[Identifying the neurostimulation target for treatment of cognitive impairment in aging and early cerebral small vessel disease]. / Vybor misheni neiromodulyatsii dlya korrektsii kognitivnykh rasstroistv pri starenii i rannei tserebral'noi mikroangiopatii.

OBJECTIVE: To develop individualized approaches to the use of neuromodulation as a non-pharmacological treatment of cognitive impairment (CI) based on the assessment of compensatory brain reserves in functional MRI (fMRI). MATERIAL AND METHODS: Twenty-one adults over 45 years of age, representing a continuum from healthy norm to mild cognitive impairment due to aging and early cerebral small vessel disease, were studied. All participants underwent fMRI while performing two executive tasks - a modified Stroop task and selective counting. To assess the ability to compensate for CI in real life, functional activation and connectivity were analyzed using the BRIEF-MoCA score as a covariate, which is the difference in ratings between the Behavior Rating Inventory of Executive Function (BRIEF) and the Montreal Cognitive Assessment Scale (MoCA). RESULTS: Both fMRI tasks were associated with activation of areas of the frontoparietal control network, as well as supplementary motor area (SMA) and the pre-SMA, the lateral premotor cortex, and the cerebellum. An increase in pre- SMA connectivity was observed during the tasks. The BRIEF-MoCA score correlated firstly with connectivity of the left dorsolateral prefrontal cortex (DLPFC) and secondly with involvement of the occipital cortex during the counting task. CONCLUSIONS: The developed technique allows identification of the functionally relevant target within the left DLPFC in patients with CI in aging and early cerebral microangiopathy.

[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.

[Machine learning technologies in CT-based diagnostics and classification of intracranial hemorrhages]. / Tekhnologii mashinnogo obucheniya v KT-diagnostike i klassifikatsii vnutricherepnykh krovoizliyanii.

This review discusses pooled experience of creation, implementation and effectiveness of machine learning technologies in CT-based diagnosis of intracranial hemorrhages. The authors analyzed 21 original articles between 2015 and 2022 using the following keywords: «intracranial hemorrhage¼, «machine learning¼, «deep learning¼, «artificial intelligence¼. The review contains general data on basic concepts of machine learning and also considers in more detail such aspects as technical characteristics of data sets used for creation of AI algorithms for certain type of clinical task, their possible impact on effectiveness and clinical experience.

[Controlled arterial hypertension and blood-brain barrier damage in patients with age-related cerebral small vessel disease and cognitive impairments]. / Kontroliruemaya arterial'naya gipertenziya i povrezhdenie gematoentsefalicheskogo bar'era u bol'nykh s vozrastzavisimoi tserebral'noi mikroangiopatiei i kognitivnymi narusheniyami.

OBJECTIVE: To evaluate the relationship between blood pressure (BP) profile and blood-brain barrier (BBB) permeability in age-related cerebral microangiopathy (CMA) in patients with- and without controlled arterial hypertension (AH). MATERIAL AND METHODS: 24-hour ambulatory BP monitoring (ABPM), brain MRI, including T1-weighted dynamic contrast images, were performed in 53 patients with CMA (age 60.1±6.8, women 69.8%, controlled hypertension/normal BP 84.8%/15.2%) and 17 healthy volunteers. RESULTS: ABPM showed good control of AH with most of the assessed parameters associated with the severity of white matter hyperintensity (WMH). The permeability of the BBB in normal-appearing white matter (NAWM) and gray matter in patients with CMA was significantly higher than in the control group and was associated with ABPM parameters. The permeability of the BBB in WMH decreased with an increase in its severity. CONCLUSION: BBB permeability is a universal mechanism of NAWM and gray matter damage that supports the progression of WMH in CMA patients with controlled AH and without AH. The relationship of increased BBB permeability with slight deviations of ABPM can be explained by common mechanisms of their development due to endothelial dysfunction due to CMA and also points to the utility of more aggressive AH treatment. It is advisable to study the effect of antihypertensive and vascular drugs on BBB permeability with a view to their potential use in CMA.

Daily blood pressure profile and blood-brain barrier permeability in patients with cerebral small vessel disease.

