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.

该项目的主要目标是建立 N-乙酰天冬氨酸 (NAA) 的 1H MRSI 测量，作为定量测量肌萎缩侧索硬化症 (ALS) 中上运动神经元 (UMN) 损失的替代标记，并在早期检测 ALS疾病的阶段。该提案使用新开发的短 TE 多层 1H MRSI 方法，具有较高的重测重现性，该方法对脂质污染最小的表面大脑皮层进行采样，并提供萎缩校正的 [NAA]、[肌酸 (Cr)]、（胆碱 (Cho)]、一项初步研究表明，MRI 分割可量化每个 MRSI 体素中的灰质和白质以及脑脊液。在我们的研究中入组 3 个月后，ALS 运动皮层的 NAA (-11.9%)、Cre (-10.7%) 和 Cho (-19.5%) 显着下降。该技术将用于研究以下受试者组。临床明确或可能的 ALS (n=20) 和临床可能或怀疑的 ALS (n=20) 将每 3 个月进行一次 MRI/1H MRSI。一项 MRI/1H MRSI。假设：l) 区域代谢变化：ALS 大脑中最大的神经元损失（根据 [NAA] 损失评估）发生在初级运动皮层和皮质脊髓束 (CST)，2) NAA 作为替代标记UMN 功能的影响：ALS 患者运动皮层和 CST 中的神经元损失（根据 [NAA] 损失进行评估）与 UMN 功能障碍的临床测量相关， 3) 预测 ALS 病程：可以通过 6-9 个月内的 2-3 次测量来预测个体运动皮层神经元损失的长期时间进程（根据 (NAA] 评估），4) 早期检测 UMN 损伤： UMN 丢失（根据（NAA] 丢失评估）发生在临床 UMN 功能障碍明显之前。除了这些假设之外，还将探讨 NAA 以外的代谢物的变化，尤其是 mI。将探索动脉自旋标记灌注 MRI 检测运动和其他大脑区域变化的能力，以及确定口服肌酸补充剂效果的小型试点研究。预计该项目将导致开发改进的诊断技术，用于评估、筛选有风险的受试者、监测 ALS 和其他运动神经元疾病的进展以及量化治疗效果。