A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol.

BACKGROUND: Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma. METHODS/DESIGN: GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland. TRIAL REGISTRATION: NCT05664464. Registered 23 December 2022.

Resolving the Smoking Paradox: No Evidence for Smoking-Induced Preconditioning in Large Vessel Occlusion Stroke.

INTRODUCTION: Smoking is an established risk factor for stroke. However, several studies have reported a better outcome after stroke for patients who smoke. According to this "smoking paradox" hypothesis, smoking might promote less severe strokes, higher collateral scores, and smaller infarct cores. METHODS: In this retrospective study, we screened data of 2,980 acute ischemic stroke patients with MCA-M1 occlusion treated with mechanical thrombectomy. Patients were categorized according to smoking status (current, former, or never). We assessed univariate associations between clinical characteristics and smoking status. Subsequently, we used adjusted regression analysis to evaluate associations of smoking with stroke severity on admission (National Institutes of Health Stroke Scale [NIHSS]; primary endpoint), infarct core volume, and collateral status (secondary endpoints). RESULTS: Out of 320 patients, 19.7% (n = 63) were current smokers and 18.8% (n = 60) were former smokers. Admission NIHSS, reperfusion success, and modified Rankin Scale (mRS) after 3-6 months were similar in all groups. Current smokers were younger, more often male and less likely to have atrial fibrillation compared to former and never smokers. In regression analyses, smoking status was neither associated with admission NIHSS (estimate 0.54, 95% confidence interval [CI]: -1.27-2.35, p = 0.557) nor with collateral status (estimate 0.79, 95% CI: 0.44-1.44, p = 0.447) or infarct core volume (estimate -0.69, 95% CI: -15.15-13.77, p = 0.925 for current vs. never smokers). CONCLUSION: We could not confirm the smoking paradox. Our results support the fact that smoking causes stroke at a younger age, highlighting the role of smoking as a modifiable vascular risk factor.

Machine-learning-based outcome prediction in stroke patients with middle cerebral artery-M1 occlusions and early thrombectomy.

BACKGROUND AND PURPOSE: Clinical outcomes vary substantially among individuals with large vessel occlusion (LVO) stroke. A small infarct core and large imaging mismatch were found to be associated with good recovery. The aim of this study was to investigate whether those imaging variables would improve individual prediction of functional outcome after early (<6 h) endovascular treatment (EVT) in LVO stroke. METHODS: We included 222 patients with acute ischemic stroke due to middle cerebral artery (MCA)-M1 occlusion who received EVT. As predictors, we used clinical variables and region of interest (ROI)-based magnetic resonance imaging features. We developed different machine-learning models and quantified their prediction performance according to the area under the receiver-operating characteristic curves and the Brier score. RESULTS: The rate of successful recanalization was 78%, with 54% patients having a favorable outcome (modified Rankin scale score 0-2). Small infarct core was associated with favorable functional outcome. Outcome prediction improved only slightly when imaging was added to patient variables. Age was the driving factor, with a sharp decrease in likelihood of favorable functional outcome above the age of 78 years. CONCLUSIONS: In patients with MCA-M1 occlusion strokes referred to EVT within 6 h of symptom onset, infarct core volume was associated with outcome. However, ROI-based imaging variables led to no significant improvement in outcome prediction at an individual patient level when added to a set of clinical predictors. Our study is in concordance with current practice, where imaging mismatch or collateral readouts are not recommended as factors for excluding patients with MCA-M1 occlusion for early EVT.

Factors predicting help seeking for mental illness among college students.

BACKGROUND: Evidence supports the contribution of various stigma-related constructs to help-seeking. These constructs have yet to be tested in a single model among college students, a group highly affected by mental illness. AIMS: Using data from 153 college students, this study examines factors contributing to help seeking for mental illness. METHOD: Using path analysis, the current study evaluated a model of the relationship between level of familiarity, personal stigma, desired social distance, label avoidance, attitudes towards treatment seeking and intentions to seek treatment. RESULTS: Findings support a model of help-seeking describing the relationship between familiarity with mental illness, personal stigma, social distance, label avoidance, attitudes and intentions to seek treatment. CONCLUSIONS: Findings suggest label avoidance, attitudes towards treatment seeking and intentions to seek treatment might be augmented through interventions aimed at increasing college students' levels of familiarity, or intimate contact, with individuals with mental illness. Additional implications for practice and further research are addressed.

