Virtual Reality vs Phantom Model: Benefits and Drawbacks of Simulation Training in Neurosurgery.

BACKGROUND AND OBJECTIVES: Traditional neurosurgical education has relied heavily on the Halstedian "see one, do one, teach one" approach which is increasingly perceived as inefficient in contemporary settings marked by a steady decline in surgical caseload. In recent years, simulation training has emerged as an effective and accessible training alternative. To date, however, there is no standardized criterion pertaining to the quality and implementation of simulators in neurosurgical education and training. This research aims to compare the efficacy of virtual reality (VR) and Phantom-based simulation training in the context of neurosurgical skill acquisition, with a focus on middle cerebral artery aneurysm clipping. METHODS: An immersive VR clipping tool and a haptic clipping simulator incorporating 3-dimensional printing, additive manufacturing, and rheological analyses were developed. Twenty-two participants, comprising 12 medical students, 6 neurosurgical residents, and 4 experienced neurosurgeons, tested and evaluated both simulators for face and content validity. Construct and predictive validity of the simulators were assessed using an objective structured assessment scale for aneurysm clipping, measuring participants' performances and progress. RESULTS: Both modalities were deemed highly advantageous for educational purposes. Objective evaluations, however, revealed measurable differences in usability, efficacy, and transferability of the learned skills with VR excelling in procedural planning and visualization while Phantom simulation being noticeably superior in conveying surgical skills. CONCLUSION: Simulation training can accelerate the neurosurgical learning curve. The results of this study highlight the importance of establishing standardized criteria for the implementation and assessment of simulation modalities, ensuring consistent quality and efficacy in neurosurgical education.

Lactococcus garviae in Lumbar Spondylodiscitis With Spinal Epidural Abscess Causing Paraparesis: A Case Report.

Spinal epidural abscess (SEA) can lead to a subacute onset of neurological deficits of the extremities and is commonly accompanied by spondylodiscitis if located anterior to the dura. Lactococcus garviae is a fish pathogen that is occasionally found in poultry, cattle, and swine. It is a rare cause of infection in humans. Most commonly it is associated with endocarditis. Until 2019, less than 30 cases of human Lactoccous garviae infection have been published. To the best of our knowledge, we present the second reported case of SEA with spondylodiscitis caused by Lactococcus garviae. How Lactococcus garviae caused SEA, remains unclear in this case.

The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis.

This study determined the expression of five novel biomarker candidates in IDH wild-type glioblastoma (GBM) tissues compared to non-malign brain parenchyma, as well as their prognostic relevance for the GBM patients' outcomes. The markers were analysed by immunohistochemistry in tumour tissues (n = 186) and healthy brain tissues (n = 54). The association with the patients' overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier and log-rank test. The prognostic value of the markers was determined using multivariate Cox proportional hazard models. AGTRAP, DIVERSIN, cytoplasmic NEDD8 (NEDD8c) and RRM1 were significantly overexpressed in tumour tissues compared to the healthy brain, while the opposite was observed for ALKBH3. AGTRAP, ALKBH3, NEDD8c and RRM1 were significantly associated with OS in univariate analysis. AGTRAP and RRM1 were also independent prognostic factors for OS in multivariate analysis. For PFS, only AGTRAP and NEDD8c reached significance in univariate analysis. Additionally, AGTRAP was an independent prognostic factor for PFS in multivariate models. Finally, combined analysis of the markers enhanced their prognostic accuracy. The combination AGTRAP/ALKBH3 had the strongest prognostic value for the OS of GBM patients. These findings contribute to a better understanding of the GBM pathophysiology and may help identify novel therapeutic targets in this type of cancer.

Enlarged tumefactive perivascular, or Virchow-Robin, spaces and hydrocephalus: do we need to treat? Illustrative cases.

