Imaging the nigrostriatal system to monitor disease progression and treatment-induced complications

Abstract

Radiotracer imaging (RTI) techniques such as positron emission tomography (PET) allow the in vivo assessment of nigrostriatal DA function in Parkinson's disease and have provided valuable insights into the mechanisms of nigrostriatal degeneration and the consequent compensatory changes. Moreover, functional imaging serves as an excellent tool in the assessment of the progression of PD and the evolution of treatment-related complications. However, various studies have shown discordance between clinical progression of PD and nigrostriatal degeneration estimated by PET or SPECT, and no RTI technique can be reliably used as a biomarker for progression of PD. Presynaptic dopaminergic imaging has consistently demonstrated an anterior-posterior gradient of dopaminergic dysfunction predominantly affecting the putamen, with side-to-side asymmetry in tracer binding. Dopaminergic hypofunction in the striatum follows a negative exponential pattern with the fastest rate of decline in early disease. Evaluation of central pharmacokinetics of levodopa action by PET has demonstrated the role of increased synaptic dopamine turnover and downregulation of the dopamine transporter in the pathophysiology of levodopa-induced dyskinesias. In PD with behavioral complications such as impulse control disorders, increased levels of dopamine release have been observed in the ventral striatum during performance of a positive reward task, as well as loss of deactivation in orbitofrontal cortex in response to negative reward prediction errors. This suggests that there is a pathologically heightened "reward" response in the ventral striatum together with loss of the capacity to respond to negative outcomes. Overall, functional imaging with PET is an excellent tool for understanding the disease and its complications; however, caution must be applied in interpretation of the results.