Experimental Broad-Based Curved Sidewall Aneurysms in Rabbits Mimicking Human Carotid Siphon Aneurysms: Proof of Feasibility and Comparability Using Computational Fluid Dynamics.

BACKGROUND/OBJECTIVE: Broad-based sidewall aneurysms of the carotid artery are primarily treated endovascularly. However, recurrence or rupture after treatment still poses a significant risk. Hence, reliable animal models mimicking this aneurysm type are essential for to evaluate the performance of new advanced endovascular devices. METHODS: Experimental aneurysms were created in 12 New Zealand white rabbits (2.5-3.5 kg). The human carotid siphon was mimicked with an end-to-end anastomosis of both common carotid arteries. A venous pouch was sutured on the convexity to mimic a broad-based side wall aneurysm. Patency and configuration were investigated 4 weeks postoperatively by 3-T magnetic resonance angiography. To compare flow conditions of broad-based sidewall aneurysms in rabbits and humans, exemplary computational fluid dynamics simulations were performed using species-specific blood viscosity values. RESULTS: We were able to achieve 0% peri- or postoperative mortality. Patency was confirmed by 3-T magnetic resonance angiography in 11 of 12 aneurysms (91.7%). Aneurysm lengths ranged from 6.4 to 9.8 mm and aneurysm necks from 7.3 to 9.8 mm. Computational fluid dynamics showed simple flow profiles with one vortex in rabbit as well as in human aneurysms. Wall shear stress rates were comparable using species-specific blood viscosity values (rabbit mean 1.65 Pa vs. human mean 1.7 Pa). CONCLUSIONS: The broad-based curved sidewall aneurysm model mimicking the carotid siphon showed high aneurysm patency rates with low morbidity. High comparability with human flow patterns and human intranaeurysmal biomechanical forces was shown using simulations.

Focal irregularities in 7-Tesla MRI of unruptured intracranial aneurysms as an indicator for areas of altered blood-flow parameters.

OBJECTIVE: In the last several decades, various factors have been studied for a better evaluation of the risk of rupture in incidentally discovered intracranial aneurysms (IAs). With advanced MRI, attempts were made to delineate the wall of IAs to identify weak areas prone to rupture. However, the field strength of the MRI investigations was insufficient for reasonable image resolution in many of these studies. Therefore, the aim of this study was to analyze findings of IAs in ultra-high field MRI at 7 Tesla (7 T). METHODS: Patients with incidentally found IAs of at least 5 mm in diameter were included in this study and underwent MRI investigations at 7 T. At this field strength a hyperintense intravascular signal can be observed on nonenhanced images with a brighter "rim effect" along the vessel wall. Properties of this rim effect were evaluated and compared with computational fluid dynamics (CFD) analyses. RESULTS: Overall, 23 aneurysms showed sufficient image quality for further evaluation. In 22 aneurysms focal irregularities were identified within this rim effect. Areas of such irregularities showed significantly higher values in wall shear stress and vorticity compared to areas with a clearly visible rim effect (p = 0.043 in both). CONCLUSIONS: A hyperintense rim effect along the vessel wall was observed in most cases. Focal irregularities within this rim effect showed higher values of the mean wall shear stress and vorticity when compared by CFD analyses. Therefore, these findings indicate alterations in blood flow in IAs within these areas.

Near-Newtonian Blood Behavior - Is It Good to Be a Camel?

From a certain level of exercise-intensity onward, hematocrit increases in horses, which brings more oxygen carriers into the bloodstream. Camels, however, when used in competitive racing could be even in need of iron supplementation and blood transfusions due to a severe reduction of their available hematocrit compared to their resting hematocrit. Since the extrinsic and intrinsic mechanical properties of camel erythrocytes (RBC) are so different compared to RBCs of other mammals, the question arises whether this observation might be a response to endurance exercise aiming at keeping the RBC count low. Rheometry indicated dromedary camel blood to behave almost Newtonian, which is unique amongst mammals. Shear thinning did increase with the hematocrit, but remained marginal compared to horses. As a result, camel whole blood viscosity (WBV) exceeded horse WBV at high shear rates, an effect, which was significantly augmented when the packed cell volume (PCV) was increased. Therefore, in camels any infusion of RBCs into the bloodstream can increase the cardiac work and the energy input into the endothelium more effectively, which should generate vascular remodeling in the long term. Yielding, however, was completely absent in camel blood, confirming low cohesion between its components at quasi-static flow. Camel blood remained a viscous liquid without a threshold even at unphysiologically high PCVs. This can help to washout lactate when camels start to dehydrate and might contribute to the sustained working ability of these animals. The subtle pseudoplastic behavior and the high viscosity contrast across the RBC membrane point to weak coupling between blood flow and red cell behavior. We predict that RBCs flow as separate entities and can show various types of motion, which can lead to friction instead of being collectively aligned to the flow direction. In comparison to horses, this behavior will become relevant at higher RBC counts in front of flow obstacles and possibly cause vascular remodeling if the PCV rises during strenuous exercise, a matter that should be avoided.

Very large and giant microsurgical bifurcation aneurysms in rabbits: Proof of feasibility and comparability using computational fluid dynamics and biomechanical testing.

