Long-term autonomy, professional activities, cognition, and overall survival after awake functional-based surgery in patients with IDH-mutant grade 2 gliomas: a retrospective cohort study.

Background: In isocitrate dehydrogenase (IDH)-mutant low-grade gliomas (LGGs), awake functional-based resection (i.e., resection based on intraoperative functional responses rather than anatomical margins) has emerged as an efficient method to reduce tumour volume (TV) while minimizing postoperative deficits. Here, our goal was to assess the long-term onco-functional outcomes after awake functional-based resection in IDH-mutant LGGs, in conjunction with clinico-radiological and molecular factors. Methods: We retrospectively studied a consecutive cohort (June 1997-January 2023) of 949 patients. Six hundred patients with IDH-mutant LGGs benefited from an awake functional-based resection with a median follow-up of 7.8 years (95% Confidence interval [CI]: 7.1-8.4 years). The main outcomes were the overall survival (OS), the OS with Karnofsky performance status ≥80% (OSKPS ≥ 80%), cognition measures, and professional activities at 12 months post-surgery. Findings: 600 patients were included in the cohort (274 female [46.0%], median age: 36 years [Interquartile range, IQR: 30-44 years]). The rate of return to work was 93.7%. The impact of surgery on cognition was of limited magnitude. The median postsurgical TV of 2.5 mL (IQR: 0-8.0 mL). The median OS was over 20 years (median: NA, 95% CI: 17.0-NA years). The median OSKPS ≥ 80% was 14.7 years (95% CI: 13.2-17.2 years). Factors associated with longer OS and OSKPS ≥ P80% were 1p19q codeletion (Hazard ratio [HR]OS: 0.27, 95% CI: 0.16-0.43, HRKPS ≥ 80%:0.25, 95% CI: 0.17-0.36), supratotal resection (HROS: 0.08, 95% CI: 0.005-0.40, HRKPS ≥ 80%:0.12, 95% CI: 0.03-0.34) and total resection (HROS: 0.31, 95% CI: 0.16-0.59, HRKPS ≥ 80%:0.21, 95% CI: 0.12-0.36). Recursive partitioning analyses established three OS and OSKPS ≥ 80% prognostic groups, highlighting the contributions of histomolecular status, extent of resection, postsurgical and presurgical TV. Further propensity-matching analyses confirmed the oncological benefits of supratotal resections. Interpretation: Awake functional-based resection surgery in newly diagnosed IDH-mutant grade 2 LGG, was an effective strategy associated with long survival (median OS over 20 years) and long-term preservation of autonomy. More complete tumor resections favored better onco-functional outcomes across all molecularly-defined subtypes. Short-term effects were of limited magnitude regarding postoperative cognitive and professional outcomes. Supratotal functional-based resections offered additional survival benefits. Funding: None.

Functional and oncological outcomes following more than three consecutive surgical resections for multiple relapses of initially grade 2 IDH-mutated gliomas.

BACKGROUND: Second and third surgeries were demonstrated as safe and efficient in recurrent diffuse low-grade glioma (LGG). Here, the feasibility of more than 3 resections is investigated. METHODS: Patients who underwent 4 or 5 operations for recurrent initially WHO grade 2 IDH-mutated gliomas were consecutively selected. RESULTS: Twenty-three operations were performed in five patients (all males, mean age 27.2 ± 4 years). Three patients underwent 5 surgeries and two patients underwent 4 surgeries. Twelve procedures (52%) were achieved with awake mapping, including all 4th and 5th operations but one. Repeat electrical mapping detected changes of the cortical maps between at least two awake surgeries in 4 patients. No patients experienced permanent neurological impairment (KPS score ≥ 80 in all cases). The patients returned to work after 22 surgeries among 23 (95.6%). There were 3 oligodendrogliomas and 2 astrocytomas (4 gliomas became malignant at fourth or fifth operation). Although the preoperative tumor volume significantly increased before the fourth (p = 0.026) and fifth operation (p = 0.003) compared with the first operation, there was no significant difference between the residual tumor volume after the fourth or fifth resection versus the first one. The mean delay was 10.6 ± 3.9 years before chemotherapy and 15.4 ± 3.4 years before radiotherapy (one patient never received adjuvant treatment after 21.5 years). The mean follow-up duration was 18.3 ± 3.1 years since the first surgery (2.3 ± 1.8 years since the last surgery). Three patients were still alive at last follow-up. CONCLUSIONS: This is the first series showing that to reoperate beyond three times is feasible with a low functional risk and a long survival in multiple LGG recurrences, with the use of awake mapping in 87.5% of 4th and 5th surgeries.

