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Prior studies have described the complex interplay that exists between glioma cells and neurons; however, the electrophysiological properties endogenous to glioma cells remain obscure. To address this, we employed Patch-sequencing (Patch-seq) on human glioma specimens and found that one-third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia. To define these hybrid cells (HCs), which fire single, short action potentials, and discern if they are of tumoral origin, we developed the single cell rule association mining (SCRAM) computational tool to annotate each cell individually. SCRAM revealed that HCs possess select features of GABAergic neurons and oligodendrocyte precursor cells, and include both tumor and non-tumor cells. These studies characterize the combined electrophysiological and molecular properties of human glioma cells and describe a cell type in human glioma with unique electrophysiological and transcriptomic properties that may also exist in the non-tumor brain. [Display omitted] • Patch-seq identifies spiking tumor cells in human glioma • Spiking glioma cells exhibit GABAergic and glial properties in IDH mutant gliomas • SCRAM algorithm accurately annotates tumor and non-tumor cells from Patch-seq data • Spiking glioma cells confer increased survival in IDH mutant glioma Curry et al. employ simultaneous electrophysiological and genomic profiling of single cells from human glioma to identify glioma cells that fire action potentials (APs). This study introduces single cell rule association mining (SCRAM), a computational tool that provides integrated genomic and transcriptomic profiles for each single cell. [ABSTRACT FROM AUTHOR]

Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG. 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up. The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy. [ABSTRACT FROM AUTHOR]

The transcallosal retroforniceal transchoroidal approach represents an advanced neurosurgical technique that allows access to lesions located within the posterior third ventricle and mesencephalon. It relies on a comprehensive understanding of microsurgical anatomy and embryology, integrating modern neurosurgical operative techniques to minimize retraction and injury to the normal neuronal structures. We report the cases of 2 patients undergoing treatment via this approach, one presenting with a thalamic cavernoma and the other with cystic low-grade glioma of the midbrain. In these 2 cases, the decision to use the transcallosal approach was mainly due to improved trajectory, gravitational retraction of the hemisphere, and improved delivery of the lesion into the operative field by gravity alone. Through a detailed description of the surgical approach and anatomy, we illustrate the feasibility of the transcallosal retroforniceal transchoroidal approach for accessing lesions located deeply in the brain. [ABSTRACT FROM AUTHOR]

This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. The paper underscores the importance of integrating modern MRI modalities, such as diffusion-weighted imaging and perfusion MRI, which are essential for assessing glioma malignancy and predicting tumor behavior. Special attention is given to the 2021 WHO Classification of Tumors of the Central Nervous System, emphasizing the integration of molecular diagnostics in glioma classification, significantly impacting treatment decisions. The review also explores radiogenomics, which correlates imaging features with molecular markers to tailor personalized treatment strategies. Despite technological progress, MRI protocol standardization and result interpretation challenges persist, affecting diagnostic consistency across different settings. Furthermore, the review addresses MRI's capacity to distinguish between tumor recurrence and pseudoprogression, which is vital for patient management. The necessity for greater standardization and collaborative research to harness MRI's full potential in glioma diagnosis and personalized therapy is highlighted, advocating for an enhanced understanding of glioma biology and more effective treatment approaches. • Modern MRI techniques are key in diagnosing and guiding glioma treatment. • Modern MRI techniques are key in diagnosing and guiding glioma treatment. • Standardizing MRI protocols remains challenging, needing more research and collaboration. • Differentiating tumor recurrence from pseudoprogression is crucial; advanced MRI often needs biopsy validation. [ABSTRACT FROM AUTHOR]

Glioma resection is associated with prolonged survival, but neuro-oncological trials have frequently refrained from quantifying the extent of resection. The Response Assessment in Neuro-Oncology (RANO) resect group is an international, multidisciplinary group that aims to standardise research practice by delineating the oncological role of surgery in diffuse adult-type gliomas as defined per WHO 2021 classification. Favourable survival effects of more extensive resection unfold over months to decades depending on the molecular tumour profile. In tumours with a more aggressive natural history, supramaximal resection might correlate with additional survival benefit. Weighing the expected survival benefits of resection as dictated by molecular tumour profiles against clinical factors, including the introduction of neurological deficits, we propose an algorithm to estimate the oncological effects of surgery for newly diagnosed gliomas. The algorithm serves to select patients who might benefit most from extensive resection and to emphasise the relevance of quantifying the extent of resection in clinical trials. [ABSTRACT FROM AUTHOR]

Magnetization transfer ratio asymmetry (MTRasym) analysis is used for chemical exchange saturation transfer (CEST) in patients with gliomas; however, this approach has limitations. CEST imaging using a multi-pool model (MPM) may allow a more detailed assessment of gliomas; however, its mechanism remains unknown. This study aimed to assess the relationship between CEST imaging by MPM, intravoxel incoherent motion (IVIM), and 11C-methionine (11C-MET) uptake on positron emission tomography/computed tomography (PET/CT) to clarify the clinical significance of CEST imaging using MPM in gliomas. This retrospective study included 17 patients with gliomas who underwent 11C-MET PET/CT at our institution between January 2020 and January 2022. Two-dimensional axial CEST imaging was conducted using single-shot fast-spin echo acquisition at 3 T. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), f, MTRasym (3.5 ppm), parameters of MPM-based CEST imaging, and tumor-to-contralateral normal brain tissue (T/N) ratio were calculated using a region-of-interest analysis. Shapiro–Wilk test, weighted kappa coefficient, and Spearman's rank correlation coefficients were used for statistical analysis. Significant correlations were found between APT_T1 and T/N ratio (ρ = 0.87, p < 0.001), APT_T2 and T/N ratio (ρ = 0.47, p < 0.05), MTRasym and T/N ratio (ρ = 0.55, p < 0.01), and T2/T1 and T/N ratio (ρ = −0.36, p < 0.05). Furthermore, significant correlations were observed between APT_T1 and ADC (ρ = −0.67, p < 0.001), APT_T1 and D (ρ = −0.70, p < 0.001), APT_T2 and D* (ρ = −0.45, p < 0.05), and T2/T1 and D (ρ = 0.39, p < 0.05). These preliminary findings indicate that MPM-based CEST imaging parameters correlate with IVIM and 11C-MET uptake on PET/CT in patients with gliomas. In particular, the new parameter APT_T1 correlated more strongly with 11C-MET uptake compared to the traditional CEST parameter MTRasym. [ABSTRACT FROM AUTHOR]

The early differential diagnosis of the postoperative recurrence or pseudoprogression (psPD) of a glioma is of great guiding significance for individualized clinical treatment. This study aimed to evaluate the ability of a multiparametric magnetic resonance imaging (MRI)-based radiomics model to distinguish between the postoperative recurrence and psPD of a glioma early on and in a noninvasive manner. A total of 52 patients with gliomas who attended the Hainan Provincial People's Hospital between 2000 and 2021 and met the inclusion criteria were selected for this study. 1137 and 1137 radiomic features were extracted from T1 enhanced and T2WI/FLAIR sequence images, respectively.After clearing some invalid information and LASSO screening, a total of 9 and 10 characteristic radiological features were extracted and randomly divided into the training set and the test set according to 7:3 ratio. Select-Kbest and minimum Absolute contraction and selection operator (LASSO) were used for feature selection. Support vector machine and logistic regression were used to form a multi-parameter model for training and prediction. The optimal sequence and classifier were selected according to the area under the curve (AUC) and accuracy. Radiomic models 1, 2 and 3 based on T1WI, T2FLAIR and T1WI + T2T2FLAIR sequences have better performance in the identification of postoperative recurrence and false progression of T1 glioma. The performance of model 2 is more stable, and the performance of support vector machine classifier is more stable. The multiparameter model based on CE-T1 + T2WI/FLAIR sequence showed the best performance (AUC:0.96, sensitivity: 0.87, specificity: 0.94, accuracy: 0.89,95% CI:0.93–1). The use of multiparametric MRI-based radiomics provides a noninvasive, stable, and accurate method for differentiating between the postoperative recurrence and psPD of a glioma, which allows for timely individualized clinical treatment. [ABSTRACT FROM AUTHOR]

This study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). The 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). Compared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. The functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs. • Distinguishing non-enhancing tumors from vasogenic edema is a challenge. • Functional MRI could guide sub-volume segmentation for non-enhancing gliomas. • Dose-painting proton radiotherapy guided by functional MRI is feasible. • The strategy improves TCP with no or minimal increase of NTCP. [ABSTRACT FROM AUTHOR]

