Whole-brain analysis of amyotrophic lateral sclerosis by using echo-planar spectroscopic imaging

Abstract

Purpose: To detect regional metabolic differences in amyotrophic lateral sclerosis (ALS) with whole-brain echo-planar spectroscopic imaging.

Materials and methods: Sixteen patients with ALS (nine men, seven women; mean age, 56.6 years), five persons suspected of having ALS (four men, one woman; mean age, 62.6 years), and 10 healthy control subjects (five men, five women; mean age, 56.1 years) underwent echo-planar spectroscopic imaging after providing informed consent. The study was approved by the institutional review board and complied with HIPAA. Data were analyzed with the Metabolic Imaging and Data Analysis System software, and processed metabolite maps were coregistered and normalized to a standard brain template. Metabolite maps of creatine (Cr), choline (Cho), and N-acetylaspartate (NAA) were segmented into 81 regions with Automated Anatomical Labeling software to measure metabolic changes throughout the brains of patients with ALS. Statistical analysis involved an unpaired, uncorrected, two-sided Student t test.

Results: The NAA/Cho ratio across six regions was significantly lower by a mean of 23% (P ≤ .01) in patients with ALS than in control subjects. These regions included the caudate, lingual gyrus, supramarginal gyrus, and right and left superior and right inferior occipital lobes. The NAA/Cr ratio was significantly lower (P ≤ .01) in eight regions in the patient group, by a mean of 16%. These included the caudate, cuneus, frontal inferior operculum, Heschl gyrus, precentral gyrus, rolandic operculum, and superior and inferior occipital lobes. The Cho/Cr ratio did not significantly differ in any region between patient and control groups.

Conclusion: Whole-brain echo-planar spectroscopic imaging permits detection of regional metabolic abnormalities in ALS, including not only the motor cortex but also several other regions implicated in ALS pathophysiologic findings.

Figure 1:

Regions showing significantly lower NAA/Cho ratios (red), NAA/Cr ratios (blue), or both (purple) in the patient group. Regions are highlighted through four of 18 different section levels in the brain, moving from inferior to superior in the left-to-right direction.

Figure 2:

Representative spectra from the right precentral lobe of a 55-year-old woman with ALS (red) and a 57-year-old healthy female control subject (black), along with the corresponding voxel localization overlaid onto a coregistered T1-weighted image.