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.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL090005-04
Application #
6289502
Study Section
Special Emphasis Panel (LDRR)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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