Local failure remains the major concern in grade 4 glioma or glioblastoma (GBM). Pilot studies have shown a radiotherapy (RT) dose–response relationship in GBM. Here we present our preliminary data of RT dose escalation using 68Ga-Pentixafor PET scan. High 68Ga-pentixafor uptake in glioma cells helps in sharp demarcation between tumour and normal brain. This phase II prospective study was conducted from 2018 to 2020. Thirty, biopsy-proven cases of grade 4 glioma were included. All patients underwent post-operative MRI of the brain and 68Ga-Pentixafor PET scan. RT was planned in 2-phases. Phase-1 GTV (GTV1) comprised of T2/flair abnormality, PET-avid disease and post-op cavity. A margin of 2cm was given to GTV-1 to create phase-1 CTV (CTV1), which was further expanded to 0.5cm to generate phase-1 PTV (PTV1). A radiation dose of 46Gy/23fr was prescribed to PTV-1. Phase-2 GTV (GTV2) consisted of CT/MRI contrast-enhancing lesion, PET avid disease and post-op cavity. A margin of 0.5 cm was given to GTV2 to create phase-2 CTV (CTV2) which was expanded to 0.5 cm to create phase-2 PTV (PTV2). RT dose of 14 Gy/7 fr was prescribed to PTV2. PET avid disease was delineated as GTV PET and a margin of 3mm was given to generate PTV-PET which received escalated RT dose of 21 Gy/7fr by simultaneous integrated boost (SIB) in phase 2 (Total dose to PTV PET = 67 Gy/30 fr). All patients received concurrent and adjuvant temozolomide. The data was prospectively maintained in Microsoft Excel sheet. SPSS v 23 was used for statistical analysis. The primary endpoints were estimation of the overall survival (OS) and progression-free survival (PFS), and secondary endpoint was to measure the incidence of radiation necrosis. Categorical variables were reported as frequency and percentage and quantitative variables were reported as median and range. Data from thirty patients were analysed. A median OS of 23 months was observed with estimated 1, 2 and 3 years OS of 90%, 40% and 17.8% respectively. A significant association of OS was seen with the extent of surgery (p = 0.04) and kernofsky performance status (p = 0.007). No patient developed significant radiation necrosis. The index study did not show any survival benefit from dose escalation RT. However, all of the patients tolerated the treatment well and none of them developed radiation necrosis. Considering the small sample size as a limitation of the index study, the role of 68Ga-pentixafor PET scan for radiation dose escalation should be further explored. CTRI/2019/05/019146. • Radiotherapy dose escalation in grade 4 glioma using 68Ga-Pentixafor PET scan. • Increased RT dose (67Gy/30#/6 weeks) was used for PET avid lesion. • None of the patients developed radiation necrosis. • No survival benefit from RT dose escalation. • Limitation – Small sample size. [ABSTRACT FROM AUTHOR]

The conflicting results about the relationship between certain psychiatric disorders and glioma has been reported in previous studies. Moreover, little is known about the common pathogenic mechanism between psychiatric symptoms and glioma. This study aims to find out mental disorders related etiology of glioma and to interpret the underlying biological mechanisms. A panel of SNPs significantly associated with eight psychiatric disorders (ADHD, SCZ, Insomnia, NEU, MDD, MI, BIP, and SWB) were identified as exposure related genetic instruments. Summary GWAS data for glioma comes from eight independent datasets. Two sample Mendelian randomization study was undertaken by IVW, RAPS, MR.Corr, and BWMR methods. This study incorporated the glioma associated CGGA cohort and Rembrandt cohort. ssGSEA, variance expression, and KEGG were conducted to analyze the psychiatric disorders associated genes expression profiling and associated functional enrichment in the glioma patients. ADHD has a suggestive risk effect on all glioma (OR = 1.15, 95%CI = 1.01‐–1.29, P = 0.028) and a significant causal effect on non-GBM glioma (OR = 1.33, 95%CI = 1.12‐–1.58, P = 0.001). Similarly, SCZ displayed a causal relationship with all glioma (OR = 1.09, 95%CI = 1.04–1.14, P = 3.47 × 10−4) and non-GBM glioma (OR = 1.14, 95%CI = 1.08–1.21, P = 7.37 × 10−6). Besides, insomnia was correlated with the risk of non-GBM glioma (OR = 1.49, 95%CI = 1.03–2.17, P = 0.036). The ADHD/SCZ/Insomnia associated DEGs of glioma patients were enriched in neurotransmitter signaling pathway, immune reaction, adhesion, invasion, and metastasis, regulating the pluripotency of stem cells, metabolism of glycan, lipid and amino acids. The extensibility of the conclusion to other ethnic and geographical groups should be careful because the data used in this study come from European. This study provides genetic evidence to suggest ADHD, SCZ, and insomnia as causes of glioma and common pathogenic process between ADHD/Insomnia/SCZ and glioma. • There is a suggestive causal relationship between ADHD, insomnia, NEU or SCZ and all glioma. • The common mechanisms between psychiatric disorders and glioma are neurotransmitter signaling pathway and immune reaction. • GLIS3 is the specific psychiatric associated gene of glioma. [ABSTRACT FROM AUTHOR]

Gliomas are associated with high rates of disability and mortality, and currently, there is a lack of specific and sensitive biomarkers for diagnosis. The ideal biomarkers should be detected early through noninvasive methods. Our research aims to develop a rapid, convenient, noninvasive diagnostic method for gliomas, as well as for grading and differentiation. We retrospectively collected data from patients who underwent surgery for glioma, trigeminal neuralgia/hemifacial spasmschwannoma, and those diagnosed with multiple sclerosis at our institution from January 2018 to December 2020. Inflammatory markers and coagulation factor levels were collected on admission, and neutrophil count (NLR), (WBC count minus neutrophil count) / lymphocyte count, platelet count / lymphocyte count, lymphocyte count / monocyte count, and albumin count [g/L] + total lymphocyte count × 5 were calculated for patients. Analyze the significance of biomarkers in the diagnosis and grading of gliomas, the diagnosis of MS, and the differential diagnosis of them. We evaluated 155 healthy individuals, 64 trigeminal neuralgia/hemifacial spasm patients, 47 MS patients, 316 schwannoma patients, and 814 with glioma patients. Compared with healthy controls and MS group, the preoperative levels of NLR, (WBC count minus neutrophil count) / lymphocyte count, D-dimer, Fibrinogen, Antithrobin, and Factor VIII of glioma patients were significantly higher in glioma patients and positively correlated with the grade of glioma. Conversely, 0020 lymphocyte count / Monocyte count and albumin count [g/L] + total lymphocyte count × 5 were significantly lower and negatively correlated with glioma grading. ROC curves confirmed that for the diagnosis of glioma, NLR showed a maximum area under the curve value of 0.8616 (0.8322–0.8910), followed by D-dimer and Antithrombin, with area under the curve values of 0.8205 (0.7601–0.8809) and 0.8455 (0.8153–0.8758), respectively. NLR and d-dimer also showed great sensitivity in the diagnosis of MS and differential diagnosis with gliomas. Our study demonstrated that multiple inflammatory markers and coagulation factors could be utilized as biomarkers for the glioma diagnosis, grading, and differential diagnosis of MS. Furthermore, the combination of these markers exhibited high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Glioma is an aggressive malignant brain tumor with a very poor prognosis for survival. The poor tumor targeting efficiency and tumor microenvironment penetration barrier also as troubles inhibited the effective glioma chemotherapy. Here, we design a core-shell structure cascade amplified hybrid catalytic nanopotentiators CFpAD with DM1 encapsulated to overcome the glioma therapeutic obstacles. NIR laser-based BBB penetrating enhances the tumor accumulation of CFpAD. When CFpAD, as the cascade amplified drug, is treated on the cancer cells, the bomb-like CFpAD releases gold nanoparticles as glucose oxidase (GOx) and ferric oxide nanoparticles (FNPs) as peroxides (POx) after blasting, producing ROS via a cascade amplification for tumor cell apoptosis. Gold nanoparticles can rest CAFs and reduce ECM secretion, achieving deep penetration of CFpAD. Moreover, CFpAD also cuts off the nutritional supply of the tumor, reduces the pH value, and releases free radicals to destroy the cancer. The glioma cell viability was significantly decreased through DNA damage and ROS aggregation due to the DM1-based chemotherapy synergistically combined with interventional photothermal therapy (IPTT) and radiotherapy (RT). This domino cascade amplified loop, combined with starvation therapy with IPTT and RT, has good tumor penetration and outstanding antitumor efficacy, and is a promising glioma treatment system. Schematic illustration of a combined interventional therapy strategy for enhancing glioma penetration and CFpAD anti-tumor efficacy through cascade amplification. (A) Preparation of FNCp, FpA, and CFpAD. (B) The blood-brain barrier is temporarily opened with IPTT. (C) Hybrid nanopotentiators reduce interstitial fluid pressure through CAF quiescence and increase the permeability of therapeutic agents. (D) Hybrid nanopotentiators consume glucose to reduce tumor pH, produce oxygen to improve tumor hypoxia, and generate ROS to inhibit tumor proliferation. [Display omitted] • Dual cascade amplified hybrid nanopotentiators are designed for glioma. • Hybrid nanopotentiators can not only enhance the deep penetration of nanoparticle, but also enhance its catalytic ability. • Nanopotentiators have effective antitumor activity. [ABSTRACT FROM AUTHOR]

Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true progression (TP) from pseudoprogression (PsP). This review aims to discuss imaging techniques and liquid biopsies used to distinguish TP from PsP. This review synthesizes existing literature to examine advances in imaging techniques, such as magnetic resonance diffusion imaging (MRDI), perfusion-weighted imaging (PWI) MRI, and liquid biopsies, for identifying TP or PsP through tumor markers and tissue characteristics. Advanced imaging techniques, including MRDI and PWI MRI, have proven effective in delineating tumor tissue properties, offering valuable insights into glioma behavior. Similarly, liquid biopsy has emerged as a potent tool for identifying tumor-derived markers in biofluids, offering a non-invasive glimpse into tumor evolution. Despite their promise, these methodologies grapple with significant challenges. Their sensitivity remains inconsistent, complicating the accurate differentiation between TP and PSP. Furthermore, the absence of standardized protocols across platforms impedes the reliability of comparisons, while inherent biological variability adds complexity to data interpretation. Their potential applications have been highlighted, but gaps remain before routine clinical use. Further research is needed to develop and validate these promising methods for distinguishing TP from PsP in gliomas. [ABSTRACT FROM AUTHOR]

Homozygous deletion (HD) of CDKN2A/B holds important prognostic value in gliomas. This study aimed to explore the predictive potential of conventional MRI characteristics combined with dynamic contrast-enhanced MRI parameters in predicting CDKN2A/B HD status in gliomas. Preoperative MRI data of 105 patients (69 without CDKN2A/B HD, and 36 with CDKN2A/B homozygous deletion) with gliomas were retrospectively collected. Conventional MRI features and dynamic contrast-enhanced-MRI qualitative parameter time-intensity curve type, quantitative parameters Ktrans, K ep , V e , V p , and iAUC were obtained. Logistic regression models for prediction of CDKN2A/B HD status were constructed in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. Multivariate analysis for all patients demonstrated that age (OR = 1.103, p = 0.002) and Ktrans (OR = 1.051, p < 0.001) independently predicted CDKN2A/B HD. In IDH-mutant subgroup, multivariate analysis results indicated that Ktrans (OR = 1.098, p = 0.031) emerged as autonomous predictors of CDKN2A/B HD. In IDH-wild subgroup, age (OR = 1.111, p = 0.002) and Ktrans (OR = 1.032, p = 0.001) were independent predictors of CDKN2A/B HD according to the multivariate analysis. The areas under the receiver operating characteristic curve of the corresponding models were 0.90, 0.95 and 0.84, respectively. Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients. [ABSTRACT FROM AUTHOR]

Diffuse midline glioma (DMG) is a fatal tumor traditionally treated with radiation therapy (RT) and previously characterized as having a noninflammatory tumor immune microenvironment (TIME). FLASH is a novel RT technique using ultra-high dose rate that is associated with decreased toxicity and effective tumor control. However, the effect of FLASH and conventional (CONV) RT on the DMG TIME has not yet been explored. Here, we performed single-cell RNA sequencing (scRNA-seq) and flow cytometry on immune cells isolated from an orthotopic syngeneic murine model of brainstem DMG after the use of FLASH (90 Gy/sec) or CONV (2 Gy/min) dose-rate RT and compared to unirradiated tumor (SHAM). At day 4 post-RT, FLASH exerted similar effects as CONV in the predominant microglial (MG) population, including the presence of two activated subtypes. However, at day 10 post-RT, we observed a significant increase in the type 1 interferon α/β receptor (IFNAR+) in MG in CONV and SHAM compared to FLASH. In the non-resident myeloid clusters of macrophages (MACs) and dendritic cells (DCs), we found increased type 1 interferon (IFN1) pathway enrichment for CONV compared to FLASH and SHAM by scRNA-seq. We observed this trend by flow cytometry at day 4 post-RT in IFNAR+ MACs and DCs, which equalized by day 10 post-RT. DMG control and murine survival were equivalent between RT dose rates. Our work is the first to map CONV and FLASH immune alterations of the DMG TIME with single-cell resolution. Although DMG tumor control and survival were similar between CONV and FLASH, we found that changes in immune compartments differed over time. Importantly, although both RT modalities increased IFN1, we found that the timing of this response was cell-type and dose-rate dependent. These temporal differences, particularly in the context of tumor control, warrant further study. [ABSTRACT FROM AUTHOR]

Diffuse intrinsic pontine gliomas are aggressive tumors that carry a poor prognosis with a 2-year survival rate of <10%. The imaging appearance is often pathognomonic, and surgical biopsy is not mandatory to initiate treatment in children. Studies of biopsy samples provide insight into the disease's molecular pathobiology and open prospects for targeted therapy. This study was conducted to determine the diagnostic yield and safety of stereotactic biopsies. This is a prospective observational study from a single tertiary health care center. All patients with clinical and radiological features diagnostic of diffuse intrinsic pontine gliomas (DIPGs) who underwent biopsy from July 2018 to June 2023 were included. Biopsies were performed using either stereotactic frame-based, frameless, or endoscopic techniques. A total of 165 patients with DIPGs were evaluated in the study period. The option of biopsy with its associated risks and benefits was offered to all patients. A total of 76 biopsies were performed in 74 patients (40 children and 34 adults, including 2 repeat biopsies). The median age was 15 years. Diffuse midline gliomas, H3K27M altered, was the most common histopathological diagnosis (85% pediatric and 55.9% adults). The diagnostic efficacy of the procedure was 94.7%. The complication rate was 10.8%, with no permanent neurological deficits due to surgery. There was no procedure-related mortality. Establishing the safety of the procedure could be an important step toward popularizing the concept, which might offer a better understanding of the disease. Brainstem eloquence and a lack of direct benefit to patients are the primary obstacles to brainstem biopsy. [ABSTRACT FROM AUTHOR]

Despite the growing acceptance of neuronavigation in the field of neurosurgery, there is limited comparative research with contradictory results. This study aimed to compare the effectiveness (tumor resection rate and survival) and safety (frequency of neurological complications) of surgery for brain gliomas with or without neuronavigation. This retrospective cohort study evaluated data obtained from electronic records of patients who underwent surgery for gliomas at Dr. Alejandro Dávila Bolaños Military Hospital and the Clinic Hospital of Barcelona between July 2016 and September 2022. The preoperative and postoperative clinical and radiologic characteristics were analyzed and compared according to the use of neuronavigation. This study included 110 patients, of whom 79 underwent surgery with neuronavigation. Neuronavigation increased gross total resection by 57% in patients in whom it was used; gross total resection was performed in 56% of patients who underwent surgery with neuronavigation as compared with 35.5% in those who underwent surgery without neuronavigation (risk ratio [RR], 1.57; P = 0.056). The incidence of postoperative neurologic deficits (transient and permanent) decreased by 79% with the use of neuronavigation, (12% vs. 33.3%; RR, 0.21; P = 0.0003). Neuronavigation improved survival in patients with grade IV gliomas (15 months vs. 13.8 months), but it was not statistically significant (odds ratio (OR), 0.19; P = 0.13). Neuronavigation improved the effectiveness (greater gross total resection of tumors) and safety (fewer neurological deficits) of brain glioma surgery. However, neuronavigation does not significantly influence the survival of patients with grade IV gliomas. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is a multisystemic autosomal dominant disorder that includes intracranial lesions such as unidentified bright objects (UBOs)—areas of increased T2 signal on magnetic resonance imaging (MRI)—and tumors known as gliomas. The presence of these lesions in the corpus callosum (CC) has not been previously studied in a large cohort. We reviewed medical records of 681 patients (aged three months to 86 years) followed at our institution from 2000 to 2023 with NF1 and one or more brain MRI. Patients with lesions in the CC were identified, and RAPNO/RANO criteria were used to determine changes in size over time, where a change of 25% in the product of perpendicular measurements indicates growth or shrinkage. Forty-seven patients had CC UBOs, most of which were in the splenium (66.0%). Seventeen patients had CC gliomas (10% of those with any glioma), two of whom had two gliomas. Seventeen of 19 gliomas were in the splenium. Over follow-up, eight of 19 remained stable, three shrunk, and eight grew. The mean percentage change in the product of the dimensions was 311.5% (ranging from −46.7% to 2566.6%). Of the eight lesions that grew, one required treatment. There is a 6.9% and 2.5% prevalence of CC UBOs and gliomas, respectively, in our cohort of patients with NF1. Most lesions are present in the splenium, and although some gliomas demonstrate significant growth, they rarely require treatment. This work is the largest series of CC lesions in NF1 and adds to the growing data to inform appropriate follow-up. [ABSTRACT FROM AUTHOR]

