Early detection and longitudinal changes in amyotrophic lateral sclerosis by ¹ H MRSI

Abstract

Objective-To determine 1) the reproducibility of metabolite measurements by 1 H MRS in the motor cortex; 2) the extent to which 1 H MRS imaging (MRSI) detects abnormal concentrations of N-acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS.Methods-Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice 1 H MRSI. 1 H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain.Results-The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS.Conclusion-Metabolite changes measured by 1 H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.ALS is a neurodegenerative disorder that causes rapid loss of motor neurons in the brain and spinal cord leading to paralysis and death. Diagnosis is based solely on clinical data, and there is no definitive diagnostic test for ALS and no surrogate marker for directly measuring disease progression. Therefore, an objective and quantitative method would be extremely helpful to evaluate viability and functioning of upper motor neurons in ALS, identify individuals at an early stage of the disease, and monitor responses to treatment. In addition to NAA, 1 H MRS measures resonances from choline (Cho)-and creatine (Cre)-containing compounds in the brain. Cre represents a combination of creatine and phosphocreatine, a putative marker of gliosis, 3,6 and Cho is thought to be a marker associated with membrane phospholipids. 7In most previous MRS studies of ALS,4,[8][9][10][11][12][13][14][15][16][17][18][19][20] sampling of metabolite signals from the motor cortex was limited, because measurements were restricted to a rectangular region within the brain that was sufficiently distant from the skull to avoid interferences with an intense signal from extracranial lipids. Furthermore, because the selected regions of interest were generally large, including unavoidably some white matter and nonmotor tissue, results from these studies may have been skewed to the extent that white matter and nonmotor regions contributed to the metabolite signal from the motor cortex. With use of a multiplana...

Degeneration of the Mid-Cingulate Cortex in Amyotrophic Lateral Sclerosis Detected In Vivo with MR Spectroscopy

“…Previous studies measuring absolute metabolites in ALS have inconsistently found increased Cho, yet all additionally documented decreased NAA. 14,23,[48][49][50] Compared with absolute quantitation, ratio determination provides a simpler and more reliable method with less experimental error. It would be worthwhile to follow up these findings with a study that incorporates absolute quantitation but with a larger sample size.…”

“…In this regard, Cho was chosen as an internal reference metabolite because previous spectroscopic studies have revealed larger effect sizes and accuracy profiles for NAA/Cho compared with NAA/Cr. 8,[12][13][14][15] Voxels were assigned to the MCC, thalamus, and motor cortex (PCG) (Fig 1). Metabolite ratios for each region (ie, MCC, thalamus, and PCG) were calculated by determining the average ratio for all voxels assigned to that region.…”

The neurochemical profile quantified by in vivo 1H NMR spectroscopy

“…The neuronal marker NAA has been shown to be associated to reduced neuronal integrity and neurodegeneration in ALS. Compared to healthy individuals, ALS patients show reduced levels of NAA the primary motor cortex (Gredal et al, 1997;Han and Ma, 2010;Nelles et al, 2008;Pioro et al, 1994;Pohl et al, 2001;Sarchielli et al, 2001;Suhy et al, 2002;Wang et al, 2006) and brain stem (Cwik et al, 1998;Pioro et al, 1999). Reduced NAA to total creatine ratio in motor cortex of ALS patients correlates with ALS Functional Rating Scale that depicts ALS progression (Sivák et al, 2010).…”

Detecting neuronal dysfunction of hand motor cortex in ALS: A MRSI study

“…It appears that spectrum quality and reproducibility may degrade when voxels are located away from the magnet isocenter or near the tissue-bone interface. Positioning of voxel becomes even more critical when the motor cortex is sampled, which may have contributed to relatively lower reproducibility of NAA measurement in this region (Suhy et al 2002). Previously we found that the voxels localized in the central part of the ROI have higher SNR ratios and better spectral quality (see illustrations in Figure 1).…”