[PET/CT with 11C-methionine in assessment of brain glioma metabolism]. / Pozitronnaya emissionnaya tomografiya v sochetanii s komp'yuternoi tomografiei i 11S-metioninom v otsenke metabolizma gliom golovnogo mozga.

OBJECTIVE: To study 11C-methionine (MET) metabolism in gliomas using CNS tumor biobank imaging data. MATERIAL AND METHODS: MRI and 11C-MET PET/CT were performed in 225 patients (49±14 years, M/F=84/101) according to standard protocols with analysis of 11C-MET accumulation index and volumetric parameters (V_FLAIR, V_PET and V_PET/FLAIR). These results were compared with molecular genetic testing and 2-year overall survival. RESULTS: We examined 225 patients with gliomas (97 glioblastomas, 70 astrocytomas, 58 oligodendrogliomas). Accumulation index and volume of 11C-MET in glioblastomas were significantly higher in the general group (AI=2.90, Se 69%, Sp 76%, AUC 0.76; V_PET=24.3 cm3, Se 67%, Sp 60%, AUC 0.65; V_PET/FLAIR 0.46, Se 60%, Sp 69%, AUC 0.67) and within the group of astrocytomas (AI=2.93, Se 68%, Sp 89%, AUC 0.84; V_PET=8.06 cm3, Se 91%, Sp 35%, AUC 0.66; V_PET/FLAIR 0.27, Se 77%, Sp 60%, AUC 0.71). The median 2-year overall survival in patients with glioblastomas was 13 months that was significantly lower compared to IDH «+¼ gliomas (p<0.0001). There was a relationship between high accumulation index of 11C-MET and shorter overall survival in patients with glioblastomas. Significantly higher AI >3.59 (Se 89%, Sp 67%, AUC 0.79) was additionally obtained in subgroup of patients with glioblastomas >50 years (n=34) for EGFR «+¼ tumors. CONCLUSION: We found variable 11C-MET metabolism in WHO 2021 gliomas and confirmed significant difference in metabolic activity and volume of 11C-MET accumulation in glioblastomas compared to IDH «+¼ gliomas. Moreover, we revealed the relationship between high accumulation index and shorter survival. Analysis of 11C-MET metabolism in patients over 50 years old revealed higher accumulation index in the EGFR «+¼ group. Further comparison of these imaging methods and assessment of other significant mutations are necessary to identify the anatomical and metabolic patterns of IDH «+¼ gliomas.

[Prognosis of overall and disease-free survival in patients with grade 3 astrocytomas (anaplastic astrocytoma, WHO 2016)]. / Faktory, opredelyayushchie prognoz obshchei i bezretsidivnoi vyzhivaemosti u patsientov s astrotsitomami grade 3 (anaplasticheskimi astrotsitomami, WHO 2016).

Anaplastic astrocytoma (AA) is a rare intracerebral tumor. Therefore, the number of studies devoted to risk factors of overall and disease-free survival is small. This single-center clinical study is devoted to various factors influencing prognosis of treatment in this group of patients. MATERIAL AND METHODS: A retrospective study included 389 patients diagnosed with grade 3 astrocytoma. We analyzed dependence of overall and disease-free survival from the following factors: gender, age of onset of disease, tumor extent, surgery, neurological disorders before and after surgery (NANO grading system), Ki67 index, postoperative radio- and chemotherapy (number courses, treatment regimens). RESULTS: Significant risk factors for overall and disease-free survival were spread and volume of tumor, postoperative neurological aggravation, Ki67 index, IDH mutation, radio- and chemotherapy. Age, frontal lobe tumor and disease manifestation variant were significant only for overall, but not for disease-free survival. CONCLUSION: This study was based on material of one of the largest clinical series of patients with AA operated on in one center in «molecular¼ era. Our results are consistent with previous data. Analysis of tumor biology and risk factors for IDH-negative AA without molecular signs of glioblastoma may be perspective.

[Role of TERT mutation for treatment prognosis in patients with IDH-negative anaplastic astrocytoma]. / Znachenie TERT-mutatsii v opredelenii prognoza lecheniya patsientov s IDH-negativnymi anaplasticheskimi astrotsitomami.

OBJECTIVE: To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH-negative diffuse astrocytomas grade III (anaplastic gliomas). MATERIAL AND METHODS: The study included 45 patients aged 45.5 years. Forty-two patients underwent resection of tumor, other 3 ones - stereotactic biopsy. TERT mutation was identified in 21 patients. External beam radiation therapy was performed in 35 patients (60 Gy), chemotherapy - in 34 patients (mainly temozolomide). Follow-up data were available in 44 patients. RESULTS: Median of overall survival in patients with TERT mutation was 15.3 months, in patients with TERT-negative tumors - 65.1 months. Median of relapse-free survival in patients with TERT-positive anaplastic astrocytoma (AA) was 13.3 months, in patients with TERT-negative glioma - 57.7 months. These differences were not significant. Relapse-free survival was higher in patients with AA and no TERT mutation at all intervals, but especially at early stages (12 and 24 months). CONCLUSION: Inclusion of TERT mutation in mandatory examination panel for gliomas in general and, in particular, gliomas grade II/III without IDH mutation can lead to sub-classification of these tumors in the near future. Routine analysis of TERT mutation in these patients will be valuable for correct medical consultation regarding prognosis and adequate adjuvant treatment.

