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Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

We prospectively investigated how to integrate indocyanine green (ICG) angiography in an augmented reality (AR) setting for aneurysm surgery.In 20 patients with a total of 22 aneurysms, the head-up display of the operating microscope (Kinevo900) was used for AR. ICG-AR was established directly by the head-up display superimposing the ICG angiography as green live video overlay. In addition, the reconstructed outline of the three-dimensional (3D) vessel architecture was visualized by AR applying intraoperative low-dose computed tomography (vessel-AR).In all patients, ICG-AR and vessel-AR were successfully implemented. The flow in the vessels could be observed directly in the white light view of the microscope oculars without being distracted from the surgical site by looking on separate screens. This factor enabled also surgical manipulation during ICG angiography. In parallel, AR additionally visualized the 3D vessel architecture, enhancing the understanding of the 3D anatomy (target registration error, 0.71 ± 0.21 mm; intraoperative low-dose computed tomography effective dose, 42.7 μSv). Linear (n = 28; range, 1-8.5 mm) and rotational (n = 3; range, 2.9°-14.4°) navigation adjustments performed in 18 of 20 patients resulted in a close matching of the vessel-AR outline with the real vessel situation after preparation, compensating for shifting.ICG-AR could be successfully implemented. It facilitated surgical manipulation and flow interpretation during ICG angiography because it could be observed directly while looking through the microscope oculars in white light instead of being distracted from the surgical site while looking on separate screens. Additional AR visualizing the vessel architecture improved understanding of 3D anatomy for preparation and clipping.

Glioblastoma multiforme (GBM) is the most aggressive type of brain cancer with a median survival of only 15 months. To complement standard treatments including surgery, radiation and chemotherapy, it is essential to understand the contribution of the GBM tumor microenvironment. Brain macrophages and microglia particularly contribute to tumor angiogenesis, a major hallmark of GBM. ADAM8, a metalloprotease-disintegrin strongly expressed in tumor cells and associated immune cells of GBMs, is related to angiogenesis and correlates with poor clinical prognosis. However, the specific contribution of ADAM8 to GBM tumorigenesis remains elusive. Knockdown of ADAM8 in U87 glioma cells led to significantly decreased angiogenesis and tumor volumes of these cells after stereotactic injection into striate body of mice. We found that the angiogenic potential of ADAM8 in GBM cells and in primary macrophages is mediated by the regulation of osteopontin (OPN), an important inducer of tumor angiogenesis. By in vitro cell signaling analyses, we demonstrate that ADAM8 regulates OPN via JAK/STAT3 pathway in U87 cells and in primary macrophages. As ADAM8 is a dispensable protease for physiological homeostasis, we conclude that ADAM8 could be a tractable target to modulate angiogenesis in GBM with minor side-effects.

Study Design: A prospective, case-based, observational study. Objectives: To investigate how microscope-based augmented reality (AR) support can be utilized in various types of spine surgery. Methods: In 42 spinal procedures (12 intra- and 8 extradural tumors, 7 other intradural lesions, 11 degenerative cases, 2 infections, and 2 deformities) AR was implemented using operating microscope head-up displays (HUDs). Intraoperative low-dose computed tomography was used for automatic registration. Nonlinear image registration was applied to integrate multimodality preoperative images. Target and risk structures displayed by AR were defined in preoperative images by automatic anatomical mapping and additional manual segmentation. Results: AR could be successfully applied in all 42 cases. Low-dose protocols ensured a low radiation exposure for registration scanning (effective dose cervical 0.29 ± 0.17 mSv, thoracic 3.40 ± 2.38 mSv, lumbar 3.05 ± 0.89 mSv). A low registration error (0.87 ± 0.28 mm) resulted in a reliable AR representation with a close matching of visualized objects and reality, distinctly supporting anatomical orientation in the surgical field. Flexible AR visualization applying either the microscope HUD or video superimposition, including the ability to selectively activate objects of interest, as well as different display modes allowed a smooth integration in the surgical workflow, without disturbing the actual procedure. On average, 7.1 ± 4.6 objects were displayed visualizing target and risk structures reliably. Conclusions: Microscope-based AR can be applied successfully to various kinds of spinal procedures. AR improves anatomical orientation in the surgical field supporting the surgeon, as well as it offers a potential tool for education.

Objective To integrate 3-dimensional (3D) intraoperative ultrasound (iUS) data in spinal navigation. Methods In 11 patients with intradural spinal tumors, 3D-iUS was performed before and after tumor resection. Intraoperative computed tomography (iCT) was used for automatic patient registration for spinal navigation; fiducial-based registration was performed in 1 case. The outlines of the vertebra were defined in preoperative image data by automatic mapping; risk and target structures were segmented manually; all these data were rigidly and if necessary non-rigidly registered with iCT. For 3D-iUS acquisition, tracked convex-shaped transducers (contact surface: 29 x 10 mm; scanning frequency: 10–3.8 MHz or 13–5 MHz) were used. Results Navigated 3D-iUS was successfully implemented in all cases; 3D-iUS datasets were acquired and could be used as 3D image data for further navigation after iUS scanning. The 3D objects defined in preoperative image data, outlining the vertebra, target and risk structures, could be visualized in the 3D-iUS data. Navigated 3D-iUS allowed to reliably evaluate the extent of resection in all cases and updating of navigation, ensuring high navigational accuracy. The target registration error applying iCT-based automatic registration was 0.78 ± 0.23 mm. The effective dose for iCT was 0.11 ± 0.077 mSv for cervical and 1.75 ± 0.72 mSv for thoracic scans. Conclusions Using 3D-iUS can be successfully integrated in spinal navigation. Automatic registration applying low-dose iCT and non-linear image registration offers displaying preoperative images in the same orientation as the 3D-iUS scan, as well as visualizing segmented structures in the navigated 3D-iUS data. This greatly facilitates image interpretation. Navigated 3D-iUS provides a possibility for navigation updating and immediate online quality control.

Microscope-based augmented reality (AR) is commonly used in cranial surgery; however, until recently, this technique was not implemented for spinal surgery. We prospectively investigated, how AR can be applied for intradural spinal tumor surgery. For ten patients with intradural spinal tumors (ependymoma, glioma, hemangioblastoma, meningioma, and metastasis), AR was provided by head-up displays (HUDs) of operating microscopes. User-independent automatic AR registration was established by low-dose intraoperative computed tomography. The objects visualized by AR were segmented in preoperative imaging data; non-linear image registration was applied to consider spine flexibility. In all cases, AR supported surgery by visualizing the tumor outline and other relevant surrounding structures. The overall AR registration error was 0.72 ± 0.24 mm (mean ± standard deviation), a close matching of visible tumor outline and AR visualization was observed for all cases. Registration scanning resulted in a low effective dose of 0.22 ± 0.16 mSv for cervical and 1.68 ± 0.61 mSv for thoracic lesions. The mean HUD AR usage in relation to microscope time was 51.6 ± 36.7%. The HUD was switched off and turned on again in a range of 2 to 17 times (5.7 ± 4.4 times). Independent of the status of the HUD, the AR visualization was displayed on monitors throughout surgery. Microscope-based AR can be reliably applied to intradural spinal tumor surgery. Automatic AR registration ensures high precision and provides an intuitive visualization of the extent of the tumor and surrounding structures. Given this setting, all advanced multi-modality options of cranial AR can also be applied to spinal surgery.

