Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Predictors of cognition after glioma surgery: connectotomy, structure-function phenotype, plasticity.

Determining preoperatively the maximal extent of resection that would preserve cognitive functions is the core challenge of brain tumour surgery. Over the past decade, the methodological framework to achieve this goal has been thoroughly renewed: the population-level topographically-focused voxel-based lesion-symptom mapping has been progressively overshadowed by machine learning (ML) algorithmics, in which the problem is framed as predicting cognitive outcomes in a patient-specific manner from a typically large set of variables. However, the choice of these predictors is of utmost importance, as they should be both informative and parsimonious. In this perspective, we first introduce the concept of connectotomy: instead of parameterizing resection topography through the status (intact/resected) of a huge number of voxels (or parcels) paving the whole brain in the Cartesian 3D-space, the connectotomy models the resection in the connectivity space, by computing a handful number of networks disconnection indices, measuring how the structural connectivity sustaining each network of interest was hit by the resection. This connectivity-informed reduction of dimensionality is a necessary step for efficiently implementing ML tools, given the relatively small number of patient-examples in available training datasets. We further argue that two other major sources of interindividual variability must be considered to improve the accuracy with which outcomes are predicted: the underlying structure-function phenotype and neuroplasticity, for which we provide an in-depth review and propose new ways of determining relevant predictors. We finally discuss the benefits of our approach for precision surgery of glioma.

Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas.

Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomofunctional architecture. This propensity is particularly exemplified by diffuse low-grade glioma, a subtype of primary brain tumour. However, functional plasticity is not boundless, and surgical resections directed at structures with limited neuroplasticity can lead to incapacitating impairments. Yet, maximizing diffuse low-grade glioma resections offers substantial oncological benefits, especially when the resection extends beyond the tumour margins (i.e. supra-tumour or supratotal resection). In this context, the primary objective of this study was to identify which cerebral structures were associated with less favourable cognitive outcomes after surgery, while accounting for intra-tumour and supra-tumour features of the surgical resections. To achieve this objective, we leveraged a unique cohort of 400 patients with diffuse low-grade glioma who underwent surgery with awake cognitive mapping. Patients benefitted from a neuropsychological assessment consisting of 18 subtests administered before and 3 months after surgery. We analysed changes in performance and applied topography-focused and disconnection-focused multivariate lesion-symptom mapping using support vector regressions, in an attempt to capture resected cortico-subcortical structures less amenable to full cognitive compensation. The observed changes in performance were of a limited magnitude, suggesting an overall recovery (13 of 18 tasks recovered fully despite a mean resection extent of 92.4%). Nevertheless, lesion-symptom mapping analyses revealed that a lack of recovery in picture naming was linked to damage in the left inferior temporal gyrus and inferior longitudinal fasciculus. Likewise, for semantic fluency abilities, an association was established with damage to the left precuneus/posterior cingulate. For phonological fluency abilities, the left dorsomedial frontal cortex and the frontal aslant tract were implicated. Moreover, difficulties in spatial exploration were associated with injury to the right dorsomedial prefrontal cortex and its underlying connectivity. An exploratory analysis suggested that supra-tumour resections were associated with a less pronounced recovery following specific resection patterns, such as supra-tumour resections of the left uncinate fasciculus (picture naming), the left corticostriatal tract and the anterior corpus callosum (phonological fluency), the hippocampus and parahippocampus (episodic memory) and the right frontal-mesial areas (visuospatial exploration). Collectively, these patterns of results shed new light on both low-resilient neural systems and the prediction of cognitive recovery following glioma surgery. Furthermore, they indicate that supra-tumour resections were only occasionally less well tolerated from a cognitive viewpoint. In doing so, they have deep implications for surgical planning and rehabilitation strategies.

Cortical resting motor threshold difference in asleep-awake craniotomy for motor eloquent gliomas: WHO grading influences motor pathway excitability.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal-Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

The oncological role of resection in newly diagnosed diffuse adult-type glioma defined by the WHO 2021 classification: a Review by the RANO resect group.

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.

Visualization of Brain Tumors with Infrared-Labeled Aptamers for Fluorescence-Guided Surgery.