Recursive partitioning analysis for survival stratification and early imaging prediction of molecular biomarker in glioma patients.

BACKGROUND: Glioma is the most common primary brain tumor with high mortality and disability rates. Recent studies have highlighted the significant prognostic consequences of subtyping molecular pathological markers using tumor samples, such as IDH, 1p/19q, and TERT. However, the relative importance of individual markers or marker combinations in affecting patient survival remains unclear. Moreover, the high cost and reliance on postoperative tumor samples hinder the widespread use of these molecular markers in clinical practice, particularly during the preoperative period. We aim to identify the most prominent molecular biomarker combination that affects patient survival and develop a preoperative MRI-based predictive model and clinical scoring system for this combination. METHODS: A cohort dataset of 2,879 patients was compiled for survival risk stratification. In a subset of 238 patients, recursive partitioning analysis (RPA) was applied to create a survival subgroup framework based on molecular markers. We then collected MRI data and applied Visually Accessible Rembrandt Images (VASARI) features to construct predictive models and clinical scoring systems. RESULTS: The RPA delineated four survival groups primarily defined by the status of IDH and TERT mutations. Predictive models incorporating VASARI features and clinical data achieved AUC values of 0.85 for IDH and 0.82 for TERT mutations. Nomogram-based scoring systems were also formulated to facilitate clinical application. CONCLUSIONS: The combination of IDH-TERT mutation status alone can identify the most distinct survival differences in glioma patients. The predictive model based on preoperative MRI features, supported by clinical assessments, offers a reliable method for early molecular mutation prediction and constitutes a valuable scoring tool for clinicians in guiding treatment strategies.

Diffuse low-grade glioma: What is the optimal linear measure to assess tumor growth?

Background: Radiological follow-up of diffuse low-grade gliomas (LGGs) growth is challenging. Approximative visual assessment still predominates over objective quantification due to the complexity of the pathology. The infiltrating character, diffuse borders and presence of surgical cavities demand LGG-based linear measurement rules to efficiently and precisely assess LGG evolution over time. Methods: We compared optimized 1D, 2D, and 3D linear measurements with manual volume segmentation as a reference to assess LGG tumor growth in 36 patients with LGG (340 magnetic resonance imaging scans), using the clinically important mean tumor diameter (MTD) and the velocity diameter expansion (VDE). LGG-specific progression thresholds were established using the high-grade gliomas-based RECIST, Macdonald, and RANO criteria, comparing the sensitivity to identify progression/non-progression for each linear method compared to the ground truth established by the manual segmentation. Results: 3D linear volume approximation correlated strongly with manually segmented volume. It also showed the highest sensitivity for progression detection. The MTD showed a comparable result, whereas the VDE highlighted that caution is warranted in the case of small tumors with multiple residues. Novel LGG-specific progression thresholds, or the critical change in estimated tumor volume, were increased for the 3D (from 40% to 52%) and 2D methods (from 25% to 33%) and decreased for the 1D method (from 20% to 16%). Using the 3D method allowed a ~5-minute time gain. Conclusions: While manual volumetric assessment remains the gold standard for calculating growth rate, the 3D linear method is the best time-efficient standardized alternative for radiological evaluation of LGGs in routine use.

Longitudinal assessment of quality of life, neurocognition, and psychopathology in patients with low-grade glioma on first-line temozolomide: A feasibility study.

