Glial Brain Tumors Research Articles

Clinically Integrated Sequencing Alters Therapy in Children and Young Adults With High-Risk Glial Brain Tumors.

Brain tumors have become the leading cause of cancer-related mortality in young patients. Novel effective therapies on the basis of the unique biology of each tumor are urgently needed. The goal of this study was to evaluate the feasibility, utility, and clinical impact of integrative clinical sequencing and genetic counseling in children and young adults with high-risk brain tumors. Fifty-two children and young adults with brain tumors designated by the treating neuro-oncologist to be high risk (> 25% chance for treatment failure; mean age, 10.2 years; range, 0 to 39 years) were enrolled in a prospective, observational, consecutive case series, in which participants underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing and genetic counseling. Results were discussed in a multi-institutional brain tumor precision medicine teleconference. Sequencing revealed a potentially actionable germline or tumor alteration in 25 (63%) of 40 tumors with adequate tissue, of which 21 (53%) resulted in an impact on treatment or change of diagnosis. Platelet-derived growth factor receptor or fibroblast growth factor receptor pathway alterations were seen in nine of 20 (45%) glial tumors. Eight (20%) sequenced tumors harbored an oncogenic fusion isolated on RNA sequencing. Seventeen of 20 patients (85%) with glial tumors were found to have a potentially actionable result, which resulted in change of therapy in 14 (70%) patients. Patients with recurrent brain tumors receiving targeted therapy had a median progression-free survival (from time on therapy) of 4 months. Selection of personalized agents for children and young adults with highrisk brain tumors on the basis of integrative clinical sequencing is feasible and resulted in a change in therapy in more than two thirds of children and young adults with high-risk glial tumors.

Epidemiology of Nervous System Tumors According to WHO 2007 Classification: A Report of 1,164 Cases from a Single Hospital

Background: The central nervous system (CNS) belongs to heterogeneous group of glial and non-glial brain tumors. Increase in the frequency of brain and CNS tumors in Iran have been a cause for debate and concern. Objectives: The aim of this study was to estimate the frequency of the principal CNS cancers, using CNS cancer data records in a 7-year period in a hospital in Mashhad, Iran. Methods: This study is based on the records of department of surgical pathology, Razavi hospital, Mashhad, Iran. We analyzed 1,164 brain tumors and CNS cancers diagnosed from 2006 to 2013. It includes data on spinal cord tumors, primary brain such as lymphomas, which are hematological malignancies and metastatic tumors originating from external to the central nervous system. The frequency varies widely across this 7-year period. Results: The majority of brain tumor locations were frontal (13.2), pituitary (11.7), parietal (10.6), Spinal (8.9), Temporal (8), and base of skull (6.3). The most frequently reported histologies were meningiomas (33.6) and glioblastomamultiforme (15.8) that are strongly influenced the overall results. Higher numbers for glioblastoma, myxopapillaryependymoma, fibrillary astrocytoma, craniopharyngioma, hemangio-blastoma, oligodendro-glioma, and sarcoma were observed in male than in female patients. Meningioma, neurofibroma, and choroid plexus papilloma were the only tumors with a significant excess in female. Conclusions: We noted that higher frequency of brain tumors and CNS cancers occurred at age group of 51 to 60 years. Although data are hospital-based, is the first study to delineate the brain tumors and CNS cancers burden in north-east of Iran by age, sex, histology type, anatomical site, and laterality. © 2018, Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences.

Diagnostic Efficacy of Perfusion Magnetic Resonance Imaging in Supratentorial Glioma Grading

