Rare germline variants in POLE and POLD1 encoding the catalytic subunits of DNA polymerases ε and δ in glioma families.

Pathogenic germline variants in the DNA polymerase genes POLE and POLD1 cause polymerase proofreading-associated polyposis, a dominantly inherited disorder with increased risk of colorectal carcinomas and other tumors. POLE/POLD1 variants may result in high somatic mutation and neoantigen loads that confer susceptibility to immune checkpoint inhibitors (ICIs). To explore the role of POLE/POLD1 germline variants in glioma predisposition, whole-exome sequencing was applied to leukocyte DNA of glioma patients from 61 tumor families with at least one glioma case each. Rare heterozygous POLE/POLD1 missense variants predicted to be deleterious were identified in glioma patients from 10 (16%) families, co-segregating with the tumor phenotype in families with available DNA from several tumor patients. Glioblastoma patients carrying rare POLE variants had a mean overall survival of 21 months. Additionally, germline variants in POLD1, located at 19q13.33, were detected in 2/34 (6%) patients with 1p/19q-codeleted oligodendrogliomas, while POLE variants were identified in 2/4 (50%) glioblastoma patients with a spinal metastasis. In 13/15 (87%) gliomas from patients carrying POLE/POLD1 variants, features of defective polymerase proofreading, e.g. hypermutation, POLE/POLD1-associated mutational signatures, multinucleated cells, and increased intratumoral T cell response, were observed. In a CRISPR/Cas9-derived POLE-deficient LN-229 glioblastoma cell clone, a mutator phenotype and delayed S phase progression were detected compared to wildtype POLE cells. Our data provide evidence that rare POLE/POLD1 germline variants predispose to gliomas that may be susceptible to ICIs. Data compiled here suggest that glioma patients carrying POLE/POLD1 variants may be recognized by cutaneous manifestations, e.g. café-au-lait macules, and benefit from surveillance colonoscopy.

SlicerCBM: automatic framework for biomechanical analysis of the brain.

PURPOSE: Brain shift that occurs during neurosurgery disturbs the brain's anatomy. Prediction of the brain shift is essential for accurate localisation of the surgical target. Biomechanical models have been envisaged as a possible tool for such predictions. In this study, we created a framework to automate the workflow for predicting intra-operative brain deformations. METHODS: We created our framework by uniquely combining our meshless total Lagrangian explicit dynamics (MTLED) algorithm for computing soft tissue deformations, open-source software libraries and built-in functions within 3D Slicer, an open-source software package widely used for medical research. Our framework generates the biomechanical brain model from the pre-operative MRI, computes brain deformation using MTLED and outputs results in the form of predicted warped intra-operative MRI. RESULTS: Our framework is used to solve three different neurosurgical brain shift scenarios: craniotomy, tumour resection and electrode placement. We evaluated our framework using nine patients. The average time to construct a patient-specific brain biomechanical model was 3 min, and that to compute deformations ranged from 13 to 23 min. We performed a qualitative evaluation by comparing our predicted intra-operative MRI with the actual intra-operative MRI. For quantitative evaluation, we computed Hausdorff distances between predicted and actual intra-operative ventricle surfaces. For patients with craniotomy and tumour resection, approximately 95% of the nodes on the ventricle surfaces are within two times the original in-plane resolution of the actual surface determined from the intra-operative MRI. CONCLUSION: Our framework provides a broader application of existing solution methods not only in research but also in clinics. We successfully demonstrated the application of our framework by predicting intra-operative deformations in nine patients undergoing neurosurgical procedures.

Eloquent Lower Grade Gliomas, a Highly Vulnerable Cohort: Assessment of Patients' Functional Outcome After Surgery Based on the LoG-Glio Registry.

Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, while occurrence was only 14% at 9-12-month follow up. 6/7 patients with mild aphasia recovered after 9-12 months, while motor deficits present at 3-month follow up were persistent in majority of patients. Eastern oncology group functional status (ECOG) significantly decreased by surgery (p < 0.001) in 31% of cases. Between 3-month and 9-12-months follow up no significant improvement was seen. In the multivariable model CTR (p=0.019, OR 31.9), and ECOG>0 (p=0.021, OR 8.5) were independent predictors for permanent postoperative deficit according to NIHSS at 3-month according to multivariable regression model. Patients harboring eloquently located LGG are highly vulnerable for permanent deficits. Almost one third of patients have a permanent reduction of their functional status based on ECOG. Risk of an extended resection has to be balanced with the respective oncological benefit. Especially, patients with impaired pre-operative status are at risk for new permanent deficits. There is a relevant improvement of neurological symptoms in the first year after surgery, especially for patients with slight aphasia.