Thera-prov: a pilot study of improv used to treat anxiety and depression.

Background: Improvisational theater exercises (improv) are used in various settings to improve mental health and medical outcomes. However, there is little documented evidence of the effectiveness of these interventions.Aims: We developed a short-term, group intervention that used improv exercises in a therapeutic manner to treat psychiatric patients.Methods: We evaluated the feasibility, acceptability and five clinical outcomes (depressive symptoms, anxious symptoms, self-esteem, perfectionism and satisfaction with social roles) of this intervention in an outpatient setting. Participants were 32 patients with symptoms of anxiety and depression and who had variable exposure to psychiatric treatment.Results: In paired samples t-tests, participants demonstrated reduced symptoms of anxiety (t(31) = 4.67, p < 0.001) and depression (t(31) = 3.78, p = 0.001), and improved self-esteem (t(31)= -3.31, p = 0.002) following the intervention. There was a trend towards reduction of perfectionism (t(31) = 1.77, p = 0.087), but no substantial change in rated satisfaction with social roles. Effect sizes were medium for reduction in symptoms of depression and anxiety.Conclusions: The results of this study indicate that a brief intervention based on improv exercises may provide a strong and efficient treatment for patients with anxiety and depression.

Changing public stigma with continuum beliefs.

BACKGROUND: Given the egregious effect of public stigma on the lives of people with mental illness, researchers have sought to unpack and identify effective components of anti-stigma programs. AIM: We expect to show that continuum messages have more positive effect on stigma and affirming attitudes (beliefs that people with mental illness recover and should be personally empowered) than categorical perspectives. The effect of continuum beliefs will interact with contact strategies. METHOD: A total of 598 research participants were randomly assigned to online presentations representing one of the six conditions: three messages (continuum, categorical, or neutral control) by two processes (education or contact). Participants completed measures of continuum beliefs (as a manipulation check), stigma and affirming attitudes after viewing the condition. RESULTS: Continuum messages had significantly better effect on views that people with mental illness are "different," a finding that interacted with contact. Continuum messages also had better effects on recovery beliefs, once again an effect that interacted significantly with contact. CONCLUSIONS: Implications of these findings for improving anti-stigma programs are discussed.

Who Comes Out With Their Mental Illness and How Does It Help?

Coming out with mental illness may be an effective strategy for reducing self-stigma. This study examined predictors and consequences of coming out. Participants (N = 106) with severe mental illness who reported being out (n = 79) or not out (n = 27) endorsed benefits of being out (BBOs) and reasons for staying in. Predictors from baseline measures were self-stigma, insight, and psychiatric diagnosis. Three outcome measures-basic psychological needs, care engagement, and depression-were also completed at baseline and 1-month follow-up. Among participants already out, BBOs and reasons for staying in were significantly and independently associated with self-stigma, insight, and lifetime affective diagnoses. In terms of consequences, BBOs were associated with cross-sectional and 1-month measures of engagement for those already out, but not for closeted participants. Among closeted participants, BBOs were associated with baseline and 1-month measures of basic psychological needs. Implications for strategies meant to promote disclosure in order to decrease self-stigma are considered.

What is the impact of self-stigma? Loss of self-respect and the "why try" effect.

BACKGROUND: The "Why Try" phenomenon, a consequence of self-stigma, is a sense of futility that occurs when people believe they are unworthy or incapable of achieving personal goals because they apply the stereotypes of mental illness to themselves. AIMS: This study examines a four-stage model of self-stigma (aware, agree, apply, and self-stigma harm) and examines the "why try" effect as a result. We do that by testing a measure of "why try." METHOD: Two hypothetical path models were tested. In the first, applying stereotypes to oneself leads to diminished self-respect and a sense of "why try". In the second, the effect of applying stereotypes on "why try" is mediated by diminished self-respect. Participants completed the "why try" measure along with measures of self-stigma, public stigma, recovery, and empowerment. RESULTS: Results show application of stereotypes to oneself predicts diminished self-respect and "why try". "Why try" was significantly associated with agreement with public stigma, depression, and diminished sense of personal recovery. CONCLUSIONS: Findings from this study reveal the complex impact of self-stigma demonstrating its emotional and behavioral consequences. Implications for impacting self-stigma are discussed.

Bilateral ganglioglioma of the trigeminal nerve in an 83-year-old man.

