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.

Resveratrol Mitigates Metabolism in Human Microglia Cells.

The recognition of the role of microglia cells in neurodegenerative diseases has steadily increased over the past few years. There is growing evidence that the uncontrolled and persisting activation of microglial cells is involved in the progression of diseases such as Alzheimer's or Parkinson's disease. The inflammatory activation of microglia cells is often accompanied by a switch in metabolism to higher glucose consumption and aerobic glycolysis. In this study, we investigate the changes induced by the natural antioxidant resveratrol in a human microglia cell line. Resveratrol is renowned for its neuroprotective properties, but little is known about its direct effect on human microglia cells. By analyzing a variety of inflammatory, neuroprotective, and metabolic aspects, resveratrol was observed to reduce inflammasome activity, increase the release of insulin-like growth factor 1, decrease glucose uptake, lower mitochondrial activity, and attenuate cellular metabolism in a 1H NMR-based analysis of whole-cell extracts. To this end, studies were mainly performed by analyzing the effect of exogenous stressors such as lipopolysaccharide or interferon gamma on the metabolic profile of microglial cells. Therefore, this study focuses on changes in metabolism without any exogenous stressors, demonstrating how resveratrol might provide protection from persisting neuroinflammation.

The effect of the size of the new contour neurovascular device for altering intraaneurysmal flow.

BACKGROUND: Recently, a novel intrasaccular device (contour neurovascular system, contour) was introduced to treat intracranial aneurysms. Contour is placed at thе aneurysm neck and reduces the intraaneurysmal blood inflow. Contour comes in a range of sizes to target different aneurysms. The efficiency of altering flow with contour and the effect of device size have not yet been investigated. Therefore, we studied the effect of the device size with patient-based aneurysm models using 2D digital subtraction angiography (DSA). METHODS: Three patient-based aneurysm models with necks ranging from 2.7 to 9.7 mm were produced, providing standardized testing conditions. Contours with diameters of 5, 11, and 14 mm were implanted into the models, four of each size. 2D DSA images were acquired before and after implanting contour (15 frames/s, manual contrast injection). After injecting angiographic contrast agent, the DSA signal was recorded over time to calculate the contrast washout time (WOT), which is a measure of flow diversion efficiency. RESULTS: All contour devices caused contrast agent stasis and increased WOT in aneurysm sac (p-value = 0.0005). The median relative WOT was largest for 5-mm contour (6.6 ± 3.2) and similar for 11-mm contour (3.4 ± 2.6) and 14-mm contour (3.2 ± 3.8). The implantation procedure might affect WOT values even for contours of the same size; the overall relative WOT ranged between 1.5 and 10.89. CONCLUSION: The 5-mm contour showed the longest WOT value in our study, while no apparent difference between 11-mm contour and 14-mm contour was found.

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.

Imaging Inflammation - From Whole Body Imaging to Cellular Resolution.

Imaging techniques have evolved impressively lately, allowing whole new concepts like multimodal imaging, personal medicine, theranostic therapies, and molecular imaging to increase general awareness of possiblities of imaging to medicine field. Here, we have collected the selected (3D) imaging modalities and evaluated the recent findings on preclinical and clinical inflammation imaging. The focus has been on the feasibility of imaging to aid in inflammation precision medicine, and the key challenges and opportunities of the imaging modalities are presented. Some examples of the current usage in clinics/close to clinics have been brought out as an example. This review evaluates the future prospects of the imaging technologies for clinical applications in precision medicine from the pre-clinical development point of view.

A realistic way to investigate the design, and mechanical properties of flow diverter stents.

PURPOSE: Braided flow diverters (FD) are highly sophisticated, delicate, and intricate mechanical devices used to treat intracranial aneurysms. Testing such devices in vitro, however, remains an unsolved challenge. Here, we evaluate methods to measure flow, design and mechanical properties in vitro. METHODS: Flow properties, cell porosity, pore density, and cell area were evaluated under geometrically realistic conditions by placing FDs in patient-derived, 3D-printed models of human vasculature. 4D flow MRI was used to measure fluid dynamics. Laser microscopy was used to measure the design properties of the FDs. New methods were developed to investigate the bending, circumferential, and longitudinal radial force of the FDs continuously over varying diameters. RESULTS: The placement and flow properties of the FD in the vasculature models were successfully measured by MRI, although artifacts occurred. Likewise, the porosity, pore density, and cell area were successfully measured inside of the models using a laser microscope. The newly developed mechanical methods allowed to measure the indicated forces - to our knowledge for the first time - continuously. CONCLUSION: Modern and specifically tailored techniques, some of which were presented here for the first time, allow detailed insights into the flow, design, and mechanical properties of braided flow diverter stents.

