Are hemodynamics responsible for inflammatory changes in venous vessel walls? A quantitative study of wall-enhancing intracranial arteriovenous malformation draining veins.

OBJECTIVE: Signal enhancement of vascular walls on vessel wall MRI might be a biomarker for inflammation. It has been theorized that contrast enhancement on vessel wall imaging (VWI) in draining veins of intracranial arteriovenous malformations (AVMs) may be associated with disease progression and development of venous stenosis. The aim of this study was to investigate the relationship between vessel wall enhancement and hemodynamic stressors along AVM draining veins. METHODS: Eight AVM patients with 15 draining veins visualized on VWI were included. Based on MR venography data, patient-specific 3D surface models of the venous anatomy distal to the nidus were segmented. The enhanced vascular wall regions were manually extracted and mapped onto the venous surface models after registration of image data. Using image-based blood flow simulations applying patient-specific boundary conditions based on phase-contrast quantitative MR angiography, hemodynamics were investigated in the enhanced vasculature. For the shear-related parameters, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated. Velocity, oscillatory velocity index (OVI), and vorticity were extracted for the intraluminal flow-related hemodynamics. RESULTS: Visual observations demonstrated overlap of enhancement with local lower shear stresses resulting from decreased velocities. Thus, higher RRT values were measured in the enhanced areas. Furthermore, nonenhancing draining veins showed on average slightly higher flow velocities and TAWSS. Significant decreases of 55% (p = 0.03) for TAWSS and of 24% (p = 0.03) for vorticity were identified in enhanced areas compared with near distal and proximal domains. Velocity magnitude in the enhanced region showed a nonsignificant decrease of 14% (p = 0.06). Furthermore, increases were present in the OSI (32%, p = 0.3), RRT (25%, p = 0.15), and OVI (26%, p = 0.3) in enhanced vessel sections, although the differences were not significant. CONCLUSIONS: This novel multimodal investigation of hemodynamics in AVM draining veins allows for precise prediction of occurring shear- and flow-related phenomena in enhanced vessel walls. These findings may suggest low shear to be a local predisposing factor for venous stenosis in AVMs.

Image-based hemodynamic simulations for intracranial aneurysms: the impact of complex vasculature.

PURPOSE: Hemodynamics play an important role in the assessment of intracranial aneurysm (IA) development and rupture risk. The purpose of this study was to examine the impact of complex vasculatures onto the intra-vessel and intra-aneurysmal blood flow. METHODS: Complex segmentation of a subject-specific, 60-outlet and 3-inlet circle of Willis model captured with 7T magnetic resonance imaging was performed. This model was trimmed to a 10-outlet model version. Two patient-specific IAs were added onto both models yielding two pathological versions, and image-based blood flow simulations of the four resulting cases were carried out. To capture the differences between complex and trimmed model, time-averaged and centerline velocities were compared. The assessment of intra-saccular blood flow within the IAs involved the evaluation of wall shear stresses (WSS) at the IA wall and neck inflow rates (NIR). RESULTS: Lower flow values are observed in the majority of the complex model. However, at specific locations (left middle cerebral artery 0.5 m/s, left posterior cerebral artery 0.25 m/s), higher flow rates were visible when compared to the trimmed counterpart. Furthermore, at the centerlines the total velocity values reveal differences up to 0.15 m/s. In the IAs, the reduction in the neck inflow rate and WSS in the complex model was observed for the first IA (IA-A δNIRmean = - 0.07ml/s, PCA.l δWSSmean = - 0.05 Pa). The second IA featured an increase in the neck inflow rate and WSS (IA-B δNIRmean = 0.04 ml/s, PCA.l δWSSmean = 0.07 Pa). CONCLUSION: Both the magnitude and shape of the flow distribution vary depending on the model's complexity. The magnitude is primarily influenced by the global vessel model, while the shape is determined by the local structure. Furthermore, intra-aneurysmal flow strongly depends on the location in the vessel tree, emphasizing the need for complex model geometries for realistic hemodynamic assessment and rupture risk analysis.

Multi-Dimensional Modeling of Cerebral Hemodynamics: A Systematic Review.

