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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS039529-01A1
Application #
6197965
Study Section
Special Emphasis Panel (ZRG1-BDCN-4 (01))
Program Officer
Kerza-Kwiatecki, a P
Project Start
2000-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
1
Fiscal Year
2000
Total Cost
$94,500
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Oh, Joonmi; Pelletier, Daniel; Nelson, Sarah J (2004) Corpus callosum axonal injury in multiple sclerosis measured by proton magnetic resonance spectroscopic imaging. Arch Neurol 61:1081-6
Oh, J; Henry, R G; Genain, C et al. (2004) Mechanisms of normal appearing corpus callosum injury related to pericallosal T1 lesions in multiple sclerosis using directional diffusion tensor and 1H MRS imaging. J Neurol Neurosurg Psychiatry 75:1281-6
Henry, Roland G; Oh, Joonmi; Nelson, Sarah J et al. (2003) Directional diffusion in relapsing-remitting multiple sclerosis: a possible in vivo signature of Wallerian degeneration. J Magn Reson Imaging 18:420-6
Pelletier, D; Nelson, S J; Oh, J et al. (2003) MRI lesion volume heterogeneity in primary progressive MS in relation with axonal damage and brain atrophy. J Neurol Neurosurg Psychiatry 74:950-2
Pelletier, D; Nelson, S J; Grenier, D et al. (2002) 3-D echo planar (1)HMRS imaging in MS: metabolite comparison from supratentorial vs. central brain. Magn Reson Imaging 20:599-606