Gliomas remain challenging brain tumors to treat due to their infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful resection. This study introduces an innovative intraoperative visualization method utilizing surgical fluorescence microscopy to precisely locate tumor cell dissemination. Here, the focus is on the development of a novel contrasting agent (IR-Glint) for intraoperative visualization of human glial tumors comprising infrared-labeled Glint aptamers. The specificity of IR-Glint is assessed using flow cytometry and microscopy on primary cell cultures. In vivo effectiveness is studied on mouse and rabbit models, employing orthotopic xenotransplantation of human brain gliomas with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. The experiments validate the potential of IR-Glint for the intraoperative visualization of gliomas using infrared imaging. IR-Glint penetrates the blood-brain barrier and can be used for both intravenous and surface applications, allowing clear visualization of the tumor. The surface application directly to the brain reduces the dosage required and mitigates potential toxic effects on the patient. The research shows the potential of infrared dye-labeled aptamers for accurately visualizing glial tumors during brain surgery. This novel aptamer-assisted fluorescence-guided surgery (AptaFGS) may pave the way for future advancements in the field of neurosurgery.

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Efficacy and indications of gamma knife radiosurgery for recurrent low-and high-grade glioma.

PURPOSE: To investigate the indications and efficacy of gamma knife radiosurgery (GKRS) as a salvage treatment for recurrent low-and high-grade glioma. METHODS: This retrospective study of 107 patients with recurrent glioma treated with GKRS between 2009 and 2022, including 68 high-grade glioma (HGG) and 39 low-grade glioma (LGG) cases. The Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). The log-rank test was used to analyze the multivariate prognosis of the Cox proportional hazards model. Adverse reactions were evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. The prognostic value of main clinical features was estimated, including histopathology, Karnofsky performance status (KPS), recurrence time interval, target location, two or more GKRS, surgery for recurrence, site of recurrence, left or right side of the brain and so on. RESULTS: The median follow-up time was 74.5 months. The median OS and PFS were 17.0 months and 5.5 months for all patients. The median OS and PFS were 11.0 months and 5.0 months for HGG, respectively. The median OS and PFS were 49.0 months and 12.0 months for LGG, respectively. Multivariate analysis showed that two or more GKRS, left or right side of the brain and brainstem significantly affected PFS. Meanwhile, the KPS index, two or more GKRS, pathological grade, and brainstem significantly affected OS. Stratified analysis showed that surgery for recurrence significantly affected OS and PFS for LGG. KPS significantly affected OS and PFS for HGG. No serious adverse events were noted post-GKRS. CONCLUSION: GKRS is a safe and effective salvage treatment for recurrent glioma. Moreover, it can be applied after multiple recurrences with tolerable adverse effects.

Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Motor seizures confer overall survival benefit in who grade 2 glioma.

OBJECTIVE: The prevalence of epilepsy in World Health Organization (WHO) grade 2 glioma is high, with seizures being the presenting symptom in 60%-90%. We explore the epidemiology of seizures in this patient population in a regional neurosurgical center. METHODS: Electronic health records of patients with histologically-proven WHO grade 2 glioma (n = 228) were reviewed between 1997 and 2021, with data collected including patient demographics, epilepsy prevalence, and seizure semiology. The influence of seizure type on overall survival was calculated using a Cox proportional hazards model. RESULTS: Overall, 197 of 228 patients (86.4%) were diagnosed with epilepsy-either at presentation or during the course of their disease. Male patients were more likely than female patients to be diagnosed with epilepsy (91.1% vs 77.1%, p = .003) and, in those with epilepsy, more likely to experience at least one focal to bilateral tonic-clonic seizure (69.4% vs 54.1%, p = .05). Patients with left-sided tumors were twice as likely to have experienced a focal to bilateral tonic-clonic seizure (p = .02, odds ratio [OR] = .47). Predominantly experiencing seizures with motor activity appeared to confer better overall survival, with a 65% decrease in the risk of death 10 years post diagnosis (hazard ratio [HR] = .35, p = .02). This is despite accounting for previously described prognostic markers including tumor histology/genetics, time from diagnosis to surgery, and the extent of tumor resection. SIGNIFICANCE: Motor seizure activity is a frequent feature in WHO grade 2 glioma and appears to confer a survival benefit regardless of histology or surgical factors. Seizures due to dominant hemisphere tumors may be more likely to propagate and cause bilateral tonic-clonic activity.

