Carotid web leads to new thrombus formation: computational fluid dynamic analysis coupled with histological evidence.

Carotid web has been recognized as a rare cause of ischemic stroke with high recurrence rate. We describe a 48-year-old woman with carotid web who developed embolic stroke. We obtained a fresh thrombus from the internal carotid artery when carotid endarterectomy was performed. A preoperative computational fluid dynamics (CFD) study showed stagnation of blood around the web structure as well as the low wall shear stress. The rheological analysis newly disclosed mechanisms of thrombus formation related to the carotid web. CFD study in the carotid web may determine indication and timing of surgical interventions with further accumulation of clinical evidence.

Enlargement of a Middle Cerebral Artery Aneurysm after Intra-Aneurysmal Embolization with Parent Artery Preservation for an Ipsilateral Large Internal Carotid Artery Aneurysm: A Case Report.

We report a 77-year-old woman with marked enlargement of a middle cerebral artery (MCA) aneurysm 4 years after the successful intra-aneurysmal embolization of an ipsilateral large internal carotid artery (ICA) aneurysm. She intially presented with right third cranial nerve palsy due to a large ICA aneurysm, 20.8 mm in diameter. Initial magnetic resonance angiography (MRA) revealed a signal decrease in the right MCA, suggesting hemodynamic disturbance based on the contrast pooling in the right large ICA aneurysm exhibiting "Windkessel phenomenon". The large ICA aneurysm was successfully managed by intra-aneurysmal embolization with parent artery preservation, and immediate post-treatment MRA demonstrated significant signal recovery in the right MCA. Meticulous follow-up by MRA identified sudden growth in the aneurysmal height within 1 week after embolization, with further growth over the following 4 years, necessitating microsurgical clipping. Enlargement of the ipsilateral distal aneurysm following the treatment of proximal large aneurysm could be altered by marked distal hemodynamic change in view of the sudden amelioration of the "Windkessel phenomenon". Thus, we recommend meticulous follow-up of the associated distal aneurysm after the management of proximal large or giant aneurysms with parent artery preservation.

Blood Flow Into Basilar Tip Aneurysms: A Predictor for Recanalization After Coil Embolization.

BACKGROUND AND PURPOSE: Hemodynamic forces may play a role in the recanalization of coiled aneurysms. The purpose of this study was to investigate the influence of presurgical hemodynamics on the efficacy of coil embolization for basilar tip aneurysms. METHODS: We identified 82 patients who underwent endovascular coil embolization for basilar tip aneurysms with a follow-up of >1 year. Presurgical hemodynamics were investigated using computational fluid dynamics with 3-dimensional data derived from rotational angiography. During postprocessing, we quantified the rate of net flow entering the aneurysm through its neck and calculated the proportion of the aneurysmal inflow rate to the basilar artery flow rate. In addition, we investigated the correlation between the basilar bifurcation configuration and the hemodynamics. RESULTS: Twenty-five of the 82 patients were excluded because of difficult vascular geometry reconstruction. Among the 57 examined patients, angiographic recanalization was observed in 19 patients (33.3%). The proportion of the aneurysmal inflow rate to the basilar artery flow rate and a coil packing density <30% were independent and significant predictors for the recanalization of coiled aneurysms. Additional investigation revealed that a small branch angle formed by the basilar artery and the posterior cerebral artery increased blood flow into the aneurysm. CONCLUSIONS: The proportion of the aneurysmal inflow rate to the basilar artery flow rate, influenced by the basilar bifurcation configuration, was an independent and significant predictor for recanalization after coil embolization in basilar tip aneurysms.

The Computational Fluid Dynamics Rupture Challenge 2013--Phase II: Variability of Hemodynamic Simulations in Two Intracranial Aneurysms.