We investigated how augmented reality (AR) can be applied to support transsphenoidal surgery.AR was established using the head-up displays integrated into operating microscopes. Navigation registration was performed with either fiducial-based or automatic registration using intraoperative computed tomography (iCT). Correct microscope calibration was ensured by checking the geometric overlap between the AR representation of the reference array and the 3-dimensional reality while focusing on the reference array.From a consecutive single-surgeon series of 288 transsphenoidal procedures, 47 patients (16.3%) had undergone microscope-based AR to visualize the target and risk structures. AR was smoothly integrated into the surgical workflow. AR accuracy depended on navigation accuracy and microscope calibration. The target registration error in patients with fiducial-based registration was 2.33 ± 1.30 mm. Automatic, user-independent iCT-based registration significantly (P0.001) increased AR accuracy (target registration error, 0.83 ± 0.44 mm). Applying low-dose iCT protocols reduced the effective dose caused by iCT registration scanning to within the range of a single chest radiograph (0.041 mSv). No vascular injuries and no aggravation of neurological deficits occurred in the present series. AR greatly facilitated orientation in the reoperations and the patients with anatomical variants, thereby increasing surgeon comfort. Enhanced AR visualizations improved the 3-dimensional perception compared with the standard display of dashed lines by the head-up display of the operating microscope.Microscope-based AR is a reliable tool to increase patient safety in complicated transsphenoidal procedures. Intraoperative imaging-based automatic patient registration is recommended.

Over the last years, diffusion imaging techniques like DTI, DSI or Q-Ball received increasing attention, especially in the neuroimaging, neurological, and neurosurgical community. An explicit geometrical reconstruction of major white matter tracts has become available by fiber tracking based on diffusion-weighted images. The goal of virtually all fiber tracking algorithms is to compute results which are analogous to what the physicians or radiologists are expecting and an extensive amount of research has therefore been focussed on this reconstruction. However, the results of fiber tracking and quantification algorithms are approximations of the reality due to limited spatial resolution (typically a few millimeters), model assumptions (e.g., diffusion assumed to be Gaussian distributed), user-defined parameter settings, and physical imaging artifacts resulting from diffusion sequences. In this book chapter, we will address the problem of uncertainty in diffusion imaging and we will show possible solutions for minimizing, measuring and visualizing the uncertainty. The possibility of fiber tracking (FT) and the quantification of diffusion parameters has established an abundance of new clinically useful applications and research studies that focus on neurosurgical planning (Nimsky et al., 2005), monitoring the progression of diseases such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS) (Griffin et al., 2001), establishing surrogate markers used in assessing the grade of brain tumors (Barboriak, 2003), or initiating therapies to ensure the best possible development of children (Pul et al., 2006). Several studies have shown that modified values of fractional anisotropy (FA), relative anisotropy, or diffusion strength (ADC) are indicators of diseases that affect white matter tissue. MS lesions have been investigated by ROI-based analysis and voxel-wise FA comparisons by which FA changes have been shown to occur in areas containing lesions and in areas of normalappearing white matter. Moreover, methods for tract-based quantification have been developed for which parameters are computed depending on the local curvature or geodesic distance from a user-defined origin. These methods allow to automatically determine DTIderived parameters along fiber bundles and have already been used to mirror disease progression and executive function in MS (Fink et al., 2009). Probabilistic methods (Friman et al., 2006) allow for tracking in regions of low anisotropy and are also used to provide a quantitative measure of the probability of the existence of a connection between two regions. These approaches aim at visualizing the uncertainty present 1

Objective: This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and ex- tratemporal lobe epilepsy (ETLE), as well as in asymptomatic cases. Methods: Four hundred fifty-eight magnetic resonance imaging scans were exam- ined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs). Results: At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval [CI] = 5.3%–15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%–7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%–5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC sub- jects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723–1.00, p = .001). Significance: Temporal encephaloceles may occur without presenting any clinical symp- toms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity.

Background The need for imaging-guided optimization of Deep Brain Stimulation (DBS) parameters is increasing with recent developments of sophisticated lead designs offering highly individualized, but time-consuming and complex programming. Objective The objective of this study was to compare changes in motor symptoms of Parkinson's Disease (PD) and the corresponding volume of the electrostatic field (VEsF) achieved by DBS programming using GUIDE XT™, a commercially available software for visualization of DBS leads within the patient-specific anatomy from fusions of preoperative magnetic resonance imaging (MRI) and postoperative computed tomography (CT) scans, versus standard-of-care clinical programming. Methods Clinical evaluation was performed to identify the optimal set of parameters based on clinical effects in 29 patients with PD and bilateral directional leads for Subthalamic Nucleus (STN) DBS. A second DBS program was generated in GUIDE XT™ based on a VEsF optimally located within the dorsolateral STN. Reduction of motor symptoms (Movement Disorders Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS) and the overlap of the corresponding VEsF of both programs were compared. Results Clinical and imaging-guided programming resulted in a significant reduction in the MDS-UPDRS scores compared to off-state. Motor symptom control with GUIDE XT™-derived DBS program was non-inferior to standard clinical programming. The overlap of the two VEsF did not correlate with the difference in motor symptom reduction by the programs. Conclusions Imaging-guided programming of directional DBS leads using GUIDE XT™ is possible without computational background and leads to non-inferior motor symptom control compared with clinical programming. DBS programs based on patient-specific imaging data may thus serve as starting point for clinical testing and may promote more efficient DBS programming.

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.

We describe a case of 49-years old female with a medical history of penicillin allergy, who suffered from brain infection caused by Actinomyces israelii. Therefore, the available therapy was metronidazole, ceftriaxone, and chloramphenicol. Due to a deterioration of the general and neurological condition of the patient, it was decided to perform a scratch skin test on penicillin, which was negative. After that, penicillin was administrated parenterally. The patient showed no hypersensitive reaction. Improvement was achieved. The patient underwent three subsequent surgeries due to primary and recurrent brain abscesses. There was a distinct improvement in her clinical status. Two months after the second re-surgery, the control computed tomography showed complete regression of the abscess. Brain abscess caused by an Actinomycess israelii is very resistant to medication. However, surgical evacuation significantly accelerates the healing process. A good medication therapy is crucial and in most cases the drug of choice is penicillin. We emphasize the importance of a combined approach for treating this unusual brain infection.