Laser interstitial thermal therapy for deep-seated perivascular brain tumors is not associated with distal ischemia.

PURPOSE: Laser interstitial thermal therapy (LITT) is a minimally invasive cytoreductive treatment option for brain tumors with a risk of vascular injury from catheter placement or thermal energy. This may be of concern with deep-seated tumors that have surrounding end-artery perforators and critical microvasculature. The purpose of this study was to assess the risk of distal ischemia following LITT for deep-seated perivascular brain tumors. METHODS: A retrospective review of a multi-institution database was used to identify patients who underwent LITT between 2013 and 2022 for tumors located within the insula, thalamus, basal ganglia, and anterior perforated substance. Demographic, clinical and volumetric tumor characteristics were collected. The primary outcome was radiographic evidence of distal ischemia on post-ablation magnetic resonance imaging (MRI). RESULTS: 61 LITT ablations for deep-seated perivascular brain tumors were performed. Of the tumors treated, 24 (39%) were low-grade gliomas, 32 (52%) were high-grade gliomas, and 5 (8%) were metastatic. The principal location included 31 (51%) insular, 14 (23%) thalamic, 13 (21%) basal ganglia, and 3 (5%) anterior perforated substance tumors. The average tumor size was 19.6 cm3 with a mean ablation volume of 11.1 cm3. The median extent of ablation was 92% (IQR 30%, 100%). Two patients developed symptomatic intracerebral hemorrhage after LITT. No patient had radiographic evidence of distal ischemia on post-operative diffusion weighted imaging. CONCLUSION: We demonstrate that LITT for deep-seated perivascular brain tumors has minimal ischemic risks and is a feasible cytoreductive treatment option for otherwise difficult to access intracranial tumors.

Repeat surgery of recurrent glioma for molecularly informed treatment in the age of precision oncology: A risk-benefit analysis.

PURPOSE: Surgery for recurrent glioma provides cytoreduction and tissue for molecularly informed treatment. With mostly heavily pretreated patients involved, it is unclear whether the benefits of repeat surgery outweigh its potential risks. METHODS: Patients receiving surgery for recurrent glioma WHO grade 2-4 with the goal of tissue sampling for targeted therapies were analyzed retrospectively. Complication rates (surgical, neurological) were compared to our institutional glioma surgery cohort. Tissue molecular diagnostic yield, targeted therapies and post-surgical survival rates were analyzed. RESULTS: Between 2017 and 2022, tumor board recommendation for targeted therapy through molecular diagnostics was made for 180 patients. Of these, 70 patients (38%) underwent repeat surgery. IDH-wildtype glioblastoma was diagnosed in 48 patients (69%), followed by IDH-mutant astrocytoma (n = 13; 19%) and oligodendroglioma (n = 9; 13%). Gross total resection (GTR) was achieved in 50 patients (71%). Tissue was processed for next-generation sequencing in 64 cases (91%), and for DNA methylation analysis in 58 cases (83%), while immunohistochemistry for mTOR phosphorylation was performed in 24 cases (34%). Targeted therapy was recommended in 35 (50%) and commenced in 21 (30%) cases. Postoperatively, 7 patients (11%) required revision surgery, compared to 7% (p = 0.519) and 6% (p = 0.359) of our reference cohorts of patients undergoing first and second craniotomy, respectively. Non-resolving neurological deterioration was documented in 6 cases (10% vs. 8%, p = 0.612, after first and 4%, p = 0.519, after second craniotomy). Median survival after repeat surgery was 399 days in all patients and 348 days in GBM patients after repeat GTR. CONCLUSION: Surgery for recurrent glioma provides relevant molecular diagnostic information with a direct consequence for targeted therapy under a reasonable risk of postoperative complications. With satisfactory postoperative survival it can therefore complement a multi-modal glioma therapy approach.

Predicting post-surgical functional status in high-grade glioma with resting state fMRI and machine learning.

