Rupture Risk of Small Unruptured Intracranial Aneurysms in Japanese Adults.

Background and Purpose- Therapeutic decision making for small unruptured intracranial aneurysms (<10 mm) is difficult. We aimed to develop a rupture risk model for small intracranial aneurysms in Japanese adults, including clinical, morphological, and hemodynamic parameters. Methods- We analyzed 338 small unruptured aneurysms; 35 ruptured during the observation period, and 303 remained stable. Clinical, morphological, and hemodynamic parameters were considered. Computational fluid dynamics was used to calculate hemodynamic parameters based on computed tomography images of all aneurysms in their unruptured state. Differences between the ruptured and unruptured groups were tested by the Mann-Whitney U or Fisher exact tests. Multivariate logistic regression was applied to obtain a rupture risk model. Its predictive ability was investigated by receiver operating characteristic analysis. Results- The risk model revealed that rupture may be more likely to in younger patients (odds ratio [OR], 0.92 for each age increase of 1 year [95% CI, 0.88-0.96] P<0.001) with multiple aneurysms (OR, 2.58 [95% CI, 1.07-6.19] P=0.03), located at a bifurcation (OR, 5.45 [95% CI, 1.87-15.85] P=0.002), with a bleb (OR, 4.09 [95% CI, 1.42-11.79] P=0.009), larger length (OR, 1.91 for each increase of 1 mm [95% CI, 1.42-2.57] P<0.001), and lower pressure loss coefficient (OR, 0.33 for each decrease of 1 unit [95% CI, 0.14-0.77] P=0.01). The sensitivity, specificity, and area under the curve were 0.800, 0.752, and 0.826 (95% CI, 0.739-0.914) respectively. Conclusions- Younger age, presence of multiple aneurysms, location at a bifurcation, presence of a bleb, larger length, and lower pressure loss coefficient were identified as risk factors for rupture of small intracranial aneurysms. The risk model should be validated in further studies.

Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics.

OBJECTIVE: Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors' goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS: Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm's shape and hemodynamics. Next, the previously developed model's discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS: The US model's AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish and Japanese data combined increased significantly to 0.83 ± 0.10. CONCLUSIONS: Developing an aneurysm rupture prediction model that applies to Japanese and Finnish aneurysms requires including data from these two cohorts for model training, as well as interaction terms between patient population and the other variables in the model. When including this information, the performance of such a model with Japanese and Finnish data is close to its performance with US or European data. These results suggest that population-specific differences determine how hemodynamics and shape associate with rupture risk in intracranial aneurysms.

Effects of different stent wire mesh densities on hemodynamics in aneurysms of different sizes.

BACKGROUND: Intracranial stents are used to treat aneurysms by diverting the blood flow from entering into the aneurysmal dome. Although delayed rupture is rare, clinical outcomes are extremely poor in such cases. Hemodynamics after stent deployment may be related to delayed rupture and a better understanding of the basic characteristics of pressure changes resulting from stent deployment is needed; therefore, this study investigated the relationships between hemodynamics in aneurysms of different sizes treated using stents of different wire mesh densities. METHODS: Using computational fluid dynamics analysis, parameters related to velocity, volume flow rate, pressure, and residual volume inside the aneurysm were evaluated in digital models of 5 basic aneurysms of differing sizes (Small, Medium, Medium-Large, Large, and Giant) and using 6 different types of stent (varying number of wires, stent pitch and wire mesh density) for each aneurysm. RESULTS: Regardless of the aneurysm size, the velocity inside the aneurysm and the volume flow rate into the aneurysm were observed to continuously decrease up to 89.2% and 78.1%, respectively, with increasing stent mesh density. In terms of pressure, for giant aneurysms, the pressure on the aneurysmal surface elevated to 10.3%, then decreased to 5.1% with increasing stent mesh density. However, in smaller aneurysms, this pressure continuously decreased with increasing stent mesh density. The flow-diverting effect of the stents was limited when a stent with low mesh density (under 20%) was used with a giant aneurysm. CONCLUSIONS: The present results indicate that the selection of appropriate stents according to aneurysm size may contribute to reduced risks of hemodynamic alternations related to stent deployment, which could reduce the incidence of delayed rupture.

Hemodynamic Characteristics and Clinical Outcome for Intracranial Aneurysms Treated with the Derivo Embolization Device, a Novel Second-Generation Flow Diverter.

