Purpose: To develop and explore a novel measure - termed cross-shell-consistency (CSC) - calculated from multishell diffusion tensor imaging (DTI) data for quantification of the stability of tensor estimates across multiple b-values and to provide proof of concept in brain tumor patients to evaluate whether CSC can potentially differentiate tumor infiltration from peritumoral vasogenic edema.Methods: The diffusion tensor was fitted to each diffusion shell of a multishell DTI sequence with multiple b values ranging from 0 to 2500 s/mm2 (0, 500, 1000, 1500, 2000, 2500). The Frobenius norm of tensor difference was then calculated for each shell pair and saved in a 3D dataset as the mean, maximum and minimum consistency values. CSC was compared in the following regions of interest (ROIs): Contrast enhancing tumor, directly adjacent peritumoral tissue, peripheral edema, and contralateral gray and white matter. Results: CSC differed significantly between the ROIs (p < 0.001), with contralateral gray and white matter showing the highest CSC, peripheral edema the lowest, and contrast-enhancing tumor and adjacent tissue showing intermediate values. A significant difference was observed between peritumoral tissue directly adjacent to the contrast-enhancing tumor and peripheral edema (p = 0.03).Conclusions: CSC is a promising new measure for multishell DTI data, possibly reflecting the degree of microstructural heterogeneity. As tissue directly adjacent to the contrast-enhancing tumor showed different CSC than peripheral edema despite comparable T1 and T2 signal characteristics, CSC may help differentiate the tumor infiltration zone from peritumoral edema.

Background/Objectives: Quantifying cerebrovascular reactivity (CVR) is essential for stroke risk assessment in patients with Moyamoya Angiopathy (MMA). Breath-hold functional MRI (bh-fMRI) is an easily implementable method to assess CVR. Determining the optimal time period of the BOLD signal for analyzing the best bh-fMRI data quality remains an open question. Methods: A retrospective analysis of 46 bh-fMRI data sets of MMA patients was conducted. The percentage BOLD signal changes were evaluated at different time periods (time point of the maximum cerebellar signal peak (TPcereb. max) ± 0 s, TPcereb. max ± 1 s, TPcereb. max ± 2 s, TPcereb. max ± 3 s, TPcereb. max ± 4 s, TPcereb. max ± 5 s). The agreement between the bh-fMRI maps and [15O]water PET maps was independently and consensually rated on a 4-point Likert scale (1 = poor, 2 = moderate, 3 = good, 4 = excellent) and compared with the Friedman test. The inter-rater agreement was calculated separately for each time period using quadratic weighted Cohen's kappa κw. Results: The selected time period had a significant impact on the agreement between bh-fMRI and [15O]water PET (χ2(5) = 79.448, p < 0.001, W = 0.345). Short time periods of TPcereb.max ± 0 s or TPcereb.max ±1 s demonstrated the highest level of concordance between bh-fMRI and [15O]water PET (median = 3.5 for TPcereb.max ± 0 s; median = 3 for TPcereb.max ± 1 s, modus = 4 in both cases). The agreement between bh-fMRI and [15O]water PET was significantly higher when evaluating time periods of TPcereb.max ± 0 s than when evaluating all time periods ≥ TPcereb. max ± 2 s. The inter-rater agreement was almost perfect for all time periods except one (TPcereb. max ± 1 s). Conclusions: Short time periods should be selected when evaluating CVR with bh-fMRI, as this study suggests a high level of validity in comparison to [15O]water PET.