Cerebral small vessel disease (CSVD) plays an important role in cognitive impairment, stroke, disability, and death. Hypertension is the main risk factor for CSVD. The use of antihypertensive therapy has not resulted in the expected decrease in CSVD complications, which may be related to the underestimation of significance of daily blood pressure profile for blood-brain barrier (BBB) permeability. 53 patients with CSVD of varying severity (mean age 60.08 ± 6.8 years, 69.8% women, subjects with treated long-standing hypertension vs. normotensive subjects - 84.8% vs. 15.2%) and 17 healthy volunteers underwent ambulatory blood pressure monitoring (ABPM) and MRI, including T1-weighted dynamic contrast-enhanced magnetic resonance imaging for assessing BBB permeability. Most of ABPM parameters in CSVD patients did not differ from controls, but were associated with the severity of white matter hyperintensity (WMH) and the total CSVD score. BBB permeability in normal-appearing white matter (NAWM) and grey matter (GM) was significantly higher in CSVD patients, and the severity of BBB permeability remained similar in patients with different stages of WMH. Among BBB permeability parameters, the area under the curve, corresponding to an increase in the contrast transit time in NAWM, had the greatest number of correlations with deviations of ABPM parameters. BBB permeability in CSVD is a universal mechanism of NAWM and GM damage associated with a slight increase in ABPM parameters. It is obvious that the treatment of hypertension in patients with not severe WMH should be more aggressive and carried out under the control of ABPM.

[Predictors and integrative index of severity of cognitive disorders in cerebral microangiopathy]. / Prediktory i integrativnyi pokazatel' tyazhesti kognitivnykh rasstroistv pri tserebral'noi mikroangiopatii.

OBJECTIVE: To search for sensitive predictors of cognitive impairment (CI) and an integrative index of their severity. MATERIAL AND METHODS: We assessed CI and diffusion-tensor MRI (DT-MRI) in the regions of interest (ROI) significant for CI in 74 patients (48 women, mean age 60.6±6.9 years) with cerebral small vessel disease (CSVD). The results of DT-MRI were used to construct a predictive model of CI using binary logistic regression and to calculate an integrative index of CI severity. RESULTS: According to the constructed model, the predictors of CI were axial diffusivity (AD) of posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB) and mid-posterior corpus callosum (CC). ROC analysis showed strong model predictive power for CI in cSVD (AUC (95% CI): 0.845 (0.740-0.950)). The threshold value of the AD predictors model for CI in cSVD was 0.53 (sensitivity 84%, specificity 76%). AD predictors of CI showed significant correlations with white matter hyperintensities volume and MoCA scores. The presence of CI as measured by neuropsychological testing and regression equation solution was corresponded to individual AD predictors of patients exceeding the CI model's threshold. CONCLUSION: Disturbances in the AD of pvNAWM, right middle CB and mid-posterior CC associated with axonal damage are a predominant factor in the development of CI in CSVD. The predictors of CI and the integrative index of CI severity calculated on their basis can potentially be used as a tool for assessing the severity of CI and the effectiveness of treatment, as well as in clarifying the interaction between vascular and degenerative pathology and in developing measures for the prevention of CI in patients with MRI signs of cSVD.

[Resting state functional MRI in neurology and psychiatry]. / Funktsional'naya MRT pokoya v nevrologii i psikhiatrii.

Resting state functional magnetic resonance imaging (fMRI) is a neuroimaging technique based on analyzing spontaneous, low frequency fluctuations in the activity of brain areas by measuring by their MRI signal to investigate the functional architecture of the brain during rest. The use of resting state fMRI opens up possibilities for assessing brain functional relationships in both normal conditions and in different CNS pathologies in order to clarify the disturbed mechanisms of brain functioning and develop approaches for therapeutic non-invasive neuromodulation. Understanding the acquisition of data, the features of their preprocessing and analysis is very important for clinicians who use resting state fMRI in their studies, since it is neurologists, psychiatrists, and neurosurgeons who set research tasks and are the final consumers of the results. The article details the methodological features of obtaining and analyzing resting state fMRI data, the advantages and disadvantages of the method. The article is intended for a wide range of specialists using this method in their work or planning to include it in their research.

Text Analysis of Radiology Reports with Signs of Intracranial Hemorrhage on Brain CT Scans Using the Decision Tree Algorithm.