The Circle of Willis (CoW) describes the arterial system in the human brain enabling the neurovascular blood supply. Neurovascular diseases like intracranial aneurysms (IAs) can occur within the CoW and carry the risk of rupture, which can lead to subarachnoid hemorrhage. The assessment of hemodynamic information in these pathologies is crucial for their understanding regarding detection, diagnosis and treatment. Multi-dimensional in silico approaches exist to evaluate these hemodynamics based on patient-specific input data. The approaches comprise low-scale (zero-dimensional, one-dimensional) and high-scale (three-dimensional) models as well as multi-scale coupled models. The input data can be derived from medical imaging, numerical models, literature-based assumptions or from measurements within healthy subjects. Thus, the most realistic description of neurovascular hemodynamics is still controversial. Within this systematic review, first, the models of the three scales (0D, 1D, 3D) and second, the multi-scale models, which are coupled versions of the three scales, were discussed. Current best practices in describing neurovascular hemodynamics most realistically and their clinical applicablility were elucidated. The performance of 3D simulation entails high computational expenses, which could be reduced by analyzing solely the region of interest in detail. Medical imaging to establish patient-specific boundary conditions is usually rare, and thus, lower dimensional models provide a realistic mimicking of the surrounding hemodynamics. Multi-scale coupling, however, is computationally expensive as well, especially when taking all dimensions into account. In conclusion, the 0D-1D-3D multi-scale approach provides the most realistic outcome; nevertheless, it is least applicable. A 1D-3D multi-scale model can be considered regarding a beneficial trade-off between realistic results and applicable performance.

Fusiform versus Saccular Intracranial Aneurysms-Hemodynamic Evaluation of the Pre-Aneurysmal, Pathological, and Post-Interventional State.

Minimally-invasive therapies are well-established treatment methods for saccular intracranial aneurysms (SIAs). Knowledge concerning fusiform IAs (FIAs) is low, due to their wide and alternating lumen and their infrequent occurrence. However, FIAs carry risks like ischemia and thus require further in-depth investigation. Six patient-specific IAs, comprising three position-identical FIAs and SIAs, with the FIAs showing a non-typical FIA shape, were compared, respectively. For each model, a healthy counterpart and a treated version with a flow diverting stent were created. Eighteen time-dependent simulations were performed to analyze morphological and hemodynamic parameters focusing on the treatment effect (TE). The stent expansion is higher for FIAs than SIAs. For FIAs, the reduction in vorticity is higher (Δ35-75% case 2/3) and the reduction in the oscillatory velocity index is lower (Δ15-68% case 2/3). Velocity is reduced equally for FIAs and SIAs with a TE of 37-60% in FIAs and of 41-72% in SIAs. Time-averaged wall shear stress (TAWSS) is less reduced within FIAs than SIAs (Δ30-105%). Within this study, the positive TE of FDS deployed in FIAs is shown and a similarity in parameters found due to the non-typical FIA shape. Despite the higher stent expansion, velocity and vorticity are equally reduced compared to identically located SIAs.

A confirmed human fatality due to envenomation by the Kunene Coral Snake (Aspidelaps lubricus cowlesi) in Namibia.

Shield-nose and Coral snakes (Aspidelaps spp.) are medium sized venomous snakes found throughout southern Africa. Little is known about the venom of these snakes and its clinical relevance, as human bites are uncommon. Neurological signs and symptoms usually develop following bites by this genus but evaluations of the severity are inconclusive. We report on the first confirmed human fatality by the Kunene Shield-nose Snake (Aspidelaps lubricus cowlesi) in a child. Envenomation by Aspidelaps and other snakes considered lesser-venomous - especially those possessing neurotoxic venom - should be treated with caution as they may result in life-threatening envenomation without established clinical management protocols.

In vitro and in silico assessment of flow modulation after deploying the Contour Neurovascular System in intracranial aneurysm models.