BACKGROUND: Perivascular spaces (PVSs) are spaces in brain parenchyma filled with interstitial fluid surrounding small cerebral vessels. Massive enlargements of PVSs are referred to as "giant tumefactive perivascular spaces" (GTPVSs), which can be classified into three types depending on their localization. These lesions are rare, predominantly asymptomatic, and often initially misinterpreted as cystic tumor formations. However, there are several reported cases in which GTPVSs have induced neurological symptoms because of their size, mass effect, and location, ultimately leading to obstructive hydrocephalus necessitating neurosurgical intervention. Presented here are three diverse clinical presentations of GTPVS. OBSERVATIONS: Here, the authors observed an asymptomatic case of type 1 GTPVS and two symptomatic cases of type 3 GTPVS, one causing local mass effect and the other hydrocephalus. LESSONS: GTPVSs are mostly asymptomatic lesions. Patients without symptoms should be closely monitored, and biopsy is discouraged. Hydrocephalus resulting from GTPVS necessitates surgical intervention. In these cases, third ventriculostomy, shunt implantation, or direct cyst fenestration are surgical options. For patients presenting with symptoms from localized mass effect, a thorough evaluation for potential neurosurgical intervention is imperative. Follow-up in type 3 GTPVS is recommended, particularly in untreated cases. Given the infrequency of GTPVS, definitive guidelines for neurosurgical treatment and subsequent follow-up remain elusive.

Unveiling rupture risk and clinical outcomes in midline aneurysms: A matched cohort analysis investigating the impact of localization within the anterior or posterior circulation.

Intracranial aneurysms (IAs) located in the anterior and posterior circulations of the Circle of Willis present differential rupture risks. This study aimed to compare the rupture risk and clinical outcomes of anterior communicating artery aneurysms (AcomA) and basilar tip aneurysms (BAs); two IA types located along the midline within the Circle of Willis. We retrospectively collected data from 1026 patients presenting with saccular IAs. Only AcomA and BAs with a 3D angiography were included. Out of 186 included IAs, a cohort of 32 BAs was matched with AcomA based on the patients' pre-existing conditions and morphological parameters of IAs. Clinical outcomes, including rupture risk, hydrocephalus development, vasospasm incidence, and patients' outcome, were compared. The analysis revealed no significant difference in rupture risk, development of hydrocephalus, need for ventricular drainage, or vasospasm incidence between the matched AcomA and BA cohorts. Furthermore, the clinical outcomes post-rupture did not significantly differ between the two groups, except for a higher Fisher Grade associated with BAs. Once accounting for morphological and patient factors, the rupture risk between AcomA and BAs is comparable. These findings underscore the importance of tailored management strategies for specific IA types and suggest that further investigations should focus on the role of individual patient and aneurysm characteristics in IA rupture risk and clinical outcomes.

Extravascular optical coherence tomography of cerebral vessel walls in vivo.

PURPOSE: Evaluation of extravascular, microscope integrated OCT (iOCT) as an in vivo imaging modality of cerebral blood vessels and as an intraoperative imaging method. METHODS: Microscope integrated optical coherence tomography of major cerebral arteries (n = 13) and superficial sylvian veins (n = 5) and one incidental cerebral vasospasm (n = 1) in (n = 10) patients. Post procedural analysis of OCT volume scans, microscopic images and videos during the time of scan as well as measurements of the diameter of vessel walls and its layers with an accuracy of 7.5 µm. RESULTS: iOCT was feasible during vascular microsurgical procedures. In all scanned arteries a clear delineation of the physiological three layered vessel wall composition could be achieved. Pathological arteriosclerotic alterations of cerebral artery walls could precisely be demonstrated. Major superficial cortical veins conversely presented a mono layered composition. First in vivo measurements of vascular mean diameters were possible. Cerebral artery walls showed a diameter of 296 µm, tunica externa 78 µm, media 134 µm and interna 84 µm. CONCLUSION: For the first time the microstructural composition of cerebral blood vessels could be illustrated in vivo. Due to an outstanding spatial resolution a clear definition of physiological and pathological characteristics was possible. Therefore, microscope integrated optical coherence tomography holds promise for basic research in the field of cerebrovascular arteriosclerotic diseases and for intraoperative guidance during microvascular surgery.

Overcoming Barriers in Neurosurgical Education: A Novel Approach to Practical Ventriculostomy Simulation.

BACKGROUND: In the high-risk, high-stakes specialty of neurosurgery, traditional teaching methods often fail to provide young residents with the proficiency needed to perform complex procedures in stressful situations, with direct effects on patient outcomes. Physical simulators provide the freedom of focused, hands-on training in a more controlled environment. However, the adoption of simulators in neurosurgical training remains a challenge because of high acquisition costs, complex production processes, and lack of realism. OBJECTIVE: To introduce an easily reproducible, cost-effective simulator for external ventricular drain placements through various ventriculostomy approaches with life-like tactile brain characteristics based on real patients' data. METHODS: Whole brain and skull reconstruction from patient's computed tomography and MRI data were achieved using freeware and a desktop 3-dimensional printer. Subsequently, a negative brain silicone mold was created. Based on neurosurgical expertise and rheological measurements of brain tissue, gelatin in various concentrations was tested to cast tactilely realistic brain simulants. A sample group of 16 neurosurgeons and medical students tested and evaluated the simulator in respect to realism, haptics, and general usage, scored on a 5-point Likert scale. RESULTS: We saw a rapid and significant improvement of accuracy among novice medical students. All participants deemed the simulator as highly realistic, effective, and superior to conventional training methods. CONCLUSION: We were able to demonstrate that building and implementing a high-fidelity simulator for one of the most important neurosurgical procedures as an effective educational and training tool is achievable in a timely manner and without extensive investments.