To construct an optimal prognostic model to assess the prognosis of patients with diffuse glioma. Preoperative magnetic resonance imaging and clinical data were retrospectively collected from 266 patients (training cohort: validation cohort = 7:3) with pathologically confirmed diffuse gliomas. A radiomics prognostic model (R-model) based on the radiomics features was constructed. A prognostic model based on clinical factors (C-model) and a fusion model (F-model) was also constructed. Based on the optimal model of three models, the nomogram was constructed. Finally, a "Prognosis Calculator for Diffuse Glioma" was constructed based on the nomogram. The c-index of the R-, C-, and F-models in the validation cohort was 0.742, 0.796, and 0.814, respectively. In the validation cohort, the 1-year area under the curve of the R-, C-, and F-models was 0.749, 0.806, and 0.836, respectively; the 3-year area under the curve was 0.896, 0.966, and 0.963, respectively. In the training cohort, validation cohort, all cohorts, and different grades of glioma cohorts, F-model (optimal model) could identify low- and high-risk groups well. The "Prognosis Calculator for Diffuse Glioma" was available at https://github.com/HDCurry/prognosis. Among the three models, the F-model (radiomics combined with clinical factors) had optimal predictive efficacy and could more accurately assess the prognosis of diffuse glioma. The "Prognosis Calculator for Diffuse Glioma" constructed based on this model could assist clinicians in more easily and accurately assessing the prognosis of patients with diffuse glioma, thus enabling them to make more reasonable treatment strategies. [ABSTRACT FROM AUTHOR]

To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients. The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2–3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values. MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR. [Display omitted] [ABSTRACT FROM AUTHOR]

Glioma and meningioma require vastly different surgical approaches, even if only involving a simple craniotomy procedure. Diffusion weighted imaging (DWI) is useful for the postoperative evaluation of ischemic damage. The present study evaluated the expected but unproven differences in DWI findings. A total of 41 patients with meningiomas and 63 with gliomas met the inclusion criteria for adult cases with superficial lesions treated through simple supratentorial craniotomy. Postoperative DWI findings of DWI-positive rate, DWI-positive area type, and relationship with neurological deficits were evaluated. The DWI-positive rate (P = 0.01) and the proportion of rim-type lesions (P < 0.01) were significantly more common in gliomas. Patients with meningiomas and DWI-positive areas presented with higher rates of new neurological deficits (P < 0.01), and patients with meningiomas on the left side were more likely to develop new neurological deficits (P = 0.02). Patients with gliomas tended to develop new deficits with larger DWI-positive area volumes (P = 0.04). Postoperative early DWI-positive rate and rim-type lesions are more common after glioma resection than meningioma resection. Larger volumes of DWI-positive areas may be associated with postoperative neurological symptoms in gliomas. DWI-positive finding is less common after meningioma than glioma resection but more likely to be associated with new neurological symptoms. These differences are important for adequate postoperative DWI evaluation of common supratentorial brain tumors. [ABSTRACT FROM AUTHOR]

High-grade gliomas (HGGs) present a challenge in neuro-oncology, often necessitating surgical resection for optimal management. Ultrasound holds promise in achieving better gross total resection (GTR) and improving outcomes. This meta-analysis systematically evaluates literature providing robust evidence on the use of intraoperative ultrasonography (iUSG) in HGG resection. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines a comprehensive search was made across PubMed, Embase, Cochrane, and Web of Science utilized terms related to iUSG for HGG resection. The meta-analysis examined randomized trials and observational cohort studies on iUSG-guided HGG resection. GTR, subtotal resection, and postresection complications were assessed. Statistical analysis, employing R software for a single proportion analysis with confidence intervals of 95%, I2 statistics for heterogeneity, and the instrumental variables method with restricted maximum likelihood for a random effects model. A total of 178 patients were included in our study. The GTR overall rate in patients with iUSG-guided resection was found to be 64% (95% confidence interval: 46%–81%). Two-dimensional ultrasound remains dominant at 80% against other options of ultrasound. Complications were reported at a 15% rate (95% confidence interval: 7%–23%). Our study provided robust data on the utilization of iUSG-guided resection regarding the attainment of GTR and the complications related to resection. However, challenges such as outcome heterogeneity and limited complication reporting highlight the need for further research to optimize iUSG in HGG treatment. Long-term follow-up studies on patient survival and postsurgery quality of life will complement existing literature, guiding clinical practices in managing HGG. [ABSTRACT FROM AUTHOR]

Analyze the usefulness, efficacy, and safety of transoperative magnetic resonance imaging (tMRI) in glioma surgery in awake patients. Retrospective, single-center, analytical study of a cohort of patients who underwent awake surgery for gliomas by the same surgeon in a third-level Argentine center, in the period between 2012 and 2022. Only patients with pathology-confirmed gliomas, with 6-month follow-up, who had preoperative and postoperative volumetric magnetic resonance imaging, were included in this sample. Subsequently, we analyzed which patients received surgery with the tMRI protocol and the results using multivariate regression analysis. A total of 71 patients were included. A tMRI study was performed on 22 (31%) of these patients. The use of tMRI increased the percentage of resection by 20% (P = 0.03), thereby increasing the possibility of gross total resection. However, using tMRI significantly extended surgical time by 84 minutes (P < 0.001). In 55% of the patients in whom tMRI was performed, the resection was continued after it. The use of tMRI did not increase the rate of infections or the development of surgically associated neurological deficits in the long term, despite the fact that 47% of the patients showed the development of a new deficit or worsening of a previous one during the intraoperative period. The use of tMRI in awake glioma surgery proved to be a safe tool that contributes to increasing the degree of tumor resection, compared to the use of neurophysiological mapping and neuronavigation, at the expense of increased surgical times and costs. We consider tMRI in awake glioma surgery should be used in properly selected cases. [ABSTRACT FROM AUTHOR]

Diffuse midline gliomas (DMGs) encompass a set of tumors, and those tumors with H3K27 M mutation carry a poor prognosis. In recent years, machine learning (ML)-based radiomics have shown promising results in predicting gene mutation status non-invasively. Therefore, this study aims to comprehensively evaluate the diagnostic performance of ML-based magnetic resonance imaging radiomics in predicting H3K27 M mutation status in DMG patients. A systematic search was conducted using relevant keywords in PubMed/Medline, Scopus, Embase, and Web of Science from inception to May 2023. Original studies evaluating the diagnostic performance of ML models in predicting H3K27 M mutation status in DMGs were enrolled. Quality assessment of the enrolled studies was conducted using QUADAS-2. Data were analyzed using STATA version 17.0 to calculate pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic score, and diagnostic odds ratio. A total of 13 studies, including 12 retrospectives and 1 both retrospective and prospective study, enrolled 1510 (male = 777) DMG patients. Six studies underwent meta-analysis which showed a pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic score, and diagnostic odds ratio of 0.91 (95% CI 0.77–0.97), 0.81 (95% CI 0.73–0.88), 4.86 (95% CI 3.25–7.24), 0.11 (95% CI 0.04–0.29), 3.75 (95% CI 2.62–4.88), and 42.61 (95% CI 13.77–131.87), respectively. Non-invasive prediction of H3K27 M mutation status in patients with DMGs using magnetic resonance imaging radiomics is a promising tool with good diagnostic performance. However, the pooled metrics had a wide confidence interval, which required further studies to enhance ML algorithms' accuracy and facilitate their integration into daily clinical practice. [ABSTRACT FROM AUTHOR]