The aim of the study is to create, train, and test the algorithm for the analysis of brain CT text reports using a decision tree model to solve the task of simple binary classification of presence/absence of intracranial hemorrhage (ICH) signs. Materials and Methods: The initial data is a download from the Unified Radiological Information Service of the Unified Medical Information and Analytical System (URIS UMIAS) containing 34,188 studies obtained by a non-contrast CT of the brain in 56 inpatient medical settings. Data analysis and preprocessing were carried out using NLTK (Natural Language Toolkit, version 3.6.5), a library for symbolic and statistical processing of natural language, and scikit-learn, a machine learning library containing tools for classification tasks. According to 14 selected ICH-related key words, as well as 33 stop-phrases with key words denoting absence of ICH, an automatic selection of the CT investigations and their subsequent expert verification were carried out. Two classes of investigations were formed based on the sample from 3980 protocol descriptions: containing descriptions of ICH and without them. The problem of binary classification was solved using the decision tree algorithm as a model. To evaluate the performance of the model, the CT investigations were divided randomly into samples in the ratio of 7:3. Of 3980 protocols, 2786 were assigned to the training data set, 1194 - to the test one. Results: According to the test results, the designed and trained algorithm in the binary classification of the CT reports "with signs of ICH" and "without signs of ICH" has shown sensitivity of 0.94, specificity of 0.88, F-score of 0.83. Conclusion: The developed and trained algorithm for the analysis of radiology reports has demonstrated high accuracy in relation to brain CT with signs of intracranial hemorrhage and can be used to solve binary classification problems and create appropriate data sets. However, it is limited by the need for manual revision of CT studies to ensure quality control.

[Clustering of diagnostic MRI signs of cerebral microangiopathy and its relationship with markers of inflammation and angiogenesis]. / Klasterizatsiya diagnosticheskikh MRT-priznakov tserebral'noi mikroangiopatii i ee svyaz' s markerami vospaleniya i angiogeneza.

OBJECTIVE: To perform cluster analysis of MRI signs of cerebral microangiopathy (small vessel disease, SVD) and to clarify the relationship between the isolated groups and circulating markers of inflammation and angiogenesis. MATERIAL AND METHODS: The identification of groups of MRI signs (MRI types) using cluster hierarchical agglomerative analysis and iterative algorithm of k-means and assessment of their relationship with serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1-α (HIF1-α) determined by ELISA were performed in 96 patients with SVD (STRIVE, 2013) (65 women, average age 60.91±6.57 years). RESULTS: Cluster analysis of MRI signs identified two MRI types of SVD with Fazekas grade 3 of white matter hyperintensity (WMH). MRI type 1 (n=18; 6 women, mean age 59.1±6.8 years) and MRI type 2 (n=22, 15 f., mean age 63.5±6.2 years) did not differ by age, sex, severity of hypertension, presence of other risk factors. MRI type 1 had a statistically significantly more pronounced WMH in the periventricular regions, multiple lacunes and microbleeds, atrophy, severe cognitive impairment and gait disorders compared with MRI type 2. Its formation was associated with a decrease in VEGF-A level. MRI type 2 had the significantly more pronounced juxtacortical WMH, white matter lacunes, in the absence of microbleeds and atrophy, and less severe clinical manifestations compared with MRI type 1. Its formation was associated with an increase in TNF-α level. CONCLUSION: Clustering of diagnostic MRI signs into MRI types of SVD with significant differences in the severity of clinical manifestations suggests the pathogenetic heterogeneity of age-related SVD. The relationship of MRI types with circulating markers of different mechanisms of vascular wall and brain damage indicates the dominant role of depletion of angiogenesis in the formation of MRI type 1 and increased inflammation in the formation of MRI type 2. Further studies are needed to clarify the criteria and diagnostic value of differentiation of MRI types of SVD, and also their mechanisms with the definition of pathogenetically justified prevention and treatment of various forms of SVD.

[Executive functions: fMRI of healthy volunteers during Stroop test and the serial count test]. / Upravliaiushchie funktsii mozga: funktsional'naia magnitno-rezonansnaia tomografiia s ispol'zovaniem testa Strupa i testa seriinogo scheta pro sebia u zdorovykh.