Automatic framework for patient-specific modelling of tumour resection-induced brain shift.

Our motivation is to enable non-biomechanical engineering specialists to use sophisticated biomechanical models in the clinic to predict tumour resection-induced brain shift, and subsequently know the location of the residual tumour and its boundary. To achieve this goal, we developed a framework for automatically generating and solving patient-specific biomechanical models of the brain. This framework automatically determines patient-specific brain geometry from MRI data, generates patient-specific computational grid, assigns material properties, defines boundary conditions, applies external loads to the anatomical structures, and solves differential equations of nonlinear elasticity using Meshless Total Lagrangian Explicit Dynamics (MTLED) algorithm. We demonstrated the effectiveness and appropriateness of our framework on real clinical cases of tumour resection-induced brain shift.

Computer simulation of tumour resection-induced brain deformation by a meshless approach.

Tumour resection requires precise planning and navigation to maximise tumour removal while simultaneously protecting nearby healthy tissues. Neurosurgeons need to know the location of the remaining tumour after partial tumour removal before continuing with the resection. Our approach to the problem uses biomechanical modelling and computer simulation to compute the brain deformations after the tumour is resected. In this study, we use meshless Total Lagrangian explicit dynamics as the solver. The problem geometry is extracted from the patient-specific magnetic resonance imaging (MRI) data and includes the parenchyma, tumour, cerebrospinal fluid and skull. The appropriate non-linear material formulation is used. Loading is performed by imposing intra-operative conditions of gravity and reaction forces between the tumour and surrounding healthy parenchyma tissues. A finite frictionless sliding contact is enforced between the skull (rigid) and parenchyma. The meshless simulation results are compared to intra-operative MRI sections. We also calculate Hausdorff distances between the computed deformed surfaces (ventricles and tumour cavities) and surfaces observed intra-operatively. Over 80% of points on the ventricle surface and 95% of points on the tumour cavity surface were successfully registered (results within the limits of two times the original in-plane resolution of the intra-operative image). Computed results demonstrate the potential for our method in estimating the tissue deformation and tumour boundary during the resection.

Registration of vascular structures using a hybrid mixture model.

PURPOSE: Morphological changes to anatomy resulting from invasive surgical procedures or pathology, typically alter the surrounding vasculature. This makes it useful as a descriptor for feature-driven image registration in various clinical applications. However, registration of vasculature remains challenging, as vessels often differ in size and shape, and may even miss branches, due to surgical interventions or pathological changes. Furthermore, existing vessel registration methods are typically designed for a specific application. To address this limitation, we propose a generic vessel registration approach useful for a variety of clinical applications, involving different anatomical regions. METHODS: A probabilistic registration framework based on a hybrid mixture model, with a refinement mechanism to identify missing branches (denoted as HdMM+) during vasculature matching, is introduced. Vascular structures are represented as 6-dimensional hybrid point sets comprising spatial positions and centerline orientations, using Student's t-distributions to model the former and Watson distributions for the latter. RESULTS: The proposed framework is evaluated for intraoperative brain shift compensation, and monitoring changes in pulmonary vasculature resulting from chronic lung disease. Registration accuracy is validated using both synthetic and patient data. Our results demonstrate, HdMM+ is able to reduce more than [Formula: see text] of the initial error for both applications, and outperforms the state-of-the-art point-based registration methods such as coherent point drift and Student's t-distribution mixture model, in terms of mean surface distance, modified Hausdorff distance, Dice and Jaccard scores. CONCLUSION: The proposed registration framework models complex vascular structures using a hybrid representation of vessel centerlines, and accommodates intricate variations in vascular morphology. Furthermore, it is generic and flexible in its design, enabling its use in a variety of clinical applications.

Non-invasive qualitative and semiquantitative presurgical investigation of the feeding vasculature to intracranial meningiomas using superselective arterial spin labeling.