Background: The treatment timing and choice after neurosurgical resection in patients with newly diagnosed diffuse low-grade glioma (DLGG) remain controversial. Indeed, the effect of such treatments must be balanced with the possible side effects. This study evaluated the feasibility of longitudinal exhaustive quality of life (QoL) and neuropsychological assessments in patients with DLGG receiving first-line temozolomide. Methods: QoL, neurocognition, and psychological disorders were assessed prospectively until disease progression, using testing, clinician-reported, and self-reported questionnaires. The primary endpoint was the participation and adherence to this complete assessment at Baseline (before temozolomide initiation), months 6 and 12 of treatment, and month 6 post-treatment. The QoL and neuropsychological changes over time also were described. Results: Twenty-six of the twenty-nine eligible patients were enrolled (participation rate: 89.7%, 95% CI: 72.6-97.8). The adherence rate was 95.7% (95% CI: 78.1-99.9; n = 23 because 3 patients progressed in the first 12 months of treatment). Up to month 6 post-treatment, QoL and fatigue remained stable (EORTC QLQC30 and BN20, MFI-20); some specific symptoms were transitory. Both subjective (FACT-Cog) and objective (Z-scores of neurocognitive tests) neurocognitive outcomes remained stable or tended to improve. The percentage of patients with severe depression (BDI-II), anxiety (STAI-Y), or anger (STAXI-II) was stable over time. Conclusions: This prospective study demonstrated the feasibility of an exhaustive and longitudinal evaluation of QoL, neurocognition, and psychological disorders, with high acceptability by patients with DLGG undergoing chemotherapy. First-line temozolomide seems to have limited short-term effects on QoL and neurocognition. These findings must be confirmed in the long term and in a larger cohort.

Challenges and Opportunities in Awake Craniotomy for Brain Tumor Surgery in Low- and Lower-Middle-Income Countries: A Narrative Review and Perspective.

BACKGROUND: Low-income countries (LICs) and lower-middle-income countries (LMICs) are presented with unique challenges and opportunities when performing awake craniotomy (AC) for brain tumors. These circumstances arise from factors that are financial, infrastructural, educational, personnel, and sociocultural in nature. METHODS: We performed a systematic narrative review of series on AC for intra-axial brain tumors in LICs/LMICs using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, focusing on the challenges and opportunities in these settings. The PubMed, Scopus, and Web of Science databases were searched. RESULTS: After initially identifying 74 studies, inclusion-exclusion criteria were applied, leaving a total of 14 studies included in the review. These involved 409 patients who underwent AC in LICs/LMICs. These series were from India, Ghana, Nigeria, Iran, Pakistan, Morocco, the Philippines, and Egypt. The most common pathology encountered were gliomas (10-70%). Most studies (11/14, 78.5%) reported on their technique of cortical-subcortical mapping. All reported on motor mapping and 8 of these performed language mapping. The most common outcomes reported were seizure and neurologic deficits, and longest follow-up was at 1 year. Challenges noted were lack of equipment and trained personnel, need for validated tests for the local setting, and sociocultural factors. Opportunities identified were volume for training, technique innovation, and international collaboration. CONCLUSIONS: There are numerous challenges and opportunities that arise when performing AC in LICs/LMICs. A collaborative approach toward harnessing the opportunities, and seeking creative solutions to address the challenges, would provide an ideal mechanism toward advancing neurosurgical care and specialty worldwide.

Case report: when art is faced with brain surgery: acute change in creative style in a painter after glioma resection.

Background: Strong interactions between art and health are well-known. While advances in brain surgery resulted in an improved preservation of sensorimotor, visuospatial, language and cognitive functions, creative abilities received less attention. However, creativity may represent a critical issue to resume an optimal quality of life, especially in artists. Here, a unique case of sudden change in creative style in a painter who underwent glioma resection is described. This prompts to explore further creative thinking and its clinical implications in routine practice. Methods: A 36-year-old right-handed woman experienced inaugural seizures, allowing the discovery of a right frontal lesion. The patient was a professional painter and did not complain about any decline in her creativity. The preoperative neurological examination was normal. Results: Surgery was achieved with a maximal tumor resection through a frontal lobectomy. A WHO grade II oligodendroglioma was diagnosed. A regular surveillance was performed without adjuvant oncological treatment. The patient did not exhibit postoperative functional deterioration and she returned to normal activities including painting during 15 years. Remarkably, even though her creative activity was judged by the patient herself to be rich and satisfying, her style drastically changed from surrealism and mysticism to cubism whereas she was not able to explain why. Conclusion: This is the first report of acute modification of the painting style following frontal lobectomy for a low-grade glioma, supporting that brain resective surgery may impact creativity. While neglected for many decades, this complex human ability should be evaluated more regularly in neurosurgical practice, particularly in artists.