Pseudo-Enhancement in Intracranial Aneurysms on Black-Blood MRI: Effects of Flow Rate, Spatial Resolution, and Additional Flow Suppression.

BACKGROUND: Vessel-wall enhancement (VWE) on black-blood MRI (BB MRI) has been proposed as an imaging marker for a higher risk of rupture and associated with wall inflammation. Whether VWE is causally linked to inflammation or rather induced by flow phenomena has been a subject of debate. PURPOSE: To study the effects of slow flow, spatial resolution, and motion-sensitized driven equilibrium (MSDE) preparation on signal intensities in BB MRI of patient-specific aneurysm flow models. STUDY TYPE: Prospective. SUBJECTS/FLOW ANEURYSM MODEL/VIRTUAL VESSELS: Aneurysm flow models based on 3D rotational angiography datasets of three patients with intracranial aneurysms were 3D printed and perfused at two different flow rates, with and without Gd-containing contrast agent. FIELD STRENGTH/SEQUENCE: Variable refocusing flip angle 3D fast-spin echo sequence at 3 T with and without MSDE with three voxel sizes ((0.5 mm)3 , (0.7 mm)3 , and (0.9 mm)3 ); time-resolved with phase-contrast velocity-encoding 3D spoiled gradient echo sequence (4D flow MRI). ASSESSMENT: Three independent observers performed a qualitative visual assessment of flow patterns and signal enhancement. Quantitative analysis included voxel-wise evaluation of signal intensities and magnitude velocity distributions in the aneurysm. STATISTICAL TESTS: Kruskal-Wallis test, potential regressions. RESULTS: A hyperintense signal in the lumen and adjacent to the aneurysm walls on BB MRI was colocalized with slow flow. Signal intensities increased by a factor of 2.56 ± 0.68 (P < 0.01) after administering Gd contrast. After Gd contrast administration, the signal was suppressed most in conjunction with high flows and with MSDE (2.41 ± 2.07 for slow flow without MSDE, and 0.87 ± 0.99 for high flow with MSDE). A clear result was not achieved by modifying the spatial resolution . DATA CONCLUSIONS: Slow-flow phenomena contribute substantially to aneurysm enhancement and vary with MRI parameters. This should be considered in the clinical setting when assessing VWE in patients with an unruptured aneurysm. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

3D-printed, patient-specific intracranial aneurysm models: From clinical data to flow experiments with endovascular devices.

PURPOSE: Flow models of intracranial aneurysms (IAs) can be used to test new and existing endovascular treatments with flow modulation devices (FMDs). Additionally, 4D flow magnetic resonance imaging (MRI) offers the ability to measure hemodynamics. This way, the effect of FMDs can be determined noninvasively and compared to patient data. Here, we describe a cost-effective method for producing flow models to test the efficiency of FMDs with 4D flow MRI. METHODS: The models were based on human radiological data (internal carotid and basilar arteries) and printed in 3D with stereolithography. The models were printed with three different printing layers (25, 50, and 100 µm thickness). To evaluate the models in vitro, 3D rotational angiography, time-of-flight MRI, and 4D flow MRI were employed. The flow and geometry of one model were compared with in vivo data. Two FMDs (FMD1 and FMD2) were deployed into two different IA models, and the effect on the flow was estimated by 4D flow MRI. RESULTS: Models printed with different layer thicknesses exhibited similar flow and little geometric variation. The mean spatial difference between the vessel geometry measured in vivo and in vitro was 0.7 ± 1.1 mm. The main flow features, such as vortices in the IAs, were reproduced. The velocities in the aneurysms were similar in vivo and in vitro (mean velocity magnitude: 5.4 ± 7.6 and 7.7 ± 8.6 cm/s, maximum velocity magnitude: 72.5 and 55.1 cm/s). By deploying FMDs, the mean velocity was reduced in the IAs (from 8.3 ± 10 to 4.3 ± 9.32 cm/s for FMD1 and 9.9 ± 12.1 to 2.1 ± 5.6 cm/s for FMD2). CONCLUSIONS: The presented method allows to produce neurovascular models in approx. 15 to 30 h. The resulting models were found to be geometrically accurate, reproducing the main flow patterns, and suitable for implanting FMDs as well as 4D flow MRI.