Noninvasive detection of brain gliomas using plasma cell-free DNA 5-hydroxymethylcytosine sequencing.

Liquid biopsy techniques based on deep sequencing of plasma cell-free DNA (cfDNA) could detect the low-frequency somatic mutations and provide an accurate diagnosis for many cancers. However, for brain gliomas, reliable performance of these techniques currently requires obtaining cfDNA from patients' cerebral spinal fluid, which is cumbersome and risky. Here we report a liquid biopsy method based on sequencing of plasma cfDNA fragments carrying 5-hydroxymethylcytosine (5hmC) using selective chemical labeling (hMe-Seal). We first constructed a dataset including 180 glioma patients and 229 non-glioma controls. We found marked concordance between cfDNA hydroxymethylome and the aberrant transcriptome of the underlying gliomas. Functional analysis also revealed overrepresentation of the differentially hydroxymethylated genes (DhmGs) in oncogenic and neural pathways. After splitting our dataset into training and test cohort, we showed that a penalized logistic model constructed with training set DhmGs could distinguish glioma patients from healthy controls in both our test set (AUC = 0.962) and an independent dataset (AUC = 0.930) consisting of 111 gliomas and 111 controls. Additionally, the DhmGs between gliomas with mutant and wild-type isocitrate dehydrogenase (IDH) could be used to train a cfDNA predictor of the IDH mutation status of the underlying tumor (AUC = 0.816), and patients with predicted IDH mutant gliomas had significantly better outcome (P = .01). These results indicate that our plasma cfDNA 5hmC sequencing method could obtain glioma-specific signals, which may be used to noninvasively detect these patients and predict the aggressiveness of their tumors.

miR-21-5p inhibits the growth of brain glioma cells through regulating the glycolysis mediated by PFKFB2.

Brain glioma is a common gynecological tumor. MicroRNA (miRNA) plays a very important role in the pathogenesis and development of tumors. It was found that glycolysis played important regulatory roles in tumor growth. The present study aims to investigate the expression pattern of miR-21-5p in brain glioma cells. We examined miR-21-5p and PFKFB2 levels in brain glioma cells via qRT-PCR. Then we performed CCK-8 and Transwell migration assays and determined glucose uptake and lactose production to unveil the properties of miR-21-5p in invasion, cell viability, along with glycolysis in brain glioma cells. Luciferase activity assay was implemented to elucidate if PFKFB2 was a miR-21-5p target gene. Western blotting and qRT-PCR were executed to further validate that miR-21-5p targeted PFKFB2. We repeated these functional assays to observe whether miR-21-5p could impede the function of PFKFB2. qRT-PCR signified that miR-21-5p was elevated in brain glioma tissues in contrast to matching adjacent normal tissues. Functional assays disclosed that elevation of miR-21-5p promoted cell viability, invasion, together with glycolysis. Luciferase assay indicated that PFKFB2 was a miR-21-5p target gene. Moreover, miR-21-inhibit could hinder cell viability, invasion, and glycolysis triggered by overexpression of PFKFB2 in brain glioma cells. miR-21-5p level is elevated in brain glioma and can impede brain glioma cell growth via regulating the glycolysis mediated by PFKFB2, thus is a potential target of treating brain glioma.

Diagnostic performance of edited 2HG MR spectroscopy of central glioma in the clinical environment.