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.

Functional and oncological outcomes after right hemisphere glioma resection in awake versus asleep patients: a systematic review and meta-analysis.

The right hemisphere has been underestimated by being considered as the non-dominant hemisphere. However, it is involved in many functions, including movement, language, cognition, and emotion. Therefore, because lesions on this side are usually not resected under awake mapping, there is a risk of unfavorable neurological outcomes. The goal of this study is to compare the functional and oncological outcomes of awake surgery (AwS) versus surgery under general anesthesia (GA) in supratentorial right-sided gliomas. A systematic review of the literature according to PRISMA guidelines was performed up to March 2023. Four databases were screened. Primary outcome to assess was return to work (RTW). Secondary outcomes included the rate of postoperative neurological deficit, postoperative Karnofsky Performance Status (KPS) score and the extent of resection (EOR). A total of 32 articles were included with 543 patients who underwent right hemisphere tumor resection under awake surgery and 294 under general anesthesia. There were no significant differences between groups regarding age, gender, handedness, perioperative KPS, tumor location or preoperative seizures. Preoperative and long-term postoperative neurological deficits were statistically lower after AwS (p = 0.03 and p < 0.01, respectively), even though no difference was found regarding early postoperative course (p = 0.32). A subsequent analysis regarding type of postoperative impairment was performed. Severe postoperative language deficits were not different (p = 0.74), but there were fewer long-term mild motor and high-order cognitive deficits (p < 0.05) in AwS group. A higher rate of RTW (p < 0.05) was documented after AwS. The EOR was similar in both groups. Glioma resection of the right hemisphere under awake mapping is a safer procedure with a better preservation of high-order cognitive functions and a higher rate of RTW than resection under general anesthesia, despite similar EOR.

The Alcatraz-Strategy: a roadmap to break the connectivity barrier in malignant brain tumours.

In recent years, the discovery of functional and communicative cellular tumour networks has led to a new understanding of malignant primary brain tumours. In this review, the authors shed light on the diverse nature of cell-to-cell connections in brain tumours and propose an innovative treatment approach to address the detrimental connectivity of these networks. The proposed therapeutic outlook revolves around three main strategies: (a) supramarginal resection removing a substantial portion of the communicating tumour cell front far beyond the gadolinium-enhancing tumour mass, (b) morphological isolation at the single cell level disrupting structural cell-to-cell contacts facilitated by elongated cellular membrane protrusions known as tumour microtubes (TMs), and (c) functional isolation at the single cell level blocking TM-mediated intercellular cytosolic exchange and inhibiting neuronal excitatory input into the malignant network. We draw an analogy between the proposed therapeutic outlook and the Alcatraz Federal Penitentiary, where inmates faced an impassable sea barrier and experienced both spatial and functional isolation within individual cells. Based on current translational efforts and ongoing clinical trials, we propose the Alcatraz-Strategy as a promising framework to tackle the harmful effects of cellular brain tumour networks.

Is intraoperative mapping of music performance mandatory to preserve skills in professional musicians? Awake surgery for lower-grade glioma conducted from a meta-networking perspective.

OBJECTIVE: In surgery for lower-grade glioma (LGG) in professional musicians, for whom preserving music ability is essential, a critical question has emerged, namely, is it mandatory to include music performance during awake mapping, as proposed in several reports? In fact, music ability is subserved by a mosaic of interactive cognitive and emotional processes that rest on several networks. Therefore, from a meta-network perspective, the authors investigated whether an integrated multimodal monitoring of these cognitive and emotional functions during stimulation mapping could be efficient in maintaining musical skill. Indeed, it could be difficult for a patient to play a musical instrument in the surgical setting in addition to performing other tasks, such as movement and language. METHODS: An awake mapping-guided resection for LGG without intraoperative music performance was performed in 3 professional musicians. Intraoperative tests were tailored to each patient depending on the critical corticosubcortical circuits surrounding the tumor, including not only sensorimotor or language skills but also higher-order functions with a constant multitasking during the resection. RESULTS: Although music skills were not mapped during surgery, all patients resumed their professional activities, preserving the ability to play music and to perform concerts, to teach and to compose music, or to start learning a new instrument. CONCLUSIONS: A connectome-based resection without intraoperative music performance seems effective in achieving maximal glioma removal while preserving crucial networks subserving musical skills, creativity, and music learning. Neurosurgery should evolve toward a meta-networking approach to better understand higher-order functions mediating complex behavior, such as being a professional musician.

