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Updated: May 5, 2026
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Diffusion tensor imaging with free-water correction reveals distinctions between severe and attenuated subtypes in
Alena Svatkova1,2,3, Ofer Pasternak4, Julie B Eisengart1
1Department of Pediatrics, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract:
Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder leading to deleterious brain effects. While animal models suggested that MPS I severely affects white matter (WM), whole-brain diffusion tensor imaging (DTI) analysis was not performed due to MPS-related morphological abnormalities. 3T DTI data from 28 severe (MPS IH, treated with hematopoietic stem cell transplantation-HSCT), 16 attenuated MPS I patients (MPS IA) enrolled under the study protocol NCT01870375, and 27 healthy controls (HC) were analyzed using the free-water correction (FWC) method to resolve macrostructural partial volume effects and unravel differences in DTI metrics accounting for microstructural abnormalities. FWC analysis in MPS IH compared to HC revealed higher free-water fraction (FWF) in all WM regions with increased radial (RD) and mean diffusivity (MD). Higher RD, MD, and FWF in cingulate and FWF in temporal WM were observed in MPS IA relative to HC. FWF and RD in the corpus callosum (CC) were higher in MPS IH than in MPS IA. Reaction time was correlated with fractional anisotropy (FA) in frontal and parietal WM in MPS IH. FA in temporal and central WM correlated with d-prime in MPS IA. The HSCT age was related to FA in parietal WM and FWF in frontal WM in MPS IH. FWC delineated subtype-specific WM microstructural abnormalities linked to myelination that were more extensive in MPS IH than IA, with CC findings being a key differentiator between subtypes. Earlier age at HSCT was related to preserved WM microstructure in the brain of MPS IH patients. Free water-corrected DTI distinguishes severe and attenuated MPS I patients and reveals a relationship between attention, age at HSCT, and white matter microstructure.
Insights
Mucopolysaccharidosis type I (MPS I) causes brain white matter damage. Free-water corrected diffusion tensor imaging revealed subtype-specific white matter abnormalities, more severe in MPS IH than MPS IA, and linked early treatment to better outcomes.
Area of Science:
- Neuroimaging
- Biochemistry
- Genetics
Background:
- Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disorder with significant neurological impact.
- Previous studies suggested white matter (WM) involvement in MPS I, but detailed analysis was limited by morphological abnormalities.
- Diffusion Tensor Imaging (DTI) offers insights into WM microstructure, but requires advanced methods to overcome limitations in diseased brains.
Purpose of the Study:
- To investigate white matter (WM) microstructural differences in patients with severe (MPS IH) and attenuated (MPS IA) Mucopolysaccharidosis type I (MPS I) compared to healthy controls (HC).
- To utilize free-water correction (FWC) in DTI analysis to accurately assess WM abnormalities in MPS I subtypes.
- To explore correlations between WM microstructure, cognitive function (reaction time, d-prime), and treatment parameters (age at hematopoietic stem cell transplantation - HSCT).
Main Methods:
- Acquisition of 3T DTI data from 28 MPS IH, 16 MPS IA patients, and 27 HC.
- Application of the free-water correction (FWC) method to DTI data to resolve partial volume effects and analyze microstructural metrics.
- Statistical comparison of DTI metrics (FWF, RD, MD, FA) across patient groups and correlation analysis with clinical data.
Main Results:
- FWC-DTI revealed significantly higher free-water fraction (FWF), radial diffusivity (RD), and mean diffusivity (MD) in WM of MPS IH patients compared to HC.
- MPS IA patients showed increased RD, MD, and FWF in specific WM regions compared to HC.
- The corpus callosum (CC) exhibited higher FWF and RD in MPS IH than MPS IA, serving as a key differentiator.
- Cognitive measures and HSCT age correlated with specific WM microstructural integrity markers in both MPS I subtypes.
Conclusions:
- FWC-DTI effectively distinguishes WM microstructural abnormalities between severe and attenuated MPS I subtypes.
- WM abnormalities, particularly in the CC, are more pronounced in MPS IH than MPS IA.
- Earlier age at HSCT is associated with better preserved WM microstructure in MPS IH patients, highlighting the importance of timely intervention.