A comparison of input devices for precise interaction tasks in VR-based surgical planning and training.

To exploit the potential of virtual reality (VR) in medicine, the input devices must be selected carefully due to their different benefits. In this work, input devices for common interaction tasks in medical VR planning and training are compared. Depending on the specific purpose, different requirements exist. Therefore, an appropriate trade-off between meeting task-specific requirements and having a widely applicable device has to be found. We focus on two medical use cases, liver surgery planning and craniotomy training, to cover a broad medical domain. Based on these, relevant input devices are compared with respect to their suitability for performing precise VR interaction tasks. The devices are standard VR controllers, a pen-like VR Ink, data gloves and a real craniotome, the medical instrument used for craniotomy. The input devices were quantitatively compared with respect to their performance based on different measurements. The controllers and VR Ink performed significantly better than the remaining two devices regarding precision. Qualitative data concerning task load, cybersickness, and usability and appropriateness of the devices were assessed. Although no device stands out for both applications, most participants preferred using the VR Ink, followed by the controller and finally the data gloves and craniotome. These results can guide the selection of an appropriate device for future medical VR applications.

Theranostic applications of optical coherence tomography in neurosurgery?

In light of our own experiences, we value the existing literature to critically point out possible "near" future applications of optical coherence tomography (OCT) as an intraoperative neurosurgical guidance tool. "Pub Med", "Cochrane Library", "Crossref Metadata Search", and "IEEE Xplore" databases as well as the search engine "Google Scholar" were screened for "optical coherence tomography + neurosurgery", "optical coherence tomography + intraoperative imaging + neurosurgery", and "microscope integrated optical coherence tomography + neurosurgery". n = 51 articles related to the use of OCT as an imaging technique in the field of neurosurgery or neurosurgical research. n = 7 articles documented the intraoperative use of OCT in patients. n = 4 articles documented the use of microscope-integrated optical coherence tomography as a neurosurgical guidance tool. The Results demonstrate that OCT is the first imaging technique to study microanatomy in vivo. Postoperative analysis of intraoperative scans holds promise to enrich our physiological and pathophysiological understanding of the human brain. No data exists to prove that OCT-guided surgery minimizes perioperative morbidity or extends tumor resection. But results suggest that regular use of microscope-integrated OCT could increase security during certain critical microsurgical steps like, e.g., dural dissection at cavernous sinus, transtentorial approaches, or aneurysm clip placement. Endoscopy integration could aid surgery in regions which are not yet accessible to real-time imaging modalities like the ventricles or hypophysis. Theranostic instruments which combine OCT with laser ablation might gain importance in the emerging field of minimal invasive tumor surgery. OCT depicts vessel wall layers and its pathologies uniquely. Doppler OCT could further visualize blood flow in parallel. These abilities shed light on promising future applications in the field of vascular neurosurgery.

VR-based training of craniotomy for intracranial aneurysm surgery.

PURPOSE: Intracranial aneurysms can be treated micro-surgically. This procedure involves an appropriate head position of the patient and a proper craniotomy. These steps enable a proper access, facilitating the subsequent steps. To train the access planning process, we propose a VR-based training system. METHOD: We designed and implemented an immersive VR access simulation, where the user is surrounded by a virtual operating room, including medical equipment and virtual staff. The patient's head can be positioned via hand rotation and an arbitrary craniotomy contour can be drawn. The chosen access can be evaluated by exposing the aneurysm using a microscopic view. RESULTS: The evaluation of the simulation took place in three stages: testing the simulation using the think-aloud method, conducting a survey and examining the precision of drawing the contour. Although there are differences between the virtual interactions and their counterparts in reality, the participants liked the immersion and felt present in the operating room. The calculated surface dice similarity coefficient, Hausdorff distance and feedback of the participants show that the difficulty of drawing the craniotomy is appropriate. CONCLUSION: The presented training simulation for head positioning and access planning benefits from the immersive environment. Thus, it is an appropriate training for novice neurosurgeons and medical students with the goal to improve anatomical understanding and to become aware of the importance of the right craniotomy hole.

