Ultra-High Field Proton MR Spectroscopy in Early-Stage Amyotrophic Lateral Sclerosis

• Published in: Neurochemical research 2017-06, Vol.42 (6), p.1833-1844
• Main Authors: Cheong, Ian, Marjańska, Małgorzata, Deelchand, Dinesh K., Eberly, Lynn E., Walk, David, Öz, Gülin
• Format: Article
• Language: English
• Subjects: Abnormalities; Adult; Aged; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnostic imaging; Amyotrophic Lateral Sclerosis - metabolism; Biochemistry; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cohort Studies; Cortex (motor); Diagnostic systems; Female; Glutathione; Humans; Inositol; Magnetic resonance spectroscopy; Male; Middle Aged; Motor Cortex - diagnostic imaging; Motor Cortex - metabolism; Motor task performance; N-Acetylaspartate; Neurochemistry; Neurology; Neurosciences; Original Paper; Pons; Pons - diagnostic imaging; Pons - metabolism; Proton magnetic resonance; Proton Magnetic Resonance Spectroscopy - methods; Spectroscopy; Spectrum analysis; Studies
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-017-2248-2

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 ( 1 H-MRS) can potentially provide biomarkers of cerebral pathology in ALS. However, previous 1 H-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-voxel 1 H-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