Striatal and extra-striatal dopaminergic function in Parkinson's disease and the effect of dopamine agonist therapy on PD progression studies with 3D[Â¹â¸F]-dopa PET
This thesis has implemented three dimensional (3D) acquisition, reconstruction and analysis of dynamic 18F-dopa PET datasets. This has resulted in a marked improvement in sensitivity and reconstructed resolution leading to superior data quality compared with 2D acquired PET data and consequently, greater precision in the assessment of the functional integrity of the presynaptic dopaminergic system. In comparing 3D with 2D acquired 18F-dopa PET datasets in normal subjects, the mean putamen and caudate Ki° values in the 3D group (n=12) were 0.017 ± 0.002 min-1 and 0.016 ± 0.002 min-1, respectively, compared with the 2D group (n=8) values of 0.012 ± 0.003 min-1 and 0.013 ± 0.003 min-1. The average coefficient of variation in the Ki° estimates of putamen and caudate values, were 12.7% and 11.7% for 3D and 24.8% and 25.0% for 2D, respectively. 3D 18F-dopa PET reproducibility, expressed as the mean Ki° difference (the mean difference in the Ki° values between the first and second scans) in the same normal subject, was 2.4% for putamen and 5.0% for caudate (n=5), compared with a previously reported 10% reproducibility for putamen data in 2D mode. Employing 3D 18F-dopa PET and contrary to all previously reported 2D PET studies, we have demonstrated bilateral putamen dopaminergic dysfunction in early hemi-PD (H&Y -1) with all individual putamen Ki° values contralateral to the clinically unaffected side falling below the normal range. This thesis has applied statistical parametric mapping (SPM) to 3D 18F-dopa PET datasets to localise focal changes in striatal and extrastriatal dopaminergic function in early and advanced PD and in progressing from early to advanced disease. In early left hemi-PD, significant extra-striatal increases in Ki° were observed in the left anterior cingulate gyrus and dorsal midbrain region (p<0.05, corrected) along with decreases in caudate and putamen Ki°. In advanced PD, in addition to significant putamen and caudate decreases in Ki°, extra-striatal Ki° reductions were observed in the ventral and dorsal midbrain regions (p<0.05, corrected). No significant changes in Ki° were observed in the anterior cingulate region in advanced PD. In a direct comparison between the early and late PD groups, we observed relative Ki° reductions in ventral and dorsal midbrain, and dorsal pontine regions along with striatal Ki° reductions. Similiar results were found with an ROI approach and non-transformed data, except that the focal midbrain Ki° increase seen in early PD with SPM could not be replicated. Finally, this thesis has studied with 18F-dopa PET the relative rates of progression of early Parkinson’s disease (PD) in patients started on a dopamine agonist (ropinirole), or L-dopa therapy.