PURPOSE:Virtual reality (VR) is increasingly recognized as a powerful tool in medical training. It offers immersive, interactive environments ideal for exploring complex anatomy and procedures. With the advent of affordable hardware, VR can provide high-quality, cost-effective training experiences. METHODS:We developed the VR application OpenOR in Unity for medical education. It supports multi-user interaction with customizable avatars and hand-tracking for intuitive control. Designed for medical students and professionals, OpenOR enables the exploration of complete clinical case studies. This includes medical history, a virtual DICOM viewer, visualization of anatomical structures and pathologies derived from MRI segmentations, and the original 3D surgical videos for each case. In addition, the 3D MRI-based models are complemented by CAD (computer-aided design) models of real implants, such as VP shunts or aneurysm clips. A usability test was conducted with 30 medical students using structured questionnaires. RESULTS:The pilot implementation demonstrated OpenOR's educational potential. Students reported increased engagement and a perceived improvement in understanding of anatomy and surgical workflows. The multi-user mode fostered collaborative learning, while hand-tracking supported intuitive interaction. The combination of virtual PACS viewing, interactive 3D models, and surgical 3D videos provided a realistic and integrated learning experience. The evaluation feedback indicated high user satisfaction and confirmed the platform's value for neurosurgical and anatomical training. CONCLUSION:OpenOR represents a significant advancement in VR-based medical education. By integrating immersive technologies with affordable hardware, it offers practical and scalable training solutions for Neurosurgery and Neuroanatomy.

OBJECTIVES:To validate whether cerebrospinal fluid oxyhaemoglobin (CSF-Hb), measured from external ventricular or lumbar drains, is associated with secondary brain injury (SAH-SBI) after aneurysmal subarachnoid haemorrhage (aSAH) and to assess its value as a real-time monitoring biomarker. DESIGN:Pre-registered multicentre prospective observational cohort study. SETTING:Eight neurosurgical tertiary centres in Switzerland, Germany and Austria between August 2021 and June 2024. PARTICIPANTS:366 patients with aSAH (mean age 58 years; 65% women). Of these, 260 provided cerebrospinal fluid (CSF) samples via external ventricular drain (EVD; 2467 samples, median 10 days per patient) and 66 via lumbar drain (LD; 379 samples, median 6 days). INTERVENTIONS:Daily CSF samples were collected via EVD or LD from day 1 to day 14 after haemorrhage; no therapeutic interventions were tested. MAIN OUTCOME MEASURES:CSF-Hb and its metabolites were analysed post hoc in a blinded manner. The primary outcome was SAH-SBI, defined as a composite of angiographic vasospasm (aVSP), delayed cerebral ischaemia (DCI) and delayed ischaemic neurological deficits (DIND), assessed daily over 14 days. Secondary outcomes included temporal CSF-Hb profiles and associations with aneurysm location, haematoma volume, intraventricular haemorrhage, chronic hydrocephalus and 3 month functional outcome. RESULTS:CSF-Hb showed a delayed peak pattern: concentrations were low after aSAH, rose to a maximum on day 10 (EVD-derived CSF-Hb median 11.3 µM, IQR 2.64 to 25.90) and then declined. Larger haematoma volume (p<0.001) and intraventricular haemorrhage (p<0.001) were associated with higher EVD-derived CSF-Hb. SAH-SBI occurred in 209/366 patients (57%). Daily EVD-derived CSF-Hb showed no association with SAH-SBI (p=0.25) and only poor prognostic potential for same-day SAH-SBI (area under the curve 0.59, 95% CI 0.56 to 0.63), with substantial between-centre heterogeneity. In a post-hoc exploratory analysis, higher CSF methaemoglobin showed a positive point-estimate of association with SAH-SBI (OR 1.18 per log(µM), 95% CI 1.02 to 1.36). Higher acute-phase EVD-derived CSF-Hb was associated with chronic hydrocephalus and a poor 3 month functional outcome. Catheter-related infection rates were low (2.2%). CONCLUSIONS:In this preregistered multicentre validation study, EVD-derived CSF-Hb did not perform as a robust real-time monitoring biomarker for SAH-SBI, showing limited same-day discrimination and substantial between-centre heterogeneity. These findings argue against clinical implementation of CSF-Hb point-measurement as a single-parameter biomarker. Higher CSF methaemoglobin was associated with SAH-SBI; this hypothesis-generating observation requires prospective confirmation and motivates continued investigation of haemolysis-related pathways. Future work using the HeMoVal biobank will apply multi-marker, pathway-level analyses to define haemolysis-related biomarker signatures and provide a platform for robust external validation of future candidates. TRIAL REGISTRATION NUMBER:NCT04998370.