Background: Pre-operative glial brain tumor grading could determine the management. Perfusion weighted magnetic resonance imaging (PWMRI) is a promising modality for assessment and management of brain lesions. Objectives: In this study, we assessed the diagnostic efficacy of this method in the grading of supratentorial gliomas using 3 Tesla MRI. Patients and Methods: Using a 3 Tesla MRI unit, 35 (20 male, and 15 female) patients with glioma were examined one month before surgery. Imaging protocol was: 615 slices, field of view (FOV) 22 × 22 cm2 T1W spin echo: repetition time (TR) 500 -echo time (TE) 30 and (FOV) 22 × 22 cm2 T2W Turbo spin echo: TR 5000 -TE 90. Then 15 cc gadolinium was injected at the rate of 3cc/s and imaging was repeated with: TR: 2360 TE: 45, flip angle 90, band width 1346 echo planar imaging (EPI) 128 measurement 50. Mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured at enhancing and edematous regions compared to contralateral white matter. Then, an appropriate biopsy was performed from different sites of the tumor during surgical excision. Standard hispathological examination that was assessed in a double-blinded manner, was considered as gold standard. Results: Patients’ tumor distribution was grade IV in 14 (40%), grade II in 14 (40%), grade III in six (17.1%) and grade I in one (2.9%). Relative CBF (rCBF), and rCBV was significantly more in high-grade glioma (HGG) versus low-grade glioma (LGG) (P < 0.001 and P < 0.009, respectively) and rCBF difference was more than rCBV but it was not significant. MTT was statistically the same in both groups and there was no difference between them. A value of rCBV greater than 2 showed a sensitivity of 90% and specificity of 67% and rCBF greater than 1.4 showed a sensitivity of 100% and a specificity of 74% in discrimination of high grade gliomas versus low grade gliomas. Conclusion: PWMRI is more accurate than conventional MRI for noninvasive discrimination of low-grade glioma (LGG) and high-grade glioma (HGG) that could be helpful for neurosurgeons in decision making dealing with the most common tumor of the brain.

Comparison of serum and tissue values of miRNAs related to autophagy in glial brain tumors and metastases other than iymphoma

Aim: Central nervous system tumors are seen in both children and adults, and most of these tumors cause disability and death. Current studies are focused on the molecular pathogenesis to identify new targets for the diagnosis and follow-up of patients. In this study, we investigated whether serum micro ribonucleic acid (miRNA) values could be used as biomarkers of these tumors by examining miRNA levels associated with autophagy in serum and tissue. Material and Methods: We included 27 patients who underwent surgery at our clinic and were diagnosed with glial tumor or metastasis other than lymphoma after pathological examination. The serum and tissue levels of miRNAs associated with autophagy were compared, and correlations between the obtained values were determined using Student’s t-test. Results: Based on histopathological examination, there were 14 glioblastomas, 3 oligodendrogliomas, 2 anaplastic astrocytomas, 2 carcinoma metastases, 2 pilocytic astrocytomas, 1 anaplastic ependymoma, 1 anaplastic oligodendroglioma, 1 diffuse astrocytoma, and 1 ependymoma. Serum Ct values were significantly higher than tissue Ct values. Correlations were found between serum and tissue levels of 5 miRNA subtypes. In addition, we could not determine the Ct value in some serum samples for 5 of the 12 miRNA subtypes. Conclusion: Although correlations were found between serum and tissue miRNA levels in the literature, we did not find any reasonable correlation, which might be explained by the less number of patients in our study. Therefore, considering the results of this study, we believe it is too early to determine that miRNAs cannot be biomarkers of brain tumors.

Fluorescence-Guided Resection of Glial Brain Tumors with Fotoditazin

Objective: the purpose of this study was to assess the usefulness and accuracy of visualization of glial brain tumors of varying degrees of malignancy when surgically removed with fluorescent control of fotoditazine. Evaluation of the edges of tumor tissue was also carried out in order to increase the degree gross total resection (GTR), and to evaluate the specificity and sensitivity of the fluorescence method. Design and methods: thirty one glial tumor patients, with varying degrees of malignancy, underwent controlled fluorescence-guided resection in the presence of the indicator molecule fotoditazine. To detect fluorescence, a OHS-1 operating microscope Leica with a special fluorescence module was used. Evaluation of the efficacy, sensitivity and specificity of the method was assessed using various histo-morphological studies. GTR was assessed using postoperative MRI. Results: for grade I and II gliomas, the sensitivity of the surgical tumor removal method was 68.3%, and the specificity was 60.1%. For grade III and IV gliomas, the sensitivity of the surgical tumor removal method was 85.4%, and the specificity was 76.2%. The extent to which total surgical resection was achieved was 79.3% in grade I-II and 95.6% in grade III-IV. Conclusions: intraoperative fluorescent imaging with fotoditazine is a highly effective, sensitive, and specific method which permits glial tumors of various histologic types to be resected more completely and effectively.