With the increased availability of computational resources, the past decade has seen a rise in the use of computational fluid dynamics (CFD) for medical applications. There has been an increase in the application of CFD to attempt to predict the rupture of intracranial aneurysms, however, while many hemodynamic parameters can be obtained from these computations, to date, no consistent methodology for the prediction of the rupture has been identified. One particular challenge to CFD is that many factors contribute to its accuracy; the mesh resolution and spatial/temporal discretization can alone contribute to a variation in accuracy. This failure to identify the importance of these factors and identify a methodology for the prediction of ruptures has limited the acceptance of CFD among physicians for rupture prediction. The International CFD Rupture Challenge 2013 seeks to comment on the sensitivity of these various CFD assumptions to predict the rupture by undertaking a comparison of the rupture and blood-flow predictions from a wide range of independent participants utilizing a range of CFD approaches. Twenty-six groups from 15 countries took part in the challenge. Participants were provided with surface models of two intracranial aneurysms and asked to carry out the corresponding hemodynamics simulations, free to choose their own mesh, solver, and temporal discretization. They were requested to submit velocity and pressure predictions along the centerline and on specified planes. The first phase of the challenge, described in a separate paper, was aimed at predicting which of the two aneurysms had previously ruptured and where the rupture site was located. The second phase, described in this paper, aims to assess the variability of the solutions and the sensitivity to the modeling assumptions. Participants were free to choose boundary conditions in the first phase, whereas they were prescribed in the second phase but all other CFD modeling parameters were not prescribed. In order to compare the computational results of one representative group with experimental results, steady-flow measurements using particle image velocimetry (PIV) were carried out in a silicone model of one of the provided aneurysms. Approximately 80% of the participating groups generated similar results. Both velocity and pressure computations were in good agreement with each other for cycle-averaged and peak-systolic predictions. Most apparent "outliers" (results that stand out of the collective) were observed to have underestimated velocity levels compared to the majority of solutions, but nevertheless identified comparable flow structures. In only two cases, the results deviate by over 35% from the mean solution of all the participants. Results of steady CFD simulations of the representative group and PIV experiments were in good agreement. The study demonstrated that while a range of numerical schemes, mesh resolution, and solvers was used, similar flow predictions were observed in the majority of cases. To further validate the computational results, it is suggested that time-dependent measurements should be conducted in the future. However, it is recognized that this study does not include the biological aspects of the aneurysm, which needs to be considered to be able to more precisely identify the specific rupture risk of an intracranial aneurysm.

Outflow Occlusion with Occipital Artery-Posterior Inferior Cerebellar Artery Bypass for Growing Vertebral Artery Fusiform Aneurysm with Ischemic Onset: A Case Report.

Surgical treatments should be considered for vertebral artery fusiform aneurysms, which become symptomatic due to cerebral ischemia or mass effect. Ischemic complication is one of the major problems after surgical or endovascular trapping, which is associated with unfavorable outcomes. The authors present a case with growing vertebral artery (VA) fusiform aneurysm with ischemic onset successfully treated with outflow occlusion with occipital artery-posterior inferior cerebellar artery (OA-PICA) bypass. A 50-year-old woman presented with left PICA territory infarction. Left vertebral angiography (VAG) showed occlusion of the left VA at the proximal V4 segment. Right VAG revealed that the distal part of the left V4 segment with fusiform aneurysmal dilatation was reconstituted through vertebrobasilar junction, and the left PICA was the outlet of the blood flow from the fusiform aneurysm. Although the patient was treated conservatively, enlargement of the left VA fusiform aneurysm was observed 8 months after the initial presentation. Considering the potential risks for future stroke or bleeding, we performed clip occlusion of the origin of the left PICA, which could achieve outflow occlusion of the fusiform aneurysm with preservation of the perforators arising around the aneurysm. We created OA-PICA anastomosis for revascularization of the distal PICA. The postoperative course was uneventful, and the postoperative right VAG revealed occlusion of the fusiform aneurysm. Outflow occlusion instead of trapping is an effective surgical option for VA fusiform aneurysm to achieve obliterate the aneurysm with preservation of the perforator at the blind end.

Computational hemodynamic analysis of the offending vertebral artery at the site of neurovascular contact in a case of hemifacial spasm associated with subclavian steal syndrome: illustrative case.

