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, previous 1H-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 1H-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 previous 1H-MRS studies in ALS.
Bibliographical noteFunding Information:
We thank the research coordinators Susan Rolandelli, Valerie Ferment, and Pamela Droberg, and Georgios Manousakis, M.D., and Gaurav Guliani, M.D., at the University of Minnesota and Hennepin County Medical Center ALS Clinics for their help in the recruitment of human subjects, and Edward J. Auerbach, Ph.D., for the implementation of MEGA-PRESS and FASTMAP on the Siemens platforms. This work was supported by the Bob Allison Ataxia Research Center, the University of Minnesota Foundation, and the National Institute of Neurological Disorders and Stroke (NINDS) Grant R01 NS080816. The Center for Magnetic Resonance Research is supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant P41 EB015894 and the Institutional Center Cores for Advanced Neuroimaging Award P30 NS076408. Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
© 2017, Springer Science+Business Media New York.
- 7 T
- El Escorial
- ¹H magnetic resonance spectroscopy