Generation of an NFκB-Driven Alpharetroviral "All-in-One" Vector Construct as a Potent Tool for CAR NK Cell Therapy.

Immune cell therapeutics are increasingly applied in oncology. Especially chimeric antigen receptor (CAR) T cells are successfully used to treat several B cell malignancies. Efforts to engineer CAR T cells for improved activity against solid tumors include co-delivery of pro-inflammatory cytokines in addition to CARs, via either constitutive cytokine expression or inducible cytokine expression triggered by CAR recognition of its target antigen-so-called "T cells redirected for universal cytokine-mediated killing" (TRUCKs) or fourth-generation CARs. Here, we tested the hypothesis that TRUCK principles could be expanded to improve anticancer functions of NK cells. A comparison of the functionality of inducible promoters responsive to NFAT or NFκB in NK cells showed that, in contrast to T cells, the inclusion of NFκB-responsive elements within the inducible promoter construct was essential for CAR-inducible expression of the transgene. We demonstrated that GD2CAR-specific activation induced a tight NFκB-promoter-driven cytokine release in NK-92 and primary NK cells together with an enhanced cytotoxic capacity against GD2+ target cells, also shown by increased secretion of cytolytic cytokines. The data demonstrate biologically relevant differences between T and NK cells that are important when clinically translating the TRUCK concept to NK cells for the treatment of solid malignancies.

Definition and extraction of 2D shape indices of intracranial aneurysm necks for rupture risk assessment.

PURPOSE: Intracranial aneurysms are local dilations of brain vessels. Their rupture, as well as their treatment, is associated with high risk of morbidity and mortality. In this work, we propose shape indices for aneurysm ostia for the rupture risk assessment of intracranial aneurysms. METHODS: We analyzed 84 middle cerebral artery bifurcation aneurysms (27 ruptured and 57 unruptured) and their ostia, with respect to their size and shape. We extracted 3D models of the aneurysms and vascular trees. A semi-automatic approach was used to separate the aneurysm from its parent vessel and to reconstruct the ostium. We used known indices to quantitatively describe the aneurysms. For the ostium, we present new shape indices: the 2D Undulation Index (UI[Formula: see text]), the 2D Ellipticity Index (EI[Formula: see text]) and the 2D Noncircularity Index (NCI[Formula: see text]). Results were analyzed using the Student t test, the Mann-Whitney U test and a correlation analysis between indices of the aneurysms and their ostia. RESULTS: Of the indices, none was significantly associated with rupture status. Most aneurysms have an NCI[Formula: see text] below 0.2. Of the aneurysms that have an NCI[Formula: see text] above 0.5, only one is ruptured, which indicates that ruptured aneurysms often have a circular-shaped ostium. Furthermore, the ostia of ruptured aneurysms tend to have a smaller area, which is also correlated with the aneurysm's size. While also other variables were significantly correlated, strong linear correlations can only be seen between the area of the ostium with the aneurysm's volume and surface. CONCLUSION: The proposed shape indices open up new possibilities to quantitatively describe and compare ostia, which can be beneficial for rupture risk assessment and subsequent treatment decision. Additionally, this work shows that the ostium area and the size of the aneurysm are correlated. Further longitudinal studies are necessary to analyze whether stable and unstable aneurysms can be distinguished by their ostia.

Aneurysm Wall Enhancement Is Associated With Decreased Intrasaccular IL-10 and Morphological Features of Instability.

BACKGROUND: High-resolution vessel wall imaging plays an increasingly important role in assessing the risk of aneurysm rupture. OBJECTIVE: To introduce an approach toward the validation of the wall enhancement as a direct surrogate parameter for aneurysm stability. METHODS: A total of 19 patients harboring 22 incidental intracranial aneurysms were enrolled in this study. The aneurysms were dichotomized according to their aneurysm-to-pituitary stalk contrast ratio using a cutoff value of 0.5 (nonenhancing < 0.5; enhancing ≥ 0.5). We evaluated the association of aneurysm wall enhancement with morphological characteristics, hemodynamic features, and inflammatory chemokines directly measured inside the aneurysm. RESULTS: Differences in plasma concentration of chemokines and inflammatory molecules, morphological, and hemodynamic parameters were analyzed using the Welch test or Mann-Whitney U test. The concentration ΔIL-10 in the lumen of intracranial aneurysms with low wall enhancement was significantly increased compared to aneurysms with strong aneurysm wall enhancement (P = .014). The analysis of morphological and hemodynamic parameters showed significantly increased values for aneurysm volume (P = .03), aneurysm area (P = .044), maximal diameter (P = .049), and nonsphericity index (P = .021) for intracranial aneurysms with strong aneurysm wall enhancement. None of the hemodynamic parameters reached statistical significance; however, the total viscous shear force computed over the region of low wall shear stress showed a strong tendency toward significance (P = .053). CONCLUSION: Aneurysmal wall enhancement shows strong associations with decreased intrasaccular IL-10 and established morphological indicators of aneurysm instability.

