Magnetic resonance imaging of blood-spinal cord barrier disruption in mice with experimental autoimmune encephalomyelitis

Inflammation, demyelination, and blood-spinal cord barrier (BSB) breakdown occur in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. The purpose of this study was to evaluate the utility of MRI for detecting lesions and BSB disruption in vivo during EAE in the mouse lumbar spinal cord, to determine how MR features of BSB disruption change during the course of disease, and to relate such changes to clinical signs and histological features of disease. Following induction of EAE in C57BL/6 mice, contrast-enhanced (CE) T-1-weighted MR images were acquired to detect BSB disruption in the lumbar spinal cord at the early stage of disease, at peak disease, and at remission, and T-2-weighted images were obtained to monitor spinal cord morphology. Following imaging the spinal cords were assessed in situ for general features of inflammation, BSB leakage, activated macrophages/microglia, and demyelination. No focal lesions were evident on T-2-weighted MR images. BSB disruption was greatest at the onset of signs of disease, and decreased progressively thereafter. Inflammation and clemyelination were pronounced at the initial stage of disease and at peak disease, and were decreased at remission. Nonuniform contrast enhancement indicated that breakdown of the BSB occurred predominantly within the white matter (WM) of the spinal cord.