Characterizing white matter alterations subject to clinical laterality in drug‐naïve de novo Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a range of motor and nonmotor symptoms, often with the motor dysfunction initiated unilaterally. Knowledge regarding disease‐related alterations in white matter pathways can effectively help improve the understanding of the disease and propose targeted treatment strategies. Microstructural imaging techniques, including diffusion tensor imaging (DTI), allows inspection of white matter integrity to study the pathogenesis of various neurological conditions. Previous voxel‐based analyses with DTI measures, such as fractional anisotropy and mean diffusivity have uncovered changes in brain regions that are associated with PD, but the conclusions were inconsistent, partially due to small patient cohorts and the lack of consideration for clinical laterality onset, particularly in early PD. Fixel‐based analysis (FBA) is a recent framework that offers tract‐specific insights regarding white matter health, but very few FBA studies on PD exist. We present a study that reveals strengthened and weakened white matter integrity that is subject to symptom laterality in a large drug‐naïve de novo PD cohort using complementary DTI and FBA measures. The findings suggest that the disease gives rise to tissue degeneration and potential re‐organization in the early stage.

Fixel based analysis of white matter alterations in early stage cerebral small vessel disease

“…Hence our results regarding fibre density should be interpreted with the necessary care. However, we also highlight that our results regarding the fibre density can be deemed pathophysiologically plausible and that previous FBA-based analyses with a b-value of 1000 s/mm 2 also came to conclusive results 42 , 43 . Also, the effects of lower b-values should be attenuated by the application of single-shell 3-tissue constrained spherical deconvolution during processing in our analysis.…”

“…Of note, our b-value of b = 1000 s/mm 2 is smaller than the recommendation for quantifying FD 21 . However, our approach follows previous studies yielding plausible results based on single-shell data with b = 1000 s/mm 2 42 , 43 . Fibre-bundle cross-section (FC) measures differences in fibre-bundle diameters between a subject’s FOD and the FOD template.…”

“…Of note, our b-value of b = 1000 s/mm 2 is smaller than the recommendation for quantifying FD 21 . However, our approach follows previous studies yielding plausible results based on single-shell data with b = 1000 s/mm 2 42 , 43 .…”

Voxel-Based Diktiometry - Combining convolutional neural networks with voxel-based analysis and its application in diffusion tensor imaging for Parkinson’s disease

“…Using the traditional method, we have largely reproduced the results generated by the voxel-based analysis performed by Xiao et al (2021), specifically in terms of the white matter bundle extending from the cortex to the brain stem on the collateral to symptom onset. This validates that the statistical mapping method used for all three approaches is coherent with the literature.…”

“…On the PPMI dataset (Marek et al, 2011) significant alterations between healthy controls and Parkinsonian patients located within the SN, the striatum and the subthalamic nucleus (STN), pallidum, putamen and thalamus have been previously reported (Schuff et al, 2015;Cousineau et al, 2017). Xiao et al (2021) have also found significant differences in the major white matter bundles between patients and controls specifically on the side of PD onset.…”