BACKGROUND: Hemifacial spasm (HFS) is caused by neurovascular contact along the facial nerve's root exit zone (REZ). The authors report a rare HFS case that was associated with ipsilateral subclavian steal syndrome (SSS). OBSERVATIONS: A 42-year-old man with right-sided aortic arch presented with progressing left HFS, which was associated with ipsilateral SSS due to severe stenosis of the left brachiocephalic trunk. Magnetic resonance imaging showed contact between the left REZ and vertebral artery (VA), which had shifted to the left. The authors speculated that the severe stenosis at the left brachiocephalic trunk resulted in the left VA's deviation, which was the underlying cause of the HFS. The authors performed percutaneous angioplasty (PTA) to dilate the left brachiocephalic trunk. Ischemic symptoms of the left arm improved after PTA, but the HFS remained unchanged. A computational fluid dynamics study showed that the high wall shear stress (WSS) around the site of neurovascular contact decreased after PTA. In contrast, pressure at the point of neurovascular contact increased after PTA. LESSONS: SSS is rarely associated with HFS. Endovascular treatment for SSS reduced WSS of the neurovascular contact but increased theoretical pressure of the neurovascular contact. Physical release of the neurovascular contact is the best treatment option for HFS.

Incomplete stent expansion in flow-diversion treatment affects aneurysmal haemodynamics: a quantitative comparison of treatments affected by different severities of malapposition occurring in different segments of the parent artery.

Incomplete stent expansion (IncSE) is occasionally seen in flow-diversion (FD) treatment of intracranial aneurysms; however, its haemodynamic consequences remain inconclusive. Through a parametric study, we quantify the aneurysmal haemodynamics subject to different severities of IncSE occurring in different portions of the stent. Two patient cases with IncSE confirmed in vivo were studied. To investigate a wider variety of IncSE scenarios, we modelled IncSE at two severity levels respectively located in the proximal, central, or distal segment of a stent, yielding a total of 14 treatment scenarios (including the ideal deployment). We examined stent wire configurations in 14 scenarios and resolved aneurysm haemodynamics through computational fluid dynamics (CFD). A considerable degradation of aneurysm flow-reduction performance was observed when central or distal IncSE occurred, with the maximal elevations of the inflow rate (IR) and energy loss (EL) being 10% and 15%. The underlying mechanism might be the increased resistance for flow to remain within the FD stent, which forces more blood to leak into the aneurysm sac. Counter-intuitively, a slight reduction of aneurysm inflow was associated with proximal IncSE, with the maximal further reduction of the IR and EL being 5% and 8%. This may be due to the disruption of the predominant parent-artery flow by the collapsed wires, which decreased the strength and altered the direction of aneurysmal inflow. The effects of IncSE vary greatly with the location of occurrence, revealing the importance of performing individualised, patient-specific risk assessment before treatment.

Convection-enhanced delivery of a synthetic retinoid Am80, loaded into polymeric micelles, prolongs the survival of rats bearing intracranial glioblastoma xenografts.

Prognosis for the patients with glioblastoma, the most common malignant brain tumor, remains dismal. A major barrier to progress in treatment of glioblastoma is the relative inaccessibility of tumors to chemotherapeutic agents. Convection-enhanced delivery (CED) is a direct intracranial drug infusion technique to deliver chemotherapeutic agents to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. CED can provide wider distribution of infused agents compared to simple diffusion. We have reported that CED of a polymeric micelle carrier system could yield a clinically relevant distribution of encapsulated agents in the rat brain. Our aim was to evaluate the efficacy of CED of polymeric micellar Am80, a synthetic agonist with high affinity to nuclear retinoic acid receptor, in a rat model of glioblastoma xenografts. We also used systemic administration of temozolomide, a DNA-alkylating agent, which has been established as the standard of care for newly diagnosed malignant glioma. U87MG human glioma cells were injected into the cerebral hemisphere of nude rats. Rats bearing U87MG xenografts were treated with CED of micellar Am80 (2.4 mg/m(2)) on day 7 after tumor implantation. Temozolomide (200 mg/m(2)/day) was intraperitoneally administered daily for 5 days, starting on day 7 after tumor implantation. CED of micellar Am80 provided significantly longer survival than the control. The combination of CED of micellar Am80 and systemic administration of temozolomide provided significantly longer survival than single treatment. In conclusion, temozolomide combined with CED of micellar Am80 may be a promising method for the treatment of malignant gliomas.

Enhanced antitumor effect of combined-modality treatment using convection-enhanced delivery of hydrophilic nitrosourea with irradiation or systemic administration of temozolomide in intracranial brain tumor xenografts.