We design a feasibility study to obtain a set of metabolic-hemodynamic habitats for tackling tumor spatial metabolic patterns with hemodynamic information. Preoperative data from 69 high-grade gliomas (HGG) patients with subsequent histologic confirmation of HGG were prospectively collected (January 2016 to March 2020) after concurrent chemoradiotherapy (CCRT). Four vascular habitats were automatically segmented by multiparametric magnetic resonance imaging (MRI). The metabolic information, either at enhancing or edema tumor regions, was obtained by two neuroradiologists. The relative habitat volumes were used for weight estimation procedures for computing the coefficients of a linear regression model using weighted least squares (WLS) for metabolite semiquantifications (i.e. the Cho/NAA ratio and the Cho/Cr ratio) at vascular habitats. Multivariate Cox proportional hazard regression analyses are used to obtain the odds ratio (OR) and develop a nomogram using weighted estimators corresponding to each covariate derived from Cox regression coefficients. There was a strongly correlation between perfusion indexes and the Cho/Cr ratio (rCBV, r =0.71) or Cho/NAA ratio (rCBV, r =0.66) at high-angiogenic enhancing tumor habitats (HAT) habitat. Compared isocitrate dehydrogenase (IDH) mutation to their wild type, the IDH wild type had significantly decreased Cho/Cr ratio (IDH mutation: Cho/Cr ratio = 2.44 ± 0.33, IDH wildtype: Cho/Cr ratio = 2.66 ± 0.36, p =0.02) and Cho/NAA ratio (IDH mutation: Cho/Cr ratio = 4.59 ± 0.61, IDH wildtype: Cho/Cr ratio = 4.99 ± 0.66, p =0.022) at the HAT. The C -index for the median progression-free survival (PFS) prediction was 0.769 for the Cho/NAA nomogram and 0.747 for the Cho/Cr nomogram through 1000 bootstrapping validation. Our findings suggest that spatial metabolism combined with hemodynamic heterogeneity is associated with individual PFS to HGG patients post-CCRT. • Metabolic habitat is a potential method to tackle tumor spatial metabolic pattern. • Metabolic habitat has achieved great evident AUC value for IDH mutation prediction. • Nomograms show that metabolic habitat is a potential tool to predict individual PFS. [ABSTRACT FROM AUTHOR]

Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma - DIPG), is the primary cause of brain tumor-related death in pediatric patients. DIPG is characterized by a median survival of <12 months from diagnosis, harboring the worst 5-year survival rate of any cancer. Corticosteroids and radiation are the mainstay of therapy; however, they only provide transient relief from the devastating neurological symptoms. Numerous therapies have been investigated for DIPG, but the majority have been unsuccessful in demonstrating a survival benefit beyond radiation alone. Although many barriers hinder brain drug delivery in DIPG, one of the most significant challenges is the blood-brain barrier (BBB). Therapeutic compounds must possess specific properties to enable efficient passage across the BBB. In brain cancer, the BBB is referred to as the blood-brain tumor barrier (BBTB), where tumors disrupt the structure and function of the BBB, which may provide opportunities for drug delivery. However, the biological characteristics of the brainstem's BBB/BBTB, both under normal physiological conditions and in response to DIPG, are poorly understood, which further complicates treatment. Better characterization of the changes that occur in the BBB/BBTB of DIPG patients is essential, as this informs future treatment strategies. Many novel drug delivery technologies have been investigated to bypass or disrupt the BBB/BBTB, including convection enhanced delivery, focused ultrasound, nanoparticle-mediated delivery, and intranasal delivery, all of which are yet to be clinically established for the treatment of DIPG. Herein, we review what is known about the BBB/BBTB and discuss the current status, limitations, and advances of conventional and novel treatments to improving brain drug delivery in DIPG. [Display omitted] [ABSTRACT FROM AUTHOR]

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Gliomas exhibit significant molecular diversity and poor prognosis. In this issue of Cancer Cell , Curry et al. apply Patch-seq on human glioma samples uncovering hybrid cells with glial and neuronal features, capable of firing action potentials in isocitrate dehydrogenase mutant gliomas. These findings highlight the importance of neural features in tumor biology and progression. [ABSTRACT FROM AUTHOR]

Gliomas adjacent to the corticospinal tract (CST) should be carefully resected to preserve motor function while achieving maximal surgical resection. Modern high-field intraoperative magnetic resonance imaging (iMRI) enables precise visualization of the residual tumor and intraoperative tractography. We prospectively evaluated the extent of resection and distance between the tumor resection cavity and CST using 3-T iMRI combined with motor evoked potentials (MEP) in glioma surgery. Participants comprised patients who underwent surgery for solitary supratentorial glioma located within 10 mm of the CST. All cases underwent surgery using neuronavigation with overlaid CST under MEP monitoring. The correlation between distance from CST and transcortical MEP amplitude was calculated using Spearman rank correlation. Among the 63 patients who underwent surgery, 27 patients were enrolled in the study. Gross total resections were achieved in 26 of the 27 cases. Volumetric analysis showed the extent of resection was 98.6%. Motor function was stable or improved in 24 patients (Stable/Improved group) and deteriorated in 3 patients (Deteriorated group). All patients in the Deteriorated group showed motor deficit before surgery. Mean intraoperative minimal distance was significantly longer in the Stable/Improved group (7.3 mm) than in the Deteriorated group (1.1 mm; P < 0.05). MEP amplitude correlated with minimal distance between the resection cavity and CST (R = 0.64). Resection of gliomas adjacent to CST with a navigation system using 3-T iMRI could result in an ultimate EOR >98%. The combination of intraoperative tractography and MEP contributes to maximal removal of motor-eloquent gliomas. [ABSTRACT FROM AUTHOR]

This study analyzed the effectiveness and safety of ultra-low dose fluorescein sodium (FL)-guided malignant glioma resection and its potential to predict the pathological characteristics of glioma. Sixty patients who underwent FL-guided glioma resection were randomly divided into test (1 mg/kg) and control (5 mg/kg) groups. A retrospective analysis included 30 patients with gliomas who did not undergo FL-guided surgery; these patients were included as a blank control group. Surgical outcomes, Karnofsky performance scores (KPS), and progression-free survival (PFS) at 6 months postoperatively were compared between the 3 groups. The sensitivity and specificity of FL and the relationship between the intensity of FL and Glial fibrillary acidic protein (GFAP) or Ki-67 expression were compared. The total tumor resection rates in the test, control, and blank control groups were 90% (27/30), 86.7% (26/30), and 60% (18/30), respectively. There were significant differences (P < 0.05) in the extent of resection, KPS, and PFS at 6 months after surgery between the test and control groups and the blank control group; however, no significant differences (P > 0.05) were observed between the test and control groups. The intensity of FL and the Ki67 positivity rate (P < 0.05) were directly proportional, but this relationship was not observed with GFAP. Ultra-low-dose FL-guided resection of malignant gliomas is safe and effective. The Ki67 positivity rate was directly proportional to the intensity of FL, indicating its potential to predict gliomas during pathological examination. [ABSTRACT FROM AUTHOR]

The symbiotic interactions between glioma cells and immune cells are critical for glioma progression and are regulated by epigenetic remodeling. Epigenetic alterations in glioma cells not only affect tumor growth and progression but also regulate the biology (e.g., infiltration and activation) of immune cells (e.g., myeloid cells and T cells) in the tumor microenvironment. Epigenetic reprogramming in immune cells contributes to immunosuppression and tumor progression. Therapeutic targeting epigenetic-regulated tumor-immune symbiosis inhibits tumor progression and improves the antitumor efficiency of immunotherapies in glioma. Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME. [ABSTRACT FROM AUTHOR]

• Cortico-cortical evoked potentials (CCEPs) were obtained in minimally invasive resection for glioma in awake and asleep patients. • Optimal stimulation and recording sites were guided by awake Penfield stimulation and analyzed in real time during surgery. • CCEP features were affected by tumor location and histopathology, and correlated with postoperative aphasia. We investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. We included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. Ninety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. CCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. This study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring. [ABSTRACT FROM AUTHOR]