BACKGROUND: The novel Contour Neurovascular System (Contour) has been reported to be efficient and safe for the treatment of intracranial, wide-necked bifurcation aneurysms. Flow in the aneurysm and posterior cerebral arteries (PCAs) after Contour deployment has not been analyzed in detail yet. However, this information is crucial for predicting aneurysm treatment outcomes. METHODS: Time-resolved three-dimensional velocity maps in 14 combinations of patient-based basilar tip aneurysm models with and without Contour devices (sizes between 5 and 14 mm) were analyzed using four-dimensionsal (4D) flow MRI and numerical/image-based flow simulations. A complex virtual processing pipeline was developed to mimic the experimental shape and position of the Contour together with the simulations. RESULTS: On average, the Contour significantly reduced intra-aneurysmal flow velocity by 67% (mean w/ = 0.03m/s; mean w/o = 0.12m/s; p-value=0.002), and the time-averaged wall shear stress by more than 87% (mean w/ = 0.17Pa; mean w/o = 1.35Pa; p-value=0.002), as observed by numerical simulations. Furthermore, a significant reduction in flow (P<0.01) was confirmed by the neck inflow rate, kinetic energy, and inflow concentration index after Contour deployment. Notably, device size has a stronger effect on reducing flow than device positioning. However, positioning affected flow in the PCAs, while being robust in effectively reducing flow. CONCLUSIONS: This study showed the high efficacy of the Contour device in reducing flow within aneurysms regardless of the exact position. However, we observed an effect on the flow in PCAs, which needs to be investigated further.

Is Accurate Lumen Segmentation More Important than Outlet Boundary Condition in Image-Based Blood Flow Simulations for Intracranial Aneurysms?

PURPOSE: Image-based blood flow simulations are increasingly used to investigate the hemodynamics in intracranial aneurysms (IAs). However, a strong variability in segmentation approaches as well as the absence of individualized boundary conditions (BCs) influence the quality of these simulation results leading to imprecision and decreased reliability. This study aims to analyze these influences on relevant hemodynamic parameters within IAs. METHODS: As a follow-up study of an international multiple aneurysms challenge, the segmentation results of five IAs differing in size and location were investigated. Specifically, five possible outlet BCs were considered in each of the IAs. These are comprised of the zero-pressure condition (BC1), a flow distribution based on Murray's law with the exponents n = 2 (BC2) and n = 3 (BC3) as well as two advanced flow-splitting models considering the real vessels by including circular cross sections (BC4) or anatomical cross sections (BC5), respectively. In total, 120 time-dependent blood flow simulations were analyzed qualitatively and quantitatively, focusing on five representative intra-aneurysmal flow and five shear parameters such as vorticity and wall shear stress. RESULTS: The outlet BC variation revealed substantial differences. Higher shear stresses (up to Δ9.69 Pa), intrasaccular velocities (up to Δ0.15 m/s) and vorticities (up to Δ629.22 1/s) were detected when advanced flow-splitting was applied compared to the widely used zero-pressure BC. The tendency of outlets BCs to over- or underestimate hemodynamic parameters is consistent across different segmentations of a single aneurysm model. Segmentation-induced variability reaches Δ19.58 Pa, Δ0.42 m/s and Δ957.27 1/s, respectively. Excluding low fidelity segmentations, however, (a) reduces the deviation drastically (>43%) and (b) leads to a lower impact of the outlet BC on hemodynamic predictions. CONCLUSION: With a more realistic lumen segmentation, the influence of the BC on the resulting hemodynamics is decreased. A realistic lumen segmentation can be ensured, e.g., by using high-resolved 2D images. Furthermore, the selection of an advanced outflow-splitting model is advised and the use of a zero-pressure BC and BC based on Murray's law with exponent n = 3 should be avoided.

Regulatory Measures to Improve the Safety of CAR-T-Cell Treatment.

Introduction: Regulatory activities aim to facilitate the safe use of novel therapeutics such as genetically engineered chimeric antigen receptor (CAR)-T cells. Toxicities associated with CAR-T-cell therapies have led to modified safety management guidance in clinical trials and the implementation of post-marketing requirements. The aim of this study was to estimate the effect of individual risk-minimizing measures to evaluate the appropriateness of regulatory activities. Methods: We re-examined clinical trial data prior to and after the introduction of revised treatment guidelines; we analysed spontaneous adverse drug reaction (ADR) reports submitted to the EudraVigilance database in 2019/2020 regarding their completeness; and we performed a survey of treatment centres in Germany that have been qualified for the use of commercial CAR-T cells. Results: Lower combined incidences of severe cytokine release syndrome (CRS) as well as neurotoxicity occurred following CAR-T-cell treatment after a revision of management guidelines, suggesting earlier intervention compared to before (12.6% vs. 20.5%). Numerous post-marketing ADR reports lacked information important for case assessment. Full details on treatment indication, CRS onset, outcome, and grading were available for just 38.3% of CRS cases. Survey responses support the majority of regulatory requirements for centre qualification. Time investment was highest for training of healthcare professionals, which required an average of 6.5 staff members (range 2-20) and lasted more than 2 days per person in half of the facilities. The need to harmonize the regulatory requirements for the different CAR-T-cell therapeutics was emphasized. Conclusion: Defined regulatory measures can support the safe and effective use of new therapies and are indicated for structured recording of post-marketing data, and the evaluation of such measures appears to be necessary for the continuous improvement.