BACKGROUND: We investigated the relationship between hemodynamic characteristics and clinical outcomes for aneurysms treated by the Derivo embolization device, a novel second-generation flow-diverter stent, using computational fluid dynamics (CFD). METHODS: Data were retrospectively obtained from 2 centers between 2017 and 2019. During the period, 23 patients were treated for 23 aneurysms with the Derivo embolization device. In 17 patients we were able to conduct CFD analysis as 6 were excluded due to precoiling, unsuitable arterial geometry, and complex geometric form. Aneurysm occlusion was rated with the O'Kelly-Marotta grading scale on digital subtraction angiography 6 months after stent placement in all patients. Hemodynamic and morphologic parameters were statistically compared between 2 groups: with full occlusion and with a remnant. RESULTS: Full occlusion was observed in 17 of 23 (73.9%) patients. In the group suitable for CFD analysis, we observed 13 fully occluded aneurysms and 4 with any remnant (specifically 1 O'Kelly-Marotta C, 1 B, and 2 A). The energy loss per volume, which indicates the energy loss through the aneurysm, was significantly larger in prestenting and post stenting (P < 0.05) in the complete occlusion cases. In addition, the inflow concentration index and inflow area ratio of the remnant cases were significantly larger and lower, respectively (P < 0.05). CONCLUSIONS: Our CFD results indicate that the energy loss involved with the blood flow passing through an aneurysm and concentrated inflow into an aneurysm were the most important factors to determine whether an aneurysm will become a complete occlusion or remnant case.

Role of patient-specific blood properties in computational fluid dynamics simulation of flow diverter deployed cerebral aneurysms.

BACKGROUND: Hemodynamics and their clinical outcome of cerebral aneurysms treated with flow diverter (FD) stents have thus far been investigated using computational fluid dynamics (CFD) simulations. Although human blood is characterized as a non-Newtonian patientspecific fluid, non-patient-specific blood properties (PSBP) were applied in most extant studies. OBJECTIVE: To investigate the hemodynamic effects caused by PSBPs in aneurysms treated with FD stents. METHODS: We measured blood properties (density and viscosity) for 12 patients who underwent FD stent deployment. We conducted CFD simulations with the measured PSBPs and non-PSBPs quoted from previous studies. The average blood flow velocity and wall shear stress within the aneurysms were calculated and two simulation patterns were compared. RESULTS: The velocity and wall shear stress changed by 2.93% and 3.16% on average, respectively, without an FD stent deployed. Conversely, with the FD stents deployed, the change rates increased to 11.1% and 9.06% on average, respectively. CONCLUSIONS: The change in hemodynamic parameters if PSBPs are considered, may not be negligible when conducting CFD simulations of FD stent deployed aneurysms To obtain an adequate hemodynamic environment for cerebral aneurysms with FD stents deployed, it is recommended to use PSBPs for CFD simulations.

Extraction of patient-specific boundary conditions from 4D-DSA and their influence on CFD simulations of cerebral aneurysms.

We developed a new technique for extracting patient-specific inflow conditions, such as the pulse cycle duration and blood flow velocity, from four-dimensional digital subtraction angiography images and experimentally examined its validity. The maximum error between the values extracted by the technique and measured values was 14.3%. We performed blood flow simulations and calculated representative haemodynamic parameters. The maximum differences between the parameters obtained using general and patient-specific inflow conditions were approximately 400%, 150%, and 50% for the velocity, normalised wall shear stress, and pressure loss coefficient, respectively. These results indicate that patient-specific conditions are critical for accurately reproducing aneurysmal haemodynamics.

Greater Trochanteric Fracture with Lesser Trochanter Extension: A Report of 2 Cases and CT-Based Finite Element Analysis.

CASE: Two patients (aged 71 and 82 years) presented with a greater trochanteric fracture with lesser trochanter extension. These cases were successfully treated by prophylactic osteosynthesis to prevent secondary intertrochanteric/cervical fracture and to facilitate an early return to daily life. We also clarified the mechanical strength of the area that escaped bone fracture using the patient-specific computed tomography-based finite element method (CT/FEM). CONCLUSIONS: The present fractured femurs were shown to halve the axial compression strength and had only one-sixth torsional strength in patient-specific CT/FEM. These data support prophylactic surgery to prevent the secondary fractures because of this injury.

Hemodynamic Investigation of the Effectiveness of a Two Overlapping Flow Diverter Configuration for Cerebral Aneurysm Treatment.