To enhance the prediction of mutation status of isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter, which are crucial for glioma prognostication and therapeutic decision-making, via sub-regional radiomics analysis based on multiparametric magnetic resonance imaging (MRI). A retrospective study was conducted on 401 participants with adult-type diffuse gliomas. Employing the K-means algorithm, tumours were clustered into two to four subregions. Sub-regional radiomics features were extracted and selected using the Mann–Whitney U -test, Pearson correlation analysis, and least absolute shrinkage and selection operator, forming the basis for predictive models. The performance of model combinations of different sub-regional features and classifiers (including logistic regression, support vector machines, K-nearest neighbour, light gradient boosting machine, and multilayer perceptron) was evaluated using an external test set. The models demonstrated high predictive performance, with area under the receiver operating characteristic curve (AUC) values ranging from 0.918 to 0.994 in the training set for IDH mutation prediction and from 0.758 to 0.939 for TERT promoter mutation prediction. In the external test sets, the two-cluster radiomics features and the logistic regression model yielded the highest prediction for IDH mutation, resulting in an AUC of 0.905. Additionally, the most effective predictive performance with an AUC of 0.803 was achieved using the four-cluster radiomics features and the support vector machine model, specifically for TERT promoter mutation prediction. The present study underscores the potential of sub-regional radiomics analysis in predicting IDH and TERT promoter mutations in glioma patients. These models have the capacity to refine preoperative glioma diagnosis and contribute to personalised therapeutic interventions for patients. • Sub-regional MRI radiomics predicts IDH and TERT mutations in gliomas. • Various model combinations of sub-regional features and classifiers were assessed. • LR and SVM outperformed in predicting IDH and TERT mutations, respectively. • Enhanced models support precision in glioma therapeutic decisions. [ABSTRACT FROM AUTHOR]

To investigate the application of the T2-weighted (T2)-fluid-attenuated inversion recovery (FLAIR) mismatch sign and machine learning-based multiparametric magnetic resonance imaging (MRI) radiomics in predicting 1p/19q non-co-deletion of lower-grade gliomas (LGGs). One hundred and forty-six patients, who had pathologically confirmed isocitrate dehydrogenase (IDH) mutant LGGs were assigned randomly to the training cohort (n= 102) and the testing cohort (n= 44) at a ratio of 7:3. The T2-FLAIR mismatch sign and conventional MRI features were evaluated. Radiomics features extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), FLAIR, apparent diffusion coefficient (ADC), and contrast-enhanced T1WI images (CE-T1WI). The models that displayed the best performance of each sequence were selected, and their predicted values as well as the T2-FLAIR mismatch sign data were collected to establish a final stacking model. Receiver operating characteristic curve (ROC) analyses and area under the curve (AUC) values were applied to evaluate and compare the performance of the models. The T2-FLAIR mismatch sign was more common in the IDH mutant 1p/19q non-co-deleted group (p< 0.05) and the area under the curve (AUC) value was 0.692 with sensitivity 0.397, specificity 0.987, and accuracy 0.712, respectively. The stacking model showed a favourable performance with an AUC of 0.925 and accuracy of 0.882 in the training cohort and an AUC of 0.886 and accuracy of 0.864 in the testing cohort. The stacking model based on multiparametric MRI can serve as a supplementary tool for pathological diagnosis, offering valuable guidance for clinical practice. • Noninvasive detection of 1p/19q non-codeleted is important for the prognosis of LGGs. • T2-FLAIR mismatch is a clinically useful biomarker, however, with low sensitivity. • Multiparametric MRI-based stacking model could improve the diagnostic performance. [ABSTRACT FROM AUTHOR]

Glioma is recognized as the most infiltrative and lethal form of central nervous system tumors and is known for its limited response to standard therapeutic interventions, high recurrence rate, and unfavorable prognosis. Recent progress in gene and immunotherapy presents a renewed sense of optimism in the treatment of glioblastoma. However, the barriers to overcome include the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), as well as the suppressive immune microenvironment. Overcoming these barriers remains a significant challenge. Here, we developed a lipid nanoparticle platform incorporating a dual-functional peptide (cholesterol-DP7-ACP-T7-modified DOTAP or DAT-LNP) capable of targeting glioma across the BBB and BBTB for brain tumor immunotherapy. This system was designed to achieve two key functions. First, the system could effectively penetrate the BBB during accumulation within brain tissue following intravenous administration. Second, this system enhances the maturation of dendritic cells, the polarization of M1 macrophages, and the activation of cytotoxic CD8+ T cells. This multifaceted approach effectively mitigates the immunosuppressive tumor microenvironment of glioma and promotes robust antitumor immune responses. Overall, the intravenous administration of the delivery system designed in this study demonstrates significant therapeutic potential for glioma and holds promising applications in the field of cancer immunotherapy. [Display omitted] • The peptide DAT was designed based on the immunomodulatory transmembrane peptide DP7 and brain tumor targeting T7. • DAT modified siRNA delivery system can overcome the blood-brain barrier and blood-brain tumor barrier. • The DAP-LNP/siRNA delivery system is capable of reshaping the immunosuppressive tumor microenvironment to treat glioma. [ABSTRACT FROM AUTHOR]

Challenges for glioma treatment with nanomedicines include physio-anatomical barriers (the blood-brain barrier and blood-brain tumor barrier), low drug loading capacity, and limited circulation time. Here, a red blood cell membrane-coated docetaxel drug nanocrystal (pV-RBCm-NC(DTX)), modified with pHA-VAP (pV) for all-stage targeting of glioma, was designed. The NC(DTX) core exhibited a high drug loading capacity but low in vivo stability, and the RBCm coating significantly enhanced the stability and prolonged in vivo circulation. Moreover, the Y-shaped targeting ligand pV was modified by a mild avidin-biotin interaction, which endowed RBCm-NC(DTX) with superior barrier-crossing ability and therapeutic efficacy. The integration of nanocrystal technology, cell membrane coating, and the avidin-biotin insertion method into this active targeting biomimetic formulation represents a promising drug delivery strategy for glioma. [Display omitted] [ABSTRACT FROM AUTHOR]

Numerous attempts have been devoted to designing anti-angiogenic agents as a strategy to slow tumor growth and progression. Clinical applications of conventional anti-angiogenic agents face some challenges, e.g., off-target effects for TKIs and also low solid tumor penetration for mAbs. Furthermore, although anti-angiogenic therapy provides a normalization window for better chemo-RT response, in long-term treatments, tumor hypoxia as a result of total removal of VEGF-A by mAbs from the TME or complete blockade of TK receptors induces over-activation of compensatory angiogenic pathways, causing escape. Herein, we investigate the efficacy of si-DOX-DC-EVs to reduce glioma angiogenesis and invasiveness. Mature DCs were generated from PBMC and EVs were isolated from the DCs culture media. siRNA and Doxorubicin were loaded into EVs by EP and incubation. Afterward, the uptake of DC-EVs was assessed by flow cytometry, and the subcellular localization of EVs was tested by confocal imaging. Tube formation assay was performed to assess the efficacy of si-DOX-DC-EVs to reduce tumor angiogenesis which was analyzed by DHM. Morphometric analysis of apoptotic cells was performed by DHM and confocal imaging and further, ELISA was performed for hypoxia-related and angiogenic cytokines. The impact of our theranostic system "si-DOX-DC-MVs" on the formation of vascular mimics, colonies, and invasion of C6 cells was checked in vitro. Afterward, orthotropic rat models of glioma were generated and the optimal administration route was selected by in vivo fluorescent analysis. Then, the microvessel density, vimentin expression, and accumulation of immune cells in tumoral tissues were assessed by IHC. Finally, necropsy and autopsy analyses were performed to check the safety of our theranostic agent. DC-EVs loaded with si-DOX-DC-EVs were successfully uptaken by cells with different subcellular trafficking for MVs and exosomes, reduced tumor angiogenesis in DHM analysis, and induced apoptosis in tumoral cells. Moreover, using DHM, we performed a detailed label-free analysis of tip cells which suggested that the tip cells in si-DC-MV treatments lost their geometrical migration capacity to form tube-like structures. Furthermore, the ELISAs performed highlighted that there is a mild overactivation of compensatory Tie2/Ang2 pathway after VEGF-A blockade which confers with severe hypoxia and sustains normal angiogenesis which is the optimal goal of anti-angiogenesis therapy for cancer to avoid resistance.The results of our VM analyses indicated that si-DOX-DC-MVs completely inhibited VM process. Moreover, the invasion, migration, and colony formation of the C6 cells treated with si-DOX-MVs were the least among all treatments. IN was the optimal route of administration. The MVD analyses indicated that si-DOX-DC-MVs reduced the number of tumoral microvessels and normalized vessel morphology. Intense CD8+ T cells were observed near the tumoral vessels in the si-DOX-DC-MVs group and with minimal activation of MT (low Vimentin expression). Necropsy and toxicology results proved that the theranostic system proposed is safe. DC-EVs loaded with VEGF-A siRNA and Doxorubicin were more potent than BV alone as a multi-disciplinary strategy that combats glioma growth by cytotoxic impacts of DOX and inhibits angiogenesis by VEGF-A siRNAs with excess immunologic benefits from DC-EVs. This next-generation anti-angiogenic agent normalizes tumor vessel density rather than extensively eliminating tumor vessels causing hypoxia and mesenchymal transition. [Display omitted] [ABSTRACT FROM AUTHOR]