Gangliogliomas are well-differentiated, mixed glio-neuronal tumors of the CNS that are most frequently localized within the temporal lobe. In a minority of cases, gangliogliomas have been described in the brain stem where they may critically impinge anatomical structures. Rarely, ganglioglioma develop in cranial nerves, almost exclusively in the optic pathway, where they usually present as singular space-occupying masses. Here, we report on an 83-year-old patient who presented with unusual symmetrical, bilateral gangliogliomas of the trigeminal nerves. These tumors showed an exophytic growth within the subarachnoid space toward the Gasserian ganglion and surprisingly appeared as isointense masses on T1- and T2-weighted MRI. Due to their bilateral appearance, we performed array-comparative genomic hybridization (aCGH) on the gangliogliomas to address the possibility of an underlying tumor syndrome in this patient. To our knowledge, this is the first case of bilateral ganglioglioma of the trigeminal nerve described so far.

Validation of echo planar imaging based diffusion-weighted magnetic resonance imaging on a 0.35 T MR-Linac.

Background and Purpose: The feasibility of acquiring diffusion-weighted imaging (DWI) images on an MR-Linac for quantitative response assessment during radiotherapy was explored. DWI data obtained with a Spin Echo Echo Planar Imaging sequence adapted for a 0.35 T MR-Linac were examined and compared with DWI data from a conventional 3 T scanner. Materials and Methods: Apparent diffusion coefficient (ADC) measurements and a distortion correction technique were investigated using DWI-calibrated phantoms and in the brains of seven volunteers. All DWI utilized two phase-encoding directions for distortion correction and off-resonance field estimation. ADC maps in the brain were analyzed for automatically segmented normal tissues. Results: Phantom ADC measurements on the MR-Linac were within a 3 % margin of those recorded by the 3 T scanner. The maximum distortion observed in the phantom was 2.0 mm prior to correction and 1.1 mm post-correction on the MR-Linac, compared to 6.0 mm before correction and 3.6 mm after correction at 3 T. In vivo, the average ADC values for gray and white matter exhibited variations of 14 % and 4 %, respectively, for different selections of b-values on the MR-Linac. Distortions in brain images before correction, estimated through the off-resonance field, reached 2.7 mm on the MR-Linac and 12 mm at 3 T. Conclusion: Accurate ADC measurements are achievable on a 0.35 T MR-Linac, both in phantom and in vivo. The selection of b-values significantly influences ADC values in vivo. DWI on the MR-Linac demonstrated lower distortion levels, with a maximum distortion reduced to 1.1 mm after correction.

MRI-based radiomics for predicting histology in malignant salivary gland tumors: methodology and "proof of principle".

Defining the exact histological features of salivary gland malignancies before treatment remains an unsolved problem that compromises the ability to tailor further therapeutic steps individually. Radiomics, a new methodology to extract quantitative information from medical images, could contribute to characterizing the individual cancer phenotype already before treatment in a fast and non-invasive way. Consequently, the standardization and implementation of radiomic analysis in the clinical routine work to predict histology of salivary gland cancer (SGC) could also provide improvements in clinical decision-making. In this study, we aimed to investigate the potential of radiomic features as imaging biomarker to distinguish between high grade and low-grade salivary gland malignancies. We have also investigated the effect of image and feature level harmonization on the performance of radiomic models. For this study, our dual center cohort consisted of 126 patients, with histologically proven SGC, who underwent curative-intent treatment in two tertiary oncology centers. We extracted and analyzed the radiomics features of 120 pre-therapeutic MRI images with gadolinium (T1 sequences), and correlated those with the definitive post-operative histology. In our study the best radiomic model achieved average AUC of 0.66 and balanced accuracy of 0.63. According to the results, there is significant difference between the performance of models based on MRI intensity normalized images + harmonized features and other models (p value < 0.05) which indicates that in case of dealing with heterogeneous dataset, applying the harmonization methods is beneficial. Among radiomic features minimum intensity from first order, and gray level-variance from texture category were frequently selected during multivariate analysis which indicate the potential of these features as being used as imaging biomarker. The present bicentric study presents for the first time the feasibility of implementing MR-based, handcrafted radiomics, based on T1 contrast-enhanced sequences and the ComBat harmonization method in an effort to predict the formal grading of salivary gland carcinoma with satisfactory performance.

Neurologic involvement in cystinosis: Focus on brain lesions and new evidence of four-repeat (4R-) Tau immunoreactivity.

