Magnetic resonance spectroscopy of the cervical cord in amyotrophic lateral sclerosis

Abstract

The objective of this study was to use magnetic resonance spectroscopy (MRS) to compare metabolite ratios in the cervical spinal cord of ALS patients to healthy controls. Fourteen ALS patients and 16 controls were scanned using a 3T scanner. A rectangular voxel (8 × 5 × 35 mm) was placed along the main axis of the cord with the lower limit at the inferior aspect of the C2 vertebral body. MRS was performed with a point-resolved spectroscopy (PRESS) sequence. Water signals were suppressed using a three-pulse chemical shift selective (CHESS) saturation sequence. Relative concentrations of choline (Cho), creatine (Cr), myo-inositol (Myo), and NAA were computed from metabolite peaks. Differences in metabolite ratios between ALS patients and controls were assessed with a Wilcoxon rank-sum test. The relationship of metabolite ratios to clinical measures (ALSFRS-R and FVC) was determined by Pearson correlation. The NAA/Cr and NAA/Myo ratios were reduced by 40% and 38%, respectively, in ALS patients. The reduction in NAA/Myo and NAA/Cho correlated significantly with FVC, with correlation coefficients of 0.66 and 0.60, respectively. In conclusion, MR spectra can reliably be obtained from the cervical spinal cord in ALS. MRS of the cervical cord may be a useful biomarker of disease progression.

1H-MR Spectroscopy in the Human Spinal Cord

“…Cooke et al 5 recommended a voxel size of 9 ϫ 7 ϫ 35 mm 3 and appropriate placement so that the lower limit of the voxel level is aligned with the inferior border of the C2 vertebral body. In some investigations, the voxel dimensions are kept constant but smaller than the previously recommended size, to ensure that the voxel size fits even in subjects with a small spinal cord diameter, 9,14,19,22,29,30,33,36,37 whereas others adapt the voxel size to each individual subject. 17,18,20,21 Edden et al 26 introduced 1D…”

“…They noticed a decrease of the NAA/Cr ratio and an increase of Cho/NAA in patients, without presentingquality indicators apart from 2 exemplary spectra with relatively low SNR. Carew et al 22 and Pineda-Alonso et al 28 used their previously published methods 27 to investigate amyotrophic lateral sclerosis in 14 patients (On-line Table 2) and 16 controls (On-line Table 1). They could show that NAA/Cr and NAA/myo-inositol were reduced in patients with amyotrophic lateral sclerosis, and the reduction correlated significantly with clinical parameters.…”

“…1 Therefore, the water peak is usually suppressed (or reduced), for example, with chemical shift selective 43 water suppression, 3,5,9,16,[20][21][22][23]27,28 or with asymmetric variable power RF pulses with optimized relaxation delays (VAPOR). 29,30,44 In addition, Hock et al 19,30 showed that MR spectroscopy in the spinal cord is possible without water suppression by using the metabolite-cycling technique.…”

Presymptomatic spinal cord neurometabolic findings in SOD1 -positive people at risk for familial ALS

“…The study size represented all available data as of March 2010. As described previously, 10 the subjects with ALS were recruited from the Emory University EMG laboratory, an ongoing clinical trial of arimoclomol in SOD1ϩ familial ALS as well as people with ALS who are registered with the Muscular Dystrophy Association. The healthy controls were recruited from several sources including spouses and other relatives of patients with ALS and a registry of healthy subjects maintained by one of the investigators (M.B.)…”

“…A number of studies have demonstrated a reduction in N-acetylaspartate (NAA), a marker of neuronal loss, in patients with ALS compared to controls expressed as absolute concentrations, 11,12 or as ratios of other metabolites like choline (Cho) and creatine (Cr) 10,[13][14][15][16][17][18][19][20][21][22][23][24] in the primary motor cortex, 13,17,19,23,25,26 centrum semiovale, internal capsule, corticospinal tract, cervical spine, 10,12,23 medulla, 5 and brainstem. Whether similar findings might be evident in people at risk for developing ALS, however, remains an unanswered question.…”