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. 2021 Apr 15;42(6):1910-1919.
doi: 10.1002/hbm.25338. Epub 2021 Jan 8.

White matter hyperintensities induce distal deficits in the connected fibers

Yanpeng Liu  1 , Yiwei Xia  2 , Xiaoxiao Wang  1 , Yanming Wang  1 , Du Zhang  1 , Benedictor Alexander Nguchu  1 , Jiajie He  1 , Yi Wang  2 , Lumeng Yang  2 , Yiqing Wang  2 , Yunqing Ying  2 , Xiaoniu Liang  3 , Qianhua Zhao  3 , Jianjun Wu  2   4 , Zonghui Liang  5 , Ding Ding  3 , Qiang Dong  2 , Bensheng Qiu  1 , Xin Cheng  2 , Jia-Hong Gao  1   6   7
Affiliations

White matter hyperintensities induce distal deficits in the connected fibers

Yanpeng Liu et al. Hum Brain Mapp. .

Abstract

White matter hyperintensities (WMH) are common in elderly individuals and cause brain network deficits. However, it is still unclear how the global brain network is affected by the focal WMH. We aimed to investigate the diffusion of WMH-related deficits along the connecting white matters (WM). Brain magnetic resonance imaging data and neuropsychological evaluations of 174 participants (aged 74 ± 5 years) were collected and analyzed. For each participant, WMH lesions were segmented using a deep learning method, and 18 major WM tracts were reconstructed using automated quantitative tractography. The diffusion characteristics of distal WM tracts (with the WMH penumbra excluded) were calculated. Multivariable linear regression analysis was performed. We found that a high burden of tract-specific WMH was related to worse diffusion characteristics of distal WM tracts in a wide range of WM tracts, including the forceps major (FMA), forceps minor (FMI), anterior thalamic radiation (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a higher mean diffusivity (MD) of distal tracts was linked to worse attention and executive function in the FMI, right CCG, left ILF, SLFP, SLFT, and UNC. The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions beyond the penumbra and might eventually affect attention and executive function.

Keywords: cognition; diffusion tensor imaging; microstructural integrity; tractography; white matter hyperintensities.

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Conflict of interest statement

We have no financial relationships to declare and no competing interests to disclose.

Figures

FIGURE 1
FIGURE 1
Visualization of white matter tracts and WMH. (a) An example showing the spatial distribution of 18 major WM tracts and WMH. (b) An example of the spatial analysis contours for tracts and WMH in the CST. The surface contours were dilated by 4 mm at a time from the WMH edge. L = left; R = right; WMH = white matter hyperintensities; FMA = forceps major; FMI = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; CST = corticospinal tract; ILF = inferior longitudinal fasciculus; SLFP = superior longitudinal fasciculus‐parietal; SLFT = superior longitudinal fasciculus‐temporal; UNC = uncinate fasciculus
FIGURE 2
FIGURE 2
Boxplots of the percentages of tract‐specific WMH ratios. Boxes indicate the 25th–75th percentiles of WMH ratios, and the lines and whiskers show the median and range of WMH ratios respectively. L = left; R = right; WMH = white matter hyperintensities; FMA = forceps major; FMI = forceps minor; ATR = anterior thalamic radiation; CAB = cingulum angular bundle; CCG = cingulum cingulate gyrus; CST = corticospinal tract; ILF = inferior longitudinal fasciculus; SLFP = superior longitudinal fasciculus‐parietal; SLFT = superior longitudinal fasciculus‐temporal; UNC = uncinate fasciculus
FIGURE 3
FIGURE 3
Measurements of the MD values of the distal WM tracts. All participants (n = 174) were divided into three groups (G1 < G2 < G3) by tertile of tract‐specific WMH volume, with 58 participants in each group. Participants in the G1 group had the smallest WMH volume and those in the G3 group had the largest WMH volume. Boxes indicate the 25th–75th percentiles of MD, and the lines and whiskers show the median and range of MD respectively. One‐way ANOVA analysis and post‐hoc testing with Bonferroni correction were used. *p < .05. **p < .01. ***p < .001. MD = mean diffusivity; WMH = white matter hyperintensities; L = left; R = right; FMA = forceps major; FMI = forceps minor; ATR = anterior thalamic radiation; CCG = cingulum cingulate gyrus; CST = corticospinal tract; ILF = inferior longitudinal fasciculus; SLFP = superior longitudinal fasciculus‐parietal; SLFT = superior longitudinal fasciculus‐temporal; UNC = uncinate fasciculus
FIGURE 4
FIGURE 4
The average MD values of all participants along each tract in MNI space. The abscissa is the spatial position along the tract, the red line represents the mean MD values and the light red interval is the standard deviation. Significant correlations (p < .05, corrected by false discovery rate) between the MD of WM tracts at each position and tract‐specific WMH ratios are plotted in black *(adjusted for age and sex). The height of the blue curve represents the percentage of WMH overlap frequency along the tracts. MD = mean diffusivity; WMH = white matter hyperintensities; L = left; R = right; FMA = forceps major; FMI = forceps minor; ATR = anterior thalamic radiation; CCG = cingulum cingulate gyrus; CST = corticospinal tract; ILF = inferior longitudinal fasciculus; SLFP = superior longitudinal fasciculus‐parietal; SLFT = superior longitudinal fasciculus‐temporal; UNC = uncinate fasciculus
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