Multimodal study of multilevel pulvino-temporal connections: a new piece in the puzzle of lexical retrieval networks.

Advanced methods of imaging and mapping the healthy and lesioned brain have allowed for the identification of the cortical nodes and white matter tracts supporting the dual neurofunctional organization of language networks in a dorsal phonological and a ventral semantic stream. Much less understood are the anatomical correlates of the interaction between the two streams; one hypothesis being that of a subcortically mediated interaction, through crossed cortico-striato-thalamo-cortical and cortico-thalamo-cortical loops. In this regard, the pulvinar is the thalamic subdivision that has most regularly appeared as implicated in the processing of lexical retrieval. However, descriptions of its connections with temporal (language) areas remain scarce. Here we assess this pulvino-temporal connectivity using a combination of state-of-the-art techniques: white matter stimulation in awake surgery and postoperative diffusion MRI (n = 4), virtual dissection from the Human Connectome Project 3 and 7 T datasets (n = 172) and operative microscope-assisted post-mortem fibre dissection (n = 12). We demonstrate the presence of four fundamental fibre contingents: (i) the anterior component (Arnold's bundle proper) initially described by Arnold in the 19th century and destined to the anterior temporal lobe; (ii) the optic radiations-like component, which leaves the pulvinar accompanying the optical radiations and reaches the posterior basal temporal cortices; (iii) the lateral component, which crosses the temporal stem orthogonally and reaches the middle temporal gyrus; and (iv) the auditory radiations-like component, which leaves the pulvinar accompanying the auditory radiations to the superomedial aspect of the temporal operculum, just posteriorly to Heschl's gyrus. Each of those components might correspond to a different level of information processing involved in the lexical retrieval process of picture naming.

Integrating direct electrical brain stimulation with the human connectome.

Neurological and neurodevelopmental conditions are a major public health concern for which new therapies are urgently needed. The development of effective therapies relies on the precise mapping of the neural substrates causally involved in behaviour generation. Direct electrical stimulation (DES) performed during cognitive and neurological monitoring in awake surgery is currently considered the gold standard for the causal mapping of brain functions. However, DES is limited by the focal nature of the stimulation sites, hampering a real holistic exploration of human brain functions at the network level. We used 4137 DES points derived from 612 glioma patients in combination with human connectome data-resting-state functional MRI, n = 1000 and diffusion weighted imaging, n = 284-to provide a multimodal description of the causal macroscale functional networks subtending 12 distinct behavioural domains. To probe the validity of our procedure, we (i) compared the network topographies of healthy and clinical populations; (ii) tested the predictive capacity of DES-derived networks; (iii) quantified the coupling between structural and functional connectivity; and (iv) built a multivariate model able to quantify single subject deviations from a normative population. Lastly, we probed the translational potential of DES-derived functional networks by testing their specificity and sensitivity in identifying critical neuromodulation targets and neural substrates associated with postoperative language deficits. The combination of DES and human connectome data resulted in an average 29.4-fold increase in whole brain coverage compared to DES alone. DES-derived functional networks are predictive of future stimulation points (97.8% accuracy) and strongly supported by the anatomical connectivity of subcortical stimulations. We did not observe any significant topographical differences between the patients and the healthy population at both group and single subject level. Showcasing concrete clinical applications, we found that DES-derived functional networks overlap with effective neuromodulation targets across several functional domains, show a high degree of specificity when tested with the intracranial stimulation points of a different stimulation technique and can be used effectively to characterize postoperative behavioural deficits. The integration of DES with the human connectome fundamentally advances the quality of the functional mapping provided by DES or functional imaging alone. DES-derived functional networks can reliably predict future stimulation points, have a strong correspondence with the underlying white matter and can be used for patient specific functional mapping. Possible applications range from psychiatry and neurology to neuropsychology, neurosurgery and neurorehabilitation.