BACKGROUND: Intracranial meningiomas may be amenable to presurgical embolization to reduce bleeding complications. Detailed information usually obtained by digital subtraction angiography (DSA) on the contribution of blood supply from internal and external carotid artery branches is required to prevent non-target embolization and is helpful for pre-surgical planning. PURPOSE: To investigate the contribution of the feeding vasculature to intracranial meningiomas with superselective arterial spin labelling (sASL) as an alternative to DSA. MATERIAL AND METHODS: Consecutive patients presenting for meningioma resection were prospectively included. sASL perfusion images acquired on a clinical 3T MRI scanner were independently rated by two readers. Contribution of the external carotid artery (ECA), internal carotid artery (ICA) and vertebral/basilar artery (VA/BA) was rated as none, <50% or >50%. Correlation of sASL was performed in two patients undergoing DSA. RESULTS: 32 patients (61 ± 13 years) harboring 42 meningiomas could be included. sASL was technically successful in all patients. 19 meningiomas had ICA dominant supply, 19 had ECA dominant supply. One meningioma had mixed supply and in three meningiomas a perfusion signal could not be detected. While exclusive unilateral ECA supply was common (n = 14) and exclusive unilateral ICA was rare (n = 4), mixed supply from multiple vessels (n = 20) was a frequent finding. Interrater agreement was substantial (κ = 0.73). Agreement with DSA was perfect within our predefined categories. CONCLUSION: sASL is able to identify the presence and extent of the feeding vasculature in intracranial meningiomas.

Magnetic Resonance Imaging-Apparent Diffusion Coefficient Assessment of Vestibular Schwannomas: Systematic Approach, Methodology, and Pitfalls.

OBJECTIVE: To investigate the validity of various approaches to extract quantitative measurements of diffusion imaging (i.e., apparent diffusion coefficient [ADC]) to investigate tumors of the central nervous system. In current studies, the region of interest (ROI) for the quantitative measurements are placed arbitrarily according to morphology. Our aim is to investigate how placement patterns influence the ADC estimation in intracranial tumors. METHODS: Twenty consecutive patients affected by vestibular schwannoma were studied using diffusion imaging. ADC values were obtained using different ROI placement methods: segmentation ADC values of the entire volume (vADC), random ADC values were obtained in 10 different ROI points, and a single ROI in the ADC of the internal auditory canal portion of the tumor. RESULTS: ADC of the internal auditory canal portion of the tumor and vADC differed significantly (P < 0.01). vADC was different between cystic and microcystic schwannomas (P = 0.009) and between cystic and solid schwannomas (P = 0.006). CONCLUSIONS: The positioning of ROI in these measurements is pivotal. Although "whole tumor volume" measurements represent the largest amount of information, multiple seed points can be used as well. However, there must be multiple seeds and their placement must be reported. ADC can be used as a versatile tool for tumor assessment but must be used judiciously and structured to yield comparable results.

Computer-assisted planning for a concentric tube robotic system in neurosurgery.

PURPOSE: Laser-induced thermotherapy in the brain is a minimally invasive procedure to denature tumor tissue. However, irregularly shaped brain tumors cannot be treated using existing commercial systems. Thus, we present a new concept for laser-induced thermotherapy using a concentric tube robotic system. The planning procedure is complex and consists of the optimal distribution of thermal laser ablations within a volume as well as design and configuration parameter optimization of the concentric tube robot. METHODS: We propose a novel computer-assisted planning procedure that decomposes the problem into task- and robot-specific planning and uses a multi-objective particle swarm optimization algorithm with variable length. RESULTS: The algorithm determines a Pareto-front of optimal ablation distributions for three patient datasets. It considers multiple objectives and determines optimal robot parameters for multiple trajectories to access the tumor volume. CONCLUSIONS: We prove the effectiveness of our planning procedure to enable the treatment of irregularly shaped brain tumors. Multiple trajectories further increase the applicability of the procedure.

Contemporary use of intraoperative imaging in glioma surgery: A survey among EANS members.