OBJECTIVE: Oncometabolite D-2-hydroxyglutarate (2HG) is pooled in isocitrate dehydrogenase (IDH)-mutant glioma cells. Detecting 2HG by MR spectroscopy (MRS) has been proven viable in the last decade but has not entirely found its way into the clinical routine. This study aimed to explore the adoption of 2HG MRS while acknowledging factors that influence its performance in the clinical environment. METHODS: Thirty-nine MR spectra were acquired and reported prospectively in patients with suspected glioma using a 3 T system with Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence utilizing averaged free induction decay (FID) signals. Postprocessing and evaluation of spectra were performed with jMRUI and LCModel. 2HG concentration estimates, 2HG/Cr ratio, together with quality measures, including Cramér-Rao lower bounds (CRLBs), full-width at half-maximum (FWHM) values, and signal-to-noise ratio (SNR) were calculated using LCModel. Immunohistochemistry and genomic analysis results used as a ground truth were available for 15 patients. RESULTS: The threshold for test positivity was set according to the ROC curve at 1 mM. Calculated sensitivity was 57.14% (95% CI 0.20-0.88), specificity 87.5% (95% CI 0.46-0.99), positive predictive value 80%, and negative predictive value 70%. Overall diagnostic accuracy was 73.33% (95% CI 0.45-0.92). The 2HG/Cr ratio with the cutoff value 0.085 significantly improved sensitivity and overall diagnostic accuracy [85.71%, 95% CI 0.42-1.00 and 86.67%, (95% CI 0.60-0.98), respectively]. CONCLUSION: Multiple factors compromising spectral quality in the clinical adoption of edited 2HG MRS resulted in diminished sensitivity but clinically acceptable specificity. Furthermore, the 2HG/Cr ratio performs better than the sole 2HG concentration estimate in the pre-operative setting.

Radiomic Features Associated with Extent of Resection in Glioma Surgery.

Radiomics defines a set of techniques for extraction and quantification of digital medical data in an automated and reproducible way. Its goal is to detect features potentially related to a clinical task, like classification, diagnosis, prognosis, and response to treatment, going beyond the intrinsic limits of operator-dependency and qualitative description of conventional radiological evaluation on a mesoscopic scale. In the field of neuro-oncology, researchers have tried to create prognostic models for a better tumor diagnosis, histological and biomolecular classification, prediction of response to treatment, and identification of disease relapse. Concerning glioma surgery, the most significant aid that radiomics can give to surgery is to improve tumor extension detection and identify areas that are more prone to recurrence to increase the extent of tumor resection, thereby ameliorating the patients' prognosis. This chapter aims to review the fundamentals of radiomics models' creation, the latest advance of radiomics in neuro-oncology, and possible radiomic features associated with the extent of resection in the brain gliomas.

Aggregation-and-Attention Network for brain tumor segmentation.

BACKGROUND: Glioma is a malignant brain tumor; its location is complex and is difficult to remove surgically. To diagnosis the brain tumor, doctors can precisely diagnose and localize the disease using medical images. However, the computer-assisted diagnosis for the brain tumor diagnosis is still the problem because the rough segmentation of the brain tumor makes the internal grade of the tumor incorrect. METHODS: In this paper, we proposed an Aggregation-and-Attention Network for brain tumor segmentation. The proposed network takes the U-Net as the backbone, aggregates multi-scale semantic information, and focuses on crucial information to perform brain tumor segmentation. To this end, we proposed an enhanced down-sampling module and Up-Sampling Layer to compensate for the information loss. The multi-scale connection module is to construct the multi-receptive semantic fusion between encoder and decoder. Furthermore, we designed a dual-attention fusion module that can extract and enhance the spatial relationship of magnetic resonance imaging and applied the strategy of deep supervision in different parts of the proposed network. RESULTS: Experimental results show that the performance of the proposed framework is the best on the BraTS2020 dataset, compared with the-state-of-art networks. The performance of the proposed framework surpasses all the comparison networks, and its average accuracies of the four indexes are 0.860, 0.885, 0.932, and 1.2325, respectively. CONCLUSIONS: The framework and modules of the proposed framework are scientific and practical, which can extract and aggregate useful semantic information and enhance the ability of glioma segmentation.

THE SAFETY AND EFFICACY OF ROBOT-ASSISTED STEREOTACTIC BIOPSY FOR BRAIN GLIOMA: EARLIEST INSTITUTIONAL EXPERIENCES AND EVALUATION OF LITERATURE.

