Three-dimensional wall-thickness distributions of unruptured intracranial aneurysms characterized by micro-computed tomography.

Aneurysmal rupture is associated with wall thinning, but the mechanism is poorly understood. This study aimed to characterize the three-dimensional wall-thickness distributions of unruptured intracranial aneurysms. Five aneurysmal tissues were investigated using micro-computed tomography. First, the wall thickness was related to the aneurysmal wall appearances during surgery. The median wall thicknesses of the translucent and non-translucent walls were 50.56 and 155.93 µm, respectively (p < 0.05) with significant variation in the non-translucent wall thicknesses (p < 0.05). The three-dimensional observations characterized the spatial variation of wall thicknesses. Thin walls showed a uniform thickness profile ranging from 10 to 40 µm, whereas thick walls presented a peaked thickness profile ranging from 300 to 500 µm. In transition walls, the profile undulated due to the formation of focal thin/thick spots. Overall, the aneurysmal wall thicknesses were strongly site-dependent and spatially varied by 10 to 40 times within individual cases. Aneurysmal walls are exposed to wall stress driven by blood pressure. In theory, the magnitude of wall stress is inversely proportional to wall thickness. Thus, the observed spatial variation of wall thickness may increase the spatial variation of wall stress to a similar extent. The irregular wall thickness may yield stress concentration. The observed thin walls and focal thin spots may be caused by excessive wall stresses at the range of mechanical failure inducing wall injuries, such as microscopic tears, during aneurysmal enlargement. The present results suggested that blood pressure (wall stress) may have a potential of acting as a trigger of aneurysmal wall injury.

Predicting the growth of middle cerebral artery bifurcation aneurysms using differences in the bifurcation angle and inflow coefficient.

OBJECTIVE: Growing intracranial aneurysms (IAs) are prone to rupture. Previous cross-sectional studies using postrupture morphology have shown the morphological or hemodynamic features related to IA rupture. Yet, which morphological or hemodynamic differences of the prerupture status can predict the growth and rupture of smaller IAs remains unknown. The purpose of this longitudinal study was to investigate the effects of morphological features and the hemodynamic environment on the growth of IAs at middle cerebral artery (MCA) bifurcations during the follow-up period. METHODS: One hundred two patients with MCA M1-2 bifurcation saccular IAs who underwent follow-up for more than 2 years at the authors' institutions between 2011 and 2019 were retrospectively identified. During the follow-up period, cases involving growth of MCA IAs were assigned to the event group, and those with MCA IAs unchanged in size were assigned to the control group. The morphological parameters examined were aneurysmal neck length, dome height, aspect ratio and volume, M1 and M2 diameters and their ratio, and angle configurations among M1, M2, and the aneurysm. Hemodynamic parameters were flow rate and wall shear stress in M1, M2, and the aneurysm, including the aneurysmal inflow rate coefficient (AIRC), defined as the ratio of the aneurysmal inflow rate to the M1 flow rate. Those parameters were compared statistically between the two groups. Correlations between morphological and hemodynamic parameters were also examined. RESULTS: Eighty-three of 102 patients were included: 25 with growing MCA IAs (event group) and 58 with stable MCA IAs (control group). The median patient age at initial diagnosis was 66.9 (IQR 59.8-72.3) years. The median follow-up period was 48.5 (IQR 36.5-65.6) months. Both patient age and the AIRC were significant independent predictors of the growth of MCA IAs. Moreover, the AIRC was strongly correlated with sharper bifurcation and inflow angles, as well as wider inclination angles between the M1 and M2 arteries. CONCLUSIONS: The AIRC was a significant independent predictor of the growth of MCA IAs. Sharper bifurcation and inflow angles and wider inclination angles between the M1 and M2 arteries were correlated with the AIRC. MCA IAs with such a bifurcation configuration are more prone to grow and rupture.

Association of bleb formation with peri-aneurysmal contact in unruptured intracranial aneurysms.