Background: Patients&rsquo, fear of the coronavirus disease 2019 (COVID-19) may delay inevitable treatment, putting potential benefits at risk. This single-center retrospective study aims to analyze temporal relationships of the first wave of the COVID-19 pandemic in Germany with the number of patients who sought and received elective neurosurgical treatment at a German university hospital. Methods: Daily outpatient numbers (ON) and elective procedures (EP) were recorded at our department between 1 January 2020 and 30 June 2020 (baseline: between 1 January 2019 and 30 June 2019). In patients who received EP, we recorded indication, outcome, and length of stay (LOS). Moving averages of ON (MAON) and of EP were calculated. Data on governmental action taken in response to the pandemic and on coronavirus-positive cases in Germany (CPCG) were superimposed. Exponential and arc tangent curves (ATC) were fitted to the absolute numbers of CPCG. Phase shifts were estimated, and Spearman&rsquo, s rank correlation coefficient, rho, was calculated between the 2020 MAON and the derivative function of the fitted ATC (DFATC). Wilcoxon rank sum served as statistical test. Significance was assumed with p values of less than 0.05. Results: ON were significantly decreased in April 2020 as compared to April 2019 (p = 0.010). A phase shift between the German lockdown, the DFATC, and the decrease in MAON was not detected, while a phase shift of 10 days between the DFATC and the subsequent increase in MAON was detected. The DFATC was significantly negatively correlated (rho = &minus, 0.92, p &lt, 0.0001) to the MAON until 31 March 2020, and, when shifted by 10 days, the DFATC was significantly negatively correlated (rho = &minus, 0.87, p &lt, 0.0001) to the MAON from 01 April 2020. EP (p = 0.023), including the subset of non-oncological EP (p = 0.032), were significantly less performed in the first half of 2020 as compared to the first half of 2019. In March and April 2020, we conducted significantly more EP due to motor deficits (p = 0.0267, and less), visual disturbances (p = 0.0488), and spinal instability (p = 0.0012), and significantly less EP due to radicular pain (p = 0.0489), as compared to March and April 2019. LOS ranked significantly higher in patients who received cranial or spinal EP in March and April 2020 as compared to March and April 2019 (p = 0.0497). Significant differences in outcome were not observed. Conclusion: The beginning of the COVID-19 pandemic was correlated to an immediate and significant decrease in ON, and to a significant decrease in the number of EP performed. The subsequent increase in ON was delayed. Adequate measures to promote timely discharge of patients may become increasingly relevant as the pandemic proceeds. Although we observed a shift in the range of indications towards significantly more EP in patients with neurological deficiencies, care should be taken to avoid potentially deleterious delays of necessary elective treatment in future pandemic situations.

Objective: The aim of this work was to compare fiducial-based and intraoperative computed tomography (iCT)-based registration for frameless stereotactic brain biopsy. Methods: Of 50 frameless stereotactic biopsies with the VarioGuide, 30 cases were registered as iCT based and 20 as fiducial based. Statistical analysis of the target registration error (TRE), dose length product, effective radiation dose (ED), operation time, and diagnostic yield was performed. Results: The mean TRE was significantly lower using iCT-based registration (mean ± SD: 0.70 ± 0.32 vs. 2.43 ± 0.73 mm, p < 0.0001). The ED was significantly lower when using iCT-based registration compared to standard navigational CT (mean ± SD: 0.10 ± 0.13 vs. 2.23 ± 0.34 mSv, p < 0.0001). Post-biopsy iCT was associated with a significant lower (p < 0.0001) ED compared to standard CT (mean ± SD: 1.04 ± 0.18 vs. 1.65 ± 0.26 mSv). The mean surgical time was shorter using iCT-based registration, although the mean total operating room (OR) time did not differ significantly. The diagnostic yield was 96.7% (iCT group) versus 95% (fiducial group). Post-biopsy imaging revealed severe bleeding in 3.3% (iCT group) versus 5% (fiducial group). Conclusion: iCT-based registration for frameless stereotactic biopsies increases the accuracy significantly without negative effects on the surgical time or the overall time in the OR. Appropriate scan protocols in iCT registration contribute to a significant reduction of the radiation exposure. The high accuracy of the iCT makes it the more favorable registration strategy when taking biopsies of small tumors or lesions near eloquent brain areas.

Background Pathway activating models try to describe stimulation spread in deep brain stimulation (DBS). Volume of tissue activated (VTA) models are simplified model variants allowing faster and easier computation. Our study aimed to investigate, how VTA visualization can be integrated into a clinical workflow applying directional electrodes using a standard clinical DBS planning system. Methods Twelve patients underwent DBS, using directional electrodes for bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease. Preoperative 3T magnetic resonance imaging was used for automatic visualization of the STN outline, as well as for fiber tractography. Intraoperative computed tomography was used for automatic lead detection. The Guide XT software, closely integrated into the DBS planning software environment, was used for VTA calculation and visualization. Results VTA visualization was possible in all cases. The percentage of VTA covering the STN volume ranged from 25% to 100% (mean ± standard deviation: 60% ± 25%) on the left side and from 0% to 98% (51% ± 30%) on the right side. The mean coordinate of all VTA centers was: 12.6 ± 1.2 mm lateral, 2.1 ± 1.2 mm posterior, and 2.3 ± 1.4 mm inferior in relation to the midcommissural point. Stimulation effects can be compared to the VTA visualization in relation to surrounding structures, potentially facilitating programming, which might be especially beneficial in case of suboptimal lead placement. Conclusions VTA visualization in a clinical planning system allows an intuitive adjustment of the stimulation parameters, supports programming, and enhances understanding of effects and side effects of DBS.

Background Surgery is a widely accepted treatment option for drug-resistant focal epilepsy. A detailed analysis of longitudinal postoperative seizure outcomes and use of antiepileptic drugs for different brain lesions causing epilepsy is not available. We aimed to analyse the association between histopathology and seizure outcome and drug freedom up to 5 years after epilepsy surgery, to improve presurgical decision making and counselling.Methods In this retrospective, multicentre, longitudinal, cohort study, patients who had epilepsy surgery between Jan 1, 2000, and Dec 31, 2012, at 37 collaborating tertiary referral centres across 18 European countries of the European Epilepsy Brain Bank consortium were assessed. We included patients of all ages with histopathology available after epilepsy surgery. Histopathological diagnoses and a minimal dataset of clinical variables were collected from existing local databases and patient records. The primary outcomes were freedom from disabling seizures (Engel class 1) and drug freedom at 1, 2, and 5 years after surgery. Proportions of individuals who were Engel class 1 and drug-free were reported for the 11 main categories of histopathological diagnosis. We analysed the association between histopathology, duration of epilepsy, and age at surgery, and the primary outcomes using random effects multivariable logistic regression to control for confounding.Findings 9147 patients were included, of whom seizure outcomes were available for 8191 (89.5%) participants at 2 years, and for 5577 (61.0%) at 5 years. The diagnoses of low-grade epilepsy associated neuroepithelial tumour (LEAT), vascular malformation, and hippocampal sclerosis had the best seizure outcome at 2 years after surgery, with 77.5% (1027 of 1325) of patients free from disabling seizures for LEAT, 74.0% (328 of 443) for vascular malformation, and 71.5% (2108 of 2948) for hippocampal sderosis. The worst seizure outcomes at 2 years were seen for patients with focal cortical dysplasia type I or mild malformation of cortical development (50.0%, 213 of 426 free from disabling seizures), those with malformation of cortical development-other (52.3%, 212 of 405 free from disabling seizures), and for those with no histopathological lesion (53.5%, 396 of 740 free from disabling seizures). The proportion of patients being both Engel class 1 and drug-free was 0-14% at 1 year and increased to 14-51% at 5 years. Children were more often drug-free; temporal lobe surgeries had the best seizure outcomes; and a longer duration of epilepsy was associated with reduced chance of favourable seizure outcomes and drug freedom. This effect of duration was evident for all lesions, except for hippocampal sclerosis.Interpretation Histopathological diagnosis, age at surgery, and duration of epilepsy are important prognostic factors for outcomes of epilepsy surgery. In every patient with refractory focal epilepsy presumed to be lesional, evaluation for surgery should be considered. Copyright (C) 2020 Elsevier Ltd. All rights reserved.