Multimodal exploration of the intracranial aneurysm wall.

PURPOSE: Intracranial aneurysms (IAs) are pathological changes of the intracranial vessel wall, although clinical image data can only show the vessel lumen. Histology can provide wall information but is typically restricted to ex vivo 2D slices where the shape of the tissue is altered. METHODS: We developed a visual exploration pipeline for a comprehensive view of an IA. We extract multimodal information (like stain classification and segmentation of histologic images) and combine them via 2D to 3D mapping and virtual inflation of deformed tissue. Histological data, including four stains, micro-CT data and segmented calcifications as well as hemodynamic information like wall shear stress (WSS), are combined with the 3D model of the resected aneurysm. RESULTS: Calcifications were mostly present in the tissue part with increased WSS. In the 3D model, an area of increased wall thickness was identified and correlated to histology, where the Oil red O (ORO) stained images showed a lipid accumulation and the alpha-smooth muscle actin (aSMA) stained images showed a slight loss of muscle cells. CONCLUSION: Our visual exploration pipeline combines multimodal information about the aneurysm wall to improve the understanding of wall changes and IA development. The user can identify regions and correlate how hemodynamic forces, e.g. WSS, are reflected by histological structures of the vessel wall, wall thickness and calcifications.

Assessment of the flow-diverter efficacy for intracranial aneurysm treatment considering pre- and post-interventional hemodynamics.

Endovascular treatment of intracranial aneurysms with flow diverters (FD) has become one of the most promising interventions. Due to its woven high-density structure they are particularly applicable for challenging lesions. Although several studies have already conducted realistic hemodynamic quantification of the FD efficacy, a comparison with morphologic post-interventional data is still missing. This study analyses the hemodynamics of ten intracranial aneurysm patients treated with a novel FD device. Based on pre- and post-interventional 3D digital subtraction angiography image data, patient-specific 3D models of both treatment states are generated applying open source threshold-based segmentation methods. Using a fast virtual stenting approach, the real stent positions available in the post-interventional data are virtually replicated and both treatment scenarios were characterized using image-based blood flow simulations. The results show FD-induced flow reductions at the ostium by a decrease in mean neck flow rate (51%), inflow concentration index (56%) and mean inflow velocity (53%). Intraluminal reductions in flow activity for time-averaged wall shear stress (47%) and kinetic energy (71%) are present as well. However, an intra-aneurysmal increase in flow pulsatility (16%) for the post-interventional cases can be observed. Patient-specific FD simulations demonstrate the desired flow redirection and activity reduction inside the aneurysm beneficial for thrombosis formation. Differences in the magnitude of hemodynamic reduction exist over the cardiac cycle which may be addressed in a clinical setting by anti-hypertensive treatment in selected cases.

Geometric uncertainty in intracranial aneurysm rupture status discrimination: a two-site retrospective study.

OBJECTIVES: Assessing the risk associated with unruptured intracranial aneurysms (IAs) is essential in clinical decision making. Several geometric risk parameters have been proposed for this purpose. However, performance of these parameters has been inconsistent. This study evaluates the performance and robustness of geometric risk parameters on two datasets and compare it to the uncertainty inherent in assessing these parameters and quantifies interparameter correlations. METHODS: Two datasets containing 244 ruptured and unruptured IA geometries from 178 patients were retrospectively analysed. IAs were stratified by anatomical region, based on the PHASES score locations. 37 geometric risk parameters representing four groups (size, neck, non-dimensional, and curvature parameters) were assessed. Analysis included standardised absolute group differences (SADs) between ruptured and unruptured IAs, ratios of SAD to median relative uncertainty (MRU) associated with the parameters, and interparameter correlation. RESULTS: The ratio of SAD to MRU was lower for higher dimensional size parameters (ie, areas and volumes) than for one-dimensional size parameters. Non-dimensional size parameters performed comparatively well with regard to SAD and MRU. SAD was higher in the posterior anatomical region. Correlation of parameters was strongest within parameter (sub)groups and between size and curvature parameters, while anatomical region did not strongly affect correlation patterns. CONCLUSION: Non-dimensional parameters and few parameters from other groups were comparatively robust, suggesting that they might generalise better to other datasets. The data on discriminative performance and interparameter correlations presented in this study may aid in developing and choosing robust geometric parameters for use in rupture risk models.