Robot-assisted brain tumor biopsy is becoming one of the most important innovative technologies in neurosurgical practice. The idea behind its engagement is to advance the safety and efficacy of the biopsy procedure, which is much in demand when planning the management of endocranial tumor pathology. Herein, we provide our earliest institutional experiences in utilizing this mesmerizing technology. Cranial robotic device was employed for stereotactic robot-assisted brain glioma biopsy in three consecutive patients from our series: an anaplastic isocitrate dehydrogenase (IDH) negative astrocytoma (WHO grade III) located in the right trigone region of the periventricular white matter; a low grade diffuse astrocytoma (WHO grade II) of bilateral thalamic region spreading into the right mesencephalic area; and an IDH-wildtype glioblastoma (WHO grade IV) of the right frontal lobe producing a contralateral midline shifting. Robot-assisted tumor biopsy was successfully performed to get tissue samples for histopathologic and immunohistochemical analysis. The adjacent tissue iatrogenic damage of the eloquent cortical areas was minimal, while the immediate postoperative recovery was satisfactory in all patients. In conclusion, considering the preliminary results of our early experiences, robot-assisted tumor biopsy was proven to be a feasible and accurate procedure when surgery for brain glioma was not an option. It may increase safety and precision, without expanding surgical time, being similarly effective when compared to standard stereotactic and manual biopsy. Using this method to provide accurate sampling for histopathologic and immunohistochemical analysis is a safe and easy way to determine management strategies and outcome of different types of brain glioma.

In vivo 1 H MRS detection of cystathionine in human brain tumors.

PURPOSE: To report the technical aspects of noninvasive detection of cystathionine in human brain glioma with edited MRS, and to investigate possible further acquisition improvements for robust quantification of this metabolite. METHODS: In vivo 1 H MR spectra were acquired at 3 T in 15 participants with an isocitrate dehydrogenase-mutated glioma using a MEGA-PRESS (MEscher GArwood point resolved spectroscopy) sequence previously employed for 2-hydroxyglutarate detection (TR = 2 s, TE = 68 ms). The editing pulse was applied at 1.9 ppm for the edit-on condition and at 7.5 ppm for the edit-off condition. To evaluate the editing efficiency, spectra were acquired in 1 participant by placing the editing pulse for the edit-on condition at 1.9, 2.03, and 2.16 ppm. Cystathionine concentration was quantified using LCModel and a simulated basis set. To confirm chemical shifts and J-coupling values of cystathionine, the 1 H NMR cystathionine spectrum was measured using a high-resolution 500 MHz spectrometer. RESULTS: In 12 gliomas, cystathionine was observed in the in vivo edited MR spectra at 2.72 and 3.85 ppm and quantified. The signal intensity of the cystathionine resonance at 2.72 ppm increased 1.7 and 2.13 times when the editing pulse was moved to 2.03 and 2.16 ppm, respectively. Cystathionine was not detectable in normal brain tissue. CONCLUSION: Cystathionine can be detected in vivo by edited MRS using the same protocol as for 2-hydroxyglutarate detection. This finding may enable a more accurate, noninvasive investigation of cellular metabolism in glioma.

Realization of 19F MRI oximetry method using perfluorodecalin.

OBJECTIVE: To identify the technical aspects of the potential use of clinically approved perfluorodecalin (PFD, C10F18) for 19F magnetic resonance imaging (MRI) oximetry method at high magnetic field 7.05 T. MATERIALS AND METHODS: 19F T1 measurements were made on a set of PFD samples with different oxygen contents (0%, 21%, and 100%) at room (21 °C) and body temperature (37 °C). In vivo MRI studies were carried out on one healthy rat and two rats with C6 brain glioma. RESULTS: The selective excitation of the magnetically equivalent 19F nuclei of CF2 groups of trans-isomer of PFD, which give a doublet at a frequency of about - 140 ppm (in relation the chemical shift of trifluoroacetic acid, which is - 76.55 ppm) should be done for correct implementation of 19F MRI oximetry method. The amount of PFD equal to 30 µl is the optimal for obtaining reliable data on the measured T1 values. In this case, the standard deviation of T1 does not exceed 5%. In vivo MRI studies showed that the values of the partial pressure of oxygen (pO2) decrease from normal values of about 38 mmHg (healthy brain) to almost 0 mmHg at the last stage of tumor growth. CONCLUSION: The study showed the feasibility of the successful application of PFD for 19F MRI oximetry method.

