MRI of optic neuritis in a rat model

Neuritis of the optic nerve is one of the most frequent early symptoms ofmultiple sclerosis. There are only scarce data correlating magneticresonance imaging (MRI) contrast alterations with the underlyingpathology, that is inflammation, demyelination, and axonal damage.Here we studied optic neuritis in a rat model of experimental autoimmuneencephalomyelitis by comparingin vivoMRI findings from multipletechniques (T1, T2, proton density, magnetization transfer) to histo-pathology. We further assessed a breakdown of the blood–brain barrierby using Gd-DTPA and indirectly estimated the intracellular accumula-tion of calcium as a consequence of axonal damage by using manganese-enhanced MRI. Hyperintensity on T2-weighted images and signalenhancement after Gd-DTPA were highly sensitive to lesions of the opticnerve but did not differentiate between mild, moderate, and severedamage. Signal reduction on T1-weighted images was less sensitive butcorrelated well with the severity of tissue damage. No significant changesin magnetization transfer ratio were observed. Manganese ions tended toaccumulate in the central parts of the inflamed optic nerve. The resultingsignal enhancement at 24 h after administration positively correlated withthe severity of axonal loss. Thus, manganese might be an indicator ofintracellular calcium accumulation that is known to be associated withaxon damage. Although none of the methods alone distinguished betweeninflammation, demyelination, and reduced axon density, their specificcapabilities should prove useful for futurein vivoMRI studies of opticneuritis in both animal models and humans.