The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending on the presence of blebs and PAC using computed tomographic angiography and magnetic resonance imaging. Aneurysmal hemodynamics were assessed using computational fluid dynamics. The independent variables associated with bleb formation were statistically assessed. Fourteen aneurysms (31.1%) had blebs, all of which were located at the site of PAC (group A). Thirty-one aneurysms (68.9%) had no bleb, of which 13 had a PAC (group B) and 18 had no PAC (group C). PAC was the only independent variable associated with bleb formation (p < 0.05). Aneurysmal volumes were significantly higher in group A, followed by groups B and C in series. Aneurysmal wall shear stress (WSS) tended to be lowest in group A, followed by groups B and C in series. The maximum WSS at the blebs was only 17% of the maximum WSS at the aneurysmal domes. This study demonstrated that bleb formation in UIAs was associated with the establishment of PAC during their growth, which may have more detrimental effects on bleb formation than hemodynamics.

Implementation of computer simulation to assess flow diversion treatment outcomes: systematic review and meta-analysis.

INTRODUCTION: Despite a decade of research into virtual stent deployment and the post-stenting aneurysmal hemodynamics, the hemodynamic factors which correlate with successful treatment remain inconclusive. We aimed to examine the differences in various post-treatment hemodynamic parameters between successfully and unsuccessfully treated cases, and to quantify the additional flow diversion achievable through stent compaction or insertion of a second stent. METHODS: A systematic review and meta-analysis were performed on eligible studies published from 2000 to 2019. We first classified cases according to treatment success (aneurysm occlusion) and then calculated the pooled standardized mean differences (SMD) of each available parameter to examine their association with clinical outcomes. Any additional flow diversion arising from the two common strategies for improving the stent wire density was quantified by pooling the results of such studies. RESULTS: We found that differences in the aneurysmal inflow rate (SMD -6.05, 95% CI -10.87 to -1.23, p=0.01) and energy loss (SMD -5.28, 95% CI -7.09 to -3.46, p<0.001) between the successfully and unsuccessfully treated groups were indicative of statistical significance, in contrast to wall shear stress (p=0.37), intra-aneurysmal average velocity (p=0.09), vortex core-line length (p=0.46), and shear rate (p=0.09). Compacting a single stent could achieve additional flow diversion comparable to that by dual-stent implantation. CONCLUSIONS: Inflow rate and energy loss have shown promise as identifiers to discriminate between successful and unsuccessful treatment, pending future research into their diagnostic performance to establish optimal cut-off values.

In Vitro Investigation of an Electrically Actuated Antireflux Valve for a Multiuse Contrast Agent Injection System.

OBJECTIVE. The purpose of this study was to determine the capability of a newly developed antireflux valve for a multiuse contrast agent injection system. MATERIALS AND METHODS. Multiuse contrast agent injection systems require an antireflux valve to eliminate the risk of cross-patient blood contamination. An electrically actuated antireflux valve developed for this purpose can control risk of contamination because it is under forced control and surveillance. In this study, the injection system was connected to a pulsatile circulation system that reproduced an aortic flow environment in vitro. The transvalvular pressure difference was measured, and flow dynamics during valve opening and closing were visualized by high-speed flow visualization. A total of 30 injection conditions were tested, which included two catheters (6- and 2-French diameter), five contrast agent concentrations (100%, 90%, 50%, 10%, and 0%), and a wide range of flow rates (0.1-25.0 mL/s). RESULTS. The transvalvular pressure difference and flow dynamics during valve opening and closing were characterized. Just before valve opening, a minimum transvalvular pressure difference of 0.20 MPa (1500 mm Hg) was confirmed. The positive pressure difference prevented regurgitation during valve opening. During valve closing, the front of the backflow was monitored continuously, and we confirmed that the front failed to reach the valve before complete closure. CONCLUSION. This study provided proof of concept for an electrically actuated antireflux valve to be used in a multiuse contrast agent injection system.

Hemodynamic and Histopathological Changes in the Early Phase of the Development of an Intracranial Aneurysm.