AIM: To assess executive function in healthy adults using fMRI. MATERIAL AND METHODS: An analysis of fMRI activation and functional connectivity during a serial count task (as a shifting function test) and color-word Stroop test (classical inhibition function test) was made for 12 healthy adults. RESULTS AND CONCLUSION: The executive control network and salience network activation was comparable in both tasks. Nevertheless, there were differences between two tests in functional connectivity of the dorsolateral prefrontal cortex (DLPFC) and the supplementary motor area (SMA) with other brain regions, that can be explained by the differences in the regulatory mechanisms of task performance. Stroop test assumes its automatic performance, and control of program realization is performed mainly by executive-control network. The connectivity between the two DLPFCs with the lower parietal lobules and with each other and inhibition by SMA connectivity with only the right hemisphere regions support this notion. Serial count task excludes the process of monotonous learning, that was confirmed by widespread SMA connections in the absence of connectivity of the DLPFC with executive control network regions. This connectivity pattern allows assuming the leading role of SMA in certain brain regions choice and switching their activity for providing attention and executive control of cognitive operations shift during task performance. These findings allow us to consider the serial count task as the relevant fMRI test for executive functions with the special focus on set shifting, also in patients with executive function deficits. Furthermore, SMA region mapping with the serial count test paradigm could be considered as a potential target for navigated transcranial magnetic stimulation (nTMS) in these patients.

[Posterior reversible encephalopathy syndrome due to hypocalcemia: a description of a case and an analysis of a pathogenic role of electrolyte disturbances]. / Sindrom zadnei obratimoi entsefalopatii pri gipokal'tsiemii: opisanie nablyudeniya i analiz patogeneticheskoi znachimosti elektrolitnykh narushenii.

Afemale patient with recurrent posterior reversible encephalopathy syndrome, severe hypocalcemia due to extirpation of the parathyroid glands is described. The disease was characterized by the acute development of headache, seizures, cognitive and behavioral disorders, mental confusion, transitory blood pressure increasing. The vasogenic edema in the posterior parts of the brain, detected by CT at the first exacerbation,was completely regressed. The residual neurological deficit and MRI changes remained after the recurrent exacerbations. Main clinical features of PRESare explained by hypocalcemia and accompanying electrolyte disturbances.The reported case shows the necessity to study blood electrolytes in patients with PRES to clarify their pathogenic role and the necessity of drug correction.

[A DTI study of the spinal cord lesion in patients with multiple sclerosis during the follow-up after relapse]. / Porazhenie spinnogo mozga u patsientov s rasseyannym sklerozom posle obostreniya po dannym diffuzionno-tenzornoi magnitno-rezonansnoi tomografii.

UNLABELLED: Spinal cord involvement is frequent in multiple sclerosis (MS) but the correlation between spinal cord damage on conventional MRI and clinical symptoms is not always obvious. Diffusion tensor imaging (DTI) is a sensitive technique for revealing tissue damage. OBJECTIVE: to investigate spinal cord DTI changes in MS patients during the relapse and in the follow-up. MATERIAL AND METHODS: Data were acquired from 25 patients with relapsing-remitting MS during the relapse characterized by unilateral light hand palsy, in three and twelve months after it. All patients underwent full neurological examination and MRI including conventional head and neck MRI and DTI of the brain and upper spinal cord in the sagittal plane. Twelve healthy subjects entered the control group. RESULTS AND CONCLUSION: Spinal cord sagittal DTI provides a reliable information about significant changes in MS patients compared tothe control group both inside demyelinating lesions and in the normal appearing spinal cord. These differences are preserved both in 3 and 12 months after the relapse and together with clinical recovery create evidence of functional compensatory mechanisms development. A tendency towards DTI parameters normalization together with faster fine motor skills recovery in patients without the asymmetrical decrease in vibration sense shows an important role that afferentation plays in recovery after the relapse.

[New approaches in the study of neuroplasticity process in patients with central nervous system lesion].

Methods which on one hand can ensure the patient's mobility and on other hand activate afferents inputs are the main in rehabilitation treatment. Recent studies has shown that plasticity is structural base of recovery after central nervous system injury. Reorganization of cortical areas and increase of preserved structures functional effectiveness (intensification afferent input) are an anatomical basis of plasticity. However, sensory correction methods, without accounting of functional condition of patients, can lead to the formation of pathological symptoms: spasticity, hyperreflexia, etc. So the main aim is to study adequate management of the neuroplasticity process. This problem cannot be solving without modern methods of neuroimaging and brain mapping. The new approach for study cortical mechanisms of neuroplasticity, responsible for locomotion, was developed in the present study. This approach is complex use of functional magnetic resonance imaging (fMRI) and navigation transcranial magnetic stimulation (nTMS). It was showed that vast fMRI activation area in the first and the second sensorimotor area emerges with passive sensorimotor paradigm using that imitate backing load during walking. The mechanical stimulator footsteps backing zones "Corvit" uses for create this paradigm, nTMS examination, which used after fMRI, help localize the motor representation of muscles which control locomotion more accurately. We guess that new approach can be used for neuroplasticity process study and assessment of neuroplasticity changes during rehabilitation for restore and correct the walking.

