This prospective study of dopaminergic biochemical deficits and motor dysfunction seeks to improve our understanding of the physiology and progression of Parkinson's disease and related movement disorders, which affect two million Americans. The primary goal is to significantly improve the in vivo analysis of structure-function correlation in the basal ganglia. This will be achieved by combining quantitative motor performance measurements, Positron Emission Tomography (PET), Magnetic Resonance Imaging (MRI) and optimized computer methods to: 1) improve the anatomic accuracy of region of interest determination in functional PET images by intrasubject co-registration of MRI and dopaminergic PET scans; 2) apply intersubject combination of dopaminergic functional PET images; 3) correlate neurochemical abnormalities with quantitative measurements of motor deficits, relating the PET data to the nature and severity of bradykinesia, rigidity and tremor found in these patients; and 4) correlate intrasubject changes in neurochemical and quantitative motor parameters through disease progression. A population of 30 Parkinsonian patients and 10 age-matched non- Parkinsonian control subjects will be enrolled in this project, and each will be followed for approximately 3 1/2 years. Patients in this study will undergo neurological evaluation and detailed quantitative motor function testing each six months; control subjects will undergo neurological and motor function testing approximately each twenty months. Paired PET and MRI with fiducial skin markers will be obtained on all scanning days, according to the following schedule: All subjects will be enrolled during the first eighteen to twenty months, and will undergo PET imaging with the L-DOPA analog [18F]-6-fluoro-L-DOPA (fluoro-DOPA) for evaluation of presynaptic dopaminergic neuronal function plus MRI imaging at the time of enrollment. Each subject will be imaged a second time near the middle of the 5-year study period, and a third time during the last eighteen months of the study period. Intrasubject coregistration of the MRI and functional PET images will be performed using fiducial markers, and a linear intercommissural line-based method will be used for the intersubject anatomic co-registration of the functional image data. The anatomically-specific functional images so obtained will be correlated with clinical and motor performance measures over time and across subjects. This novel combination of anatomic and functional imaging, image co-registration methods and detailed quantitative motor physiology data will allow improved evaluation of the functional anatomy of the nigrostriatal dopaminergic neuronal system, and could stimulate innovative approaches to patient management.
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