Extracranial-intracranial (EC-IC) bypass surgery within the middle cerebral artery (MCA) territory is the gold standard for treating Moyamoya patients once hemodynamic insufficiency is confirmed. Although the anterior (ACA) and posterior cerebral arteries (PCA) are frequently involved, revascularization of these territories is not yet part of the standard treatment regimen; most centers focus exclusively on the MCA. Our approach, however, targets all hemodynamically compromised regions by providing tailored, multi-territorial revascularizations. Indications for additional ACA and/or PCA bypasses are determined by advanced imaging, such as PET-CT or CO2-triggered breath-hold MRI (bh-fMRI), to precisely evaluate cerebrovascular reserve. Here, we present the results of the first large case series focusing on non-MCA revascularization in adult Moyamoya patients. A total of 233 Moyamoya patients were analyzed, of whom 66 (28.3

PURPOSE:Postoperative MRI plays a pivotal role in assessing residual disease and planning therapy after intracranial tumor resection. As acute perioperative infarction may mimic enhancing and non-enhancing tumor tissue in follow-up imaging, the initial postoperative MRI examination is essential for this purpose. However, conventional DWI techniques like RESOLVE are often impaired by artifacts from intracranial air. This study compares RESOLVE DWI with TGSE-BLADE DWI within early postoperative scans to improve diagnostic confidence in identifying ischemic changes. METHOD:In a retrospective, institutional review board-approved study, 33 patients (mean age 52.3 ± 25.1 years) underwent a 1.5-Tesla MRI within 48 h of resection. RESOLVE and TGSE-BLADE DWI sequences were acquired in the same orientation and slice thickness of 5 mm. Two neuroradiologists blindly evaluated geometric distortion, susceptibility artifacts, overall image quality, and diagnostic confidence. Quantitative analysis included measuring signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), apparent diffusion coefficient (ADC) values, image quality metrics and resection defect dimensions against T1-weighted images. RESULTS:TGSE-BLADE DWI exhibited significantly reduced geometric distortions and susceptibility artifacts near the resection site compared with RESOLVE DWI, producing superior qualitative image quality and diagnostic confidence (p < 0.001). Conversely, RESOLVE DWI yielded slightly higher SNR and CNR. Measurements of the resection defect on TGSE-BLADE DWI closely matched those on T1-weighted images (p = 0.974), while RESOLVE DWI showed a significant discrepancy (p < 0.001). CONCLUSIONS:TGSE-BLADE DWI significantly minimizes artifacts and geometric distortions in intracranial postoperative imaging, thereby improving the detection of perioperative ischemic changes. This robust technique serves as an effective alternative to conventional EPI-based sequences in challenging settings with pronounced B0 inhomogeneities, ultimately enhancing diagnostic confidence and patient care.

BACKGROUND:Assessment of cerebrovascular reserve capacity (CVRC) is central to treatment planning in adult Moyamoya disease. [15O]-water-PET with acetazolamide challenge (PET-ACZ) serves as the reference standard but is resource-intensive and not universally available, whereas breathhold BOLD MRI (bh-fMRI) may offer a practical noninvasive alternative for screening and triage. METHODS:This retrospective diagnostic accuracy study compared bh-fMRI and PET-ACZ in 67 adult MMD patients (1072 ROIs across 402 supratentorial vascular territories) to determine correlation and clinically useful MRI thresholds for impaired cerebrovascular reserve. Data were analyzed using Pearson's correlation and ROC curves (STARD-compliant). Cerebellum-normalized percent signal change (CN-PSC) was referenced against PET-ACZ < 66% for pathological CVRC. RESULTS:Supratentorial territories showed strong correlation (r = 0.71, 95%CI 0.62-0.80). Optimal diagnostic threshold was <28.2% CN-PSC on bh-fMRI (Youden index; sensitivity 83.8%, specificity 80.9%, AUROC = 0.87); screening threshold < 60% CN-PSC yielded sensitivity 94.6% and NPV 91.1%. No patient factors (age, Suzuki stage, etc.) influenced agreement (univariate/multivariate analyses). CONCLUSIONS:Bh-fMRI supplements PET-ACZ as a screening and diagnostic tool for cerebrovascular reserve impairment in adult MMD. PET remains the reference standard for confirmation, especially in intermediate or discordant cases, and the proposed thresholds (<30% CN-PSC: impaired CVRC; 30-60%: confirm with PET-ACZ; >60%: monitor) require prospective validation before routine decision-making use.

