Magnetic resonance imaging (MRI) were performed on four shaking Springer spaniel dogs (SD), a large animal model that has diffusely dysmyelinated axons. Various MRI measures, including single voxel spectroscopic imaging and magnetization transfer imaging were performed in the SDs at 3 weeks, 8 weeks, 1 year, and 2 years of age along with aged-matched control animals. Clearly delineated MRI findings were observed on routine imaging techniques, including evidence of hydrocephalus as a result of white matter thinning in all SDs compared with normal controls. Hypomyelination resulted in a diffusely homogeneous hyperintensity to be observed in all white matter in the SD. Single voxel spectroscopy demonstrated essentially no differences in ratio of choline to creatine, N-acetylaspartate (NAA) to choline, or NAA to creatine between the two groups of animals. Magnetization transfer ratio (MTR) and MT histograms revealed a significant shift in mean and peak MTR histogram at three different offset frequencies to lower values in shaking dogs compared to age-matched controls. These results indicate that there is less of a mag-netization transfer effect occurring in the SD compared to normal and it is most likely a direct result of fewer myelin wraps around axons. Electron micrographic and immuno-histological examinations are pending in these animals. Serial MRI studies performed in the marmoset model experimental allergic encephalo-myelitis (EAE) are being used as part of preclinical evaluation of new therapies for multiple sclerosis (MS). The serial MRI studies have demonstrated week-to-week changes in the number and distribution of EAE lesions. Histopathologic examination of the EAE lesions revealed a wide range of pathologies that closely mimic the MS lesions. Alterations in patterns or distribution of MRI and pathologic findings will be evaluated as a part of preclinical studies of immunologically directed novel therapeutic agents such as chemokine or cytokine inhibitors. Future plans include performing MRI stereotactic- directed biopsies of enhancing lesion for microchip analysis, in order to reveal the immunologic, cellular, and biochemical microenvironment of the EAE lesion.