Hemodynamic stress and chronic inflammation are closely associated with the pathogenesis of intracranial aneurysms (IAs). However, the hemodynamic and biological mechanisms triggering IA formation remain to be elucidated. To clarify them, computational fluid dynamics (CFD) and histopathological analyses in the early phase of IA development using an experimentally induced IA model in rats were conducted. Histological changes in the early phase of IA development were observed under a scanning electron microscope (SEM) and a transmission electron microscope (TEM). Using data from 7-T magnetic resonance angiography (7T-MRA), CFD analyses were performed to determine wall shear stress (WSS) and wall pressure (WP) at the prospective site of IA. A bump-like protrusion named an "intimal pad" was located in the anterior cerebral artery (ACA) immediately distal to the apex of the bifurcation. TEM showed the degeneration of the internal elastic lamina (IEL) and longitudinally elongated smooth muscle cells (SMCs) that switched from the contractile to the proliferative phenotype and penetrated between two divided layers of the degenerated IEL in the prospective site of the IA. However, no inflammatory cells were observed. CFD analyses showed no particular pattern of WSS and WP at the prospective IA site. IEL degeneration and the phenotypic change and longitudinal elongation of SMCs were identified as the early events in IA development. CFD analyses and TEM data suggest that these biological events may be derived from increased circumferential wall stress due to increased blood pressure and increased longitudinal wall strain due to the existence of the intimal pad.

Vascular responses to abrupt blood flow change after bypass surgery for complex intracranial aneurysms.

BACKGROUND: Bypass surgery for complex intracranial aneurysms (IAs) results in drastic blood flow changes in intracranial arteries. The aim of the study was to elucidate how vessels adapt to blood flow changes after bypass surgery with phase-contrast magnetic resonance imaging (PC-MRI). METHODS: This is a prospective observational study to assess changes of the blood flow in intracranial arteries after bypass surgery for IAs. Flow rates and vessel diameters were measured with PC-MRI in 52 intracranial arteries of 7 healthy volunteers and 31 arteries of 8 IA patients who underwent bypass surgery. Wall shear stress (WSS) was calculated with the Hagen-Poiseuille formula. In 18 arteries of 5 patients, the same measurement was performed 1, 3, and 12 months after surgery. RESULTS: PC-MRI showed a strong positive correlation between the flow rate and the third power of vessel diameter in both healthy volunteers (r = 0.82, P < 0.0001) and IA patients (r = 0.90, P < 0.0001), indicating the constant WSS. Of the 18 arteries in 5 patients, WSS increased in 7 arteries and decreased in 11 arteries immediately after surgery. In the WSS-increased group, WSS returned to the preoperative value in the third postoperative month. In the WSS-decreased group, WSS increased in the 12th month, but did not return to the preoperative level. CONCLUSIONS: In a physiological state, WSS was constant in intracranial arteries. Changed WSS after bypass surgery tended to return to the preoperative value, suggesting that vessel diameter and flow rate might be controlled so that WSS remains constant.

Hemodynamic features of offending vessels at neurovascular contact in patients with trigeminal neuralgia and hemifacial spasm.

