Objective: The aim of the study was to assess whether children and adolescents with epilepsy are at higher risk of behavioral disturbances when they have concomitant cognitive disturbances.Methods: Behavioral scores were generated using the Child Behavior Checklist (CBCL). Cognitive evaluation was applied by using different age appropriate versions of the Wechsler Intelligence Scale. CBCL scores (total, externalizing, internalizing) were compared between patients with and without intellectual disability (IQ score < 70 and ≥70, respectively).Results: 144 (10.2 mean age, 6.0–17.9 range) patients were recruited for the study. Patients with mild to moderate intellectual disability (full‐scale intelligence quotient (FSIQ) < 70) were not at higher risk of behavioral disturbances (total CBCL score ≥ 63) than patients without cognitive impairment. The mean total CBCL score was 62.0 ± 10.6 (range 42.0–83.5, 95% CI 57.9–62.0) and 59.3 ± 10.3 (range 38.0–80.0, CI 57.4–61.2) for patients with FSIQ < 70 and ≥70, respectively. There was no correlation between FSIQ and total CBCL scores. These findings were true for all IQ subcategories.Significance: Behavioral disturbances among children and adolescents with epilepsy occur despite the presence or absence of intellectual dysfunction with respect to full‐scale IQ.

Hypoxia-powered blood oxygen level-dependent (BOLD) MRI probes the BOLD response to a controlled transient hypoxic stimulus. We developed GLIODISSECT, an operational voxel-wise framework that separates relative response arrival, descending and recovery transitions, and threshold-defined steady state amplitude. Twenty healthy controls underwent 3-T BOLD MRI during a double hypoxic-step challenge, and three patients with newly diagnosed glioblastoma were included as proof-of-concept cases. Full-record cross-correlation and first-step 10% landmarks yielded one refined voxel-wise lag that was reused downstream. Alternative 5%/95% and 20%/80% thresholds preserved steady state map patterns (median within-subject spatial r 0.9987-0.9998), while timing measures were more threshold-dependent. Numerical criteria were satisfied in 97.789% and 97.682% of evaluable delay-to-plateau (DTP) estimates and in all evaluable delay-to-return (DTR) estimates. Leave-one-subject-out validation of the global-response-adjusted steady state model yielded a median voxel-wise Q ² of 0.345 and reduced pooled prediction error by 16.0%, improving 19 of 20 controls. In the three illustrative cases, component and deviation maps displayed spatially heterogeneous timing and steady state patterns that could not be represented by one response-amplitude summary. GLIODISSECT supports component-specific mapping and voxel-wise normative interpretation. Biological and clinical validation remain required.

Glioma imaging remains constrained by the limited ability of conventional MRI to capture biologically relevant tumor features beyond blood–brain barrier disruption. Hypoxia-modulated blood oxygen level-dependent (BOLD) MRI has emerged as a potential contrast-agent-free approach to probe oxygenation-related tumor physiology, using deoxyhemoglobin as an endogenous susceptibility contrast mechanism. By altering blood oxygenation during acquisition, the technique generates signal changes that may provide physiological information beyond structural imaging and resting perfusion measures. We performed a narrative review of 29 human and animal studies using hypoxic oxygen challenges during BOLD MRI. Substantial heterogeneity was identified in gas delivery, carbon dioxide control, MRI acquisition and analytical approaches. A recurring methodological issue was carbon dioxide control, since carbon dioxide is the dominant vasoactive stimulus and hypoxia-induced hyperventilation with secondary hypocapnia can confound BOLD signal interpretation. Preclinical brain tumor studies suggest sensitivity to spatial heterogeneity between viable and necrotic tumor regions. Early human glioblastoma studies support the feasibility and tolerability of hypoxia-modulated BOLD acquisitions and show spatially heterogeneous signal- and perfusion-related maps without exogenous contrast. Current evidence supports hypoxia-modulated BOLD MRI as a promising translational imaging approach, but clinical data remain limited and prospective validation in glioblastoma cohorts is required.