Modulation of fatty acid metabolism and immune suppression are features of in vitro tumour sphere formation in ontogenetically distinct dog cancers

Non-adherent, 3-dimensional sphere formation is used as an in vitro surrogate to evaluate cellular potential for tumour initiation and self-renewal. To determine if a shared molecular program underlies the capacity for sphere formation by cells originating from diverse tumour types, we characterized molecular and functional properties of 10 independent cell lines derived from 3 ontogenetically distinct dog cancers: hemangiosarcoma, osteosarcoma and glial brain tumours. Genome-wide gene expression profiling identified tumour-of-origin-dependent patterns of adjustment to sphere formation in a uniform culture condition. However, expression of the stem/progenitor markers CD34 and CD117, resistance to cytotoxic drugs and dye efflux (side population assays) showed no association with these gene expression profiles. Instead, primary sphere-forming capacity was inversely correlated with the ability to reform secondary spheres, regardless of tumour ontogeny. Primary sphere formation seemed to be proportional to the number of pre-existing cells with sphere-forming capacity in the cell lines. Cell lines where secondary sphere formation was more proficient than primary sphere formation showed enrichment of genes involved in fatty acid synthesis and immunosuppressive cytokines. In contrast, cell lines where secondary sphere formation was approximately equivalent to or less proficient than primary sphere formation showed upregulation of CD40 and enrichment of genes involved in fatty acid oxidation. Our data suggest that in vitro sphere formation is associated with upregulation of gene clusters involved in metabolic and immunosuppressive functions, which might be necessary for self-renewal and for tumour initiation and/or tumour propagation in vivo.

Paradoxical results obtained with Ki67-labeling and PHH3-mitosis index in glial tumors: a literature analysis.

Precise tiered tumor grading is essential for predicting prognosis, selecting different treatment options and for follow-up of brain tumor patients. Ki67 labeling index (LI) is widely employed in assessing aggressiveness of glial brain tumors. However, Ki67 is subject to interlaboratory variability, and its antigen is expressed on all cell cycle phases except G0, which hinders its usage as a precise criterion for assessing cell proliferation. Indeed, there exist peculiar observations pertinent to increases of Ki67 index in glial tumors following radiotherapy or treatment with tyrosine kinase inhibitors. Moreover, we have witnessed a reduced Ki67 labeling in a gemistocytic glioma during its rapid recurrence under temozolomide treatment. Therefore, we reviewed pitfalls in employing Ki67 indices for predicting glial tumor biology and tried to answer whether the mitotic marker PHH3 (phosphorylated histone H3) could provide additional information in predicting glial tumor biology. PHH3-based assessment of proliferating cell fraction provides novel potentials, but it has also its own weaknesses. It has not yet been determined whether it would be more advantageous to report: a mitotic count (MC) per unit-area (e.g., 10 high power fields (HPF)) or a mitotic index (MI) (per 1,000 tumor cells). Further, there exist peculiarities in terms of unexpectedly low or high PHH3 values in pilocytic astrocytomas and angiocentric gliomas, respectively. Indeed, we encountered almost no staining with PHH3 in our unique gemistocytic astrocytoma case. Hence, at least in some glial malignancies, PHH3 may not be necessary for cell proliferation. Awareness of the weaknesses of proliferation markers in brain tumors may improve patient monitoring and treatment. .