PURPOSE: High-grade glioma (HGG) is the most common and deadly malignant glioma of the central nervous system. The current standard of care includes surgical resection of the tumor, which can lead to functional and cognitive deficits. The aim of this study is to develop models capable of predicting functional outcomes in HGG patients before surgery, facilitating improved disease management and informed patient care. METHODS: Adult HGG patients (N = 102) from the neurosurgery brain tumor service at Washington University Medical Center were retrospectively recruited. All patients completed structural neuroimaging and resting state functional MRI prior to surgery. Demographics, measures of resting state network connectivity (FC), tumor location, and tumor volume were used to train a random forest classifier to predict functional outcomes based on Karnofsky Performance Status (KPS < 70, KPS ≥ 70). RESULTS: The models achieved a nested cross-validation accuracy of 94.1% and an AUC of 0.97 in classifying KPS. The strongest predictors identified by the model included FC between somatomotor, visual, auditory, and reward networks. Based on location, the relation of the tumor to dorsal attention, cingulo-opercular, and basal ganglia networks were strong predictors of KPS. Age was also a strong predictor. However, tumor volume was only a moderate predictor. CONCLUSION: The current work demonstrates the ability of machine learning to classify postoperative functional outcomes in HGG patients prior to surgery accurately. Our results suggest that both FC and the tumor's location in relation to specific networks can serve as reliable predictors of functional outcomes, leading to personalized therapeutic approaches tailored to individual patients.

Intraoperative magnetic resonance imaging in glioma surgery: a single-center experience.

PURPOSE: To investigate the effect of intraoperative magnetic resonance imaging (Io MRI) on overall and progression-free survival (OS and PFS), on the extent of resection (EOR) in patients with glioma, and impact of the radiological diagnosis on the decision to continue the surgery when a residual mass was detected on Io MRI. METHODS: The study comprised 153 glioma patients who received surgical treatment between 2013 and 2023. One-hundred twenty-five of them had Io MRI guidance during surgery. The remainder 28 patients constituted the control group who did not undergo Io MRI. All patients' age at surgery, gender, initial radiological diagnosis, primary tumor localization, EOR, last histopathological diagnosis, and the follow-up periods were recorded. RESULTS: The rate of tumor recurrence in Io MRI cases was significantly lower compared to the cases in the control group (p < .0001). It was decided to continue the operation in 45 Io MRI applied cases. This raised the gross total resection (GTR) rate from 33.6% to 49.6% in the Io MRI group. The frequency of GTR was significantly higher in patients with an initial radiological diagnosis of low grade glioma than those with high grade glioma. The shortest OS was seen in occipital gliomas. CONCLUSION: In this study, the convenience provided by the high-field MRI device was explored and proven both in reducing the tumor burden, increasing the PFS, and providing the surgeon with a maximal resection in the first operation.

Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Histopathological correlation of brain tumor recurrence vs. radiation effect post-radiosurgery as detected by MRI contrast clearance analysis: a validation study.

PURPOSE: The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression (TRP) is a major decision-making point in the follow-up of patients with brain tumors. The advent of immunotherapy, targeted therapy and radiosurgery has made this distinction difficult to achieve in several clinical situations. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas. METHODS: This is a series of 7 patients, treated between 2018 and 2023, for various brain pathologies including brain metastasis, atypical meningioma, and high-grade glioma. MRI with contrast clearance analysis was used to inform clinical decisions and patients underwent surgical resection as indicated. The histopathology findings were compared with the CCA findings in all cases. RESULTS: All seven patients had been treated with gamma knife radiosurgery and were followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from radiation necrosis arose, and subsequently underwent surgery as indicated. Concordance of CCA findings with histological findings was found in all cases (100%). CONCLUSIONS: Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology across a wide spectrum of brain tumor pathologies. CCA can provide a quick diagnosis and have a direct impact on patients' treatment and outcomes.

Non-navigated 2D intraoperative ultrasound: An unsophisticated surgical tool to achieve high standards of care in glioma surgery.