Sonothrombolysis, the enhancement of thrombolysis with ultrasound (US), is widely used in clinical practice. The use of an ultrasound contrast agent can lead to a further reduced recanalization time of the occluded blood vessel and thus to better outcome for the patient. In this study the sonothrombolytic efficacy of our new nanoscaled ultrasound contrast agent (NUSCA) was investigated. This new contrast agent has a size of less than 100 nm and should thus be able to penetrate the thrombus and achieve a thrombolysis from inside out. In this study human whole blood clots were exposed to US, US and NUSCA, US and recombinant tissue plasminogen activator (rt-Pa) or urokinase (UK), or a combination of US, NUSCA and thrombolytic drug in a closed-loop flow model. We sonicated with diagnostic US at a frequency of 2.85 MHz for 30 min. Clot mass loss of 50.6 ± 6.0% for the combination of US, NUSCA and rt-PA was found. Using UK as thrombolytic drug 57.7 ± 9.0% clot mass loss could be seen. Thus the weight loss exceeded the conventional values of up to 30%. Scanning electron microscopy (SEM) images revealed changes of the fibrin network on the thrombus surface. The NUSCA was able to loosen the network and induce large pores in the thrombus surface. The high rates of clot mass loss and the obvious changings of fibrin structure make our NUSCA a promising tool for sonothrombolytic therapy.

In surgery of C1–C2 fractures, standard navigation for screw placement based on preoperative image data was compared with intraoperative imaging guidance applying intraoperative computed tomography (iCT) with a special focus on accuracy of screw placement, workflow, and radiation exposure. A single surgeon series of 16 consecutive patients with C1–C2 trauma was retrospectively analyzed. Seven patients were operated with standard navigation; preoperative image data were registered by a 20-point surface-matching process for each vertebra. Nine patients were operated with iCT guidance, allowing automatic navigation registration. Screw placement was examined and graded with either iCT or postoperative CT. Dose length product of CT and dose area products of fluoroscopy scans were assessed; effective radiation doses were estimated based on conversion factors. Radiation doses of intraoperative and postoperative X-ray and/or CT diagnostics for each group were summarized to compare the total effective doses. A total number of 72 screws were placed, 26 in the standard navigation group including 24 screws in C1 and C2, and 46 screws in the iCT group including 34 screws in C1 and C2. 15.38% (n = 4) of the C2 screws showed a grade 1 deviation and 3.8% (n = 1) a grade 2 deviation applying standard navigation. There was no misplacement of screws in the iCT group. Mean operating time in the standard navigation group was 186.57 min versus 157.11 min in the iCT group, while the mean summarized effective dose was 1.129 mSv in the standard navigation and 2.129 mSv in the iCT group. iCT navigated surgery can lead to higher accuracy and shorter operating time compared to standard navigated operations. iCT is a safe and straightforward procedure allowing reduction in radiation exposure of the medical staff, while modified scan protocols resulted in a radiation exposure that is lower than in standard diagnostic neck CT.

Registration accuracy is a main factor influencing overall navigation accuracy. Standard fiducial- or landmark-based patient registration is user dependent and error-prone. Intraoperative imaging offers the possibility for user-independent patient registration. The aim of this paper is to evaluate our initial experience applying intraoperative computed tomography (CT) for navigation registration in cranial neurosurgery, with a special focus on registration accuracy and effective radiation dose. A total of 200 patients (141 craniotomy, 19 transsphenoidal, and 40 stereotactic burr hole procedures) were investigated by intraoperative CT applying a 32-slice movable CT scanner, which was used for automatic navigation registration. Registration accuracy was measured by at least three skin fiducials that were not part of the registration process. Automatic registration resulted in high registration accuracy (mean registration error: 0.93 ± 0.41 mm). Implementation of low-dose scanning protocols did not impede registration accuracy (registration error applying the full dose head protocol: 0.87 ± 0.36 mm vs. the low dose sinus protocol 0.72 ± 0.43 mm) while a reduction of the effective radiation dose by a factor of 8 could be achieved (mean effective radiation dose head protocol: 2.73 mSv vs. sinus protocol: 0.34 mSv). Intraoperative CT allows highly reliable navigation registration with low radiation exposure.

Objective To establish a workflow integrating preoperative 3-dimensional (3D) angiography data and intraoperative real-time vascular information in microscope-based navigation for aneurysm and arteriovenous malformation (AVM) surgery. Methods In 7 patients (3 with AVMs and 4 with aneurysms), preoperative 3D rotational angiography or computed tomography (CT) or magnetic resonance angiography data were navigated applying a 32-slice movable CT scanner for low-dose registration scanning. The 3D vasculature was segmented and visualized by microscope-based navigation along with navigated intraoperative real-time imaging data from indocyanin green angiography and duplex ultrasonography. Results Automatic registration applying intraoperative CT resulted in high accuracy (registration error, 0.80 ± 0.79 mm). The effective radiation dose of the registration CT scans (0.28–0.42 mSv) was only approximately one-sixth of a standard diagnostic head CT scan. The 3D vessel architecture could be visualized accurately in the operating microscope heads-up display and on the navigation screens in the same projection as the view angle of the surgeon, both facilitating orientation in 3D space, providing a better understanding of anatomy. In addition, intraoperative real-time modalities could be coregistered with high precision, providing further information during the course of the vascular procedure. Conclusions Registration CT imaging facilitates integrating preoperative and intraoperative vascular image data with a low registration error and low radiation exposure for the patient, improving the understanding of 3D vascular anatomy during surgery with easier identification of feeding vessels in AVMs, and of the projection and configuration of aneurysms.

Die intraoperative Bildgebung ist unmittelbare Qualitatskontrolle. Fehllagen von Elektroden oder unerwunschte inkomplette Resektion sind damit ausgeschlossen, da noch wahrend des gleichen Eingriffs das Operationsergebnis entsprechend angepasst werden kann. Ultraschall, Computertomographie (CT) und Magnet-Resonanz (MR) haben unterschiedliche Indikationen und spezifische Starken, sodass eine Kombination der verschiedenen Modalitaten die groste Flexibilitat und Sicherheit bietet.

Metastatic breast cancer affects long-term survival and is a major cause of cancer death for women worldwide. The Metalloprotease-Disintegrin ADAM8 promotes breast cancer development and brain metastasis in a mouse breast cancer model. Here, abundant ADAM8 expression was detected in primary human breast tumors and associated brain metastases. To investigate the function of ADAM8 in metastasis, MB-231 breast cancer cells with ADAM8 knockdown (MB-231_shA8) and scramble control cells (MB-231_shCtrl) were analyzed for their capability to develop metastases. In vitro, formation of metastatic complexes in hanging drops is dependent on ADAM8 and blocked by ADAM8 inhibition. MB-231_shA8 in contrast to MB-231_shCtrl cells were impaired in transmigration through an endothelial and a reconstituted blood-brain barrier. Out of 23 MMP and 22 ADAM genes, only the MMP-9 gene was affected by ADAM8 knockdown in MB-231_shA8 cells. Following re-expression of wild-type ADAM8 in contrast to ADAM8 lacking the cytoplasmic domain in MB-231_shA8 cells caused increased levels of activated pERK1/2 and pCREB (S133) that were associated with elevated MMP-9 transcription. Application of ADAM8 and MMP-9 antibodies reduced transmigration of MB-231 cells suggesting that ADAM8 affects transmigration of breast cancer cells by MMP-9 regulation. ADAM8-dependent transmigration was confirmed in Hs578t cells overexpressing ADAM8. Moreover, transmigration of MB-231 and Hs578t cells was significantly reduced for cells treated with an antibody directed against P-selectin glycoprotein ligand (PSGL-1), a substrate of ADAM8. From these data we conclude that ADAM8 promotes early metastatic processes such as transendothelial migration by upregulation of MMP-9 and shedding of PSGL-1 from breast cancer cells.