Diagnostic value of microvessel structure in brain glial tumors

Diffuse gliomas are the most common primary brain tumors with a disproportionately high mortality rate. Characteristics of microvessels are of high diagnostic and prognostic significance, however, the results of previous studies are controversial. The aim of the work is to evaluate the features of angiogenesis in diffuse gliomas on the basis of determining the qualitative and quantitative microvascular characteristics. Also important is their relationship with the histological type of tumor. Microvascular density (μm-1), total vascular area (%), total lumen area (%) and the mean diameter of microvessels (μm) were measured and calculated in diffuse brain gliomas (n=76) using GFAP-negative status of endothelium in the presence of exclusively GFAP-positive tumor cells. Proliferation of microvessels was evaluated using proliferation index of vascular epithelium (Ki-67). The possibility of routine evaluation of the angiogenesis in diffuse gliomas using GFAP and Ki-67 markers was defined. We revealed significant correlation between features of the neoplastic microvasculature and WHO Grade.

Dynamic Contrast Enhanced MRI in Glioma Diagnosis

The aim: to examine the possibility of using dynamic contrast enhanced magnetic resonance imaging (DCE MRI) in clarifying the diagnosis of glial brain tumors and the differentiation between them on the basis of the malignancy degree. In this regard, the authors evaluated the effectiveness of perfusion parameters (Ktrans, Kep, Ve and iAUC).Materials and methods.The study included examination of 54 patients with an established presence of brain glial tumors. Glioma Grade I–II diagnosed in 13 (24.1%) and glioma Grade III–IV in 41 (75.9%) cases. Morphological verification of the diagnosis obtained as a result of either surgical removal of the tumor or stereotactic biopsy was achieved in 31 (57.4%) patients: glial tumors Grade I–II identified in 6 (19.4%), and glioma Grade III–IV – 25 (80.6%) cases. Results. According to DCE increasing of the malignancy degree of glial tumors is followed by increasing of all perfusion parameters: thus, the lowest values of Ktrans, Kep, Ve and iAUC were identified in low grade gliomas (0.026 min−1, 0.845 min−1, 0.024 and 1.757, respectively), the highest in gliomas Grade III–IV (0.052 min−1 1.083 min−1, 0.06 and 2.694, respectively). The most informative parameters with sensi tivity 90% and specificity 100% in the differential diagnosis of gliomas Grade I-II and Grade III-IV are Ktrans (cut-off = 0.16 min−1) and Ve (cut-off = 0.13).Conclusion.DCE MRI can be used in differential diagnosis of glial brain tumors of different malignancy grade.

CD99: A potential Diagnostic Marker for Differentiating Sub-ependymal Giant Cell Astrocytoma From Other Mimickers: A Report of Five Cases

Tuberous sclerosis (TSC) is inherited as an autosomal dominant disease, characterized by skin lesion and tubers in vital organs, especially brain in three categories including subependymal nodules, cortical tubers and subependymal giant cell astrocytoma. Subependymal giant cell astrocytoma (SEGA) is an indolent neoplasm which usually arises at the cauda thalamic groove near foramen monro, although it occurs usually in the clinical settings of TSC, a few number of SEGA has been reported without such history. Its morphology with special cytoarchitecture could be mistaken with other glial brain tumors with similar morphology. Therefore, investigating new markers for differentiating SEGA from other mimickers seems logical rather than other glioneural immunohistochemical markers introduced before. We investigated CD99 expression in SEGA as an adjunctive marker for diagnostic purposes. Five reported cases of SEGA were studied and all of them showed CD99 expression besides usual glioneural markers. CD99 may be a useful adjunctive marker in differentiating SEGA from other mimickers.

Photodynamic therapy of cerebral glioma – long term survival

Abstract. &#x0D; Article describes the survival of patients treated in the Russian Polenov Research Institute for Neurosurgery, who used photodynamic therapy after surgical resection of the tumor. The survival median for patients in subgroup of Grade III glioma with photodynamic therapy was 40,4±7,4months; without photodynamic therapy – 23,4±3,9 months (р 0,01). The survival median for patients in subgroup of Grade IV glioma with photodynamic therapy was 21,3±5,1 months; without photodynamic therapy – 13,7±3,7 months (р0,01). Thus, it is possible to draw a conclusion from the data obtained in this research that, photodynamic therapy can lead to increase in a median of survival at patients with malignant gliomas. The use of photodynamic therapy in the complex treatment of patients with malignant glial tumors increases median survival. The use of intraoperative photodynamic therapy with photoditazin improves the indices of disease-free survival of patients with malignant brain gliomas of supratentorial localization. Photodynamic therapy using photoditazin seems promising for further use and application in the treatment of patients with glial brain tumors.

