[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.

[Nitric oxide availability in cerebral microangiopathy]. / Dostupnost' oksida azota pri tserebral'noi mikroangiopatii.

OBJECTIVE: To develop a test of individual nitric oxide (NO) availability based on changes in erythrocyte rheological properties after incubation with a NO donor and to evaluate the role of these disorders in brain damage and development of cognitive impairment (CI) in cerebral small vessel disease (cSVD). MATERIAL AND METHODS: In 73 cSVD patients (48 (65.8%) women, mean age 60.1±6.5), the rheological properties of erythrocytes before and after incubation with 10 µmol/L L-arginine-NO donor were evaluated using a laser-optical rotating cell analyzer, and the blood-brain barrier (BBB) permeability by MRI-T1 dynamic contrast. RESULTS: Among the studied parameters of erythrocyte rheological properties, the best characteristic by ROC analysis was the rate of erythrocyte disaggregation (y-dis) after incubation with L-arginine (area under the curve 0.733 (0.609-0.856), sensitivity 67%, specificity 79%). Patients with a y-dis threshold >113 sec-1 had more severe CI, arterial hypertension, white matter lesions, and increased BBB permeability in gray matter and normal-appearing white matter. CONCLUSION: The prolonged rate of erythrocyte disaggregation in cSVD patients after incubation with L-arginine indicates the risk for disease progression due to decreased NO bioavailability/disruption of the functional L-arginine-eNOS-NO system. This test can be used to assess individual NO bioavailability and potentially identify indications for modifying therapy with NO donors such as L-arginine. Clinical trials are needed to standardize and evaluate the efficacy of NO donor therapy in patients with cSVD and CI.