OBJECTIVE: Convection-enhanced delivery (CED) is a local infusion technique that delivers chemotherapeutic agents directly to the central nervous system, circumventing the blood-brain barrier and reducing systemic side effects. We previously reported the safety and efficacy of CED of ACNU (nimustine hydrochloride: 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitrosourea hydrochloride), a hydrophilic nitrosourea, in rat brain tumor models. This study evaluated the efficacy of combined-modality treatments using CED of ACNU with irradiation or systemic administration of temozolomide. METHODS: Antitumor efficacy and toxicity of the treatment were evaluated using rat 9L intracranial brain tumor models. RESULTS: Combined treatment using CED of ACNU with irradiation produced significantly longer survival time than each treatment alone (versus CED: p<0.001, versus irradiation: p<0.05, log-rank test) or systemic administration of ACNU with irradiation (p<0.001). Long-term survival (120 days) and eradication of tumor occurred only in this combined-treatment group. We also showed that CED of ACNU plus systemic administration of temozolomide significantly enhanced survival rate compared with each treatment alone (versus CED: p<0.001, versus systemic temozolomide: p<0.05). DISCUSSION: Multimodality treatment using CED of ACNU, radiotherapy and systemic chemotherapy with temozolomide is a promising strategy for treatment of brain tumors.

Revascularization of the anterior cerebral artery by Y-shaped superficial temporal artery interposition graft for the treatment of a de novo aneurysm arising at the site of A3-A3 bypass: technical case report.

The most frequently used option to reconstruct the anterior cerebral artery (ACA) is an ACA-ACA side-to-side anastomosis. The long-term outcome and complications of this technique are unclear. The authors report a case of a de novo aneurysm arising at the site of A3-A3 anastomosis. A 53-year-old woman underwent A3-A3 side-to-side anastomosis for the treatment of a ruptured right A2 dissecting aneurysm. At 44 months after surgery, a de novo aneurysm developed at the site of anastomosis. The aneurysm developed in the front wall of the anastomosis site, and projected to the anterosuperior direction. A computational fluid dynamics (CFD) study showed the localized region with high wall shear stress coincident with the pulsation in the front wall of the anastomosis site, where the aneurysm developed. A Y-shaped superficial temporal artery (STA) interposition graft was used successfully to reconstruct both ACAs, and then the aneurysm was trapped. To the authors' knowledge, this is the first case of a de novo aneurysm that developed at the site of an ACA-ACA side-to-side anastomosis. A CFD study showed that hemodynamic stress might be an underlying cause of the aneurysm formation. A Y-shaped STA interposition graft is a useful option to treat this aneurysm. Long-term follow-up is necessary to detect this rare complication after ACA-ACA anastomosis.

Impact of bifurcation angle and inflow coefficient on the rupture risk of bifurcation type basilar artery tip aneurysms.

OBJECTIVE Risk factors for aneurysm rupture have been extensively studied, with several factors showing significant correlations with rupture status. Several studies have shown that aneurysm shape and hemodynamics change after rupture. In the present study the authors investigated a static factor, the bifurcation angle, which does not change after rupture, to understand its effect on aneurysm rupture risk and hemodynamics. METHODS A hospital database was retrospectively reviewed to identify patients with cerebral aneurysms treated surgically or endovascularly in the period between 2008 and 2015. After acquiring 3D rotational angiographic data, 3D stereolithography models were created and computational fluid dynamic analysis was performed using commercially available software. Patient data (age and sex), morphometric factors (aneurysm volume and maximum height, aspect ratio, bifurcation angle, bottleneck ratio, and neck/parent artery ratio), and hemodynamic factors (inflow coefficient and wall shear stress) were statistically compared between ruptured and unruptured groups. RESULTS Seventy-one basilar tip aneurysms were included in this study, 22 ruptured and 49 unruptured. Univariate analysis showed aspect ratio, bifurcation angle, bottleneck ratio, and inflow coefficient were significantly correlated with a ruptured status. Logistic regression analysis showed that aspect ratio and bifurcation angle were significant predictors of a ruptured status. Bifurcation angle was inversely correlated with inflow coefficient (p < 0.0005), which in turn correlated directly with mean (p = 0.028) and maximum (p = 0.014) wall shear stress (WSS) using Pearson's correlation coefficient, whereas aspect ratio was inversely correlated with mean (0.012) and minimum (p = 0.018) WSS. CONCLUSIONS Bifurcation angle and aspect ratio are independent predictors for aneurysm rupture. Bifurcation angle, which does not change after rupture, is correlated with hemodynamic factors including inflow coefficient and WSS, as well as rupture status. Aneurysms with the hands-up bifurcation configuration are more prone to rupture than aneurysms with other bifurcation configurations.

