A prospective clinico-radiological study of progressive supranuclear palsy using serial MRI with registration
The purpose of this thesis is to investigate: whether cross sectional MRI can help to discriminate progressive supranuclear palsy (PSP), multiple system atrophy (Parkinsonian subtype, MSA-P) and Parkinson's disease (PD) whether established methods of serial volumetric MRI analysis can be applied to measure in-vivo rates of brain atrophy in PSP and whether cross sectional MRI and MRI-derived atrophy rates have a clinical correlate. Volumetric and diffusion-weighted MRI (DWI) scans were performed in 24 patients with PSP, 11 with MSA-P, 12 with PD and 18 healthy controls. Detailed clinical and neuropsychological assessments were undertaken, and results at the time of initial assessment and follow-up compared. Whole brain and regional brain volumes were measured on positionally matched (registered) baseline and follow up MR images. The boundary shift integral (BSI), an image analysis technique for assessing volume differences from registered MR scans was applied to whole brain, and hypothesis-driven regions of interest in order to allow quantification of atrophy rates. PSP can be reliably discriminated from MSA-P with quantitative regional volume measurements of the superior cerebellar peduncle, midbrain, pons and cerebellum (p<0.001). DWI may help to identify regional pathological change in-vivo, discriminating MSA-P and PSP using apparent diffusion coefficients in the middle cerebellar peduncle (p0.001). The mean (SD) brain atrophy rate in PSP, 1.2 (1.0) %year_1 was greater than in healthy controls 0.4(0.5)%year"1 (p=0.04) but similar to MSA-P 1.0(l.l)%year'1. In PSP, the mean midbrain atrophy rate was most significantly different from controls (p<0.001). Ponto-cerebellar atrophy rates discriminated MSA-P and PSP (p<0.05). The distinct patterns and rates of atrophy in these diseases have a meaningful clinical correlate and power calculations confirm that in PSP, regional atrophy rates are quantifiable and feasible markers of disease progression that have utility in clinical trials as a marker for evaluating disease-modifying treatments in PSP.