Imaging Biomarkers in Prodromal and Earliest Phases of Parkinson's Disease

Abstract

Assessing imaging biomarker in the prodromal and early phases of Parkinson's disease (PD) is of great importance to ensure an early and safe diagnosis. In the last decades, imaging modalities advanced and are now able to assess many different aspects of neurodegeneration in PD. MRI sequences can measure iron content or neuromelanin. Apart from SPECT imaging with Ioflupane, more specific PET tracers to assess degeneration of the dopaminergic system are available. Furthermore, metabolic PET patterns can be used to anticipate a phenoconversion from prodromal PD to manifest PD. In this regard, it is worth mentioning that PET imaging of inflammation will gain significance. Molecular imaging of neurotransmitters like serotonin, noradrenaline and acetylcholine shed more light on non-motor symptoms. Outside of the brain, molecular imaging of the heart and gut is used to measure PD-related degeneration of the autonomous nervous system. Moreover, optical coherence tomography can noninvasively detect degeneration of retinal fibers as a potential biomarker in PD. In this review, we describe these state-of-the-art imaging modalities in early and prodromal PD and point out in how far these techniques can and will be used in the future to pave the way towards a biomarker-based staging of PD.

Keywords: MRI; PET; Parkinson’s disease; biomarker; diagnosis; neuroimaging; prodromal; progression.

Fig. 1

Imaging Biomarkers of Dopaminergic Degeneration in PD. Various PET or MRI modalities can capture dopaminergic degeneration (see Table 1 for availability and use in clinical routine). Examples of normal (D–) and pathological (D+) findings. Red arrows indicate abnormality. Normal findings pointed out with green arrow. All images are in axial orientation. FP-CIT: dopamine transporter SPECT using [123I]FP-CIT; PE2I: dopamine transporter PET using [18F]FE-PE2I; FDOPA: presynaptic dopamine turnover PET using [18F]DOPA; QSM: Quantitative susceptibility mapping MRI of iron load the striatum. DNH: Dorsal nigral hyperintensity in SWI or T2* MRI, a.k.a. ‘swallow tail sign’. NMS: Neuromelanin-sensitive MRI of the substantia nigra; Courtesy Stephane Lehericy, Rahul Gaurav (Paris Brain Institute, France). FW: Free water diffusion MRI of the posterior substantia nigra; Courtesy David Vaillancourt (University of Florida, USA).