Can dynamic contrast-enhanced MRI evaluate VEGF expression in brain glioma? An MRI-guided stereotactic biopsy study.

PURPOSE: To investigate whether pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to evaluate vascular endothelial growth factor (VEGF) expression in brain glioma based on a point-to-point basis. MATERIALS AND METHODS: Forty-seven patients with treatment-naïve glioma received preoperative DCE-MRI before stereotactic biopsy. We histologically quantified VEGF from section of stereotactic biopsies, and co-registered biopsy locations with localized measurements of DCE-MRI parameters including volume transfer coefficient (Ktrans), reverse reflux rate constant (Kep), extracellular extravascular volume fraction (Ve) and blood plasma volume (Vp). The correlations between DCE-MRI parameters (Ktrans, Kep, Ve and Vp) and VEGF were determined using Spearman correlation coefficient. P≤.05 was considered statistically significant. RESULTS: Seventy-nine biopsy samples were obtained and graded into 45 high-grade gliomas (HGGs) and 34 low-grade gliomas (LGGs). Ktrans showed a significant positive correlation with VEGF expression in HGGs group (ρ=0.505, P<0.001) and in combined group (LGGs+HGGs) (ρ=0.549, P<0.001), but not in LGGs group (P>0.05). Kep, Ve or Vp was not correlated with VEGF even though a positive trend showed (P>0.05). CONCLUSIONS: DCE-MRI is a useful, non-invasive imaging technique for quantitative evaluation of VEGF, and its parameter Ktrans other than Kep, Ve or Vp may be used as a surrogate for VEGF expression in brain gliomas.

[Research on glioma magnetic resonance imaging segmentation based on dual-channel three-dimensional densely connected network].

Focus on the inconsistency of the shape, location and size of brain glioma, a dual-channel 3-dimensional (3D) densely connected network is proposed to automatically segment brain glioma tumor on magnetic resonance images. Our method is based on a 3D convolutional neural network frame, and two convolution kernel sizes are adopted in each channel to extract multi-scale features in different scales of receptive fields. Then we construct two densely connected blocks in each pathway for feature learning and transmission. Finally, the concatenation of two pathway features was sent to classification layer to classify central region voxels to segment brain tumor automatically. We train and test our model on open brain tumor segmentation challenge dataset, and we also compared our results with other models. Experimental results show that our algorithm can segment different tumor lesions more accurately. It has important application value in the clinical diagnosis and treatment of brain tumor diseases.

The Long Non-Coding RNA TP73-AS1 Interacted With miR-142 to Modulate Brain Glioma Growth Through HMGB1/RAGE Pathway.

P73 antisense RNA 1T (non-protein coding), also known as TP73-AS1 or PDAM, is a long non-coding RNA which may regulate apoptosis via regulation of p53-dependent anti-apoptotic genes. An abnormal change of TP73-AS1 expression was noticed in cancers. The effects of TP73-AS1 in brain glioma growth and the underlying mechanism remain unclear so far. In the present study, TP73-AS1 was specifically upregulated in brain glioma tissues and cell lines, and was associated with poorer prognosis in patients with glioma. TP73-AS1 knocking down suppressed human brain glioma cell proliferation and invasion in vitro, as well as HMGB1 protein. MiR-142 has been reported to play a pivotal role in cancers; here we observed that TP73-AS1 and miR-142 could negatively regulate each other. Results from luciferase assays suggested that TP73-AS1 might compete with HMGB1 for miR-142 binding. Further, HMGB1/RAGE was involved in TP73-AS1/miR-142 regulation of glioma cell proliferation and invasion. In glioma tissues, TP73-AS1 and HMGB1 expression was up-regulated, whereas miR-142 expression was down-regulated. Data from the present study revealed that TP73-AS1 promoted the brain glioma growth and invasion through acting as a competing endogenous RNA (ceRNA) to promote HMGB1 expression by sponging miR-142. In conclusion, we regarded TP73-AS1 as an oncogenic lncRNA promoting brain glioma proliferation and invasion, and a potential target for human brain glioma treatment. J. Cell. Biochem. 119: 3007-3016, 2018. © 2017 Wiley Periodicals, Inc.