VICTORIA: VIrtual neck Curve and True Ostium Reconstruction of Intracranial Aneurysms.

PURPOSE: For the status evaluation of intracranial aneurysms (IAs), morphological and hemodynamic parameters can provide valuable information. For their extraction, a separation of the aneurysm sac from its parent vessel is required that yields the neck curve and the ostium. However, manual and subjective neck curve and ostium definitions might lead to inaccurate IA assessments. METHODS: The research project VICTORIA was initiated, allowing users to interactively define the neck curve of five segmented IA models using a web application. The submitted results were qualitatively and quantitatively compared to identify the minimum, median and maximum aneurysm surface area. Finally, image-based blood flow simulations were carried out to assess the effect of variable neck curve definitions on relevant flow- and shear-related parameters. RESULTS: In total, 55 participants (20 physicians) from 18 countries participated in VICTORIA. For relatively simple aneurysms, a good agreement with respect to the neck curve definition was found. However, differences among the participants increased with increasing complexity of the aneurysm. Furthermore, it was observed that the majority of participants excluded any small arteries occurring in the vicinity of an aneurysm. This can lead to non-negligible deviations among the flow- and shear-related parameters, which need to be carefully evaluated, if quantitative analysis is desired. Finally, no differences between participants with medical and non-medical background could be observed. CONCLUSIONS: VICTORIAs findings reveal the complexity of aneurysm neck curve definition, especially for bifurcation aneurysms. Standardization appears to be mandatory for future sac-vessel-separations. For hemodynamic simulations a careful neck curve definition is crucial to avoid inaccuracies during the quantitative flow analysis.

Distance and force visualisations for improved simulation of intracranial aneurysm clipping.

PURPOSE: The treatment of cerebral aneurysms shifted from microsurgical to endovascular therapy. But for some difficult aneurysm configurations, e.g. wide neck aneurysms, microsurgical clipping is better suited. From this combination of limited interventions and the complexity of these cases, the need for improved training possibilities for young neurosurgeons arises. METHOD: We designed and implemented a clipping simulation that requires only a monoscopic display, mouse and keyboard. After a virtual craniotomy, the user can apply a clip at the aneurysm which is deformed based on a mass-spring model. Additionally, concepts for visualising distances as well as force were implemented. The distance visualisations aim to enhance spatial relations, improving the navigation of the clip. The force visualisations display the force acting on the vessel surface by the applied clip. The developed concepts include colour maps and visualisations based on rays, single objects and glyphs. RESULTS: The concepts were quantitatively evaluated via an online survey and qualitatively evaluated by a neurosurgeon. Regarding force visualisations, a colour map is the most appropriate concept. The necessity of distance visualisations became apparent, as the expert was unable to estimate distances and to properly navigate the clip. The distance rays were the only concept supporting the navigation appropriately. CONCLUSION: The easily accessible surgical training simulation for aneurysm clipping benefits from a visualisation of distances and simulated forces.

Optical coherence tomography of cranial dura mater: Microstructural visualization in vivo.

