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.
| Pa, Judy; Boxer, Adam; Chao, Linda L et al. (2009) Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment. Ann Neurol 65:414-23 |
| Hayasaka, Satoru; Du, An-Tao; Duarte, Audrey et al. (2006) A non-parametric approach for co-analysis of multi-modal brain imaging data: application to Alzheimer's disease. Neuroimage 30:768-79 |
| Rule, R R; Suhy, J; Schuff, N et al. (2004) Reduced NAA in motor and non-motor brain regions in amyotrophic lateral sclerosis: a cross-sectional and longitudinal study. Amyotroph Lateral Scler Other Motor Neuron Disord 5:141-9 |
| Suhy, J; Miller, R G; Rule, R et al. (2002) Early detection and longitudinal changes in amyotrophic lateral sclerosis by (1)H MRSI. Neurology 58:773-9 |