Nephropathic cystinosis is a rare autosomal recessive storage disorder caused by CTNS gene mutations, leading to autophagy-lysosomal pathway impairment and cystine crystals accumulation. Neurologic involvement is highly variable and includes both neurodevelopmental and neurodegenerative disturbances, as well as focal neurologic deficits. By presenting longitudinal data of a 28-year-old patient with a large infratentorial lesion, we summarized the pathology, clinical and imaging features of neurological involvement in cystinosis patients. Brain damage in form of cystinosis-related cerebral lesions occurs in advanced disease phases and is characterized by the accumulation of cystine crystals, subsequent inflammation with vasculitis-like features, necrosis, and calcification. Epilepsy is a frequent comorbidity in affected individuals. Steroids might play a role in the symptomatic treatment of "stroke-like" episodes due to edematous-inflammatory lesions, but probably do not change the overall prognosis. Lifelong compliance to depleting therapy with cysteamine still represents the main therapeutic option. However, consequences of CTNS gene defects are not restricted to cystine accumulation. New evidence of four-repeat (4R-) Tau immunoreactivity suggests concurrent progressive neurodegeneration in cystinosis patients, highlighting the need of innovative therapeutic strategies, and shedding light on the crosstalk between proteinopathies and autophagy-lysosomal system defects. Eventually, emerging easily accessible biomarkers such as serum neurofilament light chains (NfL) might detect subclinical neurologic involvement in cystinosis patients.

Transient deoxyhemoglobin formation as a contrast for perfusion MRI studies in patients with brain tumors: a feasibility study.

Background: Transient hypoxia-induced deoxyhemoglobin (dOHb) has recently been shown to represent a comparable contrast to gadolinium-based contrast agents for generating resting perfusion measures in healthy subjects. Here, we investigate the feasibility of translating this non-invasive approach to patients with brain tumors. Methods: A computer-controlled gas blender was used to induce transient precise isocapnic lung hypoxia and thereby transient arterial dOHb during echo-planar-imaging acquisition in a cohort of patients with different types of brain tumors (n = 9). We calculated relative cerebral blood volume (rCBV), cerebral blood flow (rCBF), and mean transit time (MTT) using a standard model-based analysis. The transient hypoxia induced-dOHb MRI perfusion maps were compared to available clinical DSC-MRI. Results: Transient hypoxia induced-dOHb based maps of resting perfusion displayed perfusion patterns consistent with underlying tumor histology and showed high spatial coherence to gadolinium-based DSC MR perfusion maps. Conclusion: Non-invasive transient hypoxia induced-dOHb was well-tolerated in patients with different types of brain tumors, and the generated rCBV, rCBF and MTT maps appear in good agreement with perfusion maps generated with gadolinium-based DSC MR perfusion.

A Dempster-Shafer Approach to Trustworthy AI With Application to Fetal Brain MRI Segmentation.

Deep learning models for medical image segmentation can fail unexpectedly and spectacularly for pathological cases and images acquired at different centers than training images, with labeling errors that violate expert knowledge. Such errors undermine the trustworthiness of deep learning models for medical image segmentation. Mechanisms for detecting and correcting such failures are essential for safely translating this technology into clinics and are likely to be a requirement of future regulations on artificial intelligence (AI). In this work, we propose a trustworthy AI theoretical framework and a practical system that can augment any backbone AI system using a fallback method and a fail-safe mechanism based on Dempster-Shafer theory. Our approach relies on an actionable definition of trustworthy AI. Our method automatically discards the voxel-level labeling predicted by the backbone AI that violate expert knowledge and relies on a fallback for those voxels. We demonstrate the effectiveness of the proposed trustworthy AI approach on the largest reported annotated dataset of fetal MRI consisting of 540 manually annotated fetal brain 3D T2w MRIs from 13 centers. Our trustworthy AI method improves the robustness of four backbone AI models for fetal brain MRIs acquired across various centers and for fetuses with various brain abnormalities.

Benefits of contrast-enhanced SWI in patients with glioblastoma multiforme.