2 - Genomic Analysis of Childhood High Grade Glial Brain Tumors

2 - Genomic Analysis of Childhood High Grade Glial Brain Tumors

Exosomes as a biomarker platform for detecting epidermal growth factor receptor-positive high-grade gliomas.

OBJECTIVE High-grade glial brain tumors are often characterized by an elevated expression of the tumorigenic epidermal growth factor receptor variant III ( EGFRvIII). The authors sought to establish a clinically adaptive protocol as a noninvasive diagnostic tool for EGFRvIII detection through serum exosomes. METHODS Purity of serum exosome/RNA was confirmed by electron microscopy and flow cytometry and through an RNA bioanalyzer profile. EGFRvIII amplification was initially established by semiquantitative polymerase chain reaction in tumor tissues and exosomes. Diagnostic performance of EGFRvIII transcript in tissue versus exosome was determined using a 2 × 2 clinical table approach. Overall survival was determined using Kaplan-Meier analysis. RESULTS The EGFRvIII transcript was detected in 39.5% of tumor tissue samples and in 44.7% of their paired serum exosome samples; 28.1% of biopsy tumors coexpressed wild-type EGFR and EGFRvIII. Tissue EGFRvIII amplification served as the reference-positive control for its paired serum expression. The overall clinical sensitivity and specificity of semiquantitative exosome EGFRvIII polymerase chain reaction detection assay in serum were 81.58% (95% CI 65.67%-92.26%) and 79.31% (95% CI 66.65%-88.83%), respectively. Age, sex, tumor location, and side of the body on which the tumor was located had no effect on the detection rate of exosomal EGFRvIII transcript. EGFRvIII expression either in exosomes or tissue correlated with poor survival. CONCLUSIONS The authors established a serum-based method for detection of EGFRvIII in high-grade brain tumors that might serve as an optimal noninvasive method for diagnosing EGFRvIII-positive high-grade gliomas.

A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma

Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability. RapaLink-1 associated with FKBP12, an abundant mTOR-interacting protein, enabling accumulation of RapaLink-1. RapaLink-1 showed better efficacy than rapamycin or TORKi, potently blocking cancer-derived, activating mutants of mTOR. Our study re-establishes mTOR as a central target in glioma and traces the failure of existing drugs to incomplete/nondurable inhibition of mTORC1.

Role of Multivoxel Intermediate TE 2D CSI MR Spectroscopy and 2D Echoplanar Diffusion Imaging in Grading of Primary Glial Brain Tumours.

Preoperative tumour grading is imperative owing to difference in invasive, aggressive tendencies of different grades of glial tumours implying varied prognosis, therapeutic options. Histopathological examination has inherent sampling errors. Magnetic Resonance Spectroscopy (MRS) and Diffusion Weighted Imaging (DWI) can provide non invasive information about internal mileu hence, aiding in tumour grading by adding to information provided by conventional MRI sequences. To evaluate the role of multivoxel intermediate TE 2D CSI MRS and 2D echoplanar diffusion imaging in grading of primary glial brain tumours. A prospective study was conducted in Department of Radiology, Teerthanker Mahaveer Medical College and Research Centre, Uttar Pradesh, India, from April 2015 to August 2016 after obtaining necessary approvals from Institutional Ethical Committee and written informed consent from all participants on histopathological proven cases of glial brain tumours that underwent multivoxel MRS using intermediate TE 2D chemical shift imaging and DWI using 2D echoplanar imaging. Tumour grade calculated on MRI using MRS and DWI was compared with histopathological grading. Positive Predictive Value (PPV), Negative Predictive Value (NPV), Sensitivity, specificity and accuracy were calculated for each parameter and statistical significance was evaluated using two tailed Pearson test. Choline: N Acetyl aspartate (Cho: NAA) and Choline: creatinine (Cho: Cr) ratios from MRS as well as Apparent Diffusion Coffecient (ADC) values from DWI were significantly higher with increasing severity of tumour grade. Accuracy of 58.6% was obtained with DWI while it was 83% with MRS. MRS and DWI used together provided 88.4% accuracy. All parameters evaluated showed statistical significance. Both DWI as well as MRS were found to have statistically significant roles in grading of glial brain tumours. MRS was found to be more useful than DWI.

