Position emission tomography (PET) provides non-invasive quantifications of brain glucose metabolism and neuroreceptor binding that enabling greater understanding of the pathophysiology of Parkinson’s disease (PD). However, PET studies have often been conducted separately from studies using magnetic resonance imaging (MRI) exploring connectivity and functional network.
The aim of this thesis is to map in vivo dopaminergic and serotonergic networks in patients with PD by using advanced MRI and PET with the tracer 18F-DOPA assessing Aromatic-L-Amino-Acid-Decarboxylase (AADC), 11C-PE2I and 11C-DASB, targeting dopamine transporter (DAT) and serotonin transporter (SERT) respectively
The main findings are as follows: (1) Longitudinal comparison of 11C-PE2I and 18F-DOPA PET for assessing rate of disease progression in early-moderate PD patients indicate that DAT decline is closely associated with motor progression over time, whereas no such relationship was found with AADC. (2) The combined resting-state functional MRI (fMRI) and 11C-PE2I PET study demonstrates that (a) Functional connectivity of the striatum with substantia nigra (SN) was significantly positively correlated with striatal 11C-PE2I uptake. (b) Longitudinally, reduced functional connectivity of posterior putamen with SN was significantly associated with decreases in posterior putamen 11C-PE2I uptake. (3) The combined diffusion tensor imaging (DTI) and 11C-DASB PET shows that the amygdalar 11C-DASB uptake was significantly correlated with mean diffusivity (MD) value in the amygdala.
Taken together, the findings suggest that 11C-PE2I PET is an objective biomarker for investigating the effects of novel interventions on the rate of nigrostriatal degeneration in PD, and it is more effective to evaluate efficacy of neuroprotective treatments in PD. This thesis also identifies the importance of using multi-model neuroimaging to better assess underlying PD pathology and explain PD-related clinical measures. In some circumstances where cost, accessibility and scan duration are an issue; resting-state fMRI and DTI may supersede PET in the investigation of functional and structural changes in PD.