Flow diverters (FDs) are widely employed as endovascular treatment devices for large or wide-neck cerebral aneurysms. Occasionally, overlapped FDs are deployed to enhance the flow diversion effect. In this study, we investigated the hemodynamics of overlapping FDs via computational fluid dynamics (CFD) simulations. We reproduced the arterial geometry of a patient who had experienced the deployment of two overlapping FDs. We utilized two stent patterns, namely the patterns for one FD and two overlapping FDs. We calculated the velocity, mass flow rate, wall shear stress, and pressure loss coefficient as well as their change rates for each pattern relative to the no-FD pattern results. The CFD simulation results indicated that the characteristics of the blood flow inside the aneurysm were minimally affected by the deployment of a single FD; in contrast, the overlapping FD pattern results revealed significant changes in the flow. Further, the velocity at an inspection plane within the aneurysm sac decreased by up to 92.2% and 31.0% in the cases of the overlapping and single FD patterns, respectively, relative to the no-FD pattern. The simulations successfully reproduced the hemodynamics, and the qualitative and quantitative investigations are meaningful with regard to the clinical outcomes of overlapped FD deployment.

Development of a Virtual Stent Deployment Application to Estimate Patient-Specific Braided Stent Sizes.

A virtual stent deployment application was developed to estimate the appropriate and patient-specific size of a braided stent for patients who undergo endovascular treatment for intracranial aneurysms. Comparing between the simulated deployed and the actual stents, we evaluated the accuracy of the simulation results. Our results indicated that lengths of the virtual and actual stents matched well despite the actual stent being affected by a geometrical change of the parent artery.Clinical Relevance-Surgeons need to be well-experienced to select an appropriate braided stent size for endovascular treatment of intracranial aneurysms, because the actual length of the deployed stent changes. This simulation will be helpful to make tailor-made surgical planning regardless of the surgeons' individual skill level.

Hemodynamic and Morphologic Factors Related to Coil Compaction in Basilar Artery Tip Aneurysms.

OBJECTIVE: Coil compaction is directly related to the degree of cerebral aneurysmal recanalization. The degree of recanalization (DoR) was quantified by measuring the volume vacated by coil deformation. The purpose of this study was to clarify the hemodynamic and morphologic factors associated with coil compaction. METHODS: Computational fluid dynamics simulations were performed on 28 middle-size (5-10 mm) unruptured basilar artery tip aneurysms. The DoR was measured by comparing the coil mass shape obtained from three-dimensional digital subtraction angiography data immediately after coil embolization and again within 1-2 years of follow-up. Deployed coils were modeled using a virtual coiling technique for computational fluid dynamics simulations. Hemodynamic and morphologic factors to predict the DoR were derived using multiple linear regression. RESULTS: Aneurysmal neck area, the maximum pressure generated on the neck surface after coil embolization, and the high-pressure position on the neck surface predicted DoR with statistic significance (P < 0.001, P < 0.001, P = 0.004, respectively). The DoR tended to increase when the neck area was large, the pressure generated on the coils was high, and the high-pressure position was close to the center of the neck surface. The volume embolization ratio was not statistically relevant for the DoR in the cases of this study. CONCLUSIONS: Coil compaction occurs in cerebral aneurysms with a wide neck, high pressure generated on the coils, and high pressure in the center of the neck surface. Establishing the DoR can contribute to the prediction of recanalization after coil embolization.

Computational fluid dynamic analysis of the initiation of cerebral aneurysms.

OBJECTIVE: Relationships between aneurysm initiation and hemodynamic factors remain unclear since de novo aneurysms are rarely observed. Most previous computational fluid dynamics (CFD) studies have used artificially reproduced vessel geometries before aneurysm initiation for analysis. In this study, the authors investigated the hemodynamic factors related to aneurysm initiation by using angiographic images in patients with cerebral aneurysms taken before and after an aneurysm formation. METHODS: The authors identified 10 cases of de novo aneurysms in patients who underwent follow-up examinations for existing cerebral aneurysms located at a different vessel. The authors then reconstructed the vessel geometry from the images that were taken before aneurysm initiation. In addition, 34 arterial locations without aneurysms were selected as control cases. Hemodynamic parameters acting on the arterial walls were calculated by CFD analysis. RESULTS: In all de novo cases, the aneurysmal initiation area corresponded to the highest wall shear stress divergence (WSSD point), which indicated that there was a strong tensile force on the arterial wall at the initiation area. The other previously reported parameters did not show such correlations. Additionally, the pressure loss coefficient (PLc) was statistically significantly higher in the de novo cases (p < 0.01). The blood flow impact on the bifurcation apex, or the secondary flow accompanied by vortices, resulted in high tensile forces and high total pressure loss acting on the vessel wall. CONCLUSIONS: Aneurysm initiation may be more likely in an area where both tensile forces acting on the vessel wall and total pressure loss are large.

