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Updated: Nov 8, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Diffusion MRI Captures White Matter Microstructure Alterations in PRKN Disease
Takahiro Koinuma1, Taku Hatano1, Koji Kamagata2
1Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan.
Background:
Although pathological studies usually indicate pure dopaminergic neuronal degeneration in patients with parkin (PRKN) mutations, there is no evidence to date regarding white matter (WM) pathology. A previous diffusion MRI study has revealed WM microstructural alterations caused by systemic oxidative stress in idiopathic Parkinson's disease (PD), and we found that PRKN patients have systemic oxidative stress in serum biomarker studies. Thus, we hypothesized that PRKN mutations might lead to WM abnormalities.
Objective:
To investigate whether there are WM microstructural abnormalities in early-onset PD patients with PRKN mutations using diffusion tensor imaging (DTI).
Methods:
Nine PRKN patients and 15 age- and sex-matched healthy controls were recruited. DTI measures were acquired on a 3T MR scanner using a b value of 1,000 s/mm2 along 32 isotropic diffusion gradients. The DTI measures were compared between groups using tract-based spatial statistics (TBSS) analysis. Correlation analysis was also performed between the DTI parameters and several serum oxidative stress markers obtained in a previously conducted metabolomic analysis.
Results:
Although the WM volumes were not significantly different, the TBSS analysis revealed a corresponding decrease in fractional anisotropy and an increase in mean diffusivity and radial diffusivity in WM areas, such as the anterior and superior corona radiata and uncinate fasciculus, in PRKN patients compared with controls. Furthermore, 9-hydroxystearate, an oxidative stress marker, and disease duration were positively correlated with several parameters in PRKN patients.
Conclusion:
This pilot study suggests that WM microstructural impairments occur in PRKN patients and are associated with disease duration and oxidative stress.
Insights
Parkinson's disease (PD) patients with parkin (PRKN) mutations show white matter (WM) microstructural damage. This damage correlates with disease duration and oxidative stress markers, suggesting PRKN's role in WM integrity.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Pathological studies of parkin (PRKN) mutations in Parkinson's disease (PD) typically focus on dopaminergic neurons, with limited understanding of white matter (WM) pathology.
- Previous research linked idiopathic PD to WM microstructural alterations via oxidative stress, and PRKN patients exhibit similar oxidative stress biomarkers.
- This suggests a potential role for PRKN mutations in causing WM abnormalities.
Purpose of the Study:
- To investigate white matter (WM) microstructural abnormalities in early-onset Parkinson's disease (PD) patients with parkin (PRKN) mutations.
- To utilize diffusion tensor imaging (DTI) to assess WM integrity in PRKN mutation carriers.
Main Methods:
- Recruited nine PRKN patients and 15 healthy controls.
- Acquired diffusion MRI data using a 3T scanner with specific DTI parameters (b-value 1,000 s/mm², 32 gradients).
- Analyzed DTI measures using tract-based spatial statistics (TBSS) and correlated findings with serum oxidative stress markers.
Main Results:
- While total WM volume was unchanged, PRKN patients showed decreased fractional anisotropy and increased mean and radial diffusivity in specific WM tracts (corona radiata, uncinate fasciculus).
- These DTI changes indicate microstructural impairments in the white matter of PRKN patients.
- Serum oxidative stress markers (9-hydroxystearate) and disease duration positively correlated with DTI parameters.
Conclusions:
- This pilot study indicates that white matter (WM) microstructural impairments are present in patients with parkin (PRKN) mutations.
- These WM abnormalities are associated with both disease duration and systemic oxidative stress.
- The findings suggest PRKN plays a role in maintaining white matter integrity.
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