[Disruption of corpus callosum microstructural integrity by diffusion MRI as a predictor of progression of cerebral microangiopathy]. / Narushenie mikrostrukturnoi tselostnosti mozolistogo tela po dannym diffuzionnoi MRT kak prediktor progressirovaniya tserebral'noi mikroangiopatii.

OBJECTIVE: To assess the microstructural integrity of the corpus callosum in patients with cerebral small vessel disease (cSVD) using signal and biophysical diffusion MRI models and to identify the most sensitive markers of disease progression. MATERIAL AND METHODS: Diffusion MRI (3 Tesla) was performed in 166 patients (51.8% women; mean age 60.4±7.6) with cSVD and cognitive impairment of varying severity and in 44 healthy volunteers (65.9% women; mean age 59.6±6.8), followed by calculation of signal (diffusion tensor and diffusion kurtosis) and biophysical (WMTI, NODDI, MC-SMT) models, from which profiles of three corpus callosum segments were constructed. RESULTS: The best results were obtained for metrics in the forceps minor and body of the corpus callosum. Among the metrics of the signal models in the forceps minor, fraction anisotropy (FA) and mean diffusion (MD), which characterize the overall loss of microstructural integrity and increase in extra-axonal water, as well as indirect markers of demyelination when considering transverse diffusion parameters (radial diffusion and radial kurtosis), had the larger area under the curve according to the ROC analysis. Among the metrics of the biophysical models in the forceps minor, a larger area under the curve was found in the MC-SMT model for extra-axonal transverse diffusion (ETR), mean diffusion (EMD), and intra-axonal water fraction (INTRA), and in the WMTI model for intra-axonal water fraction (AWF). ETR had high inverse correlations with INTRA and AWF, while INTRA and AWF had high direct intercorrelations. CONCLUSION: Metrics of signaling (FA, MD, RD, RK) and biophysical patterns (ETR, EMD, INTRA, AWF) in the forceps minor and the corpus callosum body can be considered as indicators of cSVD progression. They indicate disease progression, mainly by an increase in extra-axonal water with the development of demyelination and tissue degeneration in the corpus callosum.

[A role of altered inflammation-related gene expression in cerebral small vessel disease with cognitive impairment]. / Rol' izmeneniya ekspressii genov, assotsiirovannykh s vospaleniem, pri tserebral'noi mikroangiopatii s kognitivnymi rasstroistvami.

OBJECTIVE: To identify the role of changes in the expression of inflammation-related genes in cerebral microangiopathy/cerebral small vessel disease (cSVD). MATERIAL AND METHODS: Forty-four cSVD patients (mean age 61.4±9.2) and 11 controls (mean age 57.3±9.7) were studied. Gene expression was assessed on an individual NanoString nCounter panel of 58 inflammation-related genes and 4 reference genes. A set of genes was generated based on converging results of complete genome-wide association studies (GWAS) in cSVD and Alzheimer's disease (AD) and circulating markers associated with vascular wall and Brain lesions in cSVD. RNA was isolated from blood leukocytes and analyzed with the nCounter Analysis System, followed by analysis in nSolver 4.0. Results were verified by real-time PCR. RESULTS: CSVD patients had a significant decrease in BIN1 (log2FC=-1.272; p=0.039) and VEGFA (log2FC=-1.441; p=0.038) expression compared to controls, which showed predictive ability for cSVD. The cut-off for BIN1 expression was 5.76 a.u. (sensitivity 73%; specificity 75%) and the cut-off for VEGFA expression was 9.27 a.u. (sensitivity 64%; specificity 86%). Reduced expression of VEGFA (p=0.011), VEGFC (p=0.017), CD2AP (p=0.044) was associated with cognitive impairment (CI). There was a significant direct correlation between VEGFC expression and the scores on the Montreal Cognitive Assessment test and between BIN1 and VEGFC expression and delayed memory. CONCLUSION: The possible prediction of cSVD by reduced expression levels of BIN1, VEGFA and the association of clinically significant CI with reduced VEGFA and VEGFC expression indicate their importance in the development and progression of the disease. The established importance of these genes in the pathogenesis of AD suggests that similar changes in their expression profile in cSVD may be one of the conditions for the comorbidity of the two pathologies.