Blood Flow Analysis in Coil Embolized Aneurysms: Difference between Porous Media and Real Coil Geometry Model.

To clarify the mechanism of aneurysmal recanalization, it is necessary to understand the characteristics of the blood flow inside the aneurysm in particular the flow resistance generated by the coil. In studies using computational fluid dynamics (CFD), mainly two approaches have been used to model the coil embolized aneurysm; modeling the coils as porous media or by real coil geometries. In this study, we calculated the pressure drop along a vessel through a coiled region modeled as porous media or by real coil geometry and compared the pressure drop generated by the two coil models. The porous media model was described by Darcy's law and Ergun's equation, while the real coil geometry was generated using finite element method (FEM) structural analysis. We calculated the pressure drop for inlet velocities from 0.1 m/s to 1.0 m/s in steps of 0.1 m/s. Our results indicated that the porous media model may produce larger pressure drops than the real coil geometry model under low packing density. The value of the pressure drop was also changed due to the difference of coil distribution even if the packing density was the same.

Multivariate Analysis For Predicting Internal Carotid (IC) And Middle Cerebral (MC) Aneurysmal Rupture By Hemodynamic Parameters.

Currently, aneurysmal rupture can hardly be predicted and the search for an objective and precise indicator is ongoing. The objective of this study was to find a rupture prediction indicator (RPI) based on hemodynamic parameters of unruptured aneurysms focusing on the internal carotid (IC) and middle cerebral (MC) arteries. Computational fluid dynamics simulations were performed and hemodynamic parameters were calculated using three-dimensional C-arm computed tomography (3D C-arm CT) images of a total of 137 unruptured aneurysms (69 IC and 68 MC artery aneurysms) with known outcomes of rupture or unrupture. Multivariate analysis was applied to build an RPI model. The final RPI models contained the pressure-loss coefficient at the time maximum (TMAXPLc). Ruptured aneurysms were found to have lower TMAXPLc than unruptured aneurysms. The mean values were 1.002 (95%CI 0.827 to 1.177) and 1.466 (95%CI 1.352 to 1.579), respectively (P=0.002). TMAXPLc may thus be a useful parameter for rupture prediction of IC and MC artery aneurysms.

Hemodynamic Change In A Cerebral Aneurysm Treated By Double Stenting Technique.

Rupture of cerebral aneurysms often causes subarachnoid hemorrhage which is a life-threatening condition with high mortality rates. Larger aneurysms are believed to be more likely to rupture and should therefore be treated. Recently, flow diverters (FDs) are widely used to treat large or wide neck aneurysms. However, it can be difficult to treat them by deployment of a single FD because of its insufficient flow disturbance. To overcome this problem, double stenting technique is sometimes applied with the aim to improve the effect of blood velocity reduction. In this study, we used computational fluid dynamics (CFD) to investigate the hemodynamic changes in an aneurysm when deploying virtual FDs. The results showed that the characteristics of the blood flow field inside the aneurysm did not changed much after the deployment of a single FD but underwent a large change after the deployment of two FDs. Furthermore, the velocity reduction in the aneurysm sac at a plane away from the parent artery increased from 25.9% to 92.8% when two FDs were deployed instead of one compared to no stenting. Double stenting was effective to decrease blood velocity in large or wide neck aneurysms.

Relationship between hemodynamic parameters and cerebral aneurysm initiation.

Research on the relationship between cerebralaneurysm initiation and hemodynamic parameters, but several open questions remain on initiation and growth mechanisms of cerebral aneurysms. If factors contributing to initiation were identified, it would be possible to predict the initiation of aneurysms. The purpose of this study is to investigate the relationship between cerebral aneurysm initiation and hemodynamic factors. Blood flow simulations in aneurysms of three patients were performed using computational fluid dynamics (CFD) based on the cerebral blood vessel geometry before aneurysm initiation. We evaluated pressure, wall shear stress (WSS), wall shear stress gradient (WSSG), oscillatory shear index (OSI) and gradient oscillatory number (GON) since these factors are known to be associated with aneurysmal initiation. We also focused on the wall shear stress divergence (WSSD) in particular on the direction of WSS. Our results indicated that only high WSSD regions corresponded to the initiation regions, and the value of WSSD was remarkably high. Stretching force to the vessel wall may be related to the initiation of cerebral aneurysms.