LYSOLECITHIN-INDUCED DEMYELINATION IN PRIMATES - PRELIMINARY IN-VIVO STUDY WITH MR AND MAGNETIZATION-TRANSFER

PURPOSE: To study bystander demyelination in multiple sclerosis with a n experimental in vivo model of toxic demyelination. METHODS: Toxic de myelinating lesions were created in two monkeys by injection of lysoph osphatidylcholine in the centrum semiovale. Follow-up was done clinica lly and with serial MR studies, including T2-weighted and gadolinium-e nhanced T1-weighted images and measurement of magnetization transfer r atio, until the animals were killed at days 14 and 34, respectively. L ight and electron microscopy analysis was compared with MR data. RESUL TS: Interval measurement of magnetization transfer ratio during the co urse of the experiment revealed a maximum decrease at day 7 to day 8, associated with the greatest clinical manifestations. The lowest value s of magnetization transfer ratio correlated with histopathologic find ings of myelin and axon destruction. Magnetization transfer ratio meas urements appear to be sensitive to macromolecular destruction and spec ifically to membrane disorganization. At no time was gadolinium enhanc ement observed in this model of toxic demyelination. CONCLUSION: Preli minary results of this study indicated that magnetization transfer is a good technique to follow in vivo matrix destruction in brain parench yma lesions. The results suggest also that phases of toxic demyelinati on in multiple sclerosis might not show gadolinium enhancement. Differ entiation between demyelinating activity and associated inflammation i n multiple sclerosis lesions should be considered in further in vivo w ork.