Im Jahr 2014 haben wir unser Marburg Cardiac Arrest Center (MCAC) nach 2-jahriger Pilotphase offiziell eroffnet. Ziel war es, eine konzernierte Bundelung aller Ressourcen in der Versorgung von reanimierten Patienten vorzunehmen. Es bedeutete, Hurden zu uberwinden und Uberzeugungsarbeit zu leisten, denn es fuhlten sich einige berufen, diese Patienten auch versorgen zu konnen. Dies ist allerdings ein groses Problem an deutschen Kliniken, denn obwohl in Deutschland nach praklinischem Herz-Kreislauf-Stillstand etwa 40 % der Falle erfolgreich durch den Rettungsdienst in die Krankenhauser gebracht werden, versterben mit Spontankreislauf (ROSC; return of spontaneous circulation) dann die deutliche Mehrzahl dieser schwer erkrankten Patienten in der Klinik, sodass zumeist nur ein Drittel der primar erfolgreich Reanimierten lebend aus der Klinik entlassen werden konnen. Die Grunde fur den innerklinischen Tod basieren ganz uberwiegend auf einem erneuten kardialen Versagen, einer irreversiblen zerebralen Hypoxie sowie unklaren innerklinischen Versorgungskompetenzen, die in dieser Notfallsituation zu einer Verzogerung der kausalen Therapie fuhren. Die Etablierung einer spezialisierten klinischen Versorgungsstruktur in Form eines Cardiac Arrest Centers stellt hier einen neuen Weg dar, die Versorgung reanimierter Patienten zu optimieren.

Purpose Epilepsy surgery is an evidence-based treatment for drug-refractory focal epilepsy. We aimed to evaluate how well preoperative outcome estimates of epilepsy surgery in clinical practice correlated with postoperative outcome and to compare prediction by the clinical team with available scores (m-SFS, ESN). Method Retrospective cohort study including patients with drug-refractory focal epilepsy who underwent resective epilepsy surgery at Epilepsy Center Hessen, Marburg, between 1998-2016. Patients were categorized into four groups based on their estimated chance of postoperative seizure freedom documented in preoperative medical records. Variables required for calculation of m-SFS and ESN were also extracted from presurgical medical records. Seizure outcome using Engel/ILAE classifications was extracted from postoperative medical records. Results 148 patients were included and 98 had follow-up at 5 years. 69 (70%) had Engel I and 50 (51%) ILAE 1 outcome. Observed 5-year outcome for very good candidates was 20/22 (91%) Engel I and 14/22 (64%) ILAE 1, for good candidates 29/40 (73%) Engel I and 21/40 (53%) ILAE 1, for candidates with slightly reduced chance 11/18 (61%) Engel I and 9/18 (50%) ILAE 1 and for candidates with considerably reduced chance 1/5 (20%) Engel I and 1/5 (20%) ILAE 1.There were no significant differences in discrimination or overall performance between predictions by the clinical team, ESN and m-SFS. Conclusions Preoperative outcome estimates corresponded well with observed outcome indicating adequate patient counseling.

Objective: To implement a straightforward workflow that allows to establishing augmented reality (AR) support in spine surgery. Methods: Intraoperative computed tomography (iCT) applying a 32-slice movable scanner was used for navigation registration in a series of 10 patients who underwent surgery[for full text, please go to the a.m. URL], 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Objective To establish microscope-based augmented reality (AR) support for degenerative spine surgery. Methods Head-up displays of operating microscopes were used to establish AR in a series of 10 patients. Segmentation of the vertebra and additional target structures, which were visualized by AR, was based on preoperative magnetic resonance and computed tomography (CT) images, that were nonrigidly fused to low-dose intraoperative CT (iCT) data. AR registration was achieved by automatic registration applying iCT and microscope calibration. Results AR support could be smoothly implemented in the surgical workflow. AR allowed to visualize the target structures reliably in the surgical field, facilitating surgical orientation. Flexible placement of the reference array enabled AR implementation for anterior, lateral, posterior median, and posterior paramedian approaches. Identification of bony and artificial landmarks allowed validating registration accuracy; the measured target registration error was 1.11 ± 0.42 mm (mean ± standard deviation). The effective dose for registration scanning ranged from 0.52 to 8.71 mSv, which is on average about one-third of a standard diagnostic spine scan. This depended mainly on the scan length (mean scan length cervical/thoracic/lumbar: 99/218/118 mm). Longest scan ranges were in the mid-thoracic region to ensure unambiguous vertebra assignment as prerequisite for reliable nonlinear registration (mean cervical/thoracic/lumbar effective dose: 0.52/6.14/2.99 mSv). Conclusions Reliable microscope-based AR support is possible because of automatic registration based on intraoperative imaging. Application of AR in degenerative spine surgery has a big potential; it might be especially helpful in complex anatomical situations and resident education.

Background Reliable visualization of the optic radiations (OR) is of major importance in tumor surgery close to the OR to prevent permanent visual field deficits. Diffusion tensor imaging (DTI) based fiber tractography (FT) has become a standard tool to visualize major white matter tracts and to support the prevention of postoperative deficits. Nevertheless, FT of the OR is notoriously challenging due to its high neuroanatomical complexity. Methods To improve FT of the OR we analyzed the effect of a more complex diffusion model and the effect of different voxel shapes and orientations. MRI data of 21 healthy subjects was acquired using isometric and anisometric voxel sizes and standard and adapted slice angulation. FT was performed using the DTI based approach and an orientation distribution function (ODF) based approach. Results were visually inspected, and fiber tract volumes were compared. Results DTI based FT led to poor results, failing to reconstruct plausible tracts at all in up to 26.11 % of all cases. The ODF based approach resulted in more compound and solid tracts showing also significantly larger tract volumes. Voxel shape or orientation did not influence DTI but ODF based FT. Isometric or anisometric voxels with standard slice orientation revealed highest tract volumes. Adapted orientation in combination with anisometric voxels led to significantly smaller tract volumes. Conclusions Plausible tractography of the OR can be achieved using ODF based fiber tracking within a clinically feasible timeframe. Voxel shape and orientation seem to be of minor importance and might be kept to isometric voxel for flexible application of FT.

Objective Deep brain stimulation (DBS) is an effective treatment for movement disorders. Stereotactic electrode placement can be guided by intraoperative imaging, which also allows for immediate intraoperative quality control. This article is about implementation and refining a workflow applying intraoperative computed tomography (iCT) for DBS. Methods Eighteen patients underwent DBS with bilateral implantation of directional electrodes applying a 32-slice movable computed tomography scanner in combination with microelectrode recording. Results iCT led to a significant decrease in overall procedural time, despite performing multiple scans. In 3 of the initial 5 cases, iCT caused an adjustment of the final electrodes demonstrating the learning curve and the necessity to integrate road mapping for the exchange of microelectrode to final electrode. Implementation of low-dose computed tomography protocols added microelectrode iCT to the refined workflow, resulting in an intraoperative adjustment of a trajectory in 1 patient. Low-dose protocols lowered the total effective dose to 1.15 mSv, that is, a reduction by a factor of 3.5 compared to a standard non-iCT DBS procedure, despite repeated iCTs. Intraoperative lead detection based on final iCT revealed a radial error of 1.04 ± 0.58 mm and a vector error of 2.28 ± 0.97 mm compared to the preoperative planning, adjusted by the findings of microelectrode recording. Conclusions iCT can be easily integrated into the surgical workflow resulting in an overall efficient time-saving procedure. Repeated intraoperative scanning ensures reliable electrode placement, although low-dose scanning protocols prevent extensive radiation exposure. iCT of microelectrodes is feasible and led to the adjustment of 1 electrode.