Tectal plate gliomas (TPGs) are a heterogeneous group of uncommon brain tumors. TPGs are considered indolent and are usually managed conservatively but they have the potential to transform into higher-grade tumors. The aims of this study were to investigate the natural history of adult TPG, treatment outcomes, and overall survival. A retrospective cohort analysis was performed of adult patients with TPG between 1993 and 2021. Baseline clinical, radiologic, and management characteristics were collected. The primary outcome was tumor progression, defined as increasing size on radiologic assessment or new gadolinium contrast enhancement. Secondary outcomes included management and mortality. Thirty-nine patients were included, of whom 23 (52.2%) were men. Median age at diagnosis was 35 years (interquartile range, 27–53). Radiologic tumor progression was observed in 8 patients (20.5%). The 10-year progression-free survival was 72.6% (95% confidence interval [CI], 0.58–0.91). The 10-year overall survival was 86.5% (95% confidence interval, 0.75–1.0). Cerebrospinal fluid diversion procedures were used in 62% of the cohort (n = 24). Seventeen patients (43.6%) underwent at least 1 endoscopic third ventriculostomy, whereas only 6 patients (15.4%) underwent at least 1 ventriculoperitoneal shunt. TPG has an overall favorable clinical prognosis, although progression occurs in 1 in 5 patients. Showing accurate factors by which patients with TPG may be risk stratified should be a key area of further research. A follow-up duration of 10 years would be a reasonable window based on the radiologic progression rates in this study; however, larger cohort studies are needed to answer both questions definitively. [ABSTRACT FROM AUTHOR]

Protein corona has long been a source of concern, as it might impair the targeting efficacy of targeted drug delivery systems. However, engineered up-regulating the adsorption of certain functional serum proteins could provide nanoparticles with specific targeting drug delivery capacity. Herein, apolipoprotein A-I absorption increased nanoparticles (SPC-PLGA NPs), composed with the Food and Drug Administration approved intravenously injectable soybean phosphatidylcholine (SPC) and poly (DL-lactide- co -glycolide) (PLGA), were fabricated for enhanced glioma targeting. Due to the high affinity of SPC and apolipoprotein A-I, the percentage of apolipoprotein A-I in the protein corona of SPC-PLGA NPs was 2.19-fold higher than that of nanoparticles without SPC, which made SPC-PLGA NPs have superior glioma targeting ability through binding to scavenger receptor class B I on blood-brain barrier and glioma cells both in vitro and in vivo. SPC-PLGA NPs loaded with paclitaxel could effectively reduce glioma invasion and prolong the survival time of glioma-bearing mice. In conclusion, we provided a good example of the direction of achieving targeting drug delivery based on protein corona regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc−) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment. Albumin and lactoferrin hybrid nanoparticles (Alb/LF NP) loaded with DDC/Cu-Fe are developed for glioma therapy by activating anti-tumor immunity and inducing ferroptosis. The Alb/LF NP can efficiently target the glioma, remodel the immune microenvironment, and suppress the GSH/GPX4 system to augment ferroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

• LncRNA COX10-AS1 was significantly increased in glioma. • Inhibition of COX10-AS1 suppressed cell proliferation, migration and invasion in GBM cells. • COX10-AS1 positively regulated OCR6 through spongy miR-1-3p in GBM cells. • COX10-AS1 promoted tumorigenesis of the GBM cells in vivo through modulating the miR-1-3p/ORC6 axis. Glioma is one of the most common and difficult to cure malignant primary tumors of the central nervous system. Long non-coding RNA (lncRNA) has been reported to play important functions in biological processes of many tumors, including glioma. In our study, we aimed to reveal the role and molecular mechanisms of lncRNA COX10-AS1 in regulating the progression of glioma. First of all, we showed that lncRNA COX10-AS1 was significantly increased in glioma tissues and cell lines, and high-expressed COX10-AS1 was associated with a poor prognosis in glioma patients. Moreover, through performing the functional experiments, including CCK-8, colony formation and Transwell assays, we confirmed that COX10-AS1 ablation curbed cell proliferation, migration and invasion in glioblastoma (GBM) cells. In addition, we uncovered that there existed a regulatory relationship that COX10-AS1 upregulated OCR6 by sponging miR-1-3p in GBM cells, and the following rescue assays demonstrated that both miR-1-3p downregulation and origin recognition complex subunit 6 (ORC6) overexpression rescued cell viability, migration and invasion in the COX10-AS1-deficient GBM cells. Consistently, we also verified that COX10-AS1 promoted tumorigenesis of the GBM cells in vivo through modulating the miR-1-3p/ORC6 axis. On the whole, our findings indicated a novel ceRNA pattern in which COX10-AS1 elevated OCR6 expression via sponging miR-1-3p, therefore boosting tumorigenesis in glioma, and we firstly discussed the underlying mechanisms by which the COX10-AS1/miR-1-3p/ORC6 axis affected the progression of glioma. [ABSTRACT FROM AUTHOR]

Ideal research models are urgently needed to explore the mechanisms of glioma invasion along white matter tracts (WMs), which is a determinant for the therapeutic effect of surgery in patients with glioblastoma multiforme (GBM). Various methods with different characteristics, including nanomaterial models and nerve fiber culture models, simulate tumor and nerve interactions. Furthermore, brain slice, cerebral organoid, and microfluidic chip models can be used to simulate the complicated microenvironmental interaction of GBM invasion along WMs. These in vitro models can also be applied to perineural invasion of peripheral solid tumors, peripheral solid tumor-induced axonogenesis, neurogenesis, and neural reprogramming to study the mechanism of brain metastasis of peripheral solid tumors and the relationship between tumors and nerves. White matter tracts (WMs) are one of the main invasion paths of glioblastoma multiforme (GBM). The lack of ideal research models hinders our understanding of the details and mechanisms of GBM invasion along WMs. To date, many potential in vitro models have been reported; nerve fiber culture models and nanomaterial models are biocompatible, and the former have electrically active neurons. Brain slice culture models, organoid models, and microfluidic chip models can simulate the real brain and tumor microenvironment (TME), which contains a variety of cell types. These models are closer to the real in vivo environment and are helpful for further studying not only invasion along WMs by GBM, but also perineural invasion and brain metastasis by solid tumors. [ABSTRACT FROM AUTHOR]

Viruses are critical for the regulation of cancer development and for therapy. Human adenovirus C (HadVC) has been detected in central nervous system and glioma tissue. The objective of the present study was the development of a robust prognostic model based on HadVC infection (HadVCi)-relevant genes. The genome, transcriptome, and virome were systemically analyzed using The Cancer Genome Atlas dataset for training and 2 cohorts from the Chinese Glioma Genome Atlas and an immunotherapy trial cohort with 17 patients receiving anti-PD-1 treatment for validation. HadVCi-relevant gene selection from differentially expressed genes between HadVC-infected and non–HadVC-infected glioma patients using least absolute shrinkage and selection operator regression was followed by Cox regression modeling to establish a prognostic HadVCi score. Kaplan-Meier and receiver operating characteristic curve analyses were performed to estimate the predictive capacity of the HadVCi score. The χ2, Spearman, and Mann-Whitney U tests were used to identify the correlation with the clinicopathological parameters, treatment responsiveness, and immune landscape. Temozolomide-resistant glioma cells were established and analyzed at the transcriptional level using RNA sequencing data. The HadVCi score was (−0.2526673∗TRPC6) + (−0.2244276∗RNF207) + (−0.0894468∗SEC31B) + (−0.0190214∗ZCRB1) + (−0.017122∗DNPH1) + (0.0495818∗CCDC34) + (0.1196349∗PURG) + (0.1778997∗LILRA5). The score possesses a strong ability to predict overall survival. Further analysis revealed a higher HadVCi score correlated with a malignant phenotype and poorer treatment responsiveness to temozolomide-based chemotherapy and combined therapies. Additionally, transcriptomic analysis showed malignancy-, stemness-, and radioresistant-related gene activation in the HadVCi group, which characterized the poor outcomes and limited sensitivity to standard therapy. The HadVCi score could be an effective tool for survival prediction and treatment guidance for patients with glioma. [ABSTRACT FROM AUTHOR]