Brain investigations of rodent disease models by chemical exchange saturation transfer at 21.1 T.

This study explores opportunities opened up by ultrahigh fields for in vivo saturation transfer brain magnetic resonance imaging experiments. Fast spin-echo images weighted by chemical exchange saturation transfer (CEST) effects were collected on Sprague-Dawley rats at 21.1 T, focusing on two neurological models. One involved a middle cerebral artery occlusion emulating ischemic stroke; the other involved xenografted glioma cells that were followed over the course of several days as they developed into brain tumors. A remarkably strong saturation-derived contrast was observed for the growing tumors when calculating magnetization transfer ratios at c. 3.8 ppm. This large contrast originated partially from an increase in the contribution of the amide CEST effect, but mostly from strong decreases in the Overhauser and magnetization transfer contributions to the upfield region, whose differential attenuations could be clearly discerned thanks to the ultrahigh field. The high spectral separation arising at 21.1 T also revealed numerous CEST signals usually overlapping at lower fields. Ischemic lesions were also investigated but, remarkably, magnetization and saturation transfer contrasts were nearly absent when computing transfer asymmetries using either high or low saturation power schemes. These behaviors were consistently observed at 24 hours post-occlusion, regardless of the data processing approach assayed. Considerations related to how various parameters defining these experiments depend on the magnetic field, primarily chemical shifts and T1 values, are discussed.

Downregulation of HIF-1a sensitizes U251 glioma cells to the temozolomide (TMZ) treatment.

PURPOSE: The aim of this study was to investigate the effect of downregulation of HIF-1α gene on human U251 glioma cells and examine the consequent changes of TMZ induced effects and explore the molecular mechanisms. METHODS: U251 cell line stably expressing HIF-1α shRNA was acquired via lentiviral vector transfection. The mRNA and protein expression alterations of genes involved in our study were determined respectively by qRT-PCR and Western blot. Cell proliferation was measured by MTT assay and colony formation assay, cell invasion/migration capacity was determined by transwell invasion assay/wound healing assay, and cell apoptosis was detected by flow cytometry. RESULTS: We successfully established a U251 cell line with highly efficient HIF-1α knockdown. HIF-1a downregulation sensitized U251 cells to TMZ treatment and enhanced the proliferation-inhibiting, invasion/migration-suppressing, apoptosis-inducing and differentiation-promoting effects exerted by TMZ. The related molecular mechanisms demonstrated that expression of O(6)-methylguanine DNA methyltransferase gene (MGMT) and genes of Notch1 pathway were significantly upregulated by TMZ treatment. However, this upregulation was abrogated by HIF-1α knockdown. We further confirmed important regulatory roles of HIF-1α in the expression of MGMT and activation of Notch1 pathways. CONCLUSION: HIF-1α downregulation sensitizes U251 glioma cells to the temozolomide treatment via inhibiting MGMT expression and Notch1 pathway activation.

Efficacy of NGR peptide-modified PEGylated quantum dots for crossing the blood-brain barrier and targeted fluorescence imaging of glioma and tumor vasculature.

Delivery of imaging agents to brain glioma is challenging because the blood-brain barrier (BBB) functions as a physiological checkpoint guarding the central nervous system from circulating large molecules. Moreover, the ability of existing probes to target glioma has been insufficient and needs to be improved. In present study, PEG-based long circulation, CdSe/ZnS quantum dots (QDs)-based nanoscale and fluorescence, asparagines-glycine-arginine peptides (NGR)-based specific CD13 recognition were integrated to design and synthesize a novel nanoprobe by conjugating biotinylated NGR peptides to avidin-PEG-coated QDs. Our data showed that the NGR-PEG-QDs were nanoscale with less than 100 nm and were stable in various pH (4.0~8.0). These nanomaterials with non-toxic concentrations could cross the BBB and target CD13-overexpressing glioma and tumor vasculature in vitro and in vivo, contributing to fluorescence imaging of this brain malignancy. These achievements allowed groundbreaking technological advances in targeted fluorescence imaging for the diagnosis and surgical removal of glioma, facilitating potential transformation toward clinical nanomedicine.