OBJECTIVES: In glioma surgery, intraoperative imaging is regarded highly valuable to improve extent of resection. Current distribution of intraoperative imaging techniques is largely unknown. Further, controversy exists which method might be most beneficial. PATIENTS AND METHODS: We performed a web-based survey among members of the European Association of Neurological Surgeons(EANS) from April to May 2017. Our questionnaire included intraoperative MRI(iMRI), 5-aminolevulinic acid(5-ALA), intraoperative ultrasound(iUS),Na-Fluorescein and intraoperative CT(iCT). The value of each method in resection of glioblastoma(GB) and low-grade-glioma(LGG) and their role for intraoperative orientation and usability were rated based on Likert-scales from 1(not valuable/important) to 5(very valuable/important). A total score was calculated based on each sub-score. Mann-Whitney-U-test was used to compare ratings of imaging methods. RESULTS: Among the 310 participants, iMRI and 5-ALA were regarded as the most valuable intraoperative imaging methods in GB-surgery (iMRIvs.5-ALA,p=0.573;mean 4.05(SE0.149)vs.4.22(SE0.216)). Both were considered significantly more valuable than iUS, Na-Fluorescein and iCT(p≤0.001).Compared to all other methods, iMRI received significantly higher ratings for the resection of LGGs (p<0.01,mean 4.21(SE 0.143)) as well as for intraoperative orientation (mean 4.00(SE0.166)).5-ALA was rated highest regarding intraoperative usability (mean 4.07(SE0.082)). iMRI showed the highest total score compared to all other imaging modalities(p<0.001,mean 15.95(SE 0.484)). CONCLUSION: iMRI and 5-ALA were rated most valuable for GB-surgery, while only iMRI reached higher ratings in LGG cases. iMRI was the best imaging method for intraoperative orientation as well as the most valuable method in overall rating. Considering the total score, 5-ALA and iUS received similar values and were rated second highest, followed by Na-Fluorescein and iCT.

A Survey of auditory display in image-guided interventions.

PURPOSE: This article investigates the current state of the art of the use of auditory display in image-guided medical interventions. Auditory display is a means of conveying information using sound, and we review the use of this approach to support navigated interventions. We discuss the benefits and drawbacks of published systems and outline directions for future investigation. METHODS: We undertook a review of scientific articles on the topic of auditory rendering in image-guided intervention. This includes methods for avoidance of risk structures and instrument placement and manipulation. The review did not include auditory display for status monitoring, for instance in anesthesia. RESULTS: We identified 15 publications in the course of the search. Most of the literature (60%) investigates the use of auditory display to convey distance of a tracked instrument to an object using proximity or safety margins. The remainder discuss continuous guidance for navigated instrument placement. Four of the articles present clinical evaluations, 11 present laboratory evaluations, and 3 present informal evaluation (2 present both laboratory and clinical evaluations). CONCLUSION: Auditory display is a growing field that has been largely neglected in research in image-guided intervention. Despite benefits of auditory displays reported in both the reviewed literature and non-medical fields, adoption in medicine has been slow. Future challenges include increasing interdisciplinary cooperation with auditory display investigators to develop more meaningful auditory display designs and comprehensive evaluations which target the benefits and drawbacks of auditory display in image guidance.

Evaluation of Diffusion Tensor Imaging-Based Tractography of the Corticospinal Tract: A Correlative Study With Intraoperative Magnetic Resonance Imaging and Direct Electrical Subcortical Stimulation.

