Reduction in metabolite transverse relaxation times in amyotrophic lateral sclerosis

Abstract 

Background: 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 (T₂). While the ratio approach appears to be valid in normal brain, pathology may affect T₂, thereby leading to misinterpretation of the apparent changes in metabolite ratios. The objective of the present study was to determine if any T₂ changes might affect the apparent metabolite ratio measures, which we have previously reported as being abnormal in amyotrophic lateral sclerosis (ALS). Methods: ¹H MRS data were acquired from the brainstems of ALS and control subjects, for a range of TE times, to calculate T₂ 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 T₂ values. Results: The T₂'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 T₂ 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 T₂ values when making ratio measurements in disease states.

Keywords:  Amyotrophic lateral sclerosis, Magnetic resonance spectroscopy, Metabolite T₂, N-acetylaspartate, Creatine, Choline