Quantitative assessment of amide proton transfer (APT) and nuclear overhauser enhancement (NOE) imaging with extrapolated semisolid magnetization transfer reference (EMR) signals: II. Comparison of three EMR models and application to human brain glioma at 3 Tesla.

PURPOSE: To evaluate the use of three extrapolated semisolid magnetization transfer reference (EMR) methods to quantify amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signals in human glioma. METHODS: Eleven patients with high-grade glioma were scanned at 3 Tesla. aEMR(2) (asymmetric magnetization-transfer or MT model to fit two-sided, wide-offset data), sEMR(2) (symmetric MT model to fit two-sided, wide-offset data), and sEMR(1) (symmetric MT model to fit one-sided, wide-offset data) were assessed. ZEMR and experimental data at 3.5 ppm and -3.5 ppm were subtracted to calculate the APT and NOE signals (APT(#) and NOE(#)), respectively. RESULTS: The aEMR(2) and sEMR(1) models provided quite similar APT(#) signals, while the sEMR(2) provided somewhat lower APT(#) signals. The aEMR(2) had an erroneous NOE(#) quantification. Calculated APT(#) signal intensities of glioma (∼4%), much larger than the values reported previously, were significantly higher than those of edema and normal tissue. Compared with normal tissue, gadolinium-enhancing tumor cores were consistently hyperintense on the APT(#) maps and slightly hypointense on the NOE(#) maps. CONCLUSION: The sEMR(1) model is the best choice for accurately quantifying APT and NOE signals. The APT-weighted hyperintensity in the tumor was dominated by the APT effect, and the MT asymmetry at 3.5 ppm is a reliable and valid metric for APT imaging of gliomas at 3T.

Design of a PKCδ-specific small peptide as a theragnostic agent for glioblastoma.

Glioblastoma is an aggressive malignant brain tumor that starts in the brain or spine and frequently recurs after anticancer treatment. The development of an accurate diagnostic system combined with effective cancer therapy is essential to improve prognosis of glioma patients. Peptides, produced from phage display, are attractive biomolecules for glioma treatment because of their biostability, nontoxicity, and small size. In this study, we employed phage display methodology to screen for peptides that specifically recognize the target PKCδ as a novel biomarker for glioma. The phage library screening yielded four different peptides displayed on phages with a 20- to 200-pM Kd value for the recombinant PKCδ catalytic domain. Among these four phage peptides, we selected one to synthesize and tagged it with fluorescein isothiocyanate (FITC) based on the sequence of the PKCδ-binding phage clone. The synthetic peptide showed a relative binding affinity for antibody and localization in the U373 glioma cell. The kinase activity of PKCδ was inhibited by FITC-labeled peptide with an IC50 of 1.4 µM in vitro. Consequently, the peptide found in this study might be a promising therapeutic agent against malignant brain tumor.

In vitro and in vivo brain-targeting chemo-photothermal therapy using graphene oxide conjugated with transferrin for Gliomas.

Current therapies for treating malignant glioma exhibit low therapeutic efficiency because of strong systemic side effects and poor transport across the blood brain barrier (BBB). Herein, we combined targeted chemo-photothermal glioma therapy with a novel multifunctional drug delivery system to overcome these issues. Drug carrier transferrin-conjugated PEGylated nanoscale graphene oxide (TPG) was successfully synthesized and characterized. When loaded on the proposed TPG-based drug delivery (TPGD) system, the anticancer drug doxorubicin could pass through the BBB and improve drug accumulation both in vitro and in vivo. TPGD was found to perform dual functions in chemotherapy and photothermal therapy. Targeted TPGD combination therapy showed higher rates of glioma cell death and prolonged survival of glioma-bearing rats compared with single doxorubicin or PGD therapy. In conclusion, we developed a potential nanoscale drug delivery system for combined therapy of glioma that can effectively decrease side effects and improve therapeutic effects.

