估诊断技术，筛查处于风险，监测ALS和其他运动神经元疾病的治疗作用的风险，监测和量化的治疗效果。