Towards Clinical Implementation of Dynamic Positron Emission Tomography in Neurodegenerative Diseases

Abstract: Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative disorders worldwide. Positron emission tomography (PET), together with suitable biomarkers, can aid in the clin-ical evaluation as well as in research investigations of these diseases. Straightforward and quantitative assessments of the parameters of inter-est estimated on a voxel-level, as parametric images, are possible when PET data is acquired over time. Prerequisites to facilitate clinical use of dynamic PET are simplified analysis methods and scan protocols suita-ble for clinical routine.The aim of this thesis was to validate simplified analysis methods, suitable for clinical use, for quantification of dopamine transporter (DAT) availability in patients with parkinsonism using [11C]PE2I PET and tau accumulation in AD patients with [18F]THK5317 PET.The included subjects comprised of both healthy controls and pa-tients with parkinsonism, AD or mild cognitive impairment and each subject underwent a dynamic PET scan with either [11C]PE2I or [18F]THK5317. Models for quantitative voxel-based analysis, resulting in parametric images of tracer binding and overall brain function, were validated in both patients and controls. These parametric methods were compared to region-based values acquired using both plasma- and refer-ence-input models. Clinically feasible scan durations were evaluated for both [11C]PE2I and [18F]THK5317, and a clustering method to obtain a reference time activity curve directly from the dynamic PET data was validated. Furthermore, images of DAT availability and overall brain functional activity, generated from one single dynamic [11C]PE2I PET scan, were compared to a dual-scan approach using [123I]FP-CIT single photon emission computed tomography (SPECT) and [18F]FDG PET, for differential diagnosis of patient with parkinsonism.Study I-III supply valuable information on the feasibility of dynamic [11C]PE2I in a clinical setting for differential diagnosis of parkinsonian disorders, by having easily accessible images of DAT availability and overall brain functional activity. The work in study IV-V showed that reference methods can be used for quantification of tau accumulation, and suggests that simplified analysis methods and shorter scan durations can be applied to further facilitate applications of dynamic [18F]THK5317 PET.