[Incidence and causes of early end in awake surgery for language mapping not directly related to eloquence]. / Incidencia y causas de finalización anticipada de la cirugía con paciente despierto para mapeo del lenguaje, no relacionadas directamente con la elocuencia.

The incidence and causes that may lead to an early end (unfinished cortical/subcortical mapping) of awake surgery for language mapping are little known. A study was conducted on 41 patients with brain glioma located in the language area that had awake surgery under conscious sedation. Surgery was ended early in 6 patients. The causes were: tonic-clonic seizure (1), lack of cooperation due to fatigue/sleep (4), whether or not word articulation was involved, a decreased level of consciousness for ammonia encephalopathy that required endotracheal intubation (1). There are causes that could be expected and in some cases avoided. Tumour size, preoperative aphasia, valproate treatment, and type of anaesthesia used are variables to consider to avoid failure in awake surgery for language mapping. With these results, the following measures are proposed: l) If the tumour is large, perform surgery in two times to avoid fatigue, 2) if patient has a preoperative aphasia, do not use sedation during surgery to ensure that sleepiness does not cause worse word articulation, 3) if the patient is on valproate treatment, it is necessary to rule out the pre-operative symptoms that are not due to ammonia encephalopathy.

Prognostic impact of sodium fluorescein-guided microsurgery on cognitive function, neuropeptide dynamics, and short-term outcomes in brain glioma patients.

This study conducted a retrospective analysis on 107 brain glioma patients treated from January 2018 to February 2020 to assess the impact of sodium fluorescein-guided microsurgery on postoperative cognitive function and short-term outcomes. Patients were divided into two groups: a control group (n=50 patients) undergoing routine surgery and a research group (n=57 patients) receiving sodium fluorescein-guided microsurgery. The study compared postoperative total resection rates, changes in cognitive scores, and neuropeptide levels in cerebrospinal fluid between the groups. The findings revealed that the research group experienced shorter surgical time and hospitalization duration, reduced blood loss, and higher total resection rates compared to the control group. Furthermore, the research group demonstrated improvements in cognitive scores and an increase in neuropeptide levels after surgery. There was no significant difference in the comparison of the incidence of postoperative complications between the two groups. The WHO classification and preoperative performance scores were independent prognostic factors for the evaluation of 3-year survival, highlighting the clinical significance of sodium fluorescein-guided microsurgery in improving quality of life and cognitive functions of patients without compromising their long-term survival outcomes.

Utilizing the amide proton transfer technique to characterize diffuse gliomas based on the WHO 2021 classification of CNS tumors.

PURPOSE: Diffuse gliomas present a significant challenge for healthcare systems globally. While brain MRI plays a vital role in diagnosis, prognosis, and treatment monitoring, accurately characterizing gliomas using conventional MRI techniques alone is challenging. In this study, we explored the potential of utilizing the amide proton transfer (APT) technique to predict tumor grade and type based on the WHO 2021 Classification of CNS Tumors. METHODS: Forty-two adult patients with histopathologically confirmed brain gliomas were included in the study. They underwent 3T MRI imaging, which involved APT sequence. Multinomial and binary logistic regression models were employed to classify patients into clinically relevant groups based on MRI findings and demographic variables. RESULTS: We found that the best model for tumor grade classification included patient age along with APT values. The highest sensitivity (88%) was observed for Grade 4 tumors, while Grade 3 tumors showed the highest specificity (79%). For tumor type classification, our model incorporated four predictors: APT values, patient's age, necrosis, and the presence of hemorrhage. The glioblastoma group had the highest sensitivity and specificity (87%), whereas balanced accuracy was the lowest for astrocytomas (0.73). CONCLUSION: The APT technique shows great potential for noninvasive evaluation of diffuse gliomas. The changes in the classification of gliomas as per the WHO 2021 version of the CNS Tumor Classification did not affect its usefulness in predicting tumor grade or type.