Altered Spontaneous Brain Activity Related to Neurologic Dysfunction in Patients With Cerebral Small Vessel Disease.

Mengmeng Feng,Changhu Liang,Nan Zhang,Haotian Xin,Hongwei Wen,Lingfei Guo

doi:10.3389/fnagi.2021.731585

Abstract

Cerebral small vessel disease (CSVD) encompasses several diseases affecting the small arteries, arterioles, venules, and capillaries of the brain and refers to several pathological processes and etiologies. Neuroimaging is considered the gold standard for detecting CSVD, which can present diverse features on MRI. Cerebral microbleeds (CMBs) in CSVD have been demonstrated to play a synergistic role in both cerebrovascular and neurodegenerative pathology. Considering previous studies on brain structural abnormalities in CSVD, in the present study, we aimed to explore altered spontaneous brain activity among CSVD patients using amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) methods based on resting-state functional MRI. In this study, we recruited 24 CSVD patients with CMBs (CSVD-c), 42 CSVD patients without CMBs (CSVD-n) and 36 healthy controls from outpatient clinics in Shandong Provincial Hospital affiliated to Shandong First Medical University between September 2018 and June 2019. All subjects underwent 3-T MRI, including blood oxygen level-dependent (BOLD) and susceptibility-weighted imaging (SWI). Anatomic structures were segmented, ALFF/fALFF values were calculated, and ReHo maps were generated. Further statistical analysis was applied to study the difference in ALFF/fALFF/ReHo among the three groups and the association between ALFF/fALFF/ReHo changes in different brain regions and clinical characteristics. Twenty-four CSVD-c patients (age: 67.54 ± 6.00 years, 10 females), 42 CSVD-n patients (age: 66.33 ± 5.25 years, 22 females) and 36 healthy subjects (age: 64.14 ± 8.57 years, 19 females) were evaluated. Compared with controls, the CSVD-c group showed significantly increased ALFF values in the right insula, putamen and left precuneus; decreased fALFF values in the right precentral gyrus and postcentral gyrus; and increased ReHo values in the left precuneus, fusiform gyrus, right supplementary motor area (SMA), and superior frontal gyrus. Notably, the mean ALFF values of the right insula and putamen were not only significantly related to all clinical parameters but also demonstrated the best performance in Receiver Operating Characteristic (ROC) curve analysis. These findings reveal CSVD-c patients have dysfunctions in the default mode network, sensorimotor network and frontoparietal network, which may implicate the underlying neurophysiological mechanisms of intrinsic brain activity. The correlation between altered spontaneous neuronal activity and clinical parameters provides early useful diagnostic biomarkers for CSVD.

Highlights

Cerebral small vessel disease (CSVD) encompasses multiple pathological processes and etiologies that affect small cerebral blood vessels, such as arteries, arterioles, capillaries, and small veins of the brain (Cuadrado-Godia et al, 2018)
cerebral microbleeds (CMBs) are most observed in T2-weighted gradient-recalled echo (GRE) or susceptibility-weighted imaging (SWI) sequences, usually as round or ovoid small hypointense areas with associated blooms seen on GRE scans (Shi and Wardlaw, 2016), which is not easy to see on CT scans, T2 fluid-attenuated inversion recovery images, or T1-weighted images
CSVD with CMBs (CSVD-c) group showed significantly increased regional homogeneity (ReHo) in the clusters of the left precuneus, fusiform gyrus and right supplementary motor area (SMA), superior frontal gyrus compared with controls, and showed significantly increased ReHo in the clusters of the left middle frontal gyrus, superior frontal gyrus and right SMA compared with controls

Summary

Introduction

Cerebral small vessel disease (CSVD) encompasses multiple pathological processes and etiologies that affect small cerebral blood vessels, such as arteries, arterioles, capillaries, and small veins of the brain (Cuadrado-Godia et al, 2018). The pathogenesis of CSVD is not well known, but blood-brain barrier (BBB) leakage seems to be a common and primeval mechanism (Farrall and Wardlaw, 2009). The characteristic MRI features of CSVD include cerebral microbleeds (CMBs), white matter (WM) hyperintensities (WMHs), recent small subcortical infarcts, lacunes, perivascular spaces (PVSs), and brain atrophy (Qiu et al, 2018). CMBs are one of the three factors that affect the total CSVD score. Regardless of the size, location and number of microbleeds, the presence or absence of microbleeds can directly affect the CSVD score (Amin Al Olama et al, 2020), so microbleeds are a more important feature in CSVD patients. We divided the subjects into three subgroups: CSVD with CMBs (CSVD-c), CSVD without CMBs (CSVD-n) and control; these groups were evaluated to further illustrate the changes in brain function in CSVD-c patients

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