MOLECULAR ASPECTS OF ANGIOGENESIS IN BRAIN GLIOBLASTOMAS

It is known that angiogenesis plays a critical role in the growth and progression of brain gliomas. Inducing factor in neoangiogenesis are changes primarily occur within the intra-tumoral events: changing the structure of the microvasculature of tumor tissue, increased hypoxia adaptation of tumor cells and the synthesis of angiogenic factors, cell growth. Due to the location of abnormal blood vessels in the tumor tissue generated chaotic flow of blood, which leads to severe hypoxia - as a key factor in inducing the angiogenesis process. Hypoxia-inducible factor 1 (HIF-1) is the main molecule that regulates the growth and progression of glial tumors. Glioma cells, with their inherent properties of stem cells actively synthesized HIF-1. This population of cells called - “glioma stem cells” inducing synthesis of vascular endothelial growth factor (VEGF). It VEGF is central to the process of angiogenesis. A promising area of targeted therapy of brain gliomas is the anti-angiogenic therapy. Applications, both direct and indirect angiogenesis inhibitors, significantly improved the prognosis of patients with glial brain tumors. Undoubtedly an integrated approach to the study of microvascular disturbances, hypoxia, biology and cell behavior of “glioma stem cells” and the role of various factors of cell growth in the tumorigenesis of brain gliomas of the brain allows us to develop new and effective methods of diagnosis and treatment of this disease in the near future.

Influence of vascular endothelial growth factor and radiation on gap junctional intercellular communication in glioblastoma multiforme cell lines.

Glioblastoma multiforme (GBM) is a highly aggressive glial brain tumor with an unfavorable prognosis despite all current therapies including surgery, radiation and chemotherapy. One characteristic of this tumor is a strong synthesis of vascular endothelial growth factor (VEGF), an angiogenesis factor, followed by pronounced vascularization. VEGF became a target in the treatment of GBM, for example with bevacizumab or the tyrosine kinase inhibitor axitinib, which blocks VEGF receptors. To improve patients’ prognosis, new targets in the treatment of GBM are under investigations. The role of gap junctions in GBM remains unknown, but some experimental therapies affect these intercellular channels to treat the tumor. Gap junctions are composed of connexins to allow the transport of small molecules between adjacent cells through gap junctional intercellular communication (GJIC). Based on data derived from astrocytes in former studies, which show that VEGF is able to enhance GJIC, the current study analyzed the effects of VEGF, radiation therapy and VEGF receptor blockade by axitinib on GJIC in human GBM cell lines U-87 and U-251. While VEGF is able to induce GJIC in U-251 cells but not in U-87 cells, radiation enhances GJIC in both cell lines. VEGF receptor blockade by axitinib diminishes radiation induced effects in U-251 partially, while increases GJIC in U-87 cells. Our data indicate that VEGF and radiation are both modifying components of GJIC in pathologic brain tumor tissue.

