Fig. 2: Emerging imaging measures in Parkinson’s disease.

A Imaging measures for accurate diagnosis of Parkinson’s disease (PD) include: 1. Dopaminergic imaging: axial 123I-FP-CIT single-photon emission computed tomography (SPECT) scans for neuropathologically-confirmed degenerative parkinsonism; adapted from Nicastro et al.²¹ (Released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license). 2. Cardiac meta-iodobenzylguanidine (MIBG) scintigraphy: Absent tracer uptake in the heart (dotted circle) in a patient with dementia with Lewy Bodies (DLB) compared to a control. Heart-to-mediastinum ratios (heart: dotted circles, upper mediastinum: rectangle) can be calculated. Adapted from ref. ³⁶; 3. Imaging of the Substantia Nigra (SN): Neuromelanin-sensitive MRI (NM-MRI) to visualise SN atrophy, with earliest changes involving signal loss in nigrosome-1 territory, caudal and mediolateral portions of the SN. Loss of nigrosome-1 shown here in a PD patient in an NM-MRI image (c) and QSM image (d) compared to a control (a: NM-MRI, b: QSM). Adapted with permission from ref. ⁴² (Released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license). B Neuroimaging measures for risk stratification and tracking disease progression in PD: 4. Imaging of White Matter: Fixel-based analysis shows reduced white matter fibre cross-section in PD patients who later developed poor outcomes over 3-year follow-up. Colour scale represents percentage reduction in fibre cross-section in PD patients with poor vs PD patients with good outcomes. Adapted from ref. ¹⁴²; 5 Structural connectivity: Widespread reductions in structural connectivity, mostly in frontal and parietal-occipital connections, seen at baseline in PD patients who progress to poor outcomes within 3 years, from ref. ¹⁴²; 6. Free water imaging: Longitudinal changes in free water within the SN seen in PD patients compared to controls. Loss of signal is seen in the midbrain of a PD patient over 4 years. Adapted with permissions¹⁷⁹, (released under a Creative Commons Attribution-NonCommercial 4.0 International license) 7. Iron-sensitive imaging: QSM signal at baseline correlates with longitudinal worsening of (a)motor and (b)cognitive scores in PD patients over 3 years. Colour bar represents p-value family-wise error-corrected for multiple comparisons, grey scale represents susceptibility values. Adapted from ref. ¹⁷³ 8. Cortical thickness: Cortical thinning patterns in patients with mild PD compared to controls after 2 and 4-year follow-up. Statistically-significant regions shown in blue, corrected for multiple comparisons using false discovery rate. Colour bar represents t-values. Adapted with permission from Fillippi et al.¹²³(Released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license). CBS Corticobasal syndrome, CTL Control, DLB Dementia with Lewy bodies, L Left; MCI Mild cognitive impairment, MIBG meta-iodobenzylguanidine MSA-P Multiple system atrophy parkinsonian type, NM-MRI Neuromelanin-sensitive MRI, PD Parkinson’s disease, PSP Progressive supranuclear palsy; QSM Quantitative susceptibility mapping, R Right; SN Substantia nigra.