Reduction in metabolite transverse relaxation times in amyotrophic lateral sclerosis

Proton magnetic resonance spectroscopy (1H MRS) is used frequently to evaluate normal and pathological states in brain. MRS results are often reported as ratios of peak areas from spectra acquired at a single echo time, primarily for the peaks arising from N-acetyl groups (NA), creatine/phosphocreatine (t-Cr), and choline (Cho). Peak areas, however, are affected not only by metabolite concentration, but also by transverse relaxation times (T(2)). While the ratio approach appears to be valid in normal brain, pathology may affect T(2), thereby leading to misinterpretation of the apparent changes in metabolite ratios. The objective of the present study was to determine if any T(2) changes might affect the apparent metabolite ratio measures, which we have previously reported as being abnormal in amyotrophic lateral sclerosis (ALS).

1H MRS data were acquired from the brainstems of ALS and control subjects, for a range of TE times, to calculate T(2) times for each of NA, t-Cr, and Cho. Metabolite ratios were measured experimentally at TE=120 ms and calculated for TE=0 ms, based on measured T(2) values.

The T(2)'s for the ALS vs. control group were NA=272+/-10 ms vs. 351+/-58 ms (p<0.01), t-Cr=132+/-17 vs. 184+/-42 ms (p<0.02), and Cho=223+/-55 vs. 245+/-50 ms (p>0.05). The effect of these T(2) changes on metabolite ratios showed both the NA/t-Cr (ALS=0.98+/-0.13, Control=1.44+/-0.10, p<0001) and Cho/t-Cr (ALS=1.01+/-0.12, Control=1.34+/-0.24, p<0.001) ratios to differ significantly between groups.

This study confirms the presence of significant abnormalities in metabolite concentration in ALS brainstem and the importance of evaluating the effects of metabolite T(2) values when making ratio measurements in disease states.