Circumferential wall enhancement in evolving intracranial aneurysms on magnetic resonance vessel wall imaging.

OBJECTIVE: Recent MR vessel wall imaging studies have indicated intracranial aneurysms in the active state could show circumferential enhancement along the aneurysm wall (CEAW). While ruptured aneurysms frequently show CEAW, CEAW in unruptured aneurysms at the evolving state (i.e., growing or symptomatic) has not been studied in detail. The authors quantitatively assessed the degree of CEAW in evolving unruptured aneurysms by comparing it separately to that in stable unruptured and ruptured aneurysms. METHODS: A quantitative analysis of CEAW was performed in 26 consecutive evolving aneurysms using MR vessel wall imaging. Three-dimensional T1-weighted fast spin echo sequences were obtained before and after contrast media injection, and the contrast ratio of the aneurysm wall against the pituitary stalk (CRstalk) was calculated as the indicator of CEAW. Aneurysm characteristics of evolving aneurysms were compared with those of 69 stable unruptured and 67 ruptured aneurysms. RESULTS: The CRstalk values in evolving aneurysms were significantly higher than those in stable aneurysms (0.54 vs 0.34, p < 0.0001), and lower than those in ruptured aneurysms (0.54 vs 0.83, p < 0.0002). In multivariable analysis, CRstalk remained significant when comparing evolving with stable aneurysms (odds ratio [OR] 12.23, 95% confidence interval [CI] 3.53-42.41), and with ruptured aneurysms (OR 0.083, 95% CI 0.022-0.310). CONCLUSIONS: The CEAW in evolving aneurysms was higher than those in stable aneurysms, and lower than those in ruptured aneurysms. The degree of CEAW may indicate the process leading to rupture of intracranial aneurysms, which can be useful additional information to determine an indication for surgical treatment of unruptured aneurysms.

Circumferential Wall Enhancement on Magnetic Resonance Imaging is Useful to Identify Rupture Site in Patients with Multiple Cerebral Aneurysms.

BACKGROUND: Identification of rupture sites in patients with multiple intracranial aneurysms is largely based on aneurysm size, location, and shape. Finding circumferential enhancement along the aneurysm wall (CEAW) on magnetic resonance (MR) vessel wall imaging was recently shown to be indicative of ruptured aneurysm. OBJECTIVE: To investigate the hypothesis that a higher degree of CEAW would identify the site of rupture in patients with multiple aneurysms. METHODS: We prospectively performed quantitative analysis of CEAW in consecutive patients with both aneurysmal subarachnoid hemorrhage and multiple aneurysms (26 patients with a total of 62 aneurysms), using MR vessel wall imaging. Three-dimensional T1-weighted fast spin-echo sequences were obtained before and after injection of contrast media, and the wall enhancement index (WEI) was calculated. Aneurysm characteristics (size, location, irregular shape, aspect ratio [neck-to-dome length/neck width], and WEI) were compared between ruptured and unruptured aneurysms. Odds ratios with 95% confidence intervals for ruptures were calculated with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size. RESULTS: Large aneurysm size, high aspect ratio, WEI (above the median values), and irregular shape were significantly associated with aneurysm rupture. After adjustment for aneurysm size, WEI (adjusted odds ratio: 8.8; 95% confidence interval, 1.1-72.6) as well as irregular shape and aspect ratio showed a strong association with rupture. CONCLUSION: CEAW is associated with rupture of intracranial aneurysm independent of aneurysm size and patient characteristics. Contrast-enhanced MR vessel wall imaging helps to identify the site of rupture in patients with multiple aneurysms.

Real-World Variability in the Prediction of Intracranial Aneurysm Wall Shear Stress: The 2015 International Aneurysm CFD Challenge.