INTRODUCTION: SWI can help to identify high-grade gliomas (HGG). The objective of this study was to analyse SWI and CE-SWI characteristics, i.e. the relationship between contrast-induced phase shifts (CIPS) and intratumoral susceptibility signals (ITSS) and their association with tumour volume in patients with glioblastoma multiforme (GBM). MATERIALS AND METHODS: MRI studies of 29 patients were performed to evaluate distinct susceptibility signals comparing SWI and CE-SWI characteristics. The relationship between these susceptibility signals and CE-T1w tumour volume was analysed by using Spearman's rank correlation coefficient and Kruskal-Wallis-test. Tumour biopsies of different susceptibility signals were performed in one patient. RESULTS: Comparison of SWI and CE-SWI demonstrated different susceptibility signals. Susceptibility signals visible on SWI images are consistent with ITSS; those only seen on CE-SWI were identified as CIPS. Correlation with CE-T1w tumour volume revealed that CIPS were especially present in small or medium-sized GBM (Spearman's rho r = 0.843, P < 0.001). Histology identified the area with CIPS as the tumour invasion zone, while the area with ITSS represented micro-haemorrhage, highly pathological vessels and necrosis. CONCLUSION: CE-SWI adds information to the evaluation of GBM before therapy. It might have the potential to non-invasively identify the tumour invasion zone as demonstrated by biopsies in one case. KEY POINTS: • MRI is used to help differentiate between low- and high-grade gliomas. • Contrast-enhanced susceptibility-weighted MRI (CE-SWI) helps to identify patients with glioblastoma multiforme. • CE-SWI delineates the susceptibility signal (CIPS and ITSS) more than the native SWI. • CE-SWI might have the potential to non-invasively identify the tumour invasion zone.

Assessing Perfusion in Steno-Occlusive Cerebrovascular Disease Using Transient Hypoxia-Induced Deoxyhemoglobin as a Dynamic Susceptibility Contrast Agent.

BACKGROUND AND PURPOSE: Resting brain tissue perfusion in cerebral steno-occlusive vascular disease can be assessed by MR imaging using gadolinium-based susceptibility contrast agents. Recently, transient hypoxia-induced deoxyhemoglobin has been investigated as a noninvasive MR imaging contrast agent. Here we present a comparison of resting perfusion metrics using transient hypoxia-induced deoxyhemoglobin and gadolinium-based contrast agents in patients with known cerebrovascular steno-occlusive disease. MATERIALS AND METHODS: Twelve patients with steno-occlusive disease underwent DSC MR imaging using a standard bolus of gadolinium-based contrast agent compared with transient hypoxia-induced deoxyhemoglobin generated in the lungs using an automated gas blender. A conventional multi-slice 2D gradient echo sequence was used to acquire the perfusion data and analyzed using a standard tracer kinetic model. MTT, relative CBF, and relative CBV maps were generated and compared between contrast agents. RESULTS: The spatial distributions of the perfusion metrics generated with both contrast agents were consistent. Perfusion metrics in GM and WM were not statistically different except for WM MTT. CONCLUSIONS: Cerebral perfusion metrics generated with noninvasive transient hypoxia-induced changes in deoxyhemoglobin are very similar to those generated using a gadolinium-based contrast agent in patients with cerebrovascular steno-occlusive disease.

Risk of ischemia in glioma surgery: comparison of first and repeat procedures.

The role of repeat resection in the multimodal treatment of gliomas is unclear. Repeat surgery theoretically carries a higher risk of inducing neurological deficits, which might even out any advantage of cytoreduction. We sought to determine whether the occurrence of perioperative infarction is higher for repeat surgery than for first surgery, and sought to identify factors associated with the occurrence of postoperative infarction. Therefore, we searched our database to identify patients who were operated for primary or recurrent glial tumors between October 2007 and October 2010. We analyzed 177 procedures, of which 130 (73.4%) were first surgeries and 47 (26.5%) were repeat. Initial WHO grades, KPS scores, and age were evenly distributed between the groups. Forty-six (26.0%) patients had new DWI lesions on their postoperative MRI scan. Eighteen (10.2%) patients had new lesions greater than 4 cm(3). Among these were 11 (6.2%) patients, for whom the new lesion caused neurologic deficit. There was no difference between first and repeat surgery with regard to the occurrence of new DWI lesions (27.7 vs. 21.3%, P = 0.77) or neurological deficits (10.0 vs. 10.6%, P = 1.0). Tumor location in the insula, operculum, and temporal lobe was found to be significantly associated with the occurrence of new DWI lesions. We conclude that repeat surgery should not be withheld as a treatment option for patients with recurrent gliomas for fear of a higher risk of postoperative infarction or new neurologic deficit than the first surgery.

Optimizing the extent of resection in eloquently located gliomas by combining intraoperative MRI guidance with intraoperative neurophysiological monitoring.