Objective Motor cortex stimulation (MCS) is an alternative treatment modality for central neuropathic pain, if conservative treatment failed. Study aim was outcome assessment after MCS. Material and Methods This study is a retrospective case series review of patients who had undergone MCS for central pain ( n = 8), deafferentation pain ( n = 3) and neuropathic trigeminal pain ( n = 9) between April 2001 and May 2011. In all patients, four contact-paddle electrodes were placed in the epidural space overlying the motor cortex via burr hole trepanation under local anesthesia. The follow-up period was 6 months to 6 years. Pain control was assessed by the visual analog scale (VAS). Results A total of 22 patients (11 men, 11 women) were treated; after trial stimulation two male patients were excluded for incompliance reasons. The mean patient age was 59.8 years (range: 31–79 years). In the central pain group, three patients reported complete, and four patients satisfactory pain control. In the trigeminal neuropathic pain group, seven patients reported complete, and two patients satisfactory pain control. In the deafferentation pain group, one patient reported complete, and two patients satisfactory pain control. None of the patients showed new neurologic deficits after the MCS. Conclusions MCS is an effective treatment modality for central neuropathic pain and trigeminal pain with low morbidity and mortality. Future studies are necessary to evaluate and optimize this treatment option in more detail.

In this contribution, we used the GrowCut segmentation algorithm publicly available in three-dimensional Slicer for three-dimensional segmentation of vertebral bodies. To the best of our knowledge, this is the first time that the GrowCut method has been studied for the usage of vertebral body segmentation. In brief, we found that the GrowCut segmentation times were consistently less than the manual segmentation times. Hence, GrowCut provides an alternative to a manual slice-by-slice segmentation process., Comment: 10 pages

Background: Metastases are the most frequent tumors in the brain. Most often used scoring systems to predict the outcome are the RPA (Recursive Partitioning Analysis) classification and the DS-GPA (Diagnosis-Specific Graded Prognostic Assessment) score. The goal of our study was to determine prognostic factors which influence outcome in patients who undergo surgery for brain metastases and to compare different outcome scores. Methods: Two hundred and twenty-nine patients who underwent surgery for brain metastases in our institution between January 2005 and December 2014 were included in the study. Patient data were evaluated retrospectively. Results: The mean survival time was 19.2 months (median survival time, MST: 8 months), for patients with a single metastasis (n = 149) 17.6 months (MST: 8 months), and for patients with multiple metastases (n = 80) 17.9 months (MST: 6 months). Significant influence on MST had age 70% (11 vs. 4 months, P < 0.001), and postoperative radiotherapy (8 vs. 5 months, P < 0.002). To evaluate the diagnostic power of DS-GPA and RPA score in respect of survival, two Cox regressions were modeled, where the RPA classification showed a better predictive power. Conclusion: Favorable factors for prolonged survival were KPS >70%, RPA Class I and II, age

Object The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA. Methods Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible. Results Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years. Conclusions The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

Intraoperative MRI (iMRI) increases gross total resection (GTR) rates in transsphenoidal surgery; however, long-term follow-up data is lacking. The objective is to assess the outcome of patients with nonfunctioning pituitary adenomas (NFA) at a mean follow-up of > 5 years. Patients with NFA operated in a single institution with resection control by a 1.5 T intraoperative magnetic resonance imaging (iMRI) scanner and no previous pituitary surgery were included. Microscopical transsphenoidal approaches with optional endoscopy were used. The iMRI was chosen for spacious suprasellar or retrosellar and/or invasive tumours. IMRI-scans were made if GTR or if nonresectable remnants were presumed. The patients had a full neuroradiological, endocrinological and ophthalmological follow-up at the institution. Eighty-five patients (67 % male;55 ± 14 years) with a follow-up of 5.6 ± 1.9 years were included. The initial GTR rate on iMRI was 44 %. In 83 %, further resections were possible, resulting in a final GTR rate of 66 %. In invasive tumours, the GTR rate was increased by 29 %. The detection of remnants by iMRI had high sensitivity and specificity (100 %), as opposed to endoscopy (21 %;78 %). During follow-up, four (7 %) tumours recurred and 14 (64 %) remnants grew. The recurrence and regrowth rate were 0.013 and 0.114 patients/years, respectively. Seventy-nine percent of the growing remnants were seen < 5 years postoperatively. The use of iMRI for transsphenoidal resection leads to low recurrence rates. Even in case of invasive tumours, distinctly more patients show long tumour-free follow-ups. Tumour remnants detected by iMRI are at high risk to grow within 5 years after surgery.

The diagnosis of certain spine pathologies, such as scoliosis, spondylolisthesis and vertebral fractures, is part of the daily clinical routine. Very frequently, magnetic resonance image data are used to diagnose these kinds of pathologies in order to avoid exposing patients to harmful radiation, like X-ray. We present a method which detects and segments all acquired vertebral bodies, with minimal user intervention. This allows an automatic diagnosis to detect scoliosis, spondylolisthesis and crushed vertebrae. Our approach consists of three major steps. First, vertebral centres are detected using a Viola-Jones like method, and then the vertebrae are segmented in a parallel manner, and finally, geometric diagnostic features are deduced in order to diagnose the three diseases. Our method was evaluated on 26 lumbar datasets containing 234 reference vertebrae. Vertebra detection has 7.1% false negatives and 1.3% false positives. The average Dice coefficient to manual reference is 79.3% and mean distance error is 1.76iź?mm. No severe case of the three illnesses was missed, and false alarms occurred rarely-0% for scoliosis, 3.9% for spondylolisthesis and 2.6% for vertebral fractures. The main advantages of our method are high speed, robust handling of a large variety of routine clinical images, and simple and minimal user interaction.

