SPECT and PET in Atypical Parkinsonism

Over the past decade, presynaptic dopaminergic SPECT and PET agents have served as clinically useful diagnostic agents (in Europe), as tools for drug development trials, and as a means for elucidating pathophysiology in vivo in cross-sectional and longitudinal studies of patients with movement disorder. From a clinical perspective, much of the work has been done in idiopathic PD, which comprises the great bulk of the parkinsonisms, and in distinguishing DLB from Alzheimer disease. Nonetheless, the limitations of presynaptic dopaminergic imaging are well understood even as more sophisticated applications of these wellused tracers remain to be established; in particular, this means pushing back the time to make the include patients at risk for the disorder as well as patients with very early clinical signs and symptoms that do not yet meet the criteria for a diagnosis. These efforts are energized by the promise of disease-modifying drugs where the urgency for an early and accurate diagnosis becomes more acute. As the tools for molecular imaging are expanded with new tracers, new analytic techniques for old tracers, incorporation of large-scale and wellvetted normal imaging databases, and more sophisticated clinical imaging algorithms for combining neuroimaging techniques, we should be able to make molecular diagnoses with imaging biomarkers available for smarter treatments. Hence, the applications of these biomarkers are becoming more complex across the spectrum, from detecting molecular changes in at-risk patients27 to establishing firm differential diagnosis based on an in vivo pathology read-out to monitoring progression of disease and response to therapy on the clinical side. From a research perspective, the application of these biomarkers helps to foster smarter recruitment into clinical trials, assess mechanistic efficacy of novel treatments, and enhance understanding of pathophysiology of Parkinson spectrum disorders.