Long-term outcome of patients with vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis.

We present the long-term outcomes of 44 patients who developed cerebral venous sinus thrombosis after vaccination with the adenoviral vector ChAdOx1 nCoV-19 COVID-19 vaccine. Assessment of the Extended Glasgow Outcome Scale was performed within 3-6 months after the initial hospital admissions. Patient outcomes ranged from good recovery (13 patients, 29.6%) to moderate disability (11 patients, 25.0%) and severe disability or vegetative state (6 patients, 13.6%). Fatal outcomes were reported in 14 patients (31.8%).

Simulation of the FDA nozzle benchmark: A lattice Boltzmann study.

BACKGROUND AND OBJECTIVE: Contrary to flows in small intracranial vessels, many blood flow configurations such as those found in aortic vessels and aneurysms involve larger Reynolds numbers and, therefore, transitional or turbulent conditions. Dealing with such systems require both robust and efficient numerical methods. METHODS: We assess here the performance of a lattice Boltzmann solver with full Hermite expansion of the equilibrium and central Hermite moments collision operator at higher Reynolds numbers, especially for under-resolved simulations. To that end the food and drug administration's benchmark nozzle is considered at three different Reynolds numbers covering all regimes: (1) laminar at a Reynolds number of 500, (2) transitional at a Reynolds number of 3500, and (3) low-level turbulence at a Reynolds number of 6500. RESULTS: The lattice Boltzmann results are compared with previously published inter-laboratory experimental data obtained by particle image velocimetry. Our results show good agreement with the experimental measurements throughout the nozzle, demonstrating the good performance of the solver even in under-resolved simulations. CONCLUSION: In this manner, fast but sufficiently accurate numerical predictions can be achieved for flow configurations of practical interest regarding medical applications.

Effect of flow diverter stent malposition on intracranial aneurysm hemodynamics-An experimental framework using stereoscopic particle image velocimetry.

BACKGROUND: Flow-diverting stents are increasingly used for the minimally-invasive treatment of intracranial aneurysms. However, a correct positioning of such devices can be challenging due to varying vessel diameters as well as the complex anatomy of the neurovasculature. As a consequence, unsuccessful treatment outcomes are increasingly reported requiring an improvement of the understanding of stent-induced flow modification. METHODS: To evaluate the effect of different degrees of flow diverter stent malposition on intra-aneurysmal hemodynamic changes, a controlled hemodynamic configuration was created using an idealized intracranial aneurysms model. Afterwards, four different treatment scenarios were reproduced comprising of 1) the ideal treatment, 2) an insufficient wall apposition in the region of the ostium, 3) a distorted device migrating into the aneurysm sac and 4) an inaccurately deployed stent due to wrong release location. For the assessment of the individual flow modifications, high-resolution stereoscopic particle image velocimetry (PIV) measurements were carried out. RESULTS: The analysis of the precise in-vitro PIV measurements reveals that in all cases a considerable reduction of the cycle-averaged and peak-systolic velocity was obtained. Compared to the untreated aneurysm configuration, the flow reduction ranged from 63% (scenario 4) up to 89% (scenario 3). The ideal treatment reached a reduction of 78%, which is known to be sufficient for a successful therapy. However, inaccurate device positioning leads to increased oscillating flow towards the lateral directions reducing the chances of sufficient thrombus formation. CONCLUSIONS: High-resolution in-vitro PIV measurements enable an accurate quantification of the treatment efficacy for flow-diverting devices. Furthermore, insufficient treatment outcomes can be reproduces allowing for an assessment of intra-aneurysmal hemodynamic changes.

Influence of Spatial Resolution and Compressed SENSE Acceleration Factor on Flow Quantification with 4D Flow MRI at 3 Tesla.

