(1) Purpose: To determine the borders of malignant gliomas with diffusion kurtosis and perfusion MRI biomarkers. (2) Methods: In 50 high-grade glioma patients, diffusion kurtosis and pseudo-continuous arterial spin labeling (pCASL) cerebral blood flow (CBF) values were determined in contrast-enhancing area, in perifocal infiltrative edema zone, in the normal-appearing peritumoral white matter of the affected cerebral hemisphere, and in the unaffected contralateral hemisphere. Neuronavigation-guided biopsy was performed from all affected hemisphere regions. (3) Results: We showed significant differences between the DKI values in normal-appearing peritumoral white matter and unaffected contralateral hemisphere white matter. We also established significant (p < 0.05) correlations of DKI with Ki-67 labeling index and Bcl-2 expression activity in highly perfused enhancing tumor core and in perifocal infiltrative edema zone. CBF correlated with Ki-67 LI in highly perfused enhancing tumor core. One hundred percent of perifocal infiltrative edema tissue samples contained tumor cells. All glioblastoma samples expressed CD133. In the glioblastoma group, several normal-appearing white matter specimens were infiltrated by tumor cells and expressed CD133. (4) Conclusions: DKI parameters reveal changes in brain microstructure invisible on conventional MRI, e.g., possible infiltration of normal-appearing peritumoral white matter by glioma cells. Our results may be useful for plotting individual tumor invasion maps for brain glioma surgery or radiotherapy planning.

Magnetic resonance (MR) relaxometry is a quantitative imaging method that measures tissue relaxation properties. This review discusses the state of the art of clinical proton MR relaxometry for glial brain tumors. Current MR relaxometry technology also includes MR fingerprinting and synthetic MRI, which solve the inefficiencies and challenges of earlier techniques. Despite mixed results regarding its capability for brain tumor differential diagnosis, there is growing evidence that MR relaxometry can differentiate between gliomas and metastases and between glioma grades. Studies of the peritumoral zones have demonstrated their heterogeneity and possible directions of tumor infiltration. In addition, relaxometry offers T2* mapping that can define areas of tissue hypoxia not discriminated by perfusion assessment. Studies of tumor therapy response have demonstrated an association between survival and progression terms and dynamics of native and contrast-enhanced tumor relaxometric profiles. In conclusion, MR relaxometry is a promising technique for glial tumor diagnosis, particularly in association with neuropathological studies and other imaging techniques.

В настоящее время широкое распространение получила нейротрофическая гипотеза патогенеза депрессивных расстройств. Данный обзор затрагивает роль системы мозгового нейротрофического фактора (BDNF) в патогенезе депрессии и, в частности, большого депрессивного расстройства. Описаны структура гена BDNF, механизмы его экспрессии, особенности синтеза и процессинга BDNF, функциональными продуктами которого, помимо зрелой формы BDNF, являются pro-BDNF и pro-пептид BDNF. Обобщены сведения о сигнальных каскадах системы BDNF, их роли в поддержании долговременного синаптического потенцирования (зрелая форма BDNF) и долговременной депрессии (pro-BDNF). Исследования, суммированные в данном обзоре, включают не только клинические работы, но эксперименты, выполненные на животных моделях. Приведенные морфологические данные свидетельствуют о наличии связи между изменением BDNF-сигналинга при депрессии и дегенеративными изменениями в центральной нервной системе, в первую очередь, в гиппокампе и префронтальной коре. Среди механизмов развития депрессии упомянуты функциональные изменения рецепторов BDNF (TrkB и p75NTR), а также влияние полиморфизма гена BDNF. Терапевтическая часть обзора затрагивает влияние антидепрессантов на уровни BDNF, продуктов его процессинга и рецепторов в биологических средах, в первую очередь, сыворотке крови. Следует заключить, что молекулы системы BDNF в настоящее время являются не только объектом фундаментального изучения, но также имеют перспективы в установлении диагноза депрессивных расстройств, проведении дифференциальной диагностики, а также мониторинге...

The aim of the study was to evaluate the relationship between tumor blood flow (TBF) measured by the pseudo-continuous arterial spin labeling (PCASL) method and IDH1 mutation status of gliomas as well as Ki-67 proliferative index. Methods. The study included 116 patients with newly diagnosed gliomas of various grades. They received no chemotherapy or radiotherapy before MRI. IDH1 status assessment was performed after tumor removal in 106 cases—48 patients were diagnosed with wildtype gliomas (Grade 1–2—6 patients, Grade 3–4—42 patients) and 58 patients were diagnosed with mutant forms of gliomas (Grade 1–2—28 patients, Grade 3–4—30 patients). In 64 cases out of 116 Ki-67 index was measured. Absolute and normalized tumor blood flow values were measured on 3D PCASL maps. Results. TBF and normalized TBF (nTBF) in wildtype gliomas were significantly higher than in IDH1-mutant gliomas (p < 0.001). ASL perfusion showed high values of sensitivity and specificity in the differential diagnosis of gliomas with distinct IDH1 status (for TBF: specificity 75%, sensitivity 77.6%, AUC 0.783, cutoff 80.57 mL/100 g/min, for nTBF: specificity 77.1%, sensitivity 79.3%, AUC 0.791, cutoff 4.7). TBF and nTBF in wildtype high-grade gliomas (HGG) were significantly higher than in mutant forms (p < 0.001). ASL perfusion showed the following values of sensitivity and specificity in the diagnosis of mutant HGG and wildtype HGG (for TBF: specificity 83.3%, sensitivity 60%, AUC 0.719, cutoff 84.18 mL/100 g/min, for nTBF: specificity 88.1%, sensitivity 60%, AUC 0.729, cutoff 4.7). There was a significant positive correlation between tumor blood flow and Ki-67 (for TBF Rs = 0.63, for nTBF Rs = 0.61). Conclusion. ASL perfusion may be an informative factor in determining the IDH1 status in brain gliomas preoperative and tumor proliferative activity.

Although new passive and active immunotherapy methods are emerging, unconjugated monoclonal antibodies remain the only kind of biological preparations approved for high-grade glioma therapy in clinical practice. In this review, we combine clinical and experimental data discussion. As antiangiogenic therapy is the standard of care for recurrent glioblastoma multiforme (GBM), we analyze major clinical trials and possible therapeutic combinations of bevacizumab, the most common monoclonal antibody to vascular endothelial growth factor (VEGF). Another humanized antibody to gain recognition in GBM is epidermal growth factor (EGFR) antagonist nimotuzumab. Other antigens (VEGF receptor, platelet-derived growth factor receptor, hepatocyte growth factor and c-Met system) showed significance in gliomas and were used to create monoclonal antibodies applied in different malignant tumors. We assess the role of genetic markers (isocitrate dehydrogenase, O6-methylguanine-DNA methyltransnsferase) in GBM treatment outcome prediction. Besides antibodies studied in clinical trials, we focus on perspective targets and briefly list other means of passive immunotherapy.