DCE-MRI IN BRAIN TUMOR DIAGNOSIS

The aim : to examine the possibility of using dynamic contrast enhanced magnetic resonance imaging (DCE MRI) in clarifying the diagnosis of glial brain tumors and the differentiation between them on the basis of the malignancy degree. In this regard, the authors evaluated the effectiveness of perfusion parameters (Ktrans, Kep, Ve and iAUC). Materials and methods. The study included examination of 54 patients with an established presence of brain glial tumors. Glioma Grade I–II diagnosed in 13 (24.1%) and glioma Grade III–IV in 41 (75.9%) cases. Morphological verification of the diagnosis obtained as a result of either surgical removal of the tumor or stereotactic biopsy was achieved in 31 (57.4%) patients: glial tumors Grade I–II identified in 6 (19.4%), and glioma Grade III–IV – 25 (80.6%) cases. Results . According to DCE increasing of the malignancy degree of glial tumors is followed by increasing of all perfusion parameters: thus, the lowest values of Ktrans, Kep, Ve and iAUC were identified in low grade gliomas (0.026 min−1, 0.845 min−1, 0.024 and 1.757, respectively), the highest in gliomas Grade III–IV (0.052 min−1 1.083 min−1, 0.06 and 2.694, respectively). The most informative parameters with sensi tivity 90% and specificity 100% in the differential diagnosis of gliomas Grade I-II and Grade III-IV are Ktrans (cut-off = 0.16 min−1) and Ve (cut-off = 0.13). Conclusion. DCE MRI can be used in differential diagnosis of glial brain tumors of different malignancy grade.

Ultrastructural characteristics of gap junctions in human glial brain tumors

to conduct an electron microscopic study of intercellular communication in the samples of gemistocytic astrocytoma, oligodendroglioma, and glioblastoma. Surgically resected tumor tissue fragments were fixed in 2.5% glutaraldehyde solution, afterfixed in 1% OsO4 solution, dehydrated, and embedded in epoxy resin. Ultrathin sections were examined using a Jem 1011 electron microscope (Jeol, Japan). Solitary and closely spaced gap junctions (GJs) formed by the thin processes that have the ultrastructure of an astroglial processes were identified in the astrocytoma samples. In this case, chemical synapses were noted to be completely absent in gemistocytic astrocytoma and glioblastoma. The identified GJs had a small length and deformed nexuses. The oligodendroglioma samples exhibited intact astroglial processes around the chemical synapses; however, interglial GJs were not found. The investigation showed the presence of intercellular GJs with some ultrastructural differences in the samples of low- and high-grade astroglial tumors. According to current data, astrocytomic GJs are able to create a stable self-sustaining network that promotes tumor progression and provides resistance to a therapeutic intervention. At the same time, the noticeable reduction in the number of GJs, which is most pronounced in the oligodendroglioma sample, can accelerate tumor cell migration into the surrounding parenchyma. The investigation of GJs should be, of course, continued using a group of a larger number of glial tumors to confirm the intercellular communication features revealed in this study.

A FUSED PET/MRI IN A PLANNING AND PERFORMING STEREOTACTIC OPERATIONS IN BRAIN TUMORS

Objective – study of the diagnostic capabilities of MRI and PET/CT scanners and the available user programs for processing DICOM-images in the implementation of the preoperative planning of stereotactic interventions in patients with deep cerebral gliomas in terms of fusion the scans of a brain. Material and methods. 35 stereotactic surgeries (biopsies and treatment cryoablations) were preplanned and then conducted in patients with brain deep-seated tumors. Patients underwent MRI-scanning in stereotactic conditions and PET/CT scanning with the tumor-specific radiotracer 11C-methionine for stereotactic targeting in preoperative period. Stereotactic planning was conducted on fused MRI/PET images. A co-registration was carried out using a diagnostic workstation Philips and neuronavigation station Medtronic StealthStation S7. Results. A fusion of MRI and PET images using application software is a convenient tool for precise planning of target points and trajectories for insertion stereotactic cannula into a brain. On a fused image the PET-component enables to plan target areas for biopsy and selective ablation of the tumor, due to the ability of a radiotracer to accumulate selectively in the most malignant sites of a tumor. While MRI component, providing a clear anatomical visualization, allows the planning safe trajectories of stereotactic access out of eloquent areas, pathways of brain and intracerebral vessels, which reduces the risk of intraoperative complications. In addition, MRI provides imaging of fiducial markers for stereotactic calculations. Conclusion. High efficiency of preoperative planning on fused MRI/PET scans was demonstrated. The proposed planning method allows to increase the effectiveness of biopsies and to prevent the prolonged growth of brain glial tumors, even when their selective stereotactic ablation, as well as to ensure a low level of postoperative complications.