PURPOSE: In an era characterized by rapid progression in neurosurgical technologies, traditional tools such as the non-navigated two-dimensional intraoperative ultrasound (nn-2D-IOUS) risk being overshadowed. Against this backdrop, this study endeavors to provide a comprehensive assessment of the clinical efficacy and surgical relevance of nn-2D-IOUS, specifically in the context of glioma resections. METHODS: This retrospective study undertaken at a single center evaluated 99 consecutive, non-selected patients diagnosed with both high-grade and low-grade gliomas. The primary objective was to assess the proficiency of nn-2D-IOUS in generating satisfactory image quality, identifying residual tumor tissue, and its influence on the extent of resection. To validate these results, early postoperative MRI data served as the reference standard. RESULTS: The nn-2D-IOUS exhibited a high level of effectiveness, successfully generating good quality images in 79% of the patients evaluated. With a sensitivity rate of 68% and a perfect specificity of 100%, nn-2D-IOUS unequivocally demonstrated its utility in intraoperative residual tumor detection. Notably, when total tumor removal was the surgical objective, a resection exceeding 95% of the initial tumor volume was achieved in 86% of patients. Additionally, patients in whom residual tumor was not detected by nn-2D-IOUS, the mean volume of undetected tumor tissue was remarkably minimal, averaging at 0.29 cm3. CONCLUSION: Our study supports nn-2D-IOUS's invaluable role in glioma surgery. The results highlight the utility of traditional technologies for enhanced surgical outcomes, even when compared to advanced alternatives. This is particularly relevant for resource-constrained settings and emphasizes optimizing existing tools for efficient patient care. NCT05873946 - 24/05/2023 - Retrospectively registered.

Preoperative vascular heterogeneity based on dynamic susceptibility contrast MRI in predicting spatial pattern of locally recurrent high-grade gliomas.

OBJECTIVES: To investigate if spatial recurrence pattern is associated with patient prognosis, and whether MRI vascular habitats can predict spatial pattern. METHODS: In this retrospective study, 69 patients with locally recurrent high-grade gliomas (HGGs) were included. The cohort was divided into intra-resection cavity recurrence (ICR) and extra-resection cavity recurrence (ECR) patterns, according to the distance between the location of the recurrent tumor and the resection cavity or surgical region. Four vascular habitats, high angiogenic tumor, low angiogenic tumor, infiltrated peripheral edema, and vasogenic peripheral edema, were segmented and vascular heterogeneity parameters were analyzed. The survival and diagnostic performance under different spatial recurrence patterns were analyzed by Kaplan-Meier and ROC. A nomogram model was constructed by regression analysis and validated by bootstrapping technique. RESULTS: Progression-free survival (PFS) and overall survival (OS) were longer for ICR (n = 32) than those for ECR (n = 37) (median PFS: 8 vs. 5 months, median OS: 17 vs. 13 months, p < 0.05). MRI vascular habitat analyses showed ECR had higher median relative cerebral blood volume (rCBVmedian) at each habitat than ICR (all p < 0.01). The rCBVmedian at IPE had good diagnostic performance (AUC: 0.727, 95%CI: 0.607, 0.828). The AUC of the nomogram based on MRI vascular habitats and clinical factors was 0.834 (95%CI: 0.726, 0.913) and was confirmed as 0.833 (95%CI: 0.830, 0.836) by bootstrapping validation. CONCLUSIONS: The spatial pattern of locally recurrent HGGs is associated with prognosis. MRI vascular heterogeneity parameter could be used as a non-invasive imaging marker to predict spatial recurrence pattern. CLINICAL RELEVANCE STATEMENT: Vascular heterogeneity parameters based on MRI vascular habitat analyses can non-invasively predict the spatial patterns of locally recurrent high-grade gliomas, providing a new diagnostic basis for clinicians to develop the extent of surgical resection and postoperative radiotherapy planning. KEY POINTS: • Intra-resection cavity pattern was associated with longer progression-free survival and overall survival in locally recurrent high-grade gliomas. • Higher vascular heterogeneities in extra-resection cavity recurrence than in intra-resection cavity recurrence and the vascular heterogeneity parameters had good diagnostic performance in discriminating spatial recurrence pattern. • A nomogram model based on MRI vascular habitats and clinical factors had good performance in predicting spatial recurrence pattern.

Structural connectome combining DTI features predicts postoperative language decline and its recovery in glioma patients.