[Anaplastic pleomorphic xanthoastrocytoma - single-center analysis of 42 patients]. / Anaplasticheskaya pleomorfnaya ksantoastrotsitoma ­ analiz 42 nablyudenii iz odnoi kliniki.

Anaplastic pleomorphic xanthoastrocytoma is a rare tumor. There are still no objective data on the incidence of its diagnosis. OBJECTIVE: To study neuroimaging, morphological features of tumors, as well as factors affecting treatment and prognosis. MATERIAL AND METHODS: A retrospective study enrolled 42 patients operated on at the Burdenko Neurosurgery Center between 2003 and 2020. MR characteristics of anaplastic pleomorphic xanthoastrocytoma were analyzed. All patients underwent resection of tumor (total resection in 83.3% of cases). Redo surgeries were performed in 1/3 of patients. Mutational status of BRAF V600E was assessed in all patients. Adjuvant radio- and chemotherapy was performed in more than 80% of cases. Tyrosine kinase inhibitors were administered in 19% of cases. The follow-up period was 152 months (median 34 months). RESULTS: We found no pathognomonic MR signs of this disease. Indeed, anaplastic pleomorphic xanthoastrocytoma have the same signal characteristics as other malignant gliomas. The BRAF V600E mutation status was positive in 54.8% of cases. None patient had IDH-1 mutation. Mean Ki-67 index was 12.5%. The overall survival was 79 months (range 4-152). Seven (17%) patients are alive for more than 90 months. Only Ki-67 index and BRAF mutation significantly influenced the treatment prognosis and overall survival regardless the use of tyrosine kinase inhibitors. CONCLUSION: Such well-known factors for malignant glioma as patient age, total resection and adjuvant therapy did not significantly affect overall survival. Perhaps, searching for new molecular genetic features will reveal additional significant factors of prognosis in patients with anaplastic pleomorphic xanthoastrocytoma.

3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients.

The aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7-78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.

[Anaplastic astrocytoma and anaplastic oligodendroglioma of the brain: current state of the problem]. / Anaplasticheskie astrotsitomy i anaplasticheskie oligodendrogliomy golovnogo mozga: sovremennoe sostoyanie problemy.

This review is devoted to the problem of anaplastic cerebral gliomas. The authors consider classification, neuroimaging of these tumors including comparison of magnetic resonance imaging and positron emission tomography data. Clinical manifestations of anaplastic gliomas, issues of their histological and molecular genetic classification are discussed. Moreover, the authors compare the data of neuroimaging and genetic examinations of tumors. Other issues are multicomponent treatment and prognosis in patients with anaplastic glioma of the brain.

[Individual preoperative 3D modeling of vascular brain pathology]. / Individual'noe predoperatsionnoe 3D-modelirovanie sosudistoi patologii golovnogo mozga.

The possibility of segmenting three-dimensional objects by DICOM-series is well known and available both on specialized workstations and on personal computers. The technique, however, is relatively rarely used in clinical practice, and we believe that the benefits of preoperative preparation using segmented 3D models are underestimated. The article is devoted to our experience in using segmentation of anatomical structures based on CT and MRI for preoperative preparation for surgical operations performed in neurosurgical departments on patients with vascular pathology. The paper discusses the types and possibilities of segmentation, provides some examples describing the clinical use of the technique.

Analysis of Blood Plasma Protein Composition in Patients with Cerebral Ischemia.

Blood plasma proteome in patients with cerebral ischemia and healthy individuals was studied using comparative proteomic analysis based on tandem HPLC-MS/MS. Mass spectra were analysed in an automated mode using Progenesis LS-MS software and 256 proteins were identified. Significant quantitative differences were revealed for 20 proteins. It was found that changes in the blood plasma proteome in subjects with cerebral ischemia involved a wide range of proteins: molecular chaperones, fibrinolysis, angiogenesis, and immune system proteins, proteins involved in homeostasis maintenance, cell differentiation and proliferation, regulators of apoptosis, and cytoskeleton proteins.

[The phenomenon of long-term survival in glioblastoma patients. Part I: the role of clinical and demographic factors and an IDH1 mutation (R 132 H)]. / Fenomen dlitel'noi vyzhivaemosti patsientov s glioblastomami. Chast' I: rol' kliniko-demograficheskikh faktorov i mutatsii IDH1 (R 132 H).

