The Bi-(AID-1-T) G-Quadruplex Has a Janus Effect on Primary and Recurrent Gliomas: Anti-Proliferation and Pro-Migration.

High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients' tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence.

Optical Differentiation of Brain Tumors Based on Raman Spectroscopy and Cluster Analysis Methods.

In the present study, various combinations of dimensionality reduction methods with data clustering methods for the analysis of biopsy samples of intracranial tumors were investigated. Fresh biopsies of intracranial tumors were studied in the Laboratory of Neurosurgical Anatomy and Preservation of Biological Materials of N.N. Burdenko Neurosurgery Medical Center no later than 4 h after surgery. The spectra of Protoporphyrin IX (Pp IX) fluorescence, diffuse reflectance (DR) and Raman scattering (RS) of biopsy samples were recorded. Diffuse reflectance studies were carried out using a white light source in the visible region. Raman scattering spectra were obtained using a 785 nm laser. Patients diagnosed with meningioma, glioblastoma, oligodendroglioma, and astrocytoma were studied. We used the cluster analysis method to detect natural clusters in the data sample presented in the feature space formed based on the spectrum analysis. For data analysis, four clustering algorithms with eight dimensionality reduction algorithms were considered.

Radiomics Enhances Diagnostic and Prognostic Value of Diffusion Kurtosis Imaging in Diffuse Axonal Injury.

The aim of our study was to investigate the potential of advanced radiomics in analyzing diffusion kurtosis MRI (DKI) to increase the informativeness of DKI in diffuse axonal injury (DAI). We hypothesized that DKI radiomic features could be used to detect microstructural brain injury and predict outcomes in DAI. The study enrolled 31 patients with DAI (mean age 31.48 ± 11.10 years, 8 (25.8%) female) and 12 healthy volunteers (mean age 33.67 ± 11.06 years, 4 (33.3%) female). A total of 342,300 radiomic features were calculated (2282 features per each combination of 10 parametric DKI maps with 15 ROIs). Our results showed that several radiomic features were capable of distinguishing between healthy and injured brain tissue and accurately predicting outcomes with an accuracy of over 0.9. Advanced DKI radiomic features show high diagnostic and prognostic potential in DAI and may outperform average ROI values in DKI maps.

Effects of Plasma Treatment on the Surface and Photocatalytic Properties of Nanostructured SnO2-SiO2 Films.

In this work, we study the effects of treating nanostructured SnO2-SiO2 films derived by a sol-gel method with nitrogen and oxygen plasma. The structural and chemical properties of the films are closely investigated. To quantify surface site activity in the films following treatment, we employed a photocatalytic UV degradation test with brilliant green. Using X-ray photoelectron spectroscopy, it was found that treatment with oxygen plasma led to a high deviation in the stoichiometry of the SnO2 surface and even the appearance of a tin monoxide phase. These samples also exhibited a maximum photocatalytic activity. In contrast, treatment with nitrogen plasma did not lead to any noticeable changes in the material. However, increasing the power of the plasma source from 250 W to 500 W led to the appearance of an SnO fraction on the surface and a reduction in the photocatalytic activity. In general, all the types of plasma treatment tested led to amorphization in the SnO2-SiO2 samples.

Perifocal Zone of Brain Gliomas: Application of Diffusion Kurtosis and Perfusion MRI Values for Tumor Invasion Border Determination.

(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.

The Assessment of Glioblastoma Metabolic Activity via 11C-Methionine PET and Radiomics.

Nowadays, the quantitative analysis of PET/CT data in patients with glioblastoma is not strictly standardized in the clinic and does not exclude the human factor. This study aimed to evaluate the relationship between the radiomic features of glioblastoma 11C-methionine PET images and the tumor-to-normal brain (T/N) ratio determined by radiologists in clinical routine. PET/CT data were obtained for 40 patients (mean age 55 ± 12 years; 77.5% men) with a histologically confirmed diagnosis of glioblastoma. Radiomic features were calculated for the whole brain and tumor-containing regions of interest using the RIA package for R. We redesigned the original RIA functions for GLCM and GLRLM calculation to reduce computation time significantly. Machine learning over radiomic features was applied to predict T/N with the best median correlation between the true and predicted values of 0.73 (p = 0.01). The present study showed a reproducible linear relationship between 11C-methionine PET radiomic features and a T/N indicator routinely assessed in brain tumors. Radiomics enabled utilizing texture properties of PET/CT neuroimaging that may reflect the biological activity of glioblastoma and can potentially augment the radiological assessment.

Magnetic resonance relaxometry in quantitative imaging of brain gliomas: A literature review.

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.