Several methods have been introduced to improve the extent of resection in glioma surgery. Yet, radical tumor resections must not be attempted at the cost of neurological deterioration. We sought to assess whether the use of an intraoperative MRI (iMRI) in combination with multimodal neurophysiological monitoring is suitable to increase the extent of resection without endangering neurological function in patients with eloquently located gliomas. Fifty-four patients were included in this study. In 21 patients (38.9 %), iMRI led to additional tumor resection. A radiologically complete resection was achieved in 31 patients (57.4 %), while in 12 of these, iMRI had depicted residual tumor tissue before resection was continued. The mean extent of resection was 92.1 % according to volumetric analyses. Postoperatively, 13 patients (24.1 %) showed new or worsening of pre-existing sensory motor deficits. They were severe in 4 patients (7.4 %). There was no correlation between the occurrence of either any new (P = 0.77) or severe (P = 1.0) sensory motor deficit and continued resection after intraoperative image acquisition. Likewise, tumor location, histology, and tumor recurrence did not influence complication rate on uni- and multivariate analysis. We conclude that the combination of iMRI guidance with multimodal neurophysiological monitoring allows for extended resections in glioma surgery without inducing higher rates of neurological deficits, even in patients with eloquently located tumors.

Detection and grading of dAVF: prospects and limitations of 3T MRI.

OBJECTIVES: DSA is currently the criterion standard for the assessment of dural arteriovenous fistulas (dAVF). Recently, evolving MRA techniques have emerged as a non-invasive alternative. The aim of this study is to assess the value of 3 T MRI in detecting and describing dAVF and to determine whether MRI can replace DSA as diagnostic procedure. METHODS: A total of 19 patients with dAVF and 19 without dAVF underwent the same MRI protocol, including 3D time-of-flight MRA and time-resolved contrast-enhanced MRA. The images were evaluated retrospectively by three independent readers with different levels of experience blinded to clinical information. The readers assessed the presence, the site, the venous drainage and the feeders of dAVF. Sensitivity, specificity, accuracy, intertechnique and interobserver agreements were calculated. RESULTS: DAVF can be detected with high sensitivity, specificity and accuracy by experienced and also by less experienced readers. However, MRI has limitations when used for grading and evaluation of the angioarchitecture of the dAVF. Different experience, the limited resolution of MRI and its inability to selectively display arteries were the reasons for these limitations. CONCLUSIONS: With MRI dAVF can be detected reliably. Nevertheless, at present MRI can not fully replace DSA, especially for treatment planning.

Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial.

BACKGROUND: Intraoperative MRI is increasingly used in neurosurgery, although there is little evidence for its use. We aimed to assess efficacy of intraoperative MRI guidance on extent of resection in patients with glioma. METHODS: In our prospective, randomised, parallel-group trial, we enrolled adults (≥18 years) with contrast enhancing gliomas amenable to radiologically complete resection who presented to Goethe University (Frankfurt, Germany). We randomly assigned patients (1:1) with computer-generated blocks of four and a sealed-envelope design to undergo intraoperative MRI-guided surgery or conventional microsurgery (control group). Surgeons and patients were unmasked to treatment group allocation, but an independent neuroradiologist was masked during analysis of all preoperative and postoperative imaging data. The primary endpoint was rate of complete resections as established by early postoperative high-field MRI (1·5 T or 3·0 T). Analysis was done per protocol. This study is registered with ClinicalTrials.gov, number NCT01394692. FINDINGS: We enrolled 58 patients between Oct 1, 2007, and July 1, 2010. 24 (83%) of 29 patients randomly allocated to the intraoperative MRI group and 25 (86%) of 29 controls were eligible for analysis (four patients in each group had metastasis and one patient in the intraoperative MRI group withdrew consent after randomisation). More patients in the intraoperative MRI group had complete tumour resection (23 [96%] of 24 patients) than did in the control group (17 [68%] of 25, p=0·023). Postoperative rates of new neurological deficits did not differ between patients in the intraoperative MRI group (three [13%] of 24) and controls (two [8%] of 25, p=1·0). No patient for whom use of intraoperative MRI led to continued resection of residual tumour had neurological deterioration. One patient in the control group died before 6 months. INTERPRETATION: Our study provides evidence for the use of intraoperative MRI guidance in glioma surgery: such imaging helps surgeons provide the optimum extent of resection. FUNDING: None.