OBJECTIVELow registration errors are an important prerequisite for reliable navigation, independent of its use in cranial or spinal surgery. Regardless of whether navigation is used for trajectory alignment in biopsy or implant procedures, or for sophisticated augmented reality applications, all depend on a correct registration of patient space and image space. In contrast to fiducial, landmark, or surface matching–based registration, the application of intraoperative imaging allows user-independent automatic patient registration, which is less error prone. The authors’ aim in this paper was to give an overview of their experience using intraoperative CT (iCT) scanning for automatic registration with a focus on registration accuracy and radiation exposure.METHODSA total of 645 patients underwent iCT scanning with a 32-slice movable CT scanner in combination with navigation for trajectory alignment in biopsy and implantation procedures (n = 222) and for augmented reality (n = 437) in cranial and spine procedures (347 craniotomies and 42 transsphenoidal, 56 frameless stereotactic, 59 frame-based stereotactic, and 141 spinal procedures). The target registration error was measured using skin fiducials that were not part of the registration procedure. The effective dose was calculated by multiplying the dose length product with conversion factors.RESULTSAmong all 1281 iCT scans obtained, 1172 were used for automatic patient registration (645 initial registration scans and 527 repeat iCT scans). The overall mean target registration error was 0.86 ± 0.38 mm (± SD) (craniotomy, 0.88 ± 0.39 mm; transsphenoidal, 0.92 ± 0.39 mm; frameless, 0.74 ± 0.39 mm; frame-based, 0.84 ± 0.34 mm; and spinal, 0.80 ± 0.28 mm). Compared with standard diagnostic scans, a distinct reduction of the effective dose could be achieved using low-dose protocols for the initial registration scan with mean effective doses of 0.06 ± 0.04 mSv for cranial, 0.50 ± 0.09 mSv for cervical, 4.12 ± 2.13 mSv for thoracic, and 3.37 ± 0.93 mSv for lumbar scans without impeding registration accuracy.CONCLUSIONSReliable automatic patient registration can be achieved using iCT scanning. Low-dose protocols ensured a low radiation exposure for the patient. Low-dose scanning had no negative effect on navigation accuracy.

Among all abnormal growths inside the skull, the percentage of tumors in sellar region is approximately 10-15%, and the pituitary adenoma is the most common sellar lesion. A time-consuming process that can be shortened by using adequate algorithms is the manual segmentation of pituitary adenomas. In this contribution, two methods for pituitary adenoma segmentation in the human brain are presented and compared using magnetic resonance imaging (MRI) patient data from the clinical routine: Method A is a graph-based method that sets up a directed and weighted graph and performs a min-cut for optimal segmentation results: Method B is a balloon inflation method that uses balloon inflation forces to detect the pituitary adenoma boundaries. The ground truth of the pituitary adenoma boundaries - for the evaluation of the methods - are manually extracted by neurosurgeons. Comparison is done using the Dice Similarity Coefficient (DSC), a measure for spatial overlap of different segmentation results. The average DSC for all data sets is 77.5±4.5% for the graph-based method and 75.9±7.2% for the balloon inflation method showing no significant difference. The overall segmentation time of the implemented approaches was less than 4s - compared with a manual segmentation that took, on the average, 3.9±0.5min.

Due to the aging population, spinal diseases get more and more common nowadays; e.g., lifetime risk of osteoporotic fracture is 40% for white women and 13% for white men in the United States. Thus the numbers of surgical spinal procedures are also increasing with the aging population and precise diagnosis plays a vital role in reducing complication and recurrence of symptoms. Spinal imaging of vertebral column is a tedious process subjected to interpretation errors. In this contribution, we aim to reduce time and error for vertebral interpretation by applying and studying the GrowCut-algorithm for boundary segmentation between vertebral body compacta and surrounding structures. GrowCut is a competitive region growing algorithm using cellular automata. For our study, vertebral T2-weighted Magnetic Resonance Imaging (MRI) scans were first manually outlined by neurosurgeons. Then, the vertebral bodies were segmented in the medical images by a GrowCut-trained physician using the semi-automated GrowCut-algorithm. Afterwards, results of both segmentation processes were compared using the Dice Similarity Coefficient (DSC) and the Hausdorff Distance (HD) which yielded to a DSC of 82.99+/-5.03% and a HD of 18.91+/-7.2 voxel, respectively. In addition, the times have been measured during the manual and the GrowCut segmentations, showing that a GrowCut-segmentation - with an average time of less than six minutes (5.77+/-0.73) - is significantly shorter than a pure manual outlining., Comment: 6 pages, 5 figures, 1 table, 42 references

The most common sellar lesion is the pituitary adenoma, and sellar tumors are approximately 10-15% of all intracranial neoplasms. Manual slice-by-slice segmentation takes quite some time that can be reduced by using the appropriate algorithms. In this contribution, we present a segmentation method for pituitary adenoma. The method is based on an algorithm that we have applied recently to segmenting glioblastoma multiforme. A modification of this scheme is used for adenoma segmentation that is much harder to perform, due to lack of contrast-enhanced boundaries. In our experimental evaluation, neurosurgeons performed manual slice-by-slice segmentation of ten magnetic resonance imaging (MRI) cases. The segmentations were compared to the segmentation results of the proposed method using the Dice Similarity Coefficient (DSC). The average DSC for all datasets was 75.92% +/- 7.24%. A manual segmentation took about four minutes and our algorithm required about one second., 7 pages, 6 figures, 1 table, 16 references in Proc. SPIE 7963, Medical Imaging 2011: Computer-Aided Diagnosis, 79632T (9 March 2011). arXiv admin note: text overlap with arXiv:1103.1778

Diffusion magnetic resonance imaging (dMRI) is a medical imaging method that can be used to acquire local information about the structure of white matter pathways within the human brain. By applying computational methods termed fiber tractography on dMRI data, it is possible to estimate the location and extent of respective nerve bundles (white matter pathways). Visualizing these complex white matter pathways for neuro applications is still an open issue. Hence, interactive visualization techniques to explore and better understand tractography data are required. In this paper, we propose a new interaction technique to support exploration and interpretation of white matter pathways. Our application empowers the user to interactively manipulate manually segmented, box- or ellipsoid-shaped regions of interest (ROIs) to selectively display pathways that pass through specific anatomical areas. To further support flexible ROI design, each ROI can be assigned a Boolean logic operator and a fiber direction. The latter is particularly relevant for kissing, crossing or fanning regions, as it allows the neuroscientists to filter fibers according to their direction within the ROI. By precomputing all white matter pathways in the whole brain, interactive ROI placement and adjustment are possible. The proposed fiber selection tool provides ultimate flexibility and is an excellent approach for fiber tract selection, as shown for some real-world examples.

We investigated whether the inclusion of the PFA-100 in the preoperative screening of neurosurgical patients might reduce perioperative bleeding complications. Patients with intracranial space-occupying lesions who were scheduled for neurosurgery underwent routine preoperative PFA-100 testing. In case of an abnormal PFA test, patients received prophylactic treatment with desmopressin. 93 consecutive patients were compared to 102 consecutive patients with comparable characteristics operated before introduction of the PFA-100 testing. 2 patients (2.2%) in the PFA group and 2 patients (2.0%) in the non-PFA group experienced clinically relevant intracranial bleeding confirmed by computed tomography (OR 1.05, 95% CI 0.39–2.82; 𝑃 = 1 . 0 ). Transfusions were not significantly different between the two groups. 13 (14.0%) patients in the PFA group and 5 (4.9%) patients in the non-PFA group received desmopressin (OR 3.2, 95% CI 1.1–9.2; 𝑃 = 0 . 0 4 5 ). Preoperative screening with the PFA-100 did result in a significant increase in the administration of desmopressin, which could not reduce perioperative bleeding complications or transfusions.