Spinal dural cerebrospinal fluid fistula as a cause of spontaneous intracranial hypotension syndrome: Diagnosis and surgical treatment.

Spontaneous intracranial hypotension (SIH) syndrome most often occurs following a cerebrospinal fluid (CSF) fistula that develops in the spinal space. Neurologists and neurosurgeons lack an understanding of the pathophysiology and diagnosis of this disease, which can make timely surgical care difficult. With the correct diagnostic algorithm, it is possible to identify the exact location of the liquor fistula in 90% of cases; subsequent microsurgical treatment can save the patient from the symptoms of intracranial hypotension and restore the ability to work. Female patient, 57 years old, was admitted with SIH syndrome. Magnetic resonance imaging (MRI) of the brain with contrast confirmed signs of intracranial hypotension. Computed tomography (CT) myelography was performed to pinpoint the location of the CSF fistula. The diagnostic algorithm and successful microsurgical treatment of a patient with spinal dural CSF fistula at the Th3-4 level using a posterolateral transdural approach. The patient was discharged on day 3 after the surgery when these complaints regressed completely. At the control examination of the patient 4 months postoperatively, there were no complaints. Identification of the cause and location of spinal the CSF fistula is a complex process that requires several stages of diagnosis. Examination of the entire back with MRI, CT myelography, or subtraction dynamic myelography is recommended. Microsurgical repair of a spinal fistula is an effective method for the treatment of SIH. The posterolateral transdural approach is effective in the repair of a spinal CSF fistula located ventrally in the thoracic spine.

Meningeosis Neoplastica in Patients with Glioblastoma: Analysis of 36 Cases.

BACKGROUND: Meningeosis neoplastica is a rare manifestation of high-grade gliomas and is usually associated with a devastating outcome. The aim of this bicenter series was to investigate the clinical course and outcome of patients with meningiosis neoplastica. METHODS: This case series included patients in whom surgery was performed for World Health Organization grade IV primary and secondary glioblastoma (GBM) at the University Medical Center Göttingen, Göttingen, Germany between 2009 and 2021 and Burdenko Institute of Neurosurgery, Moscow, Russia between 2012 and 2018. Inclusion criteria were manifestation of clinical and neuroradiologic signs of leptomeningeal, ependymal, or spinal dissemination of GBM at various time points during the course of the disease. RESULTS: Meningeosis neoplastica was found in 36 patients. Nine patients developed spinal metastases and 12 ependymal dissemination and 15 patients had a leptomeningeal manifestation of high-grade glioma. The median age of patients at first diagnosis of primary tumor was 56 years. Typical symptoms were headache, nausea, vomiting, and acute paraplegia. The median overall survival was 11 months and progression-free survival was 8 months. Meningeosis neoplastica developed a median 2 months after the initial tumor diagnosis. Salvage therapies included ventriculoperitoneal shunting, decompression of spinal metastases, and spinal radiation therapy. The median time between meningeosis manifestation and death was 3 months. CONCLUSIONS: Meningeosis neoplastica is a rare manifestation of GBM. It has a poor prognosis. The overall survival after the manifestation of meningeosis was barely longer than 3 months. Salvage therapies did not improve the outcome in our patient cohort.

Median trans-atlanto-occipital membrane microsurgical approach to the posterior cranial fossa without craniotomy.

Minimally invasive approaches are becoming increasingly popular and contributing to improving the results of the surgical treatment of a wide variety of intracranial pathologies. Fifteen patients with posterior cranial fossa tumors underwent microsurgery through the atlanto-occipital membrane without resection of any bone structures. Tumors were localized in the brainstem in 8 patients and in the fourth ventricle in 7 patients. According to preoperative MRI and CT scans, the distance between the posterior arch of the atlas and the opisthion ranged from 9.9 to 16.5 mm (median 13 mm). The surgery was performed with the patient in the prone position and the head flexed. The trajectory of the surgical approach was directed from the skin incision located above the C2 spinous process 3.5-4 cm rostral along the midline. Total tumor resection was performed in 10 patients, subtotal resection in 2 patients, partial resection in 1 patient, and open biopsy in 2 patients. Surgical complications occurred in only 1 patient (meningoencephalitis). This minimally invasive trans-atlanto-occipital membrane approach for posterior cranial fossa tumors provides adequate visualization of the caudal part of the fourth ventricle and brainstem when the anthropometric parameters of the patient are suitable.

5-ALA-guided tumor resection during awake speech mapping in gliomas located in eloquent speech areas: Single-center experience.

