Objective: To evaluate the nigrostratal pathway with multimodal assessment using striatal 11C-PE2I PET and nigral Neuromelanin-sensitive MR in Parkinson’s disease.

Background: The main pathological features in Parkinson’s disease (PD) result from the progressive loss of pigmented dopaminergic neurons in substantia nigra compacta (SNc) and the subsequent reduction of dopaminergic striatal afferences. Positron Emission Tomography (PET) with 11C-PE2I has high affinity for striatal dopamine transporter (DAT) when compared with other traditional PET tracers as 18F-DOPA. Furthermore, analysis of Neuromelanin (NM) contrast of SNc with high resolution T1 weighted (T1w) MR allows distinguishing PD and healthy controls with high accuracy. Here we combined striatal BPND quantification with PE2I PET and Nigral NM-contrast T1 in the same individuals to explore PD patients’ nigrostriatal pathway.

Methods: Sixteen patients with PD recruited into Transeuro study were scanned with ¹¹C-PE2I PET, NM T1 weighted and 3D MPRAGE anatomical MR scans along with 12 healthy volunteers age-matched. Pre-processing and kinetic modelling for the ¹¹C-PE2I PET data was conducted using MIAKAT. Brain extraction was performed on the MPRAGE images segmented and registered to Montreal Neurological Institute (MNI) template using the Anterior Commissure as anatomical reference. Bilateral delineation of ROIs 10 mm² for the SNc and SCP were respectively performed and contrast ratios (CRs) calculated for the anterior, central, and posterior parts of the SNc. Contrast ratios weighted MR were compared between PD and healthy controls using non-parametric Wilcoxon’s rank test. Striatal ¹¹C-PE2I_BP and nigral MR data were correlated using Pearson coefficient.

Results: PD patients showed reduced CR of lateral SNc when compared with healthy controls (p<0.05). Significant correlations were found between NM CR in the anterior SNc and ¹¹C-PE2I_BP in the pre-commissural striatum (ventral and dorsal caudate and putamen) (p<0.001). NM CR in the central SNc correlates with ¹¹C-PE2I_BP in the pre-commissural ventral caudate (p<0.05). No correlations were found with NM CR in posterior SNc and post-commissural striatal ¹¹C-PE2I_BP.

Conclusions: Multimodal ¹¹C-PE2I PET and T1w NM imaging protocol shows for the first time the in vivo relationship between SN NM containing neurons and striatal dopaminergic terminals in early PD patients, and could be useful to assess the effect on these structures of neuroprotective/neurorestorative treatments.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multimodal-imaging-assessment-of-nigrostriatal-pathway-in-parkinsons-disease-using-11c-pe2i-pet-and-neuromelanin-sensitive-mr/