PURPOSE: Image-based computational fluid dynamics (CFD) is widely used to predict intracranial aneurysm wall shear stress (WSS), particularly with the goal of improving rupture risk assessment. Nevertheless, concern has been expressed over the variability of predicted WSS and inconsistent associations with rupture. Previous challenges, and studies from individual groups, have focused on individual aspects of the image-based CFD pipeline. The aim of this Challenge was to quantify the total variability of the whole pipeline. METHODS: 3D rotational angiography image volumes of five middle cerebral artery aneurysms were provided to participants, who were free to choose their segmentation methods, boundary conditions, and CFD solver and settings. Participants were asked to fill out a questionnaire about their solution strategies and experience with aneurysm CFD, and provide surface distributions of WSS magnitude, from which we objectively derived a variety of hemodynamic parameters. RESULTS: A total of 28 datasets were submitted, from 26 teams with varying levels of self-assessed experience. Wide variability of segmentations, CFD model extents, and inflow rates resulted in interquartile ranges of sac average WSS up to 56%, which reduced to < 30% after normalizing by parent artery WSS. Sac-maximum WSS and low shear area were more variable, while rank-ordering of cases by low or high shear showed only modest consensus among teams. Experience was not a significant predictor of variability. CONCLUSIONS: Wide variability exists in the prediction of intracranial aneurysm WSS. While segmentation and CFD solver techniques may be difficult to standardize across groups, our findings suggest that some of the variability in image-based CFD could be reduced by establishing guidelines for model extents, inflow rates, and blood properties, and by encouraging the reporting of normalized hemodynamic parameters.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation.

PURPOSE: Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. METHODS: To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. RESULTS: Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. CONCLUSIONS: MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

Initial Clinical Experience with AView-A Clinical Computational Platform for Intracranial Aneurysm Morphology, Hemodynamics, and Treatment Management.

BACKGROUND: The management of intracranial aneurysm (IA) is challenging. Clinicians often rely on varied and intuitively disparate ways of evaluating rupture risk that may only partially take into account complex hemodynamic and morphologic factors. We developed a prototype of a clinically oriented, streamlined, computational platform, AView, for rapid assessment of hemodynamics and morphometrics in clinical settings. To show the potential clinical utility of AView, we report our initial multicenter experience highlighting the possible advantages of morphologic and hemodynamic analysis of IAs. METHODS: AView software was deployed across 8 medical centers (6 in the United States, 2 in Japan). Eight clinicians were trained and used the AView software between September 2012 and January 2013. RESULTS: We present 12 illustrative cases that show the potential clinical utility of AView. For all, morphology and hemodynamics, flow visualization, and rupture resemblance score (a surrogate for rupture risk) were provided. In 3 cases, AView could confirm the clinicians' decision to treat; in 3 cases, it could suggest which aneurysms may be at greater risk among multiple aneurysms; in 5 cases, AView could provide additional information for use during treatment decisions for ambiguous situations. In one stent-assisted coiling case, flow visualization predicted that the intuitive choice for stent placement could have resulted in sacrifice of an anterior cerebral artery due to blockage by coils and led clinicians to reconsider treatment plans. CONCLUSIONS: AView has the potential to confirm decisions to treat IAs, suggest which among multiple aneurysms to treat, and guide treatment decisions. Furthermore, the flow visualization it affords can inform aneurysm treatment planning and potentially avoid poor outcomes.

Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously.

This was a proof-of-concept computational fluid dynamics (CFD) study designed to identify atherosclerotic changes in intracranial aneurysms. We selected 3 patients with multiple unruptured aneurysms including at least one with atherosclerotic changes and investigated whether an image-based CFD study could provide useful information for discriminating the atherosclerotic aneurysms. Patient-specific geometries were constructed from three-dimensional data obtained using rotational angiography. Transient simulations were conducted under patient-specific inlet flow rates measured by phase-contrast magnetic resonance velocimetry. In the postanalyses, we calculated time-averaged wall shear stress (WSS), oscillatory shear index, and relative residence time (RRT). The volume of blood flow entering aneurysms through the neck and the mean velocity of blood flow inside aneurysms were examined. We applied the age-of-fluid method to quantitatively assess the residence of blood inside aneurysms. Atherosclerotic changes coincided with regions exposed to disturbed blood flow, as indicated by low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The mean velocities of blood inside atherosclerotic aneurysms were lower than those inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older than that in nonatherosclerotic aneurysms, especially near the wall. This proof-of-concept study demonstrated that CFD analysis provided detailed information on the exchange and residence of blood that is useful for the diagnosis of atherosclerotic changes in intracranial aneurysms.