Background: Achieving maximal functionally safe resection of gliomas located within the eloquent speech areas is challenging, and there is a lack of literature on the combined use of 5-aminolevulinic acid (5-ALA) guidance and awake craniotomy. Objective: The aim of this study was to describe our experience with the simultaneous use of 5-ALA fluorescence and awake speech mapping in patients with left frontal gliomas located within the vicinity of eloquent speech areas. Materials and methods: A prospectively collected database of patients was reviewed. 5-ALA was administered at a dose of 20 mg/kg 2 h prior to operation, and an operating microscope in BLUE400 mode was used to visualize fluorescence. All patients underwent surgery using the "asleep-awake-asleep" protocol with monopolar and bipolar electrical stimulation to identify the proximity of eloquent cortex and white matter tracts and to guide safe limits of resection along with fluorescence guidance. Speech function was assessed by a trained neuropsychologist before, during, and after surgery. Results: In 28 patients operated with cortical mapping and 5-ALA guidance (12 Grade 4, 6 Grade 3, and 10 Grade 2 gliomas), Broca's area was identified in 23 cases and Wernicke's area was identified in 5 cases. Fluorescence was present in 14 cases. Six tumors had residual fluorescence due to the positive speech mapping in the tumor bed. Transient aphasia developed in 14 patients, and permanent aphasia developed in 4 patients. In 6 patients operated with cortical and subcortical speech mapping and 5-ALA guidance (4 Grade 4, 1 Grade 3, and 1 Grade 2 gliomas), cortical speech areas were mapped in 5 patients and subcortical tracts were encountered in all cases. In all cases, resection was stopped despite the presence of residual fluorescence due to speech mapping findings. Transient aphasia developed in 6 patients and permanent aphasia developed in 4 patients. In patients with Grade 2-3 gliomas, targeted biopsy of focal fluorescence areas led to upgrading the grade and thus more accurate diagnosis. Conclusion: 5-ALA guidance during awake speech mapping is useful in augmenting the extent of resection for infiltrative high-grade gliomas and identifying foci of anaplasia in non-enhancing gliomas, while maintaining safe limits of functional resection based on speech mapping. Positive 5-ALA fluorescence in diffuse Grade 2 gliomas may be predictive of a more aggressive disease course.

Sensitivity of three-dimensional time-of-flight 3.0 ​T magnetic resonance angiography in visualizing the number and course of lenticulostriate arteries in patients with insular gliomas.

Background: Neurosurgical resection of insular gliomas is complicated by the possibility of iatrogenic injury to the lenticulostriate arteries (LSAs) and is associated with devastating neurological complications, hence the need to accurately assess the number of LSAs and their relationship to the tumor preoperatively. Methods: The study included 24 patients with insular gliomas who underwent preoperative 3D-TOF MRA to visualize LSAs. The agreement of preoperative magnetic resonance imaging with intraoperative data in terms of the number of LSAs and their invasion by the tumor was assessed using the Kendall rank correlation coefficient and Cohen's Kappa with linear weighting. Agreement between experts performing image analysis was estimated using Cohen's Kappa with linear weighting. Results: The number of LSAs arising from the M1 segment varied from 0 to 9 (mean 4.3 â€‹± â€‹0.37) as determined by 3D-TOF MRA and 2-6 (mean 4.25 â€‹± â€‹0.25) as determined intraoperatively, κ â€‹= â€‹0.51 (95% CI: 0.25-0.76) and τ â€‹= â€‹0.64 (p â€‹< â€‹0.001). LSAs were encased by the tumor in 11 patients (confirmed intraoperatively in 9 patients). LSAs were displaced medially in 8 patients (confirmed intraoperatively in 8 patients). The tumor partially involved the LSAs and displaced them in 5 patients (confirmed intraoperatively in 7 patients), κ â€‹= â€‹0.87 (95% CI: 0.70-1), τ â€‹= â€‹0.93 (p â€‹< â€‹0.001). 3D-TOF MRA demonstrated high sensitivity (100%, 95% CI: 0.63-1) and high specificity (86.67%, 95% CI: 0.58-0.98) in determining the LSA-tumor interface. Conclusions: 3D-TOF MRA at 3T demonstrated sensitivity in determining the LSA-tumor interface and the number of LSAs in patients with insular gliomas.

Differentiation of glioblastoma tissues using spontaneous Raman scattering with dimensionality reduction and data classification.

