1 Department of Computer Science and Software Engineering, Concordia University, Montreal, Canada.
2 PERFORM Centre, Concordia University, Montreal, Canada.
3 Imaging Research Laboratories, Robarts Research Institute, Western University, London, Canada.
4 Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Canada.
5 School of Biomedical Engineering, Western University, London, Canada.
6 The Brain and Mind Institute, Western University, London, Canada.

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.