[Specifics of activation of cortex by stimulation of support receptors in healthy subjects and in patients with lesions of CNS].

Results of basic studies in space medicine revealed the mechanism of motor disorders and the importance of support input in regulation of the tone and posture system of the mammals. Progress in functional magnetic resonance tomography (fMRT) enabled in vivo estimation of activity of various parts of the brain during stimulation of support afferent pathways. The goal of our study was to detect specific activation of the cortex during stimulation of support input in healthy subjects and in patients with lesions of CNS. The study included 19 healthy volunteers (mean age of 38 ± 15, 13 years) and 23 patients with cortical-subcortical ischemic stroke (mean age 53 ± 9.07); all subjects underwent fMRT. During scanning of each subject, support areas of the foot soles were stimulated to imitate slow walking using the block design. In healthy volunteers, primary somatosensory cortex, premotor and dorsolateral cortex, and insula were significantly activated (corrected <0.05 at cluster level). In patients with stroke, pattern of activation of the supraspinal systems of locomotion control clearly depended on the stage of the disease. In patients with cortical-subcortical stroke undergoing motility rehabilitation, the sensomotor locomotion module was predominantly activated as the contralateral pattern.

[Activation of the sensorimotor cortex with the use of a device for the mechanical stimulation of the plantar support zones].

Studies of the control movements mechanisms have been performed in the interest of space medicine were the basis for the development of the concept about the leading role of the support afferent input in the regulation of postural-tonic system of mammals. Introduction of functional magnetic resonance imaging (fMRI) made it possible to investigate in-vivo brain mapping during stimulation of support afferent input. The aim of our study was to investigate brain activation due to mechanical support stimulation of the soles with the special device "Korvit". 12 healthy participants (6 women, 6 men; average age = 28.8 years) were scanned. fMRI protocol for each person consisted of 2 different blocked paradigms: soles stimulation in stance imitation (1) and slow walking imitation (2) modes. The results were analyzed with statistical program SPM5 for each person and then for the whole group. In all our paradigms there was significant (P(correct) < 0.05 for cluster level) activation of primary somatosensory, premotor and dorsolateral cortex, insula. During the stance imitation mode, extensive prefrontal cortex activation was observed; during the slow walking imitation mode there was activation of different primary and secondary sensorimotor cortex areas.

[Internal carotid artery dissection: localization of cerebral infarcts and mechanism of their development].

To clarify the mechanism of the development of cerebral infarcts in the internal carotid artery (ICA) dissection, the data of neuroimaging (localization of infarcts) and angiography have been analyzed in 49 patients (19 females 30 males, mean age 35,6 +/- 11,3 years). Four variants of infarct localization have been distinguished: 1 - the whole ICA territory (middle and anterior cerebral arteries - MCA, ACA) - 10%, 2 - the territory of superficial and deep branches of MCA- 37%, 3- the territory of superficial MCA branches and cortical-medullar arteries - 31% (the cortex and underlying white matter - 19%, the periventricular white matter and semiovale center - 6%, combined localization - 6%); 4 - the territory of deep (perforating) MCA branches (the basal ganglia and adjacent white matter) - 22%. In most of patients (92%) the dissection resulted in the occlusion or severe stenosis of intracranial ICA which in a half of cases extended to MCA and/or ACA. In 72% patients dissection involved the extracranial ICA. The marked obstructive process in the dissected ICA allows to assume that the hemodynamic, but not embolic, mechanism plays a key role in the development of infarcts. This is in line with the frequent infarct localization in the end or border zones (superficial and deep) of brain blood supply (31%) and the development of stroke during a sleep (49%). Arterio-arterial embolism as a mechanism of ischemic stroke development was found in 8% of patients with the isolated extracranial ICA dissection. It caused stenosis of the lumenand in 6% accompanied by the pseudoaneurism formation. Thrombi formed inside the aneurism could be the origin of the embolism.