OBJECTIVEOffending vessels at the site of neurovascular contact (NVC) in patients with trigeminal neuralgia (TN) and hemifacial spasm (HFS) may have specific hemodynamic features. The purpose of this study was to investigate the wall shear stress (WSS) of offending vessels at NVCs by conducting a computational fluid dynamics (CFD) analysis.METHODSThe authors retrospectively analyzed the cases of 20 patients (10 with TN and 10 with HFS) evaluated by 3D CT angiography and used the imaging findings for analysis of the hemodynamic parameters. The 3D CFD images were directly compared with the NVCs determined by simulated multifusion images of CT angiogram and MR cisternogram, and operative photos. The magnitudes of the WSS (WSSm) at the proximal (WSSm-p), just-beginning (WSSm-j), contact site (WSSm-s), and distal (WSSm-d) areas of each NVC were analyzed. The ratios of the WSSm-j, WSSm-s, and WSSm-d areas to the WSSm-p area were calculated individually. The direction of the WSS (WSSv) and its temporal variation (WSSvV) were depicted and morphologically compared with the NVC confirmed by simulated images and operative findings.RESULTSThe ratios of WSSm at the just-beginning and the contact site to the proximal area of the NVCs (WSSm-j/WSSm-p and WSSm-s/WSSm-p) were both significantly higher than that at the distal area (WSSm-d/WSSm-p) (p < 0.05). The WSSv and WSSvV at the NVCs showed small variation in a single cardiac cycle, especially along the areas that were in contact with the affected nerve.CONCLUSIONSAreas of relatively high WSSm and temporal variation of WSSm (WSSmV) were observed at the NVCs. Less mobility of the WSSv and WSSvV was detected along the side of the vessels in contact with the nerves. These findings may be consistent with the actual area of the NVC. Hemodynamic features of the site of NVC can be added to the preoperative simulation for MVD surgery, which may be useful for the diagnosis and treatment planning of TN and HFS.

A computational fluid dynamics (CFD) study of WEB-treated aneurysms: Can CFD predict WEB "compression" during follow-up?

BACKGROUND: Recent reports have revealed a worsening of aneurysm occlusion between WEB treatment baseline and angiographic follow-up due to "compression" of the device. OBJECTIVE: We utilized computational fluid dynamics (CFD) in order to determine whether the underlying mechanism of this worsening is flow related. METHODS: We included data from all consecutive patients treated in our institution with a WEB for unruptured aneurysms located either at the middle cerebral artery or basilar tip. The CFD study was performed using pre-operative 3D rotational angiography. From digital subtraction follow-up angiographies patients were dichotomized into two groups: one with WEB "compression" and one without. We performed statistical analyses to determine a potential correlation between WEB compression and CFD inflow ratio. RESULTS: Between July 2012 and June 2015, a total of 22 unruptured middle cerebral artery or basilar tip aneurysms were treated with a WEB device in our department. Three patients were excluded from the analysis and the mean follow-up period was 17months. Eleven WEBs presented "compression" during follow-up. Interestingly, device "compression" was statistically correlated to the CFD inflow ratio (P=0.018), although not to aneurysm volume, aspect ratio or neck size. CONCLUSION: The mechanisms underlying the worsening of aneurysm occlusion in WEB-treated patients due to device compression are most likely complex as well as multifactorial. However, it is apparent from our pilot study that a high arterial inflow is, at least, partially involved. Further theoretical and animal research studies are needed to increase our understanding of this phenomenon.

Optimal kissing balloon inflation after single-stent deployment in a coronary bifurcation model.

AIMS: To define the optimal kissing balloon inflation (KBI) after single-stent deployment in a coronary bifurcation model. METHODS AND RESULTS: We deployed stents in main vessels (MV) followed by KBI in various conditions and compared the stent configurations. A) KBI at the operator's discretion vs. under the guidelines of minimal balloon overlapping (MBO). Various stent configurations were observed after the former option, whereas similar maximal dilation points were observed under the MBO guidelines. B) Long balloon overlapping (LBO) vs. MBO with proximal MV dilated by a large balloon. The proximal MV was dilated to an ideal round shape with MBO versus an oval shape with LBO. C) Two-link vs. 3-link stents. Although the 2-link stent was advantageous to open the side branch, it incurred a risk of overdilatation of the proximal struts, whereas the 3-link stent preserved its structure. Computed simulations of coronary flow were analysed in the following left main coronary models: circle with a diameter of 4 and 5.5 mm, ellipse with longitudinal direction and tilt position. They revealed that the overdilated side was exposed to low shear stress regardless of its shape. CONCLUSIONS: Optimal KBI can be achieved with MBO and proximal dilatation by an optimally sized balloon.

Novel connecting tube for saline chaser in contrast-enhanced CT: the effect of spiral flow of saline on contrast enhancement.