Background: The accuracy of intraoperative diffusion tensor imaging (DTI)­based tractography of the corticospinal tract (CST) is crucial for its use in neurosurgical planning and its implementation in image-guided surgery. To the best of our knowledge, this is the largest prospective correlative study of the intraoperative DTI tractography of the CST and intraoperative direct electrical subcortical stimulation (DESS) of the CST, with application of intraoperative magnetic resonance imaging (iMR). Objective: To evaluate intraoperatively acquired DTI-based tractography of the CST in correlation with DESS. Methods: Twenty patients with gliomas (grades II-IV) adjacent to the CST were included in this prospective study. Bilateral DTI tractography of the CST was performed pre- and intraoperatively with application of 1.5-T iMRI and the results correlated and compared with the prevailing gold standard of DESS. Sensitivity, specificity, positive predictive value, and negative predictive value were considered to quantify the correlation of DTI tractography with DESS. The intensity of DESS was correlated with the distance from the CST. Moreover, the tissue quality of stimulation points at the wall of the resection cavity was evaluated with 5-aminolevulinic acid. The clinical and volumetric outcomes at postoperative and follow-up periods were also analyzed. Results: The mean ± SD age of the patients was 54.9 ± 12 years. A total of 40 CSTs were reconstructed and 36 stimulations were included at 20 pathological CSTs, resulting in 18 true-positive, 5 false-positive, and 13 true-negative responses. The sensitivity, specificity, positive predictive value, and negative predictive value of DTI tractography to localize the CST were 100%, 72%, 78%, and 100%, respectively. DTI-based tractography correlated well at 86% of DESSs, and a linear correlation was detected between the intensity of DESS and the distance. All of the patients improved clinically, and the mean extent of resection was 97.2%. 5-Aminolevulinic acid was valuable in visualizing tumor infiltration in the false-positive cases, suggesting an infiltration of the CST at stimulation points. Conclusion: CST visualization in the iMRI setting appears to have a high sensitivity in accurately localizing the area of the CST adjacent to the resection cavity in glioma surgery. More prospective studies with a large sample size are needed to further support the results.

Role of Delta-Notch signaling in cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) commonly known as cavernous hemangioma are associated with abnormally enlarged thin-walled blood vessels. As a result, these dilated capillaries are prone to leakage and result in hemorrhages. Clinically, such hemorrhages lead to severe headaches, focal neurological deficits, and epileptic seizures. CCM is caused by loss of function mutations in one of the three well-known CCM genes: Krev interaction trapped 1 (KRIT1), OSM, and programmed cell death 10 (PDCD10). Loss of CCM genes have been shown to be synergistically related to decreased Notch signaling and excessive angiogenesis. Despite recent evidences indicating that Notch signaling plays a pivotal role in regulating angiogenesis, the role of Notch in CCM development and progression is still not clear. Here, we provide an update literature review on the current knowledge of the structure of Notch receptor and its ligands, its relevance to angiogenesis and more precisely to CCM pathogenesis. In addition to reviewing the current literatures, this review will also focus on the cross talk between Delta-Notch and vascular endothelial growth factor (VEGF) signaling in angiogenesis and in CCM pathogenesis. Understanding the role of Notch signaling in CCM development and progression might help provide a better insight for novel anti-angiogenic therapies.

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging.

BACKGROUND: The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published. OBJECTIVE: To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging. METHODS: A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment. RESULTS: A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P < .01), whereas "failed" GTR did not differ significantly from intended subtotal-resection. Combined radiochemotherapy as adjuvant therapy was a negative prognostic factor (hazard ratio: 2.84, P < .01). Field strength of iMRI was not associated with PFS. In the binary logistic regression model, use of high-field iMRI (odds ratio: 0.51, P < .01) was positively and eloquent location (odds ratio: 1.99, P < .01) was negatively associated with GTR. GTR was not associated with increased rates of new permanent neurological deficits. CONCLUSION: GTR was an independent positive prognostic factor for PFS in LGG surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS. ABBREVIATIONS: EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor Imaging Tractography for Neurosurgery.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop. METHODS: Eight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods. RESULTS: The evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues. CONCLUSIONS: The DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making.

Assessment of quantitative corticospinal tract diffusion changes in patients affected by subcortical gliomas using common available navigation software.

OBJECTIVE: The aim of this study is to analyze the quantitative DTI parameters of the CST in patients suffering from subcortical gliomas affecting the CST using generally available navigation software. METHODS: A retrospective study was conducted on 22 subjects with diagnosis of primary cerebral glioma and preoperative motor deficits. Exclusion criteria were: involvement of motor cortex, lesion involving both hemispheres, previous surgical treatment. All patients were studied using magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) sequences. Volume, fractional anisotropy (FA) and mean diffusivity value (MD) of the entire CSTs were estimated. Moreover, distance from midline, diameters, FA and MD were calculated on axial images at the point of minimal distance between tumor and CST. Statistical analysis was performed. RESULTS: There was a statistically significant difference of CST volume between affected and non-affected hemispheres (p<0.01). Mean overall/local FA, overall/local MD and sagittal diameter of CST were also significantly different between the two sides (p<0.05). Correlation tests resulted positive between the shift of CST and overall/local MD. Moreover there is significance between CST volume of tumor hemisphere and preoperative duration of motor deficits (p<0.05). CONCLUSION: The present study has demonstrated for the first time a significant difference of DTI based quantitative parameters of the CST between a tumor affected and a non-affected hemisphere in patients with a corresponding motor deficit. This preliminary data suggests a correlation between DTI based integrity of CST and its function.

