The iron burden of cerebral microbleeds contributes to brain atrophy through the mediating effect of white matter hyperintensity
Ke Lv,
Yanzhen Liu,
Yongsheng Chen,
Sagar Buch,
Ying Wang,
Zhuo Yu,
Huiying Wang,
Chenxi Zhao,
Dingwei Fu,
Huapeng Wang,
Beini Wang,
Shengtong Zhang,
Yu Luo,
E. Mark Haacke,
Wen Shen,
Chao Chai,
Shuang Xia
Affiliations
Ke Lv
Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
Yanzhen Liu
Department of Radiology, Tianjin Chest Hospital, Tianjin, China
Yongsheng Chen
Department of Neurology, Wayne State University, Detroit, MI, USA
Sagar Buch
Department of Neurology, Wayne State University, Detroit, MI, USA
Ying Wang
Magnetic Resonance Innovations, Inc., Bingham Farms, MI, USA; Department of Radiology, Wayne State University, Detroit, MI, USA
Zhuo Yu
Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
Huiying Wang
The School of Medicine, Nankai University, Tianjin, China
Chenxi Zhao
Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
Dingwei Fu
Department of Radiology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui Province, China
Huapeng Wang
Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
Beini Wang
Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China
Shengtong Zhang
The School of Medicine, Nankai University, Tianjin, China
Yu Luo
Department of Radiology, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China
E. Mark Haacke
Department of Neurology, Wayne State University, Detroit, MI, USA; Magnetic Resonance Innovations, Inc., Bingham Farms, MI, USA; Department of Radiology, Wayne State University, Detroit, MI, USA; Department of Biomedical Engineering, Wayne State University, Detroit, MI, USA
Wen Shen
Department of Radiology, Tianjin Institute of Imaging Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China
Chao Chai
Department of Radiology, Tianjin Institute of Imaging Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China; Corresponding authors.
Shuang Xia
Department of Radiology, Tianjin Institute of Imaging Medicine, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, China; Corresponding authors.
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.