BACKGROUND:Tumor resection is a prerequisite in many studies of new glioblastoma therapeutics; however, no clear parameters for "resectability" exist. We evaluated inter-rater variability in assessing tumor resectability and potential associations between resectability and survival in a trial cohort of glioblastoma recurrence. METHODS:DIRECTOR (NCT00941460; 9/2009-6/2012) evaluated two dose-dense temozolomide regimens for first recurrent glioblastoma, yielding similar outcomes between arms. Re-resection was allowed before initiation of systemic therapy by institutional decision. Eleven surgical neuro-oncologists (blinded to final outcomes) rated whether a "meaningful resection" was achievable for each recurrent IDH-wildtype glioblastoma based on imaging and clinical data. RESULTS:MRI scans from 69 patients were available (median age: 58.2 ± 1.1 years, median survival: 10.0 months). Forty patients underwent re-resection (median age: 56.4 ± 1.7 years, median survival: 10.8 months). Surgical decision-making markedly varied between raters, ranging from 30 to 58 of 69 cases being classified as "resectable" (κ = 0.405). In patients who received re-resection, a "meaningful resection" was deemed feasible by >80% of raters in 30/40 cases (75.0%). For patients without re-resection, unanimous agreement on non-resectability occurred in only 3/29 cases (10.4%); and 5/29 tumors (17.2%) were considered resectable by >80% of raters. Knowledge of additional clinical factors virtually never changed MRI-based judgments. While patients who had a complete resection of contrast-enhancing tumor had favorable outcomes, a consensus on resectability by >80% of raters was not associated with prolonged overall survival. DISCUSSION:Feasibility assessment for re-resection is heterogeneous among neurosurgeons, challenging single-surgeon evaluation of "resectability." Those findings are limited by the number of surgical raters and the size of the DIRECTOR cohort.

Recent evidence-based guidelines recommend adjuvant therapy following surgery for most patients with WHO grade 2 and 3 gliomas. However, deviations from these recommendations are frequently observed in clinical practice. This study aimed to evaluate patterns of postoperative management across Germany, using multicentre registry data from certified neuro-oncology centres. We analysed data from the ongoing multicentre registry study, which prospectively collects adult patients with IDH-mutant WHO grade 2 and 3 diffuse gliomas. Patients treated at 14 certified neuro-oncology centres were included. Multivariate logistic regression was used to identify factors associated with observation, chemotherapy, or radiotherapy. We assessed concordance between guideline recommendations and actual treatment during the first year after surgery. A total of 217 patients with astrocytoma or oligodendroglioma were included, of whom 169 (78

