In vivo imaging markers of neurodegeneration of the substantia nigra.

Non invasive detection and monitoring of substantia nigra degeneration is a long sought aim for neuroscientists, clinicians and pharmaceutical companies with an interest in Parkinson's disease (PD). Functional imaging techniques are established tools to assess the extent of striatal dopaminergic denervation that indirectly reflects nigral degeneration. They allow characterization of the dopaminergic denervation during the premotor phase of PD and have clinical value to establish the diagnosis in parkinsonism, but have proven to be unsatisfactory as surrogate markers in recent treatment trials. There is strong research interest in developing new imaging tests for nigral degeneration using a variety of structural brain imaging techniques. Nigral hyperechogenicity assessed by transcranial sonography emerges as a robust and low cost test to diagnose PD. Additionally, various advanced magnetic resonance imaging contrasts and high field magnetic resonance spectroscopy show promising sensitivity to nigral pathology in PD. Qualification of these emerging imaging tests against defined biomarker criteria is a complex and challenging task ahead. More systematic validation studies analogous to clinical trials are needed to meet the expectations and criteria defined by regulatory bodies before imaging biomarkers can be used as surrogate endpoints for neuroprotective or restorative trials.