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Updated: Jul 16, 2025
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter
Ke Lv1, Yanzhen Liu2, Yongsheng Chen3
1Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China.
Abstract:
The goal of this work was to explore the total iron burden of cerebral microbleeds (CMBs) using a semi-automatic quantitative susceptibility mapping and to establish its effect on brain atrophy through the mediating effect of white matter hyperintensities (WMH). A total of 95 community-dwelling people were enrolled. Quantitative susceptibility mapping (QSM) combined with a dynamic programming algorithm (DPA) was used to measure the characteristics of 1309 CMBs. WMH were evaluated according to the Fazekas scale, and brain atrophy was assessed using a 2D linear measurement method. Histogram analysis was used to explore the distribution of CMBs susceptibility, volume, and total iron burden, while a correlation analysis was used to explore the relationship between volume and susceptibility. Stepwise regression analysis was used to analyze the risk factors for CMBs and their contribution to brain atrophy. Mediation analysis was used to explore the interrelationship between CMBs and brain atrophy. We found that the frequency distribution of susceptibility of the CMBs was Gaussian in nature with a mean of 201 ppb and a standard deviation of 84 ppb; however, the volume and total iron burden of CMBs were more Rician in nature. A weak but significant correlation between the susceptibility and volume of CMBs was found (r = -0.113, P < 0.001). The periventricular WMH (PVWMH) was a risk factor for the presence of CMBs (number: β = 0.251, P = 0.014; volume: β = 0.237, P = 0.042; total iron burden: β = 0.238, P = 0.020) and was a risk factor for brain atrophy (third ventricle width: β = 0.325, P = 0.001; Evans's index: β = 0.323, P = 0.001). PVWMH had a significant mediating effect on the correlation between CMBs and brain atrophy. In conclusion, QSM along with the DPA can measure the total iron burden of CMBs. PVWMH might be a risk factor for CMBs and may mediate the effect of CMBs on brain atrophy.
Insights
This study quantifies iron in cerebral microbleeds (CMBs) using quantitative susceptibility mapping (QSM) and finds periventricular white matter hyperintensities (PVWMH) mediate CMBs
Area of Science:
- Neuroimaging
- Neuropathology
- Medical Physics
Background:
- Cerebral microbleeds (CMBs) are associated with neurological conditions, but their total iron burden and impact on brain atrophy are not fully understood.
- White matter hyperintensities (WMH) are common in aging populations and may play a role in the relationship between CMBs and brain atrophy.
Purpose of the Study:
- To quantify the total iron burden of CMBs using semi-automatic quantitative susceptibility mapping (QSM).
- To investigate the mediating role of WMH in the relationship between CMBs and brain atrophy.
Main Methods:
- Quantitative susceptibility mapping (QSM) and a dynamic programming algorithm (DPA) were used to characterize 1309 CMBs in 95 participants.
- WMH were assessed using the Fazekas scale, and brain atrophy was measured using 2D linear methods.
- Statistical analyses included histogram analysis, correlation, stepwise regression, and mediation analysis.
Main Results:
- QSM-DPA successfully quantified CMBs' iron content, revealing a Gaussian distribution for susceptibility and a Rician distribution for volume and total iron burden.
- A significant correlation was found between CMB susceptibility and volume (r = -0.113, P < 0.001).
- Periventricular WMH (PVWMH) was identified as a risk factor for CMBs and brain atrophy, mediating the effect of CMBs on atrophy.
Conclusions:
- QSM combined with DPA provides a reliable method for measuring the total iron burden in CMBs.
- PVWMH plays a crucial role as a risk factor for CMBs and mediates their impact on brain atrophy, highlighting its significance in neurodegenerative processes.
