title: Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI.
abstract: To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity.
authors.affiliation: Department of Neurology, University Hospital "12 de Octubre" Madrid Neuroimaging Laboratory, Center for Biomedical Technology, Rey Juan Carlos University, Móstoles Department of Radiology, Hospital Ruber International, Madrid Department of Neurology, University Hospital "Gregorio Marañón," Madrid Department of Neurology, University Hospital of Getafe, Getafe Department of Neurology, University Hospital "Principe de Asturias" Alcalá de Henares Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Department of Medicine, Complutense University, Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Labiano-Fontcuberta
authors.forename: Virginia
authors.initials: V
authors.lastname: Mato-Abad
authors.forename: Juan
authors.initials: J
authors.lastname: Álvarez-Linera
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Hernández-Tamames
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Martínez-Ginés
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Aladro
authors.forename: Lucía
authors.initials: L
authors.lastname: Ayuso
authors.forename: Ángela
authors.initials: Á
authors.lastname: Domingo-Santos
authors.forename: Julián
authors.initials: J
authors.lastname: Benito-León
mesh_terms: D000328:Adult; D016880:Anisotropy; D015415:Biomarkers / Q000378:metabolism; D001923:Brain Chemistry; D001927:Brain Diseases / Q000000981:diagnostic imaging* / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D013030:Spain; D013577:Syndrome; D066127:White Matter / Q000473:pathology*
chemical_list: D015415:Biomarkers