Reduction in metabolite transverse relaxation times in amyotrophic lateral sclerosis

Background: Proton magnetic resonance spectroscopy (H-1 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). Methods: H-1 MRS data were acquired from the brainstems of ALS and control subjects, for a range of TE times, to calculate 7, 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. Results: 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. Conclusion: 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. (C) 2002 Elsevier Science B.V. All rights reserved.