Early detection and longitudinal changes in amyotrophic lateral sclerosis by 1 H MRSI

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Abstract
Objective: To determine 1) the reproducibility of metabolite measurements by 1H MRS in the motor cortex; 2) the extent to which 1H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. Methods: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice 1H MRSI. 1H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. Results: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. Conclusion: Metabolite changes measured by 1H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.