Background/Objectives: Postoperative MRI is crucial for detecting residual tumor, identifying complications, and planning subsequent therapy. This study evaluates accelerated deep learning reconstruction (DLR) versus standard clinical protocols for early postoperative MRI following tumor resection. Methods: This study uses a multidisciplinary approach involving a neuroradiologist, neurosurgeon, neuro-oncologist, and radiotherapist to evaluate qualitative aspects using a 5-point Likert scale, the preferred reconstruction variant and potential residual tumor of DLR and conventional reconstruction (CR) of FLAIR, T1-weighted non-contrast and contrast-enhanced (T1), and coronal T2-weighted (T2) sequences for 1.5 and 3 T MRI. Quantitative analysis included the image quality metrics Structural Similarity Index (SSIM), Multi-Scale SSIM (MS-SSIM), Feature Similarity Index (FSIM), Noise Quality Metric (NQM), signal-to-noise ratio (SNR), and Peak SNR (PSNR) with CR as a reference. Results: All raters strongly preferred DLR over CR. This was most pronounced for FLAIR images at 1.5 and 3 T (91% at 1.5 T and 97% at 3 T) and least pronounced for T1 at 1.5 T (79% for non-contrast-enhanced and 84% for contrast-enhanced sequences) and for T2 at 3 T (69%). DLR demonstrated superior qualitative image quality for all sequences and field strengths (p < 0.001), except for T2 at 3 T, which was observed across all raters (p = 0.670). Diagnostic confidence was similar at 3 T with better but non-significant differences for T2 (p = 0.134) and at 1.5 T with better but non-significant differences for non-contrast-enhanced T1 (p = 0.083) and only marginally significant results for FLAIR (p = 0.033). Both the SSIM and MS-SSIM indicated near-perfect similarity between CR and DLR. FSIM performs worse in terms of consistency between CR and DLR. The image quality metrics NQM, SNR, and PSNR showed better results for DLR. Visual assessment of residual tumor was similar at 3 T but differed at 1.5 T, with more residual tumor detected with DLR, especially by the neurosurgeon (n = 4). Conclusions: An accelerated DLR protocol demonstrates clinical feasibility, enabling high-quality reconstructions in challenging postoperative MRIs. DLR sequences received strong multidisciplinary preference, underscoring their potential to improve neuro-oncologic decision making and suitability for clinical implementation.

Associations between higher extents of re-resection for glioblastoma and prolonged survival may reflect that tumors in less functional (surgically more accessible) brain areas identify with an inherently better prognosis. This post-hoc analysis of the DIRECTOR trial aimed to (I) evaluate inter-rater variability in assessing tumor resectability and (II) investigate associations between resectability, extent of resection, and survival. DIRECTOR (NCT00941460) evaluated two different temozolomide regimens for first glioblastoma relapse. Patients were eligible for re-resection per institutional decision. The two study arms were pooled due to similar outcomes; and eleven surgical neuro-oncologists rated tumor resectability for each IDH-wildtype glioblastoma with baseline MRI available. We studied 69 patients with first IDH-wildtype glioblastoma recurrence, including 40 individuals who underwent re-resection prior to temozolomide re-challenge. In patients receiving a re-resection, a ‘meaningful resection’ was deemed feasible by 0-50% of the raters in 4/40 cases (10.0%), by 51-80% in 6/40 cases (15.0%), and by 81-100% in 30/40 cases (75.0%). Only among patients without post-operative contrast-enhancing tumor, pre-operative agreement on resectability was high. For patients without re-resection, in only 3/29 patients (10.4%) all raters agreed that tumors were not resectable; while 1-50% of the raters judged tumors as resectable in 14/29 patients (48.3%), 51-80% in 7/29 patients (24.1%), and 81-100% in 5/29 patients (17.2%). Additional knowledge of clinical factors virtually never changed the judgment based on MRI alone. Surgical decision-making markedly varied between raters, ranging from 29 to 59/69 cases being classified as ‘resectable’ (kappa-index: 0.405). Overall, consensus on resectability by >80% of the raters was not associated with favourable OS (10.4±1.8 vs 10.0±3.0 months, p=0.924) or PFS (2.0±0.5 vs 1.9±0.2 months, p=0.757). Compared to submaximal resection or patients without re-resection, patients with complete contrast-enhancement resection had longer survival, particularly in MGMT-unmethylated tumors. Assessment of feasibility for re-resections in recurrent glioblastoma varies. An objective consensus would come with implications for trials and practice. We gratefully acknowledge the DIRECTOR investigators.

