1H-MRSI of the deep gray matter structures in patients with amyotrophic lateral sclerosis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a life-threatening disease that causes degeneration in nerve cells in the brain and spinal cord. In ALS patients, voluntary control of the arms and legs are affected. Currently, there is no cure for ALS. The primary goal of treatment is to manage symptoms to the greatest extent possible. Magnetic Resonance Spectroscopy (MRS) is employed to assess the concentration of metabolites in specific brain regions. This method has not been fully explored to understand the metabolic deficits in individuals diagnosed with ALS. It is crucial to understand the metabolic effects of ALS through various brain regions, particularly at the deep gray matter structures. 1H-MRSI data for 30 ALS patients, with a mean age of 57.8±9.55 years (17 females, 13 males) and 27 healthy controls, with a mean age of 48.44±10.5 years (16 females, 11 males) were acquired using a clinical 3T Siemens magnetic resonance imaging (MRI) scanner equipped with a multivoxel semi-LASER (sLASER) sequence (TR=1700ms, TE=40ms, VOI=10x10x15 mm3). In this study it is aimed to assess the metabolic differences between ALS patients and healthy controls (HC) at the thalamus, putamen, caudate and white matter regions. To achieve this, multivoxel magnetic resonance spectral data from ALS patients and HC were analyzed and metabolites Glx, GSH, tNAA, tCho, and Tau, as well as their ratio to tCr were quantified using LCModel. A Cramer-Rao lower bound (CRLB) threshold of less than 30 was employed to identify properly fitted metabolites. The metabolite peak ratios at the thalamus, putamen, caudate, and white matter regions were then compared between these two groups. A Wilcoxon signed-rank test was used to detect statistically significant differences in metabolite peak ratios between the left and right hemispheres at the thalamus, putamen, caudate, and white matter regions. The Mann-Whitney rank-sum test was used to evaluate metabolite peak ratio differences between ALS patients and healthy controls at some deep gray matter structures and white matter. MNI152 brain atlas was consulted to define the thalamus, putamen, and caudate regions. In conclusion, in this study, it was observed that ALS patients had a higher tCho/tCr ratio at the putamen compared to HC. Additionally, there was a trend for a lower Glx/tCr ratio at the left putamen of ALS patients compared to HC. ALS patients also showed a trend towards higher tCho/tCr and GSH/tCr ratios at the left caudate compared to HC. In ALS patients, higher Glx/tCr ratios were observed in the right thalamus and putamen compared to the left side. A trend towards a lower Glx/tCr ratio at the right caudate of ALS patients was observed compared to the left side. Additionally, ALS patients showed a lower tNAA/tCr ratio at the right caudate compared to the left side. In HC, higher Glx/tCr ratios were observed at the right thalamus compared to the left side. A trend towards higher tNAA/tCr and Glx/tCr ratios at the right putamen and right white of HC compared to the left sides were also observed. In this study, metabolic alterations were detected at the deep gray matter regions associated with executive function and behavior. Results of this study showed increased gliosis because of increased tCho/tCr ratio in ALS patients, a response to oxidative stress because of elevated GSH/tCr ratio in ALS patients, and deficiency in glutamate within these structures in individuals with ALS. The results of this study can contribute to a deeper understanding of ALS. Moreover, the findings obtained from this study suggest that MRS is a significant diagnostic and monitoring tool for neurodegenerative diseases such as ALS.