title: Sodium MRI in Multiple Sclerosis is Compatible with Intracellular Sodium Accumulation and Inflammation-Induced Hyper-Cellularity of Acute Brain Lesions.
abstract: The cascade of inflammatory pathogenetic mechanisms in multiple sclerosis (MS) has no specific conventional MRI correlates. Clinicians therefore stipulate improved imaging specificity to define the pathological substrates of MS in vivo including mapping of intracellular sodium accumulation. Based upon preclinical findings and results of previous sodium MRI studies in MS patients we hypothesized that the fluid-attenuated sodium signal differs between acute and chronic lesions. We acquired brain sodium and proton MRI data of N = 29 MS patients; lesion type was defined by the presence or absence of contrast enhancement. N = 302 MS brain lesions were detected, and generalized linear mixed models were applied to predict lesion type based on sodium signals; thereby controlling for varying numbers of lesions among patients and confounding variables such as age and medication. Hierarchical model comparisons revealed that both sodium signals average tissue (χ(2)(1) = 27.89, p < 0.001) and fluid-attenuated (χ(2)(1) = 5.76, p = 0.016) improved lesion type classification. Sodium MRI signals were significantly elevated in acute compared to chronic lesions compatible with intracellular sodium accumulation in acute MS lesions. If confirmed in further studies, sodium MRI could serve as biomarker for diagnostic assessment of MS, and as readout parameter in clinical trials promoting attenuation of chronic inflammation.
authors: Multi-Dimensional Medical Imaging Lab, Department of Neuroradiology, University of Heidelberg, 69120 Heidelberg, Germany.|Department of Radiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
authors: Armin
authors: A
authors: Biller
authors: Multi-Dimensional Medical Imaging Lab, Department of Neuroradiology, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Isabella
authors: I
authors: Pflugmann
authors: Department of Biological Psychology and Neuropsychology, University of Hamburg, 20146 Hamburg, Germany.|Department of Psychology, New York University, New York, NY 10003, USA.
authors: Stephanie
authors: S
authors: Badde
authors: Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Ricarda
authors: R
authors: Diem
authors: Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Brigitte
authors: B
authors: Wildemann
authors: Division of Medical Physics in Radiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.|Department of Diagnostic and Interventional Radiology, University Medical Centre Ulm, 89070 Ulm, Germany.|Institute of Radiology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors: Armin M
authors: AM
authors: Nagel
authors: Division of Medical Physics in Radiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.|Institute of Radiology, University Hospital Erlangen, 91054 Erlangen, Germany.
authors: J
authors: J
authors: Jordan
authors: Division of Medical Physics in Radiology, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
authors: Nadia
authors: N
authors: Benkhedah
authors: Multi-Dimensional Medical Imaging Lab, Department of Neuroradiology, University of Heidelberg, 69120 Heidelberg, Germany.|Multidimensional Image Processing Group, HCI/IWR, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Jens
authors: J
authors: Kleesiek
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging*; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology; D012964:Sodium / Q000737:chemistry*; D055815:Young Adult
chemical_list: D012964:Sodium