Imaging studies: towards understanding the complications related to advanced monoaminergic disease and treatment

Parkinson's disease (PD) is the second most common neurodegenerative disorder, estimated to affect 100,000 Canadians and is characterized by deficiency of the neurotransmitter dopamine (DA) as a consequence of dopaminergic neuronal death. Existing treatments ameliorate the symptoms, but they do not seem to alter disease progression. Furthermore, treatment often induces undesired side-effects such as motor complications and high risk taking behavior such as compulsive gambling. Positron emission tomography (PET) is a non-invasive imaging modality that uses radioactive tracers to obtain information about biological function in-vivo; depending on their chemical form, radiotracers tag different biochemical processes. PET is thus ideally suited to investigate the complex neurochemical changes associated with neurodegeneration. Using PET we have already provided significant insights into the motor aspects of disease-induced complications; an alteration in the pattern of the neuronal release of DA has been identified as being involved in the occurrence of motor complication. The main goal of this research program is to further develop and use novel imaging techniques to gain insights into the impact of different treatment strategies on motor complications and into treatment-induced psychiatric complications. Studies on human volunteers will be performed on a new, state-of-the art human PET brain scanner. This scanner, existing only in 15 PET centers worldwide, while providing and unprecedented amount of information, requires development of accurate data manipulation and interpretation algorithms, which are another part of this research program. A very important aspect in medical research is the ability to develop and investigate animal models of disease to be able to investigate disease in further detail in a more controlled environment. A third important part of this research program will be the in-vivo investigation of rodent models of PD and their relation to other diseases such as, for example, Alzheimer's, since there is evidence of some clinical and pathological overlap between neurodegenerative diseases. A unique strength of this program is its ability to bridge advancement of knowledge with the advancement of methodological approaches. This aspect will contribute towards the establishment of a more comprehensive imaging environment aimed at the investigation of neurodegenerative and related disease, which is the program long term goal.