A Study On The Relationship Between Cerebral White Matter Hyperintensities And White Matter Network Microstructure

White matter hyperintensities(WMH)are common in brain magnetic resonance imaging of the elderly individuals aged 60 and above,and are associated with brain network deficits and cognitive dysfunction.However,it is still unclear whether focal WMH can cause the distal white matter network microstructure deficits,and then induce cognitive function decline.Focusing on the white matter network microstructure will help to better understand the intermediate process of cognitive impairment caused by WMH and the internal mechanism of cerebral small vessel disease.Therefore,this study aims to explore how WMH affects cognitive function by affecting the integrity of white matter microstructure in normal elderly people from the perspective of whole brain white matter structure connection and the microstructure of white matter tracts far away from WMH.Brain magnetic resonance imaging data and neuropsychological evaluations of 174 healthy participants(aged 74 ± 5 years)were collected and analyzed,For each participant,WMH lesions were segmented automatically using a deep learning method.To create the brain structural network,the whole brain white matter tracts were reconstructed by a deterministic fiber bundle tracking algorithm,and graph analysis was employed to assess the correlation between the network properties and the normalized volume of WMH under a wide range of network sparsities.In addition,eighteen major white matter tracts were reconstructed using automated quantitative tractography.The diffusion characteristics(fractional anisotropy and mean diffusivity)of distal white matter tracts(excluding the WMH penumbra)were calculated,and their relationships with tract-specific WMH ratio and cognitive function were analyzed by the multivariable linear regression analysis.Furthermore,the variation of the diffusion characteristics with the spatial position of the tracts was analyzed.This study found that there were significant correlations between the WMH volume normalized to the brain size and the following network characteristics:mean length(β=-0.231,P=0.003),density(β=-0.230,P＝0.004),average clustering coefficient(β＝-0.198,P=0.015),network characteristic path length(β=0.281,P=0.001),small world(β=-0.297,P＝0.001),global efficiency(β＝-0.269,P=0.001)and local efficiency(β＝-0.235,P=0.004).This study also found that in the major white matter tracts of the whole brain,the WMH ratios of the different tracts varied greatly.A high burden of tract-specific WMH was related to worse diffusion characteristics of distal tracts in a wide range of white matter 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 and temporal(SLFP and SLFT),and uncinate fasciculus(UNC).Furthermore,a higher mean diffusivity of distal tracts was linked to worse attention and executive function in the FMI,right CCG,left ILF,SLFP,SLFT and UNC.On the basis of the relationships between the normalized WMH volume and the white matter structural network characteristic parameters,this study shows for the first time that high burden of WMH on specific tract leads to microstructural defects in distal white matter tracts in a healthy elderly population.The effects of WMH on the microstructural integrity of white matter tracts may propagate along tracts to distal regions beyond the penumbra and might eventually induce attention and executive function decline.