BACKGROUND: Giant aneurysms are challenging lesions with unacceptable high rates of aneurysm recanalization and rerupture following embolization. Reliable in vivo models are urgently needed to test the performance of new more efficient endovascular devices. MATERIALS AND METHODS: Aneurysms were created in 11 New Zealand white rabbits (4.5-5.5kg): A long venous pouch (length 25-30mm) mimicking the aneurysm sac was derived from the external jugular vein and sutured into a microsurgically created bifurcation between both common carotid arteries. After 4 weeks the rabbits underwent 3T Magnetic resonance angiography (3T-MRA). Exemplary computational fluid dynamics (CFD) simulations were performed to compare the flow conditions of giant rabbit and human aneurysms. We used species-related boundary conditions, in particular, we measured blood viscosity values. Biaxial mechanical tests were performed for the mechanical characterization and comparison. COMPARISON WITH EXISITING METHOD(S): None. RESULTS: No peri- or postoperative mortality was observed. 3T-MRA showed aneurysm patency in 10 out of 11 aneurysms (90.9%). Aneurysm lengths ranged from 21.5-25.6mm and aneurysm necks from 7.3-9.8mm. CFD showed complex flow profiles with multiple vortices in both, rabbit and human aneurysms. Lower blood viscosity values of the rabbit (3.92mPas vs. human 5.34mPas) resulted in considerable lower wall shear stress rates (rabbit 0.38Pa vs. human 1.66Pa). Mechanical tests showed lower stiffness of rabbit aneurysms compared to unruptured human aneurysms. CONCLUSIONS: The proposed model showed favorable aneurysm patency rates, low morbidity and good hemodynamic comparability with complex flow patterns. Biomechanical testing suggests that experimental aneurysms might be even more fragile compared to human aneurysms.

Aneurysm wall thickness measurements of experimental aneurysms: in vivo high-field MR imaging versus direct microscopy.

BACKGROUND: Thin cerebral aneurysm wall thickness (AWT) is connected to high aneurysm rupture risk. MR imaging of AWT leads to overestimations. The aim of the present study was to quantify MR inaccuracy by comparison with accurate light microscopic measurements. METHODS: In 13 experimental microsurgical bifurcation aneurysms in rabbits, 3 Tesla (3 T)-MR imaging using contrast-enhanced T1 Flash sequences (resolution: 0.4 × 0.4 × 1.5 mm³) was performed. The aneurysms were retrieved immediately after MR acquisition, cut longitudinally, and calibrated photographs were obtained. AWT (dome, neck) and parent vessel thickness (PVT) were measured on the MR images and microscopic photographs by independent investigators. All parameters were statistically compared (Wilcoxon test, Spearman correlation). RESULTS: AWT and PVT could be imaged and measured in all aneurysms with good quality. Comparison with the "real" light microscopic measurements showed a progressive tendency of MR AWT overestimation with smaller AWT: AWT at the dome (0.24 ± 0.06 mm vs. MR 0.30 ± 0.08 mm; p = 0.0078; R = 0.6125), AWT at the neck (0.25 ± 0.07 mm vs. MR 0.29 ± 0.07 mm; p = 0.0469; R = 0.7451), and PVT (0.46 ± 0.06 mm vs. MR 0.48 ± 0.06 mm; p = 0.5; R = 0.8568). CONCLUSION: In this experimental setting, 3 T-MR imaging of cerebral AWT showed unacceptable inaccuracies only below the image resolution threshold. Theoretically, AWT for clinical usage could be classified in ranges, defined by the maximum image resolution.

Evaluation of cerebral aneurysm wall thickness in experimental aneurysms: comparison of 3T-MR imaging with direct microscopic measurements.

BACKGROUND: Thin aneurysm wall thickness (AWT) is thought to portend an elevated risk of intracranial aneurysm rupture. Magnetic resonance imaging (MRI) is biased by AWT overestimations. Previously, this suspected bias has been qualitatively described but never quantified. We aimed to quantify the overestimation of AWT by MRI when compared to the gold standard of AWT as measured by light microscopy of fresh aneurysm specimens (without any embedding procedure). This analysis should help to define the clinical potential of MRI estimates of AWT. METHODS: 3-Tesla (3T) MRI (contrast-enhanced T1 Flash sequences; resolution: 0.4 x 0.4 x 1.5 mm(3)) was performed in 13 experimental aneurysms. After MR acquisition, the aneurysms were retrieved, longitudinally sectioned and calibrated micrographs were obtained immediately. AWT at the dome, AWT at the neck and parent vessel wall thickness (PVT) were measured on precisely correlated MR-images and histologic micrographs by blinded independent investigators. Parameters were statistically compared (Wilcoxon test, Spearman's correlation). RESULTS: AWT was assessed and reliably measured using MRI. Interobserver variability was not significant for either method. MR overestimation was only significant below the image resolution threshold: AWT at the dome (0.24 ± 0.06 mm vs. MR 0.30 ± 0.08 mm; p = 0.0078; R = 0.6125), AWT at the neck (0.25 ± 0.07 mm vs. MR 0.29 ± 0.07 mm; p = 0.0469; R = 0.7451), PVT (0.46 ± 0.06 mm vs. MR 0.48 ± 0.06 mm; p = 0.5; R = 0.8568). CONCLUSION: In this experimental setting, MR overestimations were minimal (mean 0.02 mm) above the image resolution threshold. When AWT is classified in ranges defined by the MR resolution threshold, clinical usage may be beneficial. Further quantitative and comparative experimental and human studies are warranted to confirm these findings.