Purpose: Hypoxia-targeted blood oxygen level–dependent (BOLD) MRI is an emerging non-contrast imaging technique for characterizing tumor biology in isocitrate dehydrogenase-wildtype glioblastoma. Beyond the magnitude of BOLD signal changes, signal heterogeneity may provide valuable information about tumor aggressiveness and microenvironmental complexity. The aim was to assess both the magnitude and heterogeneity of hypoxia-targeted BOLD signal changes across subregions of glioblastomas. Methods: In this prospective pilot study, hypoxia-targeted BOLD MRI data from 12 patients with histopathologically confirmed glioblastoma were analyzed. Tumor subregions were defined using an automated segmentation framework (Oncohabitats) based on conventional MRI and dynamic susceptibility contrast (DSC) MR perfusion imaging. Voxel-wise BOLD signal changes were calculated within the following volumes of interest: highly angiogenic tumor (HAT), low angiogenic tumor (LAT), peritumoral edema, and mirrored contralateral control tissue (mCET). The magnitude of BOLD signal changes was assessed using median BOLD signal changes, while heterogeneity was quantified using interquartile ranges (IQR), and kernel density estimation-derived entropy. Friedman tests with Dunn post-hoc tests were used to assess parameter differences between the VOIs. Results: HAT demonstrated the largest BOLD signal changes compared with LAT, edema, and mCET (all FDR-adjusted p ≤ 0.017). Heterogeneity metrics revealed significantly increased IQR and entropy in HAT compared with edema and mCET (all FDR-adjusted p < 0.008), with LAT showing intermediate values. Conclusion: Hypoxia-targeted BOLD MRI reveals both greater BOLD signal changes and elevated intratumoral heterogeneity in highly angiogenic and likely aggressive glioblastoma subregions. These findings suggest that heterogeneity metrics may provide complementary information to BOLD signal magnitude alone.

Background: Diffuse cerebral gliomas are among the most common malignant brain tumors in adults. Blood oxygen level-dependent (BOLD)–MRI has been widely investigated for assessing functional, vascular, and metabolic alterations in this patient population. However, a comprehensive overview of its biological underpinnings, clinical applications, and emerging translational approaches is lacking. Methods: In the present study we conducted a narrative review on the role of BOLD–MRI in diffuse glioma imaging, from historical and clinical applications to recent translational studies including approaches to detect vascular and metabolic alterations as well as its expanding potential to enhance tumor infiltration assessment and treatment surveillance. Results: Task-based and resting-state BOLD–MRI enable localization of eloquent cortical areas and assessment of functional reorganization, though their accuracy is challenged by neurovascular uncoupling and patient-related variability. Combination with vasoactive stimuli allows cerebrovascular reactivity mapping to uncover vascular dysfunction propagating beyond visible tumor margins, correlating with tumor grade and hemodynamic impairment. Quantitative and calibrated BOLD approaches as well as oxygen modulation during BOLD sequence acquisition provide noninvasive biomarkers of tissue hypoxia, oxygen metabolism, and tumor aggressiveness. Conclusions: Despite extensive research, BOLD contrast holds unexploited potential for enhancing glioma diagnosis and management by capturing critical vascular and metabolic alterations. Although challenges remain pertaining to accuracy and standardization, emerging techniques offer substantial potential for the assessment of tumor infiltration extent and therapy surveillance. Advancing clinical integration will require robust standardization, large-scale validation, and correlation with clinical, molecular, and histopathological data.

Purpose: To assess the feasibility of using hypoxia-powered magnetic resonance imaging (MRI) to guide prospective sampling of high-response habitats beyond contrast enhancement in glioblastoma. Methods: Nine treatment-naive patients with histologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma underwent blood oxygenation level-dependent (BOLD) MRI during a controlled transient hypoxic stimulus on the evening before surgery. Anatomical segmentation and voxel-wise temporal decomposition generated normalized hypoxia response maps. Otsu thresholding defined a high-response habitat outside contrast enhancement. Targets were confirmed with the surgeon according to anatomical accessibility and eloquence, transferred to neuronavigation, and sampled before major debulking. We divided the specimen for formalin-fixed, paraffin-embedded neuropathology and frozen-tissue storage. Results: Neuronavigation transfer succeeded in all nine cases. Eight targets were accessible and sampled. Seven sampled targets contained tumor. One yielded reactive cortex and white matter without definite tumor. No target-sampling complications were observed among the eight sampled procedures. Conclusion: Hypoxia-powered MRI could be integrated into prospective neuronavigation-guided sampling beyond contrast enhancement. Tumor was identified in seven of eight sampled targets. By translating a tracer-free physiological response map into coordinate-matched tissue, the GLIOXY workflow enables prospective, targeted tissue sampling of non-enhancing glioblastoma regions.