PURPOSE: The study explores microscope integrated optical coherence tomography (OCT) as a intraoperative imaging technique to delineate the microstructural composition of human dura mater cranialis and underlying leptomeninges for surgical guidance. METHODS: OCT volume scans, light microscopic pictures and light microscopic videos of the dura mater were acquired in patients (n = 20) with indication for craniotomy. OCT volume scans and corresponding light microscopic data were analyzed post procedural. Thickness of anatomical structures was measured during this phase. RESULTS: OCT scanning of the human cranial dura mater was feasible during microsurgical dissection. A discrimination of the endosteal and inner meningeal layer of the cranial dura mater was possible in 70 % (n = 14) of the patients. Transdural OCT scans could further demonstrate subdural anatomical structures: subdural space 10 % (n = 2), subarachnoid space in 35 % (n = 7), arachnoid vessels in 80 % (n = 16) and brain cortex in 90 % (n = 16) of the patients. Orthogonal distance measurement was possible. The cranial dura mater showed a mean depth of 216 µm, the endosteal layer of 120 µm and the inner meningeal layer of 132 µm. Imaging quality of the dural segment was high - approaching spatial resolution of histopathology. Imaging quality of subdural segments was lower and demonstrated A-line artifacts in 45 % (n = 7). CONCLUSION: These results illustrate - for the first time - strengths and weaknesses of three dimensional microscope integrated OCT as an in vivo imaging method of the human cranial dura mater, underlying leptomeninges and human brain cortex as a surgical guidance tool. OCT imaging of the cranial dura mater showed extensive details. Transdural imaging of subdural micro anatomical structures was possible, but showed lower image quality with intermittent A-line artifacts. OCT stated the first intraoperative imaging tool to measure the depth of micro anatomical structures with a high spatial resolution of 7,5 µm.

Microscope integrated optical coherence tomography of a cerebral arachnoid cyst: A new technique to increase intraoperative security.

PURPOSE: This technical note illustrates microscope integrated optical coherence tomography (iOCT) as an imaging technique to delineate concealed micro anatomical structures not displayable by conventional intraoperative imaging methods in the context of a cerebral arachnoid cyst. METHODS: iOCT was used for the first time to scan a cerebral arachnoid cyst in vivo. Scanning sites were defined at the outer membrane of the arachnoid cyst, the inner membrane at the temporal cortex as well as at the fenestration site to the basal cisterns - a point out of reach and resolution for conventional intraoperative imaging methods like e. g. ultrasound or neuroendoscopy. RESULTS: iOCT was feasible during microsurgical fenestration of an arachnoid cyst. A clear delineation of the arachnoid cyst membrane was possible. The differentiation of the arachnoid cyst membrane and underlying arachnoid barrier cell membrane was possible. Trans cystic scanning at the temporal cortex could delineate the content of the subarachnoid space like subarachnoid blood vessels, trabecular sytem and vessel wall morphology of a M4 middle cerebral artery branch. Scanning of the inner membrane of the arachnoid cyst at site of fenestration to the basal cisterns excluded underlying micro anatomical structures. CONCLUSION: This case demonstrates that iOCT achieved to delineate concealed micro anatomical structures which are occult to conventional intraoperative imaging methods. Further studies are necessary to value iOCT as a tool to improve intraoperative security.

Combining visual analytics and case-based reasoning for rupture risk assessment of intracranial aneurysms.

PURPOSE: Medical case-based reasoning solves problems by applying experience gained from the outcome of previous treatments of the same kind. Particularly for complex treatment decisions, for example, incidentally found intracranial aneurysms (IAs), it can support the medical expert. IAs bear the risk of rupture and may lead to subarachnoidal hemorrhages. Treatment needs to be considered carefully, since it may entail unnecessary complications for IAs with low rupture risk. With a rupture risk prediction based on previous cases, the treatment decision can be supported. METHODS: We present an interactive visual exploration tool for the case-based reasoning of IAs. In presence of a new aneurysm of interest, our application provides visual analytics techniques to identify the most similar cases with respect to morphology. The clinical expert can obtain the treatment, including the treatment outcome, for these cases and transfer it to the aneurysm of interest. Our application comprises a heatmap visualization, an adapted scatterplot matrix and fully or partially directed graphs with a circle- or force-directed layout to guide the interactive selection process. To fit the demands of clinical applications, we further integrated an interactive identification of outlier cases as well as an interactive attribute selection for the similarity calculation. A questionnaire evaluation with six trained physicians was used. RESULT: Our application allows for case-based reasoning of IAs based on a reference data set. Three classifiers summarize the rupture state of the most similar cases. Medical experts positively evaluated the application. CONCLUSION: Our case-based reasoning application combined with visual analytic techniques allows for representation of similar IAs to support the clinician. The graphical representation was rated very useful and provides visual information of the similarity of the k most similar cases.

Design and Characterization of an "All-in-One" Lentiviral Vector System Combining Constitutive Anti-GD2 CAR Expression and Inducible Cytokines.

Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs ("T cells redirected for universal cytokine-mediated killing"), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular "all-in-one" vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the "all-in-one" vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.