Objective: Identify magnetic resonance imaging (MRI) biomarkers of nigrostriatal neurodegeneration in early-stage drug-naïve Parkinson’s disease (PD).

Background: Diffusion tensor imaging (DTI) is an MRI technique that seems appealing for developing early biomarkers of nigrostriatal neurodegeneration in PD, but current findings are controversial. We hypothesize that a pathophysiologically-relevant source of variability could be the presence of left-right asymmetries in the dysfunction of the nigrostriatal system, previously observed with single-photon emission computed tomography (SPECT). These asymmetries are often neglected by pooling patients based on the most affected side of the body, without stratifying right-onset vs left-onset patients.

Methods: The sample in this study is the open cohort of the Parkinson Progression Marker Initiative (PPMI) [3], specifically 128 PD patients at baseline and 49 healthy controls, all right-handed. T1 images were normalized to a MNI template using ANTS, and the inverse transformation was applied to the Keuken atlas [4] in order to create substantia nigra (SN) and striatum native masks. DTI datasets were pre-processed using FSL, and scalar DTI images were estimated and co-registered to the T1 images using a linear affine transformation. DTI measures included fractional anisotropy (FA), and mean (MD), radial (RD) and axial diffusivity (AD). Average values of these measures were extracted in SN and striatum masks. Patients were stratified based on the most affected side of the body: right-onset (n=75) vs. left-onset (n=53).

Results: The right-onset PD group displayed lower FA than healthy controls in the left SN, and higher FA in the left striatum. Lower FA in the SN might reflect a reduction of axonal integrity, while higher FA in the striatum might represent pruning in the complex arborisation of this structure. Conversely, the left-onset PD group displayed no differences in FA compared with healthy controls, either in right SN or striatum. Instead, this group displayed lower MD and RD than healthy controls in the right striatum.

Conclusions: These results corroborate the left hemispheric predominance of nigrostriatal dysfunction in PD, previously observed with SPECT, [2] and suggest DTI measures as promising biomarkers for both striatal and nigral neurodegeneration.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diffusion-tensor-imaging-biomarkers-of-nigrostriatal-neurodegeneration-in-early-parkinsons-disease/