Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

PLOS ONE, Dec 2019

Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definite-ALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function.

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Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy

et al. (2012) Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy. PLoS ONE 7(4): e35607. doi:10.1371/journal.pone.0035607 Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using 1 Whole-Brain H MR Spectroscopy Varan Govind 0 Khema R. Sharma 0 Andrew A. Maudsley 0 Kristopher L. Arheart 0 Gaurav Saigal 0 Sulaiman Sheriff 0 Jean-Claude Baron, University of Cambridge, United Kingdom 0 1 Department of Radiology, University of Miami School of Medicine, Miami, Florida, United States of America, 2 Department of Neurology, University of Miami School of Medicine, Miami, Florida, United States of America, 3 Department of Epidemiology, University of Miami School of Medicine , Miami, Florida , United States of America Changes in the distribution of the proton magnetic resonance spectroscopy (MRS) observed metabolites N-acetyl aspartate (NAA), total-choline (Cho), and total-creatine (Cre) in the entire intracranial corticospinal tract (CST) including the primary motor cortex were evaluated in patients with amyotrophic lateral sclerosis (ALS). The study included 38 sporadic definiteALS subjects and 70 age-matched control subjects. All received whole-brain MR imaging and spectroscopic imaging scans at 3T and clinical neurological assessments including percentage maximum forced vital capacity (FVC) and upper motor neuron (UMN) function. Differences in each individual metabolite and its ratio distributions were evaluated in the entire intracranial CST and in five segments along the length of the CST (at the levels of precentral gyrus (PCG), centrum semiovale (CS), corona radiata (CR), posterior limb of internal capsule (PLIC) and cerebral peduncle (CP)). Major findings included significantly decreased NAA and increased Cho and Cho/NAA in the entire intracranial CST, with the largest differences for Cho/NAA in all the groups. Significant correlations between Cho/NAA in the entire intracranial CST and the right finger tap rate were noted. Of the ten bilateral CST segments, significantly decreased NAA in 4 segments, increased Cho in 5 segments and increased Cho/NAA in all the segments were found. Significant left versus right CST asymmetries were found only in ALS for Cho/NAA in the CS. Among the significant correlations found between Cho/NAA and the clinical assessments included the left-PCG versus FVC and right finger tap rate, left -CR versus FVC and right finger tap rate, and left PLIC versus FVC and right foot tap rate. These results demonstrate that a significant and bilaterally asymmetric alteration of metabolites occurs along the length of the entire intracranial CST in ALS, and the MRS metrics in the segments correlate with measures of disease severity and UMN function. - Funding: This study was supported by the Stanley Glaser Foundation and National Institutes of Health grant R01 NS060874. The data processing software used was developed under R01 EB000822. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of both upper motor neurons (UMN) in the primary motor cortex (PMC) and lower motor neurons (LMN) in the brain stem and spinal cord anterior horns. Despite identification of pathologies in the PMC and corticospinal tracts (CST) of autopsy tissue samples with ALS [1,2], there are no biomarkers identified to date that reliably indicate presence of such pathologies in the brain of patients with ALS. In an effort to find neuroimaging biomarkers indicative of UMN degeneration, advanced MR techniques (e.g., magnetic resonance spectroscopy, diffusion tensor imaging and functional MRI) have been explored [3,4]. It is hypothesized that the neuropathologically proven motor neuron and CST degeneration in ALS might occur gradually with no apparent manifestation of macroscopic tissue structural changes in the early stage that are detectable by conventional MRI methods. In contrast, neurochemicals indicative of metabolic processes responsible for degeneration of the motor neurons and CST in patients with ALS can be accessed from the disease onset stage using proton MR spectroscopic (MRS) methods. Proton MRS enables noninvasive measurement of brain metabolites [5] such as N-acetyl aspartate (NAA; a marker of viability of neurons), total-choline (Cho; an indicator of cell membrane structural integrity, synthesis and degradation; MRS signal sum of all choline-moiety containing compounds), and total-creatine (Cre; an indicator of cellular energetics; MRS signal sum of creatine and phosphocreatine). Several previous cross-sectional and longitudinal studies have demonstrated the value of proton MRS for evaluation of metabolite alterations in the PM (...truncated)


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Varan Govind, Khema R. Sharma, Andrew A. Maudsley, Kristopher L. Arheart, Gaurav Saigal, Sulaiman Sheriff. Comprehensive Evaluation of Corticospinal Tract Metabolites in Amyotrophic Lateral Sclerosis Using Whole-Brain 1H MR Spectroscopy, PLOS ONE, 2012, 4, DOI: 10.1371/journal.pone.0035607