Genomes and Genes
Brain Metabolic Imaging in Amyotrophic Lateral Sclerosis
Principal Investigator: Varan Govind
Affiliation: University of Miami
Abstract: DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, affecting both upper motor neurons (UMN) (the motor cortex and corticospinal tracts (CST)) and lower motor neurons (LMN) (the brain stem and spinal cord). LMN involvement in ALS can be determined objectively using electromyography and muscle testing;however, radiologically determining UMN involvement in ALS patients is time-consuming and usually neuroimaging methods are used for eliminating the presence of other diseases/disorders that mimic ALS. In addition, sensitive biochemical markers that are specific to ALS are yet to be identified. So, currently UMN ALS is diagnosed solely based on subjective clinical assessments. The objective of this study is to use noninvasive and nondestructive whole-brain magnetic resonance techniques, namely, proton magnetic resonance spectroscopic imaging (MRSI) and diffusion tensor imaging (DTI), and evaluate their usefulness in quantifying neurochemical and microstructural changes in subjects with ALS. By combining whole-brain neurochemical and structural changes data, this study will improve the ability to identify potential markers for diagnosing UMN functional status with possibly higher specificity and sensitivity. The specific hypotheses to be tested in this study are: 1) there are changes in the concentration of specific neurochemicals, N-acetyl aspartate, and choline in the motor cortex and CST, and the changes associate with at least one of the clinically assessed UMN scores, disease severity and disease duration;2) there are microstructural changes in the axons of the CST and these changes together with neurochemical alterations correlate strongly with clinical UMN assessments. In addition, using the available whole- brain data, metabolite and structural changes in non-motor cerebral areas will be evaluated. The observed metabolite and structural changes from the non-motor areas, specifically, the frontal and temporal regions, will be associated with neuropsychological scores to ascertain the recent findings of their involvement in ALS pathogenesis. By testing these hypotheses in subjects with ALS, this brain- imaging study will further characterize cerebral metabolic and structural changes in ALS, and may lead to finding suitable metabolic biomarkers to detect this fatal progressive motor neuron disease objectively. The long-term goal of this study is to identify sensitive cerebral metabolic biomarkers specific to ALS in disease detection, diagnosis and assess efficacy of new drugs. PUBLIC HEALTH RELEVANCE: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons, and its cause is undetermined. Detecting ALS is complicated by the fact that currently there is no definitive biochemical or radiological test available. This project seeks to identify potential biochemical and imaging markers for detecting ALS.
Funding Period: 2008-09-30 - 2012-08-31
more information: NIH RePORT
- 1H MRS of basal ganglia and thalamus in amyotrophic lateral sclerosisKhema R Sharma
Department of Neurology, University of Miami, Miller School of Medicine, 1150 NW 14th St, Miami, FL 33136, USA
NMR Biomed 24:1270-6. 2011....
- Neuroimaging in amyotrophic lateral sclerosisMartin R Turner
Nuffield Department of Clinical Neurosciences, Oxford University, UK
Biomark Med 6:319-37. 2012..This comprehensive review considers the full range of neuroimaging techniques applied to amyotrophic lateral sclerosis over the last 25 years, the biomarkers they have revealed and future developments...
- Associations of age, gender and body mass with 1H MR-observed brain metabolites and tissue distributionsA A Maudsley
Department of Radiology, University of Miami School of Medicine, Miami, FL 33136, USA
NMR Biomed 25:580-93. 2012..There is, however, sufficient evidence to warrant the inclusion of body weight as a subject selection parameter, secondary to age, and as a factor in data analysis for MRS studies of some brain regions...
- Diffusion tensor imaging of basal ganglia and thalamus in amyotrophic lateral sclerosisKhema R Sharma
Department of Neurology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
J Neuroimaging 23:368-74. 2013..To assess the involvement of basal ganglia and thalamus in patients with amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI) method...
- Comprehensive evaluation of corticospinal tract metabolites in amyotrophic lateral sclerosis using whole-brain 1H MR spectroscopyVaran Govind
Department of Radiology, University of Miami School of Medicine, Miami, Florida, United States of America
PLoS ONE 7:e35607. 2012....