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Updated: Sep 7, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
White Matter Tract Injury by MRI in CADASIL Patients is Associated With Iron Accumulation
Hui Hong1, Shuyue Wang1, Xinfeng Yu1
1Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Background:
Widespread white matter (WM) injury is a hallmark feature of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, controversies about the mechanism of WM tract injury exist persistently. Excessive iron accumulation, frequently reported in CADASIL patients, might cause WM tract injury.
Purpose:
To test the association between iron accumulation and WM tract injury in CADASIL patients.
Study Type:
Retrospective.
Population:
A total of 35 CADASIL patients (age = 50.4 ± 6.4, 62.9% female) and 48 healthy controls (age = 55.7 ± 8.0, 68.8% female).
Field Strength/Sequence:
Diffusion-weighted spin-echo echo-planar sequence; enhanced susceptibility-weighted angiography (ESWAN) gradient echo sequence on a 3 T scanner.
Assessment:
The phase images acquired by ESWAN were used to calculate quantitative susceptibility mapping (QSM). Iron accumulation was evaluated in deep gray matters using QSM. WM tract injury was quantified by diffusion metrics based on WM major tracts skeleton. We compared iron deposition between groups and analyzed the correlation between WM tract injury and iron deposition in regions showing significant differences from healthy controls. Exploratory analysis was carried out to investigate whether WM tract injury mediated the relationship between iron deposition and cognitive impairment evaluated by Mini-Mental State Examination (MMSE).
Statistical Tests:
General linear model (GLM), partial correlation, stepwise linear regression and mediation analysis were used. The threshold of statistical significance was set as p < 0.05.
Results:
Compared with healthy controls, CADASIL patients had significantly increased iron deposition in the caudate and putamen. Aberrant iron deposition in these two regions was significantly associated with decreased WM fractional anisotropy (FA) (caudate, r = -0.373； putamen, r = - 0.421), and increased radial diffusivity (RD) (caudate, r = 0.372; putamen, r = 0.386). Furthermore, WM tract injury mediated the relationship between iron deposition and cognitive impairment.
Data Conclusion:
Patients with CADASIL show increased iron deposition in the caudate and putamen that is correlated to WM tract injury, which may in turn mediate the association with cognitive impairment.
Evidence Level:
2 TECHNICAL EFFICACY: Stage 2.
Insights
Iron accumulation in the brain
Area of Science:
- Neuroimaging
- Neurology
- Biochemistry
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by widespread white matter (WM) injury.
- The exact mechanism of WM tract injury in CADASIL remains debated.
- Excessive iron accumulation is frequently observed in CADASIL patients and may contribute to WM injury.
Purpose of the Study:
- To investigate the association between iron accumulation and white matter tract injury in patients with CADASIL.
- To explore the role of iron deposition in the pathogenesis of WM injury in CADASIL.
Main Methods:
- Utilized quantitative susceptibility mapping (QSM) on enhanced susceptibility-weighted angiography (ESWAN) gradient echo sequences (3T scanner) to assess iron deposition in deep gray matter.
- Quantified white matter tract injury using diffusion metrics from diffusion-weighted spin-echo echo-planar sequences.
- Employed general linear models, partial correlation, and mediation analysis to evaluate relationships between iron deposition, WM injury, and cognitive function.
Main Results:
- CADASIL patients exhibited significantly higher iron deposition in the caudate and putamen compared to healthy controls.
- Increased iron in the caudate and putamen was significantly correlated with reduced fractional anisotropy (FA) and increased radial diffusivity (RD) in white matter tracts.
- White matter tract injury was found to mediate the relationship between iron deposition and cognitive impairment.
Conclusions:
- Increased iron deposition in the caudate and putamen is associated with white matter tract injury in CADASIL patients.
- White matter tract injury may serve as a mediator linking iron accumulation to cognitive impairment in CADASIL.
- These findings suggest iron accumulation as a potential contributor to the pathophysiology of CADASIL.
