Objective: We compared 2 novel MRI techniques: neuromelanin-sensitive MRI (NM-MRI) and susceptibility weighted imaging (SWI) with [11C]PE2I PET in order to establish their validity as biomarkers for Parkinson’s disease (PD) pathology.

Background: Whilst, dopamine transporter (DAT) expression measured by either PET or SPECT imaging is the gold standard to aid the clinical diagnosis of Parkinson’s disease (PD), there are several recent MRI biomarkers that have shown promise in quantifying PD-related pathology including those that measure neuromelanin (NM) and iron deposition.

Method: 50 early PD patients (25 untreated and 25 treated with levodopa), and 25 healthy controls underwent [11C]PE2I PET scans assessing DAT expression and 3-Tesla MRI scans quantifying neuromelanin (NM) loss using NM-sensitive, and iron depositions using susceptibility weighted imaging (SWI).

Results: Compared to healthy controls, PD patients showed a loss of NM in the substantia nigra (SN), increased SWI and loss of [11C]PE2I non-displaceable binding potential (BPND) in the SN, caudate and putamen (p<0.0001). Loss of [11C]PE2I BPND was greater in the putamen (p<0.0001), while loss of NM (p<0.005) and increased SWI (p<0.0001) was greater in the SN. Longer disease duration correlated with lower NM in the SN (rho=-0.514, p<0.0001) and lower [11C]PE2I BPND in the putamen (rho=-0.659, p<0.0001). Higher MDS-UPDRS-III motor scores correlated with lower NM in the SN (rho=-0.611; p<0.0001) and with lower [11C]PE2I BPND in the caudate (rho=-0.299; p=0.035), putamen (rho=-0.712; p=0.0001), and SN (rho=-0.335; p=0.018). In comparison to healthy controls, early de novo and early levodopa-treated showed similar results, which suggests a stability of this markers to measure PD pathology at the early stages of the disease and independently of levodopa treatment.

Conclusion: These findings demonstrate that NM and SWI can be used for the valid quantification of SN pathology in PD, in comparison to the well-validated molecular imaging of DAT expression. NM and SWI closely correlates with dopaminergic striatal innervation loss, suggesting a potential role as additional readouts in clinical trials.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/imaging-parkinsons-disease-pathology-a-comparison-between-neuromelanin-sensitive-mri-susceptibility-weighted-imaging-and-11cpe2i-dat-pet/