Four-dimensional (4D) flow MRI allows quantifying flow in blood vessels-non invasively and in vivo. The clinical use of 4D flow MRI in small vessels, however, is hampered by long examination times and limited spatial resolution. Compressed SENSE (CS-SENSE) is a technique that can accelerate 4D flow dramatically. Here, we investigated the effect of spatial resolution and CS acceleration on flow measurements by using 4D flow MRI in small vessels in vitro at 3 T. We compared the flow in silicon tubes (inner diameters of 2, 3, 4, and 5 mm) measured with 4D flow MRI, accelerated with four CS factors (CS = 2.5, 4.5, 6.5, and 13) and three voxel sizes (0.5, 1, and 1.5 mm3) to 2D flow MRI and a flow sensor. Additionally, the velocity field in an aneurysm model acquired with 4D flow MRI was compared to the one simulated with computational fluid dynamics (CFD). A strong correlation was observed between flow sensor, 2D flow MRI, and 4D flow MRI (rho > 0.94). The use of fewer than seven voxels per vessel diameter (nROI) resulted in an overestimation of flow in more than 5% of flow measured with 2D flow MRI. A negative correlation (rho = -0.81) between flow error and nROI were found for CS = 2.5 and 4.5. No statistically significant impact of CS factor on differences in flow rates was observed. However, a trend of increased flow error with increased CS factor was observed. In an aneurysm model, the peak velocity and stagnation zone were detected by CFD and all 4D flow MRI variants. The velocity difference error in the aneurysm sac did not exceed 11% for CS = 4.5 in comparison to CS = 2.5 for all spatial resolutions. Therefore, CS factors from 2.5-4.5 can appear suitable to improve spatial or temporal resolution for accurate quantification of flow rate and velocity. We encourage reporting the number of voxels per vessel diameter to standardize 4D flow MRI protocols.

Virtual embolization for treatment support of intracranial AVMs using an interactive desktop and VR application.

PURPOSE: The treatment of intracranial arteriovenous malformations (AVM) is challenging due to their complex anatomy. For this vessel pathology, arteries are directly linked to veins without a capillary bed in between. For endovascular treatment, embolization is carried out, where the arteries that supply the AVM are consecutively blocked. A virtual embolization could support the medical expert in treatment planning. METHOD: We designed and implemented an immersive VR application that allows the visualization of the simulated blood flow by displaying millions of particles. Furthermore, the user can interactively block or unblock arteries that supply the AVM and analyze the altered blood flow based on pre-computed simulations. RESULTS: In a pilot study, the application was successfully adapted to three patient-specific cases. We performed a qualitative evaluation with two experienced neuroradiologist who regularly conduct AVM embolizations. The feature of virtually blocking or unblocking feeders was rated highly beneficial, and a desire for the inclusion of quantitative information was formulated. CONCLUSION: The presented application allows for virtual embolization and interactive blood flow visualization in an immersive virtual reality environment. It could serve as useful addition for treatment planning and education in clinical practice, supporting the understanding of AVM topology as well as understanding the influence of the AVM's feeding arteries.

Luminal enhancement in intracranial aneurysms: fact or feature?-A quantitative multimodal flow analysis.

PURPOSE: Intracranial aneurysm (IA) wall enhancement on post-contrast vessel wall magnetic resonance imaging (VW-MRI) is assumed to be a biomarker for vessel wall inflammation and aneurysm instability. However, the exact factors contributing to enhancement are not yet clarified. This study investigates the relationship between luminal enhancement and intra-aneurysmal flow behaviour to assess the suitability of VW-MRI as a surrogate method for determining quantitative and qualitative flow behaviour in the aneurysm sac. METHODS: VW-MRI signal is measured in the lumen of three patient-specific IA flow models and compared with the intra-aneurysmal flow fields obtained using phase-contrast magnetic resonance imaging (PC-MRI) and computational fluid dynamics (CFD). The IA flow models were supplied with two different time-varying flow regimes. RESULTS: Overall, the velocity fields acquired using PC-MRI or CFD were in good agreement with the VW-MRI enhancement patterns. Generally, the regions with slow-flowing blood show higher VW-MRI signal intensities, whereas high flow leads to a suppression of the signal. For all aneurysm models, a signal value above three was associated with velocity values below three cm/s. CONCLUSION: Regions with lower enhancements have been correlated with the slow and high flow at the same time. Thus, further factors like flow complexity and stability can contribute to flow suppression in addition to the flow magnitude. Nevertheless, VW-MRI can qualitatively assess intra-aneurysmal flow phenomena and estimate the velocity range present in the corresponding region.

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.