The overall goals of this study are: (1) to define the natural history of quantitative MRI and brainwide MTR and HMRSI in patients with primary progressive (PP)MS and healthy controls and, (2)determine the treatment effect of mitoxantrone on those imaging measures. In contrast to conventional T2 weighted imaging which does not distinguish between edema, inflammation, demyelination, and axonal loss, MTR and HMRSI provide more specific imaging markers of demyelination and axonal loss. As there are no longitudinal studies of the combination these complementary imaging measures in PPMS, this study will further our understanding of the natural history of this clinical pattern of MS which is characterized predominantly by diffuse rather than focal abnormalities in brain white matter. The goals will be accomplished by adding annual MT and HMRSI to conventional MRI scans being obtained in patients participating in an ongoing placebo-controlled trial of mitoxantrone in PPMS. Scanning will be continued in 27 placebo recipients for 4 years after completing the 1 year treatment phase of that study and comparable scanning will be obtained from 27 healthy controls.
Specific Aims : 1) To compare changes in brain wide histograms of MT ratios, T2 relaxation times and HMRSI spectral intensities of N-acetyl aspartate (NAA), creatine/phosphocreatine (Cr) and choline (Chol) in patients randomly assigned to treatment with MTXN 12 mg/m2 or placebo administered IV every third month for up to 12 months. 2) To compare cross-sectional and annual brain-wide changes in quantitative parameters derived from MT, T2 and HMRSI data for healthy controls and untreated patients with PPMS over a period of 5 years and to investigate how these data correlate with conventional imaging endnotes such as changes in brain volume, ventricular volume, T1 lesion load and T2 lesion load. 3) To determine whether annual changes in quantitative parameters derived from MT, T2 and HMRSI data from patients with PPMS correlate with annual sustained changes in clinical measures of disability and conventional imaging endpoints such as changes in brain volume, ventricular volume, Tl lesion load and T2 lesion load.