The neurosurgery of intracranial tumors is often complicated by the difficulty of distinguishing tumor center, infiltration area, and normal tissue. The current standard for intraoperative navigation is fluorescent diagnostics with a fluorescent agent. This approach can be further enhanced by measuring the Raman spectrum of the tissue, which would provide additional information on its composition even in the absence of fluorescence. However, for the Raman spectra to be immediately helpful for a neurosurgeon, they must be additionally processed. In this work, we analyzed the Raman spectra of human brain glioblastoma multiforme tissue samples obtained during the surgery and investigated several approaches to dimensionality reduction and data classificatin to distinguish different types of tissues. In our study two approaches to Raman spectra dimensionality reduction were approbated and as a result we formulated new technique combining both of them: feature filtering based on the selection of those shifts which correspond to the biochemical components providing the statistically significant differences between groups of examined tissues (center of glioblastoma multiforme, tissues from infiltration area and normally appeared white matter) and principal component analysis. We applied the support vector machine to classify tissues after dimensionality reduction of registered Raman spectra. The accuracy of the classification of malignant tissues (tumor edge and center) and normal ones using the principal component analysis alone was 83% with sensitivity of 96% and specificity of 44%. With a combined technique of dimensionality reduction we obtained 83% accuracy with 77% sensitivity and 92% specificity of tumor tissues classification.

Arterial Spin Labeling Perfusion in Determining the IDH1 Status and Ki-67 Index in Brain Gliomas.

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 cases­48 patients were diagnosed with wildtype gliomas (Grade 1−2­6 patients, Grade 3−4­42 patients) and 58 patients were diagnosed with mutant forms of gliomas (Grade 1−2­28 patients, Grade 3−4­30 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.

Noninvasive Glioma Grading with Deep Learning: A Pilot Study.

Gliomas are the most common neuroepithelial brain tumors, different by various biological tissue types and prognosis. They could be graded with four levels according to the 2007 WHO classification. The emergence of non-invasive histological and molecular diagnostics for nervous system neoplasms can revolutionize the efficacy and safety of medical care and radically reduce healthcare costs. Our pilot study aimed to evaluate the diagnostic accuracy of deep learning (DL) in subtyping gliomas by WHO grades (I-IV) based on preoperative magnetic resonance imaging (MRI) from Burdenko Neurosurgery Center's database. A total of 707 MRI studies was included. A "3D classification" approach predicting tumor type for the entire patient's MRI data showed the best result (accuracy = 83%, ROC AUC = 0.95), consistent with that of other authors who used different methodologies. Our preliminary results proved the separability of MR T1 axial images with contrast enhancement by WHO grade using DL.

Control over the Surface Properties of Zinc Oxide Powders via Combining Mechanical, Electron Beam, and Thermal Processing.

The surface properties of zinc oxide powders prepared using mechanical activation, electron beam irradiation, and vacuum annealing, as well using combinations of these types of treatments, were studied using X-ray photoelectron spectroscopy. The structure of the obtained materials was studied by an X-ray diffraction technique and by scanning electron microscopy. We found that over five hours of grinding in an attritor, the size of nanocrystals decreases from 37 to 21 nm, and microdeformations increase from 0.3% to 0.6%. It was also found that a five-hour grinding treatment promoted formation of vacancies in the zinc sublattice at the surface and diffusion of Zn2+ cations into the bulk of the material. Irradiation of commercial zinc oxide powders with an electron beam with an energy of 0.9 MeV and a dose of 1 MGy induced breaking of Zn-O bonds, diffusion of interstitial zinc ions into the bulk, and oxygen atom escape from regular positions into the gas phase. A combined treatment of five hours of grinding and electron beam irradiation promoted accumulation of interstitial zinc ions at the surface of the material. Annealing of both initial and mechanically activated ZnO powders at temperatures up to 400 °C did not lead to a significant change in the properties of the samples. Upon exceeding the 400 °C annealing temperature the X-ray photoelectron spectra show almost identical atomic composition of the two types of materials, which is related to diffusion of interstitial zinc ions from the bulk of the material to the surface.

The Role of 3D-pCASL MRI in the Differential Diagnosis of Glioblastoma and Brain Metastases.