The median overall survival of glioblastoma patients is about 15 months. Only a small number of patients survive 3 years. The factors of a favorable prognosis for the 'longevity phenomenon' in glioblastoma patients are not fully understood. OBJECTIVE: to determine the occurrence rate of long-living patients with glioblastomas, identify clinical predictors of a favorable prognosis, and identify the presence and prognostic significance of an IDH1 mutation. MATERIAL AND METHODS: Among 1494 patients operated on for glioblastoma at the Burdenko Neurosurgical Institute from 2007 to 2012, there were 84 (5.6%) patients who lived more than 3 years after primary surgery. In all the cases, histological specimens were reviewed, and immunohistochemical detection of a mutant IDH1 protein was performed. Overall survival was calculated from the time of first surgery to the date of the last consultation or death, and the recurrence-free period was calculated from the time of first surgery to MRI-verified tumor progression. RESULTS: The median age of long-living patients with glioblastoma was 45 years (19-65 years). All tumors were located supratentorially. The median Karnofsky performance status score at the time of surgery was 80 (range, 70-100). All patients underwent microsurgical resection of the tumor, followed by chemoradiotherapy. The median recurrence-free period was 36 months (5-98 months). Overall survival of 48, 60, and 84 months was achieved in 23, 15 and 6% of patients, respectively. Among 49 specimens available for the IDH1 analysis, 14 (28.6%) specimens had a mutant protein. There was no significant difference in survival rates in patients with positive and negative results for IDH1 (44.1 vs. 40.8 months; p>0.05). CONCLUSION: The significance of various factors that may be predictors of a favorable course of the disease is discussed in the literature. This work is the first part of analysis of prognostically significant factors positively affecting overall survival of glioblastoma patients. In our series, the predictors of a favorable prognosis for long-living patients with the verified diagnosis of glioblastoma were as follows: young age, the supratentorial location of the tumor, a high Karnofsky score before surgery, and tumor resection. In our series, we used immunohistochemical tests and found no prognostic significance of the IDH1 gene mutation; further analysis will require application of direct sequencing. We plan to study other morphological and molecular genetic features of tumors, which explain prolonged survival of glioblastoma patients, as well as the role of various types of combined chemoradiation treatment.

[Genetic Differentiation of the Three Species of Genus Astragalus L. of Section Cenantrum Bunge (Fabaceae)].

Genetic differentiation based on allozyme data was detected between species of the genus Astragalus L., section Cenantrum Bunge (Fabaceae): A.frigidus (L.) A. Gray s.l., A. mongholicus Bunge s. l, and A. sericeocanus Gontsch, which is endemic to the Northeast coast of Lake Baikal. The results of allozyme analysis confirm the natural division of the section into subsections based on morphological features. Differences between A. frigidus (subsection Elliptica Gontsch.) and A. mongholicus and A. sericeocanus (subsection Semilunaria Gontsch.) were observed. These differences were caused by the presence of species-specific alleles and the allele frequencies of the primary alleles, DN = 1.24. The genetic distance obtained for A. mongholicus and A. sericeocanus (0.10) corresponds to the status of closely related species of one subsection. Between populations of A. frigidus and between populations of A. mongholicus from the central part of areal, DN = 0.02 and 0.03 respectively. This genetic distance corresponds to the interpopulation level and was determined by the allele frequencies. The peripheral population of A. mongholicus is separated (DN = 0.36), which is probably due to the long isolation and the "founder effect."

Identification of Central Nervous System Proteins in Human Blood Serum and Plasma.

Mass-spectrometric identification of proteins in human blood plasma and serum was performed by comparing mass-spectra of fragmented peptides using Swiss-Prot and UniProtKB databases of amino acid sequences. After choosing the appropriate identification conditions we found that combination of spectrum search parameters are optimal for identification of CNS proteins. In the studied plasma and serum samples, 9 proteins involved into pathological processes in the nervous tissue were identified; 7 of them were identified in both plasma and serum.

[The possibility of using PlasmaDeepDive™ MRM panel in clinical diagnostics].

Concentrations of 46 proteins have been determined in human blood plasma using PlasmaDeepDive™ MRM Panel ("Biognosys AG", Switzerland). 18 of them were included into the group of proteins with higher concentrations, also identified by the shotgun proteomic analysis. Based on literature data it is concluded that the PlasmaDeepDive™ MRM Panel is applicable for studies of human plasma samples for potential biomarkers of various nervous system disorders.

[Surgical management of patients with pathological deformities of carotid arteries].

Surgical management of pathological deformities of the internal carotid arteries, a cause of chronic brain ischemia, is discussed. This pathology is very common and is found in 25% of all individuals who underwent preventive medical examination according to the ultrasonography data. Most deformities do not pose any threat to patients, while some of them may cause ischemic stroke and chronic brain ischemia. The study included 165 patients with the known follow-up history who had been operated on at the N.N. Burdenko Neurosurgical Institute since 2001. A total of 196 reconstructive interventions of carotid arteries were analyzed. The indications for surgical management of pathological deformities based on clinical symptoms and identification of the signs of vascular wall dysplasia are thoroughly discussed. The local and cerebral hemodynamics during pre- and postoperative period are analyzed. The results of pathomorphological examination of the resected fragments of the deformed arteries are presented; they show that the changes are identical to those in patients with fibromuscular dysplasia. The follow-up history of the patients was recorded; it showed a sustained regression of transitory ischemic strokes and cerebral symptoms in most cases (69%). For proper indications for surgical management, reconstructive surgical interventions are a reliable and effective method for treating chronic brain ischemia and preventing recurrent ischemic strokes in patients with deformities of carotid arteries.