Gliomas are the commonest malignant central nervous system tumours in adults and imaging is the cornerstone of diagnosis, treatment, and post-treatment follow-up of these patients. With the ever-evolving treatment strategies post-treatment imaging and interpretation in glioma remains challenging, more so with the advent of anti-angiogenic drugs and immunotherapy, which can significantly alter the appearance in this setting, thus making interpretation of routine imaging findings such as contrast enhancement, oedema, and mass effect difficult to interpret. This review details the various methods of management of glioma including the upcoming novel therapies and their impact on imaging findings, with a comprehensive description of the imaging findings in conventional and advanced imaging techniques. A systematic appraisal for the existing and emerging techniques of imaging in these settings and their clinical application including various response assessment guidelines and artificial intelligence based response assessment will also be discussed. • Post treatment imaging of glioma remains a challenging area for radiologists. • Multiparametric MRI is occasionally needed as a problem-solving tool. • Response assessment criteria are available to help standardize interpretation. • AI has shown promising results in assessing treatment response in glioblastoma. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of synthetic magnetic resonance imaging (MRI) in distinguishing high-grade gliomas (HGGs) from solitary brain metastases (SBMs) in peritumoural oedema. Thirty-five patients with HGGs and 25 patients with SBMs were recruited and scanned using synthetic MRI using a 3 T scanner. Two radiologists measured synthetic MRI-derived relaxation values independently (T1, T2, proton density [PD]) in the peritumoural oedema, which was used to generate quantitative metrics before (T1 native , T2 native , and PD native) and after (T1 post , T2 post , and PD post) contrast agent injection. Student's t -test or the Mann–Whitney U -test was performed to detect statistically significant differences in the aforementioned metrics in peritumoural oedema between HGGs and SBMs. The receiver operating characteristic (ROC) curves were plotted to evaluate the efficacy of each metric in distinguishing the two groups, and the areas under the curves (AUCs) were compared pairwise by performing the Delong test. The mean T1 native , T2 native , and T1 post values in the peritumoural oedema of HGGs were significantly lower compared with SBMs (all p< 0.05). The T1 post value had a higher AUC (0.843) in differentiating HGGs and SBMs than all other individual metrics (all p< 0.05). The combined T1 native , T2 native , and T1 post model had the best distinguishing performance with an AUC, sensitivity, and specificity of 0.987, 94.3%, and 100%, respectively. Synthetic MRI may be a potential supplement to the preoperative diagnosis of HGGs and SBMs in clinical practice, as the synthetic MRI-derived tri-parametric model in the peritumoural oedema showed significantly improved diagnostic performance in distinguishing HGGs from SBMs. • Synthetic MRI can detect the difference between HGGs and SBMs in peritumoral edema. • T 1post value showed superior distinguishing performance than other single metrics. • Combine model (T 1pre + T 2pre + T 1post) can further improve the diagnostic efficiency. [ABSTRACT FROM AUTHOR]

Glioma stem cell/glioma-initiating cell (GIC) and their niches are considered responsible for the therapeutic resistance and recurrence of malignant glioma. To clarify the molecular mechanisms of GIC maintenance/differentiation, we performed a unique integrated proteogenomics utilizing GIC clones established from patient tumors having the potential to develop glioblastoma. After the integration and extraction of the transcriptomics/proteomics data, we found that chondroitin sulfate proteoglycan 4 (CSPG4) and its glycobiosynthetic enzymes were significantly upregulated in GICs. Glyco-quantitative PCR array revealed that chondroitin sulfate (CS) biosynthetic enzymes, such as xylosyltransferase 1 (XYLT1) and carbohydrate sulfotransferase 11, were significantly downregulated during serum-induced GIC differentiation. Simultaneously, the CS modification on CSPG4 was characteristically decreased during the differentiation and also downregulated by XYLT1 knockdown. Notably, the CS degradation on CSPG4 by ChondroitinaseABC treatment dramatically induced GIC differentiation, which was significantly inhibited by the addition of CS. GIC growth and differentiation ability were significantly suppressed by CSPG4 knockdown, suggesting that CS-CSPG4 is an important factor in GIC maintenance/differentiation. To understand the molecular function of CS-CSPG4, we analyzed its associating proteins in GICs and found that CSPG4, but not CS-CSPG4, interacts with integrin aV during GIC differentiation. This event sequentially upregulates integrin-extracellular signal-regulated kinase signaling, which can be inhibited by cyclic-RGD (Arg-Gly-Asp) integrin aV inhibitor. These results indicate that CS-CSPG4 regulates the GIC microenvironment for GIC maintenance/differentiation via the CS moiety, which controls integrin signaling. This study demonstrates a novel function of CS on CSPG4 as a niche factor, so-called "glyco-niche" for GICs, and suggests that CS-CSPG4 could be a potential target for malignant glioma. [ABSTRACT FROM AUTHOR]

Studies from the UK reporting on awake craniotomy (AC) include a heterogenous group of patients which limit the evaluation of the true impact of AC in high-grade glioma (HGG) patients. This study aims to report solely the experience and outcomes of AC for HGG surgery from our centre. A prospective review of all patients who underwent AC for HGG from 2013 to 2019 were performed. Data on patient characteristics including but not limited to demographics, pre- and post-operative Karnofsky performance status (KPS), tumour location and volume, type of surgery, extent of resection (EOR), tumour histopathology, intra- and post-operative complications, morbidity, mortality, disease recurrence, progression-free survival (PFS) and overall survival (OS) from the time of surgery were collected. Fifteen patients (6 males; 9 females; 17 surgeries) underwent AC for HGG (median age = 55 years). Two patients underwent repeat surgeries due to disease recurrence. Median pre- and post-operative KPS score was 90 (range:80–100) and 90 (range:60–100), respectively. The EOR ranges from 60 to 100 % with a minimum of 80 % achieved in 81.3 % cases. Post-operative complications include focal seizures (17.6 %), transient aphasia/dysphasia (17.6 %), permanent motor deficit (11.8 %), transient motor deficit (5.9 %) and transient sensory disturbance (5.9 %). There were no surgery-related mortality or post-operative infection. The median PFS and OS were 13 (95%CI 5–78) and 30 (95%CI 21–78) months, respectively. This is the first study in the UK to solely report outcomes of AC for HGG surgery. Our data demonstrates that AC for HGG in eloquent region is safe, feasible and provides comparable outcomes to those reported in the literature. • Our high-grade glioma (HGG) service enables awake craniotomy (AC) for patients. • This is the first study in the UK to report outcomes of AC for HGG surgery alone. • Our experience in AC for HGG is comparable to those reported in the literature. [ABSTRACT FROM AUTHOR]

Intraoperative ultrasound (IOUS) images can be distorted by various artifacts. During surgeries for insular low-grade gliomas (LGGs), we repeatedly observed a distinct hyperechoic artifact adjacent to medial tumor borders, localized in brain regions with normal appearance on magnetic resonance imaging (MRI) that has not been reported before. We retrospectively evaluated saved 3-dimensional (3D) IOUS images of 20 patients harboring insular LGGs. Twelve patients were operated on between 2010 and 2015 using an older navigated 3D IOUS system. Additionally, 3D-IOUS images of 8 patients operated on between 2021 and 2023 using a new high-end 3D-IOUS system were evaluated. The investigated region was the area under medial tumor borders, which were defined using preoperative MRI. In 17 out of 20 cases (85%), a distinct hyperechoic area adjacent to medial tumor borders localized in brain regions with normal appearance on preoperative MRI was found; in the remaining 3 cases the saved images were suboptimal and did not allow evaluation of the area under the medial tumor borders. Although the causes of this bright artifact are unclear, we can hypothesize that the reverberation in between different parallel layers of white and gray matter localized under the insula could play a role in its appearance. Importantly, as this hyperechoic area was depicted already before any tumor resection, it may lead to erroneous conclusion that the tumor spreads more medially. Potential resection in this region may cause significant neurologic sequelae. [ABSTRACT FROM AUTHOR]