Moyamoya disease (MMD) may lead to perfusion deficits, stroke and brain atrophy in the long-term. Our aim was to analyse whole-brain volumetry of a large cohort of Moyamoya disease patients compared to healthy controls. 3D T1w MRI sequences of adult Moyamoya disease patients treated at our centre between 2016 and 2022 without prior revascularization were analysed for whole-brain volumetry (AssemblyNet) and compared age-controlled to healthy controls. A total of 133 different regions of interest were examined retrospectively for each patient separately by localization, structure and tissue type. All segmentations were subjected to automated and manual quality control. After quality control, 149 hemispheres from 80 Moyamoya disease patients were compared to 258 hemispheres from 129 healthy controls. A significant brain volume loss was observed in Moyamoya disease patients with increasing age, with the greatest reduction seen in bilaterally affected patients with Suzuki grade >3. As direct signs of brain atrophy, significant differences were seen across all regions of interests, emphasized in cortical grey matter with a reduction of 4.4% (95% CI 2.7-6.1%; P < 0.001) in patients aged 30-45 years and 3.4% (95% CI 2.1-4.7%; P < 0.001) aged 46-60 years. As indirect sign for atrophy, external CSF spaces increased up to 26.4% (95% CI 17.0-35.9%; P < 0.001) for 30-45 years and 28.4% (95% CI 17.1-39.7%; P < 0.001) for 46-60 years compared to healthy controls. Infratentorial, significant volume loss was observed for patients aged 46-60 years with 11.6% for cerebellar white matter (95% CI 3.7-19.5%; P = 0.0025) and with 8.5% (95% CI 3.5-13.5%; P = 0.0006) for the brainstem, likely due to secondary neurodegeneration. Moyamoya disease patients >45 year without ischaemia also had significantly less grey matter and white matter volume, with accordingly enlarged CSF spaces. Moyamoya disease may lead to significant differences in brain volume of local and global regions of interest as a sign of brain atrophy, even in the absence of infarctions. These findings might be useful for the understanding of the disease burden and in decision-making for timely revascularization.

PURPOSE:To share our clinical experience with conservative management of isolated spinal arterial aneurysms (ISAs) and to identify clinical scenarios where conservative management may be appropriate, in the context of a literature review. METHODS:We performed a retrospective review of spinal angiograms from two German neuroradiology centers and conducted a systematic literature review of reported ISA cases. We analyzed demographics, clinical presentation, imaging findings, treatments, and outcomes. RESULTS:We identified seven patients (mean age 48; 4 women) with nine ISAs, eight of which were managed conservatively. Five of them had excellent short-term outcomes, and spontaneous regression was documented in four cases. With our cases, 208 ISAs have been reported in the literature in 164 patients (mean age 51; 52% female). They most commonly present with subarachnoid hemorrhage (90%) and back pain (69%). Most are located in the thoracic (51%) or cervical spine (40%) and involve the anterior spinal circulation (63%). They may be treated by surgical intervention (47%) or conservatively (37%), less commonly by endovascular therapy (16%). 78% of patients have favorable outcomes (mRS 0-3), similar across all treatment approaches. In 52% of conservatively managed cases, spontaneous regression was documented by imaging. Clinical deterioration was primarily associated with respiratory complications and spinal cord infarction, with a documented rebleeding rate of 8% and a mortality rate of 12%. CONCLUSIONS:ISAs are a rare and potentially underrecognized cause of cerebral and spinal subarachnoid hemorrhage. In select cases, particularly small ISAs of the anterior spinal or a radiculomedullary artery and with transient neurological symptoms, conservative management appears to be a reasonable approach, supported by increasing evidence of the possibility of spontaneous regression.

Objective: In moyamoya disease (MMD), the internal carotid and proximal cerebral arteries narrow, potentially leading to stroke or hemorrhage from fragile collaterals. Disease activity and progression may be detected by contrast-enhanced (CE) high-resolution (HR) vessel wall imaging (CE-VWI) on T1-weighted MRI. However, this imaging approach needs standardization for the evaluation of signal intensity and longitudinal reproducibility. Methods: MMD patients with at least two separate CE-VWI examinations on the same and on different scanners were included. Signal intensity of the vessel wall, pituitary stalk, and temporal lobe white matter were measured and normalized using manually selected regions of interest. Intraindividual longitudinal reproducibility of MRI was analyzed and the clinical course was correlated with vessel wall enhancement data. Results: Eighty-seven patients were analyzed. Primary analysis included 60 patients with two or more CE-VWI measurements (n = 129) with median 14.8 months between examinations (range: 2–36 months) on the same scanner. Intraindividual variation in pituitary stalk enhancement (positive control) and temporal lobe white matter enhancement (negative control) showed median signal variability of 20.5% and 17.5%, respectively. The pituitary-to-temporal lobe signal intensity ratio remained stable over time (p = 0.843) with 9.4% median variability. Correlation analysis revealed a significant positive association between pituitary and temporal lobe signal changes (ρ = 0.717, p < 0.001). A total of 75% of patients showed vessel wall contrast enhancement with fluctuating signal intensity over approximately 15.9 months, likely depicting disease activity. Conclusions: CE-VWI is important for screening disease activity in moyamoya patients. Our findings demonstrate longitudinal intraindividual reproducibility when normalized to pituitary stalk, enabling quantified evaluation of disease progression through longitudinal vessel wall contrast-enhancement changes.

