Longitudinal Progression Markers of Parkinson's Disease: Current View on Structural Imaging

Advances in neuroimaging techniques pave a rich avenue for in vivo progression biomarkers, which can objectively and noninvasively assess the long-term dynamic alterations in the brain of Parkinson's disease (PD) patients. This article reviews recent progress in structural magnetic resonance imaging (MRI) tools to track disease progression in PD, and discusses specific criteria a neuroimaging tool needs to meet to be a progression biomarker of PD and the potential applications of these techniques in PD based on current evidence.

Recent longitudinal studies showed that quantitative structural MRI markers derived from T1-weighted, diffusion-weighted, neuromelanin-sensitive, and iron-sensitive imaging have the potential to track disease progression in PD. However, validation of these progression biomarkers is only beginning, and more work is required for multisite validation, the sample size for use in a clinical trial, and drug-responsiveness of most of these biomarkers. At present, the most clinical trial-ready biomarker is free-water diffusion imaging of the substantia nigra and seems well established to be used in disease-modifying studies in PD. A variety of structural imaging biomarkers are promising candidates to be progression biomarkers in PD. Further studies are needed to elucidate the sensitivity, reliability, sample size, and effect of confounding factors of these progression biomarkers.