Objective: To assess multimodal imaging of the noradrenergic system: magnetic resonance imaging (MRI) neuromelanin contrast of the locus coeruleus (LC) and noradrenalin transporter density with ¹¹C-MeNER positron emission tomography (PET).

Background: Noradrenergic dysfunction is highly prevalent in patients with Parkinson’s disease (PD) and promising MRI and PET markers of the noradrenergic system has recently emerged. However, it remains unclear, whether MRI and PET noradrenergic imaging parameters are additive or redundant.

Method: 73 subjects (26 healthy subjects (HC) and 47 PD patients) underwent MRI and ¹¹C-MeNER PET. PET scans were acquired with an ECAT HRRT; we analyzed images with PMOD 4.0 and defined six noradrenaline transporter rich regions (thalamus, hypothalamus, red nucleus, locus coeruleus, pontine, and dorsal raphe) for volume of interest (VOI) analyses using occipital cortex as reference. Axial turbo spin echo sequences were acquired (TR/TE: 600ms/9.9ms, Siemens Trio, n=39; and TR/TE: 825ms/18ms, Siemens Skyra, n=34, voxel size: 0.4*0.4*1.8mm,). VOIs for each side of the LC were transformed to the individual MRI and the 12 connected voxels with highest intensity were extracted and divided by the background (pons). Statistical analyses were performed with SPSS 24; MRI scan condition was included as co-variate in analyses.

Results: PD patients were comparable to HC subjects on age- and sex-distribution (age: 66.6±8.4 vs. 66.5±6.3, p=0.945; 68.1% vs. 50% males, p=0.141), and had a mean disease duration of 4.9±3.6 years, and H&Y stage of 2.4±0.5. PD patients exhibited lower noradrenaline transporter density in thalamus, hypothalamus, red nucleus, locus coeruleus, and dorsal raphe (ANOVA: group effect F=20.19, p<0.001, each region p<0.006) as well as lower MRI neuromelanin contrast (ANCOVA: F=11.65, p=0.001). We did not find a significant correlation of MRI contrast with noradrenaline transporter density in HC subjects, PD patients and pooled analysis.

Conclusion: PD patients showed considerable disintegration of the noradrenergic system with degradation of noradrenaline transporter density – representing synaptic dysfunction – and neuromelanin contrast of the LC – representing integrity of cell bodies. We found no association between the two imaging modalities, suggesting that progressive noradrenergic synaptic dysfunction and cell loss may be uncoupled phenomena.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/noradrenergic-terminal-and-locus-coeruleus-cell-loss-may-be-uncoupled-in-parkinsons-disease-a-pet-and-mri-multi-modal-imaging-study/