OBJECTIVE: To evaluate the effect of a newly developed connecting tube, which generates a spiral flow of saline, on aortic and hepatic contrast enhancement during hepatic-arterial phase (HAP) and portal venous phase (PVP) computed tomography (CT). METHODS: Eighty patients were randomly assigned to one of two protocols: with a new or a conventional tube. The contrast material (600 mgI/kg) was delivered over 30 s; this was followed by the administration of 25 ml saline solution delivered at the same injection rate as the contrast material. Unenhanced and contrast-enhanced CT images of the upper abdomen were obtained. We calculated the changes in the CT number (∆HU) for the aorta during HAP and PVP, and for the liver during PVP. We compared ∆HU between protocols. RESULTS: The mean ∆HU for the abdominal aorta during HAP was significantly higher with the new tube protocol than with the conventional tube protocol (322 ± 53 vs. 290 ± 53, P < 0.01). There were no significant differences in the mean ∆HU for the abdominal aorta and liver during PVP between the two protocols (P > 0.05). CONCLUSION: The new connecting tube increased the effect of a saline chaser and significantly improved aortic enhancement during HAP. KEY POINTS: • Optimal administration of intravenous contrast material is essential for optimal CT quality. • A new connecting tube can generate spiral flow, which improves intravenous administration. • The new connecting tube improved aortic contrast enhancement during the hepatic-arterial phase. • The new connecting tube increased the effect of a saline chaser.

Experimental insights into flow impingement in cerebral aneurysm by stereoscopic particle image velocimetry: transition from a laminar regime.

This study experimentally investigated the instability of flow impingement in a cerebral aneurysm, which was speculated to promote the degradation of aneurysmal wall. A patient-specific, full-scale and elastic-wall replica of cerebral artery was fabricated from transparent silicone rubber. The geometry of the aneurysm corresponded to that found at 9 days before rupture. The flow in a replica was analysed by quantitative flow visualization (stereoscopic particle image velocimetry) in a three-dimensional, high-resolution and time-resolved manner. The mid-systolic and late-diastolic flows with a Reynolds number of 450 and 230 were compared. The temporal and spatial variations of near-wall velocity at flow impingement delineated its inherent instability at a low Reynolds number. Wall shear stress (WSS) at that site exhibited a combination of temporal fluctuation and spatial divergence. The frequency range of fluctuation was found to exceed significantly that of the heart rate. The high-frequency-fluctuating WSS appeared only during mid-systole and disappeared during late diastole. These results suggested that the flow impingement induced a transition from a laminar regime. This study demonstrated that the hydrodynamic instability of shear layer could not be neglected even at a low Reynolds number. No assumption was found to justify treating the aneurysmal haemodynamics as a fully viscous laminar flow.

Numerical analysis of blood flow distribution in 4- and 3-branch vascular grafts.

Trifurcated arch grafts (3-branch grafts) are now being used to repair the thoracic aorta in addition to conventional arch grafts (4-branch grafts). The anatomical shape of the 3-branch graft is different from the original vessel, so it is necessary for clinical application to evaluate blood flow distribution in the graft to assess whether there is adequate blood flow to the target organs. To achieve this, we developed a computational fluid dynamics (CFD) method to evaluate blood flow distribution in the grafts. Aortic blood flow was measured by phase-contrast magnetic resonance imaging (PC-MRI), and flow distribution into the branched vessels was obtained. The MRI image was used to create a patient-specific image model that represents the geometry of the aortic arch. The CFD analysis method was employed to determine a boundary condition of the blood flow analysis in the aorta using a patient-specific image model. We also created simplified models of 4-branch and 3-branch grafts and used our CFD analysis method to compare blood flow distribution among simplified models. It was found that blood flow distribution in the descending aorta was 71.3 % for the 4-branch graft and 67.7 % for the 3-branch graft, indicating that a sum of branching flow in the 3-branch graft was almost the same as the one in the 4-branch graft. Therefore, there is no major concern about implanting a new 3-branch graft. Our CFD analysis method may be applied to estimate blood flow distribution of a newly developed vascular graft prior to its clinical use and provide useful information for safe use of the graft.