ORIGINAL RESEARCH article
Front. Neurol.
Sec. Applied Neuroimaging
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1605753
This article is part of the Research TopicDiffusion-Weighted Imaging: Advances and Implementations in NeurologyView all 8 articles
Investigating White Matter Alterations in Parkinson's Disease Using Multi-Shell Free-Water DTI and NODDI: Insights into Neurodegeneration and Levodopa Effects
Provisionally accepted
- 1Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, Arizona, United States
- 2School of Life Sciences, Arizona State University, Tempe, Arizona, United States
- 3Muhammad Ali Parkinson Center at Barrow Neurological Institute, Phoenix, Arizona, United States
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Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. Levodopa remains the primary treatment, temporarily restoring dopamine levels and improving motor symptoms. Advanced diffusion MRI techniques, such as free-water corrected diffusion tensor imaging (fw-DTI) and neurite orientation dispersion and density imaging (NODDI), provide insights into PD-related microstructural changes beyond conventional DTI. This study investigates white matter alterations in PD using multi-shell fw-DTI and NODDI to compare voxel-wise differences between PD patients both OFF and ON levodopa, with comparison to healthy controls (HC). Effect sizes and receiver operating characteristic (ROC) analyses assessed the discriminative power of imaging metrics. PD (OFF) exhibited increased free-water, reduced neurite density (NDI), and altered orientation dispersion (ODI) in key motor pathways in comparison to HC, while fw-FA offered robust group discrimination (AUC=0.956). Levodopa (ON state) increased NDI and NODDI-FWF, suggesting acute microstructural plasticity, though this finding contrasted with minimal fw-DTI FW changes. Additionally, voxel-based correlation analyses linked free-water and neurite integrity metrics with disease severity. Our findings suggest that fw-DTI and NODDI provide complementary information on PD-related neurodegeneration and the transient effects of levodopa. These results underscore the potential of advanced diffusion MRI techniques as biomarkers for tracking PD progression and treatment response.
Keywords: Parkinson's disease, Levodopa, diffusion MRI, White matter alterations, NODDI, free-water DTI
Received: 03 Apr 2025; Accepted: 10 Jun 2025.
Copyright: © 2025 Bergamino, Zhu, Shill and Stokes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ashley M. Stokes, Barrow Neuroimaging Innovation Center, Barrow Neurological Institute, Phoenix, Arizona, United States
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