title: Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis.
abstract: A major hurdle in the development of effective treatments for amyotrophic lateral sclerosis (ALS) has been the lack of robust biomarkers for use as clinical trial endpoints. Neurochemical profiles obtained in vivo by high field proton magnetic resonance spectroscopy (1H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous1H-MRS studies in ALS have produced conflicting findings regarding alterations in the levels of neurochemical markers such as glutamate (Glu) and myo-inositol (mIns). Furthermore, very few studies have investigated the neurochemical abnormalities associated with ALS early in its course. In this study, we measured neurochemical profiles using single-voxel1H-MRS at 7 T (T) and glutathione (GSH) levels using edited MRS at 3 T in 19 subjects with ALS who had relatively high functional status [ALS Functional Rating Scale-Revised (ALSFRS-R) mean ± SD = 39.8 ± 5.6] and 17 healthy controls. We observed significantly lower total N-acetylaspartate over mIns (tNAA/mIns) ratio in the motor cortex and pons of subjects with ALS versus healthy controls. No group differences were detected in GSH at 3 and 7 T. In subjects with ALS, the levels of tNAA, mIns, and Glu in the motor cortex were dependent on the extent of disease represented by El Escorial diagnostic subcategories. Specifically, combined probable/definite ALS had lower tNAA than possible ALS and controls (both p = 0.03), higher mIns than controls (p < 0.01), and lower Glu than possible ALS (p < 0.01). The effect of disease stage on MRS-measured metabolite levels may account for dissimilar findings among previous1H-MRS studies in ALS.
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA. cheo0043@umn.edu.
authors.forename: Ian
authors.identifier: http://orcid.org/0000-0003-3382-5458
authors.initials: I
authors.lastname: Cheong
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Marjańska
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Deelchand
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Eberly
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, USA.
authors.forename: David
authors.initials: D
authors.lastname: Walk
authors.affiliation: Department of Radiology, Center for Magnetic Resonance Research, University of Minnesota, 2021 6th St. S.E., Minneapolis, MN, 55455, USA.
authors.forename: Gülin
authors.initials: G
authors.lastname: Öz
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011149:Pons / Q000000981:diagnostic imaging / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*
keywords: 7 T; ALS; El Escorial; ¹H magnetic resonance spectroscopy