Properties of convective delivery in spinal cord gray matter: laboratory investigation and computational simulations.

OBJECT Convection-enhanced delivery (CED) is a method for distributing small and large molecules locally into the interstitial space of the spinal cord. Delivering these molecules to the spinal cord is otherwise difficult due to the blood-spinal cord barrier. Previous research has proven the efficacy of CED for delivering molecules over long distances along the white matter tracts in the spinal cord. Conversely, the characteristics of CED for delivering molecules to the gray matter of the spinal cord remain unknown. The purpose of this study was to reveal regional distribution of macromolecules in the gray and white matter of the spinal cord with special attention to the differences between the gray and white matter. METHODS Sixteen rats (F344) underwent Evans blue dye CED to either the white matter (dorsal column, 8 rats) or the gray matter (ventral horn, 8 rats) of the spinal cord. The rates and total volumes of infusion were 0.2 µl/min and 2.0 µl, respectively. The infused volume of distribution was visualized and quantified histologically. Computational models of the rat spinal cord were also obtained to perform CED simulations in the white and gray matter. RESULTS The ratio of the volume of distribution to the volume of infusion in the gray matter of the spinal cord was 3.60 ± 0.69, which was comparable to that of the white matter (3.05 ± 0.88). When molecules were injected into the white matter, drugs remained in the white matter tract and rarely infused into the adjacent gray matter. Conversely, when drugs were injected into the gray matter, they infiltrated laterally into the white matter tract and traveled longitudinally and preferably along the white matter. In the infusion center, the areas were larger in the gray matter CED than in the white matter (Mann-Whitney U-test, p < 0.01). In computational simulations, the aforementioned characteristics of CED to the gray and white matter were reaffirmed. CONCLUSIONS In the spinal cord, the gray and white matter have distinct characteristics of drug distribution by CED. These differences between the gray and white matter should be taken into account when considering drug delivery to the spinal cord. Computational simulation is a useful tool for predicting drug distributions in the normal spinal cord.

Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis.

We developed a thyroid hormone (TH) inducible primary screening assay for the identification and assessment of man-made chemicals that interfere with the TH-signalling pathway within target cells. The assay was developed in a Xenopus laevis cell line that was transduced with a self-inactivating (SIN) lentivirus vector (LV) containing a luciferase gene. The luciferase activation in this cell line was TH-specific: 3,3',5-L-triiodothyronine (T(3)) > 3,3'5-L-triiodothyroacetic acid (Triac) > 3,3',5-D-triiodothyronine (D-T(3)), > L-thyroxine (T(4)) > 3,3',5'-L-triiodothyronine (rT(3)). The application of the ligand-dependent luciferase assay for screening for thyroid system-disrupting chemicals revealed that three phthalates (dicyclohexyl phthalate, n-butylbenzyl phthalate, and di-n-butyl phthalate), two herbicides (ioxynil and pentachlorophenol) and a miticide (dicofol) had 3,3',5-L-triiodothyronine- T(3)- antagonist activity at concentrations ranging from 10(-6) to 10(-5) M. These chemicals also inhibited the expression of the endogenous primary T(3)-response TH nuclear receptor beta (TRbeta) gene. The inhibitory characteristics of these chemicals were similar for both assays performed, although the assay for T(3)-dependent activation of TRbeta gene was more sensitive than the luciferase assay. These results indicate that the luciferase assay was a rapid method with a small intra-assay variation for the primary screening of thyroid system-disrupting chemicals. Of the six chemicals, only n-butylbenzyl phthalate and pentachlorophenol exhibited T(3)-antagonist activity in an in vivo metamorphosis-based assay. It should be noted that chemicals elicited thyroid system-disrupting activity in the luciferase assay did not always interfere with the thyroid system in vivo.