Purpose: The first aim of this study was to compare the intratumoral and peritumoral blood flow parameters in glioblastomas and brain metastases measured by pseudocontinuous arterial spin labeling MRI (3D pCASL). The second aim of this study was to determine whether pCASL could aid in identifying the source of brain metastases. Materials and Methods: This study included 173 patients aged 12 to 83 years (median age-61 years), who were observed at the National Medical Research Center for Neurosurgery. All patients underwent preoperative MRI with pCASL perfusion. Thereafter patients were operated on and received histological diagnosis. No patients received preoperative chemo or radiotherapy. Results: The values of maximum and normalized intratumoral blood flow were significantly higher in the group with gliblastoma than in the group with brain metastases: 168.98 + -91.96 versus 152.1 + -173.32 and 7.6 + -8.4 versus 9.3 + -5.33 respectively (p <0.01). However, ROC analysis showed low AUC specificity and sensitivity (0.64, 70%, 60% for mTBF and 0.66, 77%, 62% for nTBF). Peritumoral blood flow parameters were also higher in the glioblastoma group (29.61 + -22.89 versus 16.58 + -6.46 for mTBF and 1.63 + -1.14 versus 0.88 + -0.38 for nTBF, respectively; p <0.01). ROC analysis showed the following measurements of AUC, specificity, and sensitivity (0.75, 68%, 73% for mTBF and 0.77, 58%, 91% for nTBF). Regarding pCASL and various histological subsets of brain metastases, the study found statistically significant differences between the lung and melanoma metastases and the lung and kidney metastases. ROC analysis gave the following values for lung and melanoma metastases: AUC-0.76, specificity-75%, and sensitivity-73% for mTBF; 0.83, 67%, and 93% respectively, for nTBF. For lung and kidney metastases: AUC-0.74, specificity-70%, and sensitivity-93% for mTBF; 0.75, 70%, and 93% respectively, for nTBF. Conclusions: pCASL could aid in differential diagnosis between glioblastoma and brain metastases. Measurement of peritumoral blood flow demonstrates higher specificity and sensitivity than with intratumoral blood flow. Moreover, pCASL provides the ability to distinguish lung metastases from kidney and melanoma metastases.

First-in-Man Noninvasive Initial Diagnostic Approach of Primary CNS Lymphoma Versus Glioblastoma Using PET With 18 F-Fludarabine and l -[methyl- 11 C]Methionine.

OBJECTIVES: This study sought to assess 18 F-fludarabine ( 18 F-FLUDA) PET/CT's ability in differentiating primary central nervous system lymphomas (PCNSLs) from glioblastoma multiformes (GBMs). PATIENTS AND METHODS: Patients harboring either PCNSL (n = 8) before any treatment, PCNSL treated using corticosteroids (PCNSLh; n = 10), or GBM (n = 13) were investigated with conventional MRI and PET/CT, using 11 C-MET and 18 F-FLUDA. The main parameters measured with each tracer were SUV T and T/N ratios for the first 30 minutes of 11 C-MET acquisition, as well as at 3 different times after 18 F-FLUDA injection. The early 18 F-FLUDA uptake within the first minute of injection was equally considered, whereas this parameter was combined with the later uptakes to obtain R FLUDA 2 and R FLUDA 3 ratios. RESULTS: No significant differences in 11 C-MET uptakes were observed among PCNSL, PCNSLh, and GBM. With 18 F-FLUDA, a clear difference in dynamic GBM uptake was observed, which decreased over time after an early maximum, as compared with that of PCNSL, which steadily increased over time, PCNSLh exhibiting intermediate values. The most discriminative parameters consisting of R FLUDA 2 and R FLUDA 3 integrated the early tracer uptake (first 60 seconds), thereby provided 100% specificity and sensitivity. CONCLUSIONS: 18 F-FLUDA was shown to likely be a promising radiopharmaceutical for differentiating PCNSL from other malignancies, although a pretreatment with corticosteroids might compromise this differential diagnostic ability. The diagnostic role of 18 F-FLUDA should be further investigating, along with its potential of defining therapeutic strategies in patients with PCNSL, while assessing the treatments' effectiveness.

'Moderate global aphasia': A generalized decline of language processing caused by glioma surgery but not stroke.

Unlike stroke, neurosurgical removal of left-hemisphere gliomas acts upon a reorganized language network and involves brain areas rarely damaged by stroke. We addressed whether this causes the profiles of neurosurgery- and stroke-induced language impairments to be distinct. K-means clustering of language assessment data (neurosurgery cohort: N = 88, stroke cohort: N = 95) identified similar profiles in both cohorts. But critically, a cluster of individuals with specific phonological deficits was only evident in the stroke but not in the neurosurgery cohort. Thus, phonological deficits are less clearly distinguished from other language deficits after glioma surgery compared to stroke. Furthermore, the correlations between language production and comprehension scores at different linguistic levels were more extensive in the neurosurgery than in the stroke cohort. Our findings suggest that neurosurgery-induced language impairments do not correspond to those caused by stroke, but rather manifest as a 'moderate global aphasia' - a generalized decline of language processing abilities.

Radiochemical Synthesis of 4-[18F]FluorobenzylAzide and Its Conjugation with EGFR-Specific Aptamers.

Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[18F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[18F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain 18F-labelled conjugates with 97% radiochemical purity for [18F]FB-GR20 and 98% for [18F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.