Disruption of the left anterior ventrolateral temporal cortex along with the inferior longitudinal fasciculus impairs the ability to retrieve famous face names: Evidence from three longitudinal case studies.

The cortical distribution of the proper name (PN) retrieval network has been widely studied contrary to its connectional anatomy. Here, we report the case of three patients with a low-grade glioma damaging the mid-to-anterior part of the left temporal lobe. A longitudinal behavioural assessment showed that the surgery caused a long-lasting decline in PN retrieval performances in all patients. Furthermore, a detailed analysis of surgery-related structural disconnections revealed that interruption of the inferior longitudinal fasciculus was the unique common denominator.

Evaluation of a nnU-Net type automated clinical volumetric tumor segmentation tool for diffuse low-grade glioma follow-up.

BACKGROUND AND PURPOSE: Diffuse low-grade gliomas (DLGG) are characterized by a slow and continuous growth and always evolve towards an aggressive grade. Accurate prediction of the malignant transformation is essential as it requires immediate therapeutic intervention. One of its most precise predictors is the velocity of diameter expansion (VDE). Currently, the VDE is estimated either by linear measurements or by manual delineation of the DLGG on T2 FLAIR acquisitions. However, because of the DLGG's infiltrative nature and its blurred contours, manual measures are challenging and variable, even for experts. Therefore we propose an automated segmentation algorithm using a 2D nnU-Net, to 1) gain time and 2) standardize VDE assessment. MATERIALS AND METHODS: The 2D nnU-Net was trained on 318 acquisitions (T2 FLAIR & 3DT1 longitudinal follow-up of 30 patients, including pre- & post-surgery acquisitions, different scanners, vendors, imaging parameters…). Automated vs. manual segmentation performance was evaluated on 167 acquisitions, and its clinical interest was validated by quantifying the amount of manual correction required after automated segmentation of 98 novel acquisitions. RESULTS: Automated segmentation showed a good performance with a mean Dice Similarity Coefficient (DSC) of 0.82±0.13 with manual segmentation and a substantial concordance between VDE calculations. Major manual corrections (i.e., DSC<0.7) were necessary only in 3/98 cases and 81% of the cases had a DSC>0.9. CONCLUSION: The proposed automated segmentation algorithm can successfully segment DLGG on highly variable MRI data. Although manual corrections are sometimes necessary, it provides a reliable, standardized and time-winning support for VDE extraction to asses DLGG growth.

Identification of Metabolomic Markers in Frozen or Formalin-Fixed and Paraffin-Embedded Samples of Diffuse Glioma from Adults.

The aim of this study was to identify metabolomic signatures associated with the gliomagenesis pathway (IDH-mutant or IDH-wt) and tumor grade of diffuse gliomas (DGs) according to the 2021 WHO classification on frozen samples and to evaluate the diagnostic performances of these signatures in tumor samples that are formalin-fixed and paraffin-embedded (FFPE). An untargeted metabolomic study was performed using liquid chromatography/mass spectrometry on a cohort of 213 DG samples. Logistic regression with LASSO penalization was used on the frozen samples to build classification models in order to identify IDH-mutant vs. IDH-wildtype DG and high-grade vs low-grade DG samples. 2-Hydroxyglutarate (2HG) was a metabolite of interest to predict IDH mutational status and aminoadipic acid (AAA) and guanidinoacetic acid (GAA) were significantly associated with grade. The diagnostic performances of the models were 82.6% AUC, 70.6% sensitivity and 80.4% specificity for 2HG to predict IDH status and 84.7% AUC, 78.1% sensitivity and 73.4% specificity for AAA and GAA to predict grade from FFPE samples. Thus, this study showed that AAA and GAA are two novel metabolites of interest in DG and that metabolomic data can be useful in the classification of DG, both in frozen and FFPE samples.