OBJECTIVES: A decline in language function is a common complication after glioma surgery, affecting patients' quality of life and survival. This study predicts the postoperative decline in language function and whether it can be recovered based on the preoperative white matter structural network. MATERIALS AND METHODS: Eighty-one right-handed patients with glioma involving the left hemisphere were retrospectively included. Their language function was assessed using the Western Aphasia Battery before and 1 week and 3 months after surgery. Structural connectome combining DTI features was selected to predict postoperative language decline and recovery. Nested cross-validation was used to optimize the models, evaluate the prediction performance of the models, and identify the most predictive features. RESULTS: Five, seven, and seven features were finally selected as the predictive features in each model and used to establish predictive models for postoperative language decline (1 week after surgery), long-term language decline (3 months after surgery), and language recovery, respectively. The overall accuracy of the three models in nested cross-validation and overall area under the receiver operating characteristic curve were 0.840, 0.790, and 0.867, and 0.841, 0.778, and 0.901, respectively. CONCLUSION: We used machine learning algorithms to establish models to predict whether the language function of glioma patients will decline after surgery and whether postoperative language deficit can recover, which may help improve the development of treatment strategies. The difference in features in the non-language decline or the language recovery group may reflect the structural basis for the protection and compensation of language function in gliomas. CLINICAL RELEVANCE STATEMENT: Models can predict the postoperative language decline and whether it can recover in glioma patients, possibly improving the development of treatment strategies. The difference in selected features may reflect the structural basis for the protection and compensation of language function. KEY POINTS: • Structural connectome combining diffusion tensor imaging features predicted glioma patients' language decline after surgery. • Structural connectome combining diffusion tensor imaging features predicted language recovery of glioma patients with postoperative language disorder. • Diffusion tensor imaging and connectome features related to language function changes imply plastic brain regions and connections.

Rethinking extent of resection of contrast-enhancing and non-enhancing tumor: different survival impacts on adult-type diffuse gliomas in 2021 World Health Organization classification.

OBJECTIVES: Extent of resection (EOR) of contrast-enhancing (CE) and non-enhancing (NE) tumors may have different impacts on survival according to types of adult-type diffuse gliomas in the molecular era. This study aimed to evaluate the impact of EOR of CE and NE tumors in glioma according to the 2021 World Health Organization classification. METHODS: This retrospective study included 1193 adult-type diffuse glioma patients diagnosed between 2001 and 2021 (183 oligodendroglioma, 211 isocitrate dehydrogenase [IDH]-mutant astrocytoma, and 799 IDH-wildtype glioblastoma patients) from a single institution. Patients had complete information on IDH mutation, 1p/19q codeletion, and O6-methylguanine-methyltransferase (MGMT) status. Cox survival analyses were performed within each glioma type to assess predictors of overall survival, including clinical, imaging data, histological grade, MGMT status, adjuvant treatment, and EOR of CE and NE tumors. Subgroup analyses were performed in patients with CE tumor. RESULTS: Among 1193 patients, 935 (78.4%) patients had CE tumors. In entire oligodendrogliomas, gross total resection (GTR) of NE tumor was not associated with survival (HR = 0.56, p = 0.223). In 86 (47.0%) oligodendroglioma patients with CE tumor, GTR of CE tumor was the only independent predictor of survival (HR = 0.16, p = 0.004) in multivariable analysis. GTR of CE and NE tumors was independently associated with better survival in IDH-mutant astrocytoma and IDH-wildtype glioblastoma (all ps < 0.05). CONCLUSIONS: GTR of both CE and NE tumors may significantly improve survival within IDH-mutant astrocytomas and IDH-wildtype glioblastomas. In oligodendrogliomas, the EOR of CE tumor may be crucial in survival; aggressive GTR of NE tumor may be unnecessary, whereas GTR of the CE tumor is recommended. CLINICAL RELEVANCE STATEMENT: Surgical strategies on contrast-enhancing (CE) and non-enhancing (NE) tumors should be reassessed considering the different survival outcomes after gross total resection depending on CE and NE tumors in the 2021 World Health Organization classification of adult-type diffuse gliomas. KEY POINTS: The survival impact of extent of resection of contrast-enhancing (CE) and non-enhancing (NE) tumors was evaluated in adult-type diffuse gliomas. Gross total resection of both CE and NE tumors may improve survival in isocitrate dehydrogenase (IDH)-mutant astrocytomas and IDH-wildtype glioblastomas, while only gross total resection of the CE tumor improves survival in oligodendrogliomas. Surgical strategies should be reconsidered according to types in adult-type diffuse gliomas.