Abstract Background The discovery of cellular tumor networks in glioblastoma, with routes of malignant communication extending far beyond the detectable tumor margins, has highlighted the potential of supramarginal resection strategies. Retrospective data suggest that these approaches may improve long-term disease control. However, their application is limited by the proximity of critical brain regions and vasculature, posing challenges for validation in randomized trials. Anterior temporal lobectomy (ATL) is a standardized surgical procedure commonly performed in patients with pharmacoresistant temporal lobe epilepsy. Translating the ATL approach from epilepsy surgery to the neuro-oncological field may provide a model for investigating supramarginal resection in glioblastomas located in the anterior temporal lobe. Methods The ATLAS/NOA-29 trial is a prospective, multicenter, multinational, phase III randomized controlled trial designed to compare ATL with standard gross-total resection (GTR) in patients with newly-diagnosed anterior temporal lobe glioblastoma. The primary endpoint is overall survival (OS), with superiority defined by significant improvements in OS and non-inferiority in the co-primary endpoint, quality of life (QoL; “global health” domain of the European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire). Secondary endpoints include progression-free survival (PFS), seizure outcomes, neurocognitive performance, and the longitudinal assessment of six selected domains from the EORTC QLQ-C30 and BN20 questionnaires. Randomization will be performed intraoperatively upon receipt of the fresh frozen section result. A total of 178 patients will be randomized in a 1:1 ratio over a 3-year recruitment period and followed-up for a minimum of 3 years. The trial will be supervised by a Data Safety Monitoring Board, with an interim safety analysis planned after the recruitment of the 57th patient to assess potential differences in modified Rankin Scale (mRS) scores between the treatment arms 6 months after resection. Assuming a median improvement in OS from 17 to 27.5 months, the trial is powered at > 80% to detect OS differences with a two-sided log-rank test at a 5% significance level. Discussion The ATLAS/NOA-29 trial aims to determine whether ATL provides superior outcomes at equal patients’ Qol compared to GTR in anterior temporal lobe glioblastoma, potentially establishing ATL as the surgical approach of choice for isolated temporal glioblastoma and redefining the standard of care for this patient population. Trial registration German Clinical Trials Register (DRKS00035314), registered on October 18, 2024.

Breath-hold functional MRI (bh-fMRI) is able to quantify cerebrovascular reactivity. Vessel stenoses can lead to delayed hemodynamic responses. We aimed to investigate whether delay correction improves the quality of bh-fMRI compared to the diagnostic standard [15O]water PET. The bh-fMRI data sets of 25 patients with Moyamoya Angiopathy were analyzed retrospectively without and with delay correction. Delay correction was calculated using time-to-peak (TTP) maps derived from dynamic susceptibility contrast (DSC) perfusion MRI. [15O]water PET maps and bh-fMRI maps without and with delay correction were presented blinded for delay correction to two neuroradiologists. The agreement between bh-fMRI without and with delay correction and [15O]water PET was independently and consensually rated on a 4-point-Likert scale (1 = poor, 2 = moderate, 3 = good, 4 = excellent) and compared with Wilcoxon signed-rank test. The agreement between bh-fMRI and [15O]water PET without delay correction was good/excellent (median = 3, modus = 4), and improved significantly after delay correction with medium effect size (median = 4, modus = 4, z = -2.121, p = 0.034, r = 0.42). Delay correction improves the quality of bh-fMRI and seems to be helpful in clinical practice.