BACKGROUND Gliomas propagate diffusely throughout and along white matter structures. Glioma-related changes in structural integrity and metabolism are not detectable by standard magnetic resonance (MR) imaging. OBJECTIVE To investigate differences in the metabolism of fiber tract alterations between gliomas grade II to IV by correlation of fiber density values with metabolite concentrations measured by fiber density mapping and MR spectroscopic imaging. METHODS Fiber density mapping and MR spectroscopic imaging were performed in 48 patients with gliomas WHO grade II to IV. Fiber density mapping data were used to define fiber tracts in tumoral and peritumoral areas. Structural integrity of fiber tracts was assessed as fiber density ipsilateral-to-contralateral ratio (FD ICR). Metabolite concentrations for choline-containing compounds and N-acetyl-aspartate were computed and correlated to FD ICR values after coregistration with anatomic MR imaging. RESULTS In tumoral areas, choline-containing compound concentrations of altered fiber tracts were significantly different between low- and high-grade glioma and showed different courses for the correlations of FD ICR and choline-containing czeompounds. In high-grade glioma, increasing fiber destruction was associated with a massive progression in cell membrane proliferation. Peritumoral fiber structures showed significantly decreased N-acetyl-aspartate concentrations for all patients, but only patients with glioblastoma multiforme had significantly decreased fiber density compared with the contralateral side. Glioma grades II and III had significantly higher peritumoral FD ICR than glioblastoma multiforme. CONCLUSION A multiparametric MR imaging strategy providing information about both structural integrity and metabolism of the tumor is required for detailed assessment of glioma-related fiber tract alterations, which in turn is essential for treatment planning.

Purpose Develop a neural fiber reconstruction method based on diffusion tensor imaging, which is not as sensitive to user-defined regions of interest as streamline tractography. Methods A simulated annealing approach is employed to find a non-rigid transformation to map a fiber bundle from a fiber atlas to another fiber bundle, which minimizes a specific energy functional. The energy functional describes how well the transformed fiber bundle fits the patient's diffusion tensor data. Results The feasibility of the method is demonstrated on a diffusion tensor software phantom. We analyze the behavior of the algorithm with respect to image noise and number of iterations. First results on the datasets of patients are presented. Conclusions The described method maps fiber bundles based on diffusion tensor data and shows high robustness to image noise. Future developments of the method should help simplify inter-subject comparisons of fiber bundles.

We present the integration of the OpenIGTLink network protocol for image-guided therapy (IGT) with the medical prototyping platform MeVisLab. OpenIGTLink is a new, open, simple and extensible network communication protocol for IGT. The protocol provides a standardized mechanism to connect hardware and software by the transfer of coordinate transforms, images, and status messages. MeVisLab is a framework for the development of image processing algorithms and visualization and interaction methods, with a focus on medical imaging. The integration of OpenIGTLink into MeVisLab has been realized by developing a software module using the C++ programming language. As a result, researchers using MeVisLab can interface their software to hardware devices that already support the OpenIGTLink protocol, such as the NDI Aurora magnetic tracking system. In addition, the OpenIGTLink module can also be used to communicate directly with Slicer, a free, open source software package for visualization and image analysis. The integration has been tested with tracker clients available online and a real tracking system.

The aims of this study were to investigate and categorize peritumoral fiber tract alterations while considering changes in metabolism and integrity of fiber structures using multimodal neuroimaging—that is, PET with O-(2-18F-fluoroethyl)-l-tyrosine and diffusion tensor imaging evaluated by fiber density mapping—and to correlate categories of fiber alterations with preoperative neurologic deficits and postoperative course. Methods: We examined 26 patients with cerebral gliomas. Fiber density data were used to segment peritumoral fiber structures and were coregistered to anatomic MR images and PET data. Fiber density and O-(2-18F-fluoroethyl)-l-tyrosine uptake values were evaluated as ipsilateral-to-contralateral ratios. Four metabolic categories were defined on the basis of O-(2-18F-fluoroethyl)-l-tyrosine values: tumor-infiltrated tissue, reactive tissue (astrogliosis and microglial activation), normal brain tissue, and tissue with attenuated amino acid metabolism. Fiber density values were grouped in 3 categories for structural integrity: compressed, normal, and attenuated fibers. Results: We evaluated and classified 103 peritumoral fiber structures with 10 patterns of fiber tract alterations. Fiber structures in tumor-infiltrated, reactive, and normal brain tissue showed compressed fibers, displaced fibers, and (partly) destroyed fibers, respectively. Attenuated amino acid metabolism was associated only with attenuated fiber density. Thirteen patients showed white matter–related neurologic deficits (paresis, hypoesthesia, aphasia, or anopia) as initial symptoms. Three patients showed tumor infiltration in the corresponding fiber tracts; all the others had reactive or normal brain tissue. Fiber structures were compressed or attenuated but not normal. The 3 patients with tumor infiltration in the corresponding fiber tracts and 1 with compressed fibers in normal brain showed no improvements or worsening of the deficits in the postoperative course. Eight patients with the corresponding fiber tracts in reactive or normal brain areas showed improvement of deficits. One patient underwent biopsy only. Conclusion: Our multimodal neuroimaging approach provides complementary information and more detailed understanding of peritumoral fiber tract alterations in gliomas which are more complex as described so far. We presented a classification model for systematic assessment of these alterations that may be helpful for treatment planning and prediction of patients’ prognoses.

In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis.

In this contribution, a medical software system for volumetric analysis of different cerebral pathologies in magnetic resonance imaging (MRI) data is presented. The software system is based on a semi-automatic segmentation algorithm and helps to overcome the time-consuming process of volume determination during monitoring of a patient. After imaging, the parameter settings-including a seed point-are set up in the system and an automatic segmentation is performed by a novel graph-based approach. Manually reviewing the result leads to reseeding, adding seed points or an automatic surface mesh generation. The mesh is saved for monitoring the patient and for comparisons with follow-up scans. Based on the mesh, the system performs a voxelization and volume calculation, which leads to diagnosis and therefore further treatment decisions. The overall system has been tested with different cerebral pathologies-glioblastoma multiforme, pituitary adenomas and cerebral aneurysms- and evaluated against manual expert segmentations using the Dice Similarity Coefficient (DSC). Additionally, intra-physician segmentations have been performed to provide a quality measure for the presented system.

A 54-year-old woman had nausea, vomiting and personality changes since a few weeks. Paresis of the abducens and hypoglossal nerves on the left side, a right sided reduction of the visual field, discrete dysarthri×a and ataxia were diagnosed. Cranial magnetic resonance imaging demonstrated a contrast enhancing circular meningeal lesion of the foramen magnum. Histological examination revealed a granulomatous lesion of the meninges with focal necrosis, vasculitis and neutrophils indicating immune complex reactions. A diagnosis of primary meningeal Wegener's disease was made. Medication with low dose prednisolone led to complete remission of the lesion 1.5 years later.

Brain edema is a hallmark of human malignant brain tumors and contributes to the clinical course and outcome of brain tumor patients. The so-called perifocal edema or brain swelling imposes in T2-weighted MR scans as high intensity areas surrounding the bulk tumor mass. The mechanisms of this increased fluid attraction and the cellular composition of the microenvironment are only partially understood. In this study, we focus on imaging perifocal edema in orthotopically implanted gliomas in rodents and correlate perifocal edema with immunohistochemical markers. We identified that areas of perifocal edema not only include the tumor invasion zone, but also are associated with increased glial fibrillary acidic protein (GFAP) and aquaporin-4 expression surrounding the bulk tumor mass. Moreover, a high number of activated microglial cells expressing CD11b and macrophage migration inhibitory factor (MIF) accumulate at the tumor border. Thus, the area of perifocal edema is mainly dominated by reactive changes of vital brain tissue. These data corroborate that perifocal edema identified in T2-weighted MR scans are characterized with alterations in glial cell distribution and marker expression forming an inflammatory tumor microenvironment.