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Guidelines for using proton MR spectroscopy in multicenter clinical MS studies

From the Department of Neurological and Behavioural Sciences (N.D.), University of Siena, Italy; Neuroimaging Research Unit (M.F.), Department of Neurology, Scientific Institute and University, Ospedale San Raffaele, Milan, Italy; NMR Research Unit (D.M.), Department of Neuroinflammation, Institute of Neurology, University College London, UK; Department of Radiology (P.J.P.), VU University Medical Centre, Amsterdam, The Netherlands; Department of Radiology (A.R.), Magnetic Resonance Unit, Hospital Vall d’Hebron, Barcelona, Spain; Department of Neurology (A.G.), University Hospital, Kantonsspital, Basel, Switzerland; Department of Neurology (C.E.), Medical University Graz, Austria; Department of Clinical Neurology (P.M.M.), Imperial College, London, UK; and McConnell Brain Imaging Centre (D.L.A.), Montreal Neurological Institute, Quebec, Canada.

Address correspondence and reprint requests to Dr. Nicola De Stefano, Neurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences, University of Siena, Viale Bracci 2, 53100 Siena, Italy destefano{at}unisi.it

Proton MR spectroscopy (MRS) allows noninvasive characterization of chemical-pathologic changes in the brain. In patients with multiple sclerosis (MS), proton MRS reveals chemical pathology in focal inflammatory lesions as well as in regions of the brain that are not associated with structural abnormalities on conventional MRI. In MS studies, it has been particularly useful as a method for the assessment of neurodegeneration based on decreases in the levels of the neuro-axonal marker compound, N-acetylaspartate. Also, MRS has provided evidence of chemical pathology and repair involving non-neuronal brain cells based on changes in metabolites, including choline, myo-inositol, glutamate, and GABA. Despite its greater pathologic specificity for axonal integrity compared to conventional MRI, MRS has been used only infrequently in clinical trials. This prompted us to review current MRS clinical applications in MS, discuss the potential and limitations of the technique, and suggest recommendations for the application of MRS to clinical trials.

GLOSSARY: ap = anterior-posterior; cc = cranio-caudal; Cho = choline-containing compounds; Cr = creatine; Lac = lactate; lr = left-right; MI = myo-inositol; MRS = proton MR spectroscopy; MS = multiple sclerosis; NAA = N-acetylaspartate; PRESS = point-resolved spectroscopy; STEAM = stimulated echo acquisition mode; TE= echo time; TR = repetition time; VOI = volume of interest.

Disclosure: The authors report no conflicts of interest.

Received August 25, 2006. Accepted in final form May 4, 2007.