Quantitative dopamine imaging in humans using magnetic resonance and positron emission tomography

Thesis

Dopamine is an important neurotransmitter that is involved in several human functions such as reward, cognition, emotions and movement. Abnormalities of the neurotransmitter itself, or the dopamine receptors through which it exerts its actions, contribute to a wide range of psychiatric and neurological disorders such as Parkinson’s disease and schizophrenia. Thus far, despite the great interest and extensive research, the exact role of dopamine and the causalities of dopamine related disorders are not fully understood.

Here we have developed multimodal imaging methods, to investigate the release of dopamine and the distribution of the dopamine D2-like receptor family in-vivo in healthy humans. We use the [¹¹C]PHNO PET ligand, which enables exploration of dopamine-related parameters in striatal regions, and for the first time in extrastriatal regions, that are known to be associated with distinctive functions and disorders. Our methods involve robust approaches for the manual and automated delineation of these brain regions, in terms of structural and functional organisation, using information from structural and diffusion MRI images. These data have been combined with [¹¹C]PHNO PET data for quantitative dopamine imaging.

Our investigation has revealed the distribution and the relative density of the D3R and D2R sites of the dopamine D2-like receptor family, in healthy humans. In addition, we have demonstrated that the release of dopamine has a functional rather than a structural specificity and that the relative densities of the D3R and D2R sites do not drive this specificity. We have also shown that the dopamine D3R receptor is primarily distributed in regions that have a central role in reward and addiction. A finding that supports theories that assigns a primarily limbic role to the D3R.

Authors: Tziortzi, A

• Publication date: 2014
• DOI: 10.5287/ora-mqp9b4vw8
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Striatum; Pallidum; MRI; PET; Dopamine; Substantia nigra; Regions of Interest; Basal ganglia; Magnetic resonance imaging; Brain; DTI; Dopamine Receptor; anatomy; Positron Emission Tomography; Diffusion weighted imaging
• Subjects: Neuroscience; Neurology; Cognitive Neuroscience; Behavioural Neuroscience; Emotion; Emotion research; Anatomy; Psychopharmacology