Neuroendoscopy and high-field intraoperative MRI: first experience.

BACKGROUND: To date, information about the use of intraoperative MRI (iMRI) in patients undergoing neuroendoscopic procedures is sparse. The benefit may be (re)definition of neuronavigation, confirmation of fenestrations and biopsies, detection of complications, and redefinition of anatomical changes during the operation. MATERIAL AND METHODS: Our setting consists of a fully integrated high-field 1.5-T MRI into the operating room. The operating room can be functionally divided into (1) the MRI scanner and (2) the operating table outside the 5 Gauss line where ferromagnetic surgical instruments can be used. We included a consecutive series of 11 adult patients who underwent 11 endoscopic operations in the iMRI setting between January 2007 and September 2011. RESULTS: The median age of patients was 54 years (range: 40-69 years). The male-to-female ratio was 4.5:1. Diagnoses leading to endoscopic treatment were aqueductal stenosis (n = 8; caused by tumors in three cases), pineal cyst (n = 1), tumor of the third ventricle (n = 1), and brain abscess with ventriculitis (n = 1). Endoscopic procedures were endoscopic third ventriculostomy with or without tumor biopsy (n = 5), aqueductoplasty (n = 4), tumor biopsy and septostomy (n = 1), and tumor resection (n = 1). All patients were scanned at least once, seven patients twice during surgery. The mean scan time per procedure was 19 minutes. The following sequences were regarded as most useful: T2 axial (placement of catheter, ruling out of complications), T2 sagittal (flow void signal), and true fast imaging (TRUFI) (fenestration defect). CONCLUSIONS: iMRI enables high-resolution imaging immediately after endoscopic operation. The combined use is technically feasible and of potential value in selected cases with complex hydrocephalus. In most of these cases, scanning can be limited to T2 axial, T2 sagittal, and TRUFI MR images.

Superselective arterial spin labeling applied for flow territory mapping in various cerebrovascular diseases.

In three example patients suffering from internal carotid artery occlusion, intracranial steno-occlusive disease, and symptomatic arteriovenous malformation (AVM), a new method named superselective pseudo-continuous arterial spin labeling (pCASL) was used in addition to clinical routine measurements. The capabilities of this method are demonstrated to gain important information in diagnosis, risk analysis, and treatment monitoring that are neither accessible by digital subtraction angiography nor by existing selective arterial spin labeling methods and thus to propose future applications in clinical routine. In all cases superselective pCASL enabled the assessment of tissue viability and of territorial brain perfusion at different levels starting from major brain feeding vessels to collateral circulation at the level of the Circle of Willis to even distal branching arteries. This made it possible to estimate the contribution of an extracranial-intracranial bypass to the brain perfusion; to depict individual arteries to important functional brain areas; to identify en-passant feeding vessels of an AVM and to track possible changes in their perfusion territories after intervention.

Growth pattern of tumor recurrence following bis-chloroethylnitrosourea (BCNU) wafer implantation in malignant glioma.

Bis-chloroethylnitrosourea (BCNU; Gliadel, Eisai, Tokyo, Japan) is the only therapeutic agent for local chemotherapy of malignant gliomas approved by the US Food and Drug Administration and the European Medicines Agency. In a small patient cohort, it has previously been shown that glioblastomas recur locally despite treatment with BCNU. This raises concern about local treatment with BCNU as a stand-alone measure. The goal of this study was to analyze the growth pattern of tumor recurrence in a larger patient group: 41 patients were included in this study. Tumor recurrences were morphologically categorized as: local, diffuse, distant or multilocular. Thirty-three of the tumors (80%) that recurred were local or diffuse. These results show that BCNU implantation does not provide lasting local tumor control. Our data support the need to incorporate BCNU in to multimodal therapy schemes. The improved survival rates of patients who receive concomitant local and systemic adjuvant treatment support using local therapy to bridge the therapy-free interval of the initial postoperative phase.