Endothelial Responses to Curvature-Induced Flow Patterns in Engineered Cerebral Aneurysms.

Hemodynamic factors have long been associated with clinical outcomes in the treatment of cerebral aneurysms. Computational studies of cerebral aneurysm hemodynamics have provided valuable estimates of the mechanical environment experienced by the endothelium in both the parent vessel and aneurysmal dome walls and have correlated them with disease state. These computational-clinical studies have recently been correlated with the response of endothelial cells (EC) using either idealized or patient-specific models. Here, we present a robust workflow for generating anatomic-scale aneurysm models, establishing luminal cultures of ECs at physiological relevant flow profiles, and comparing EC responses to curvature mediated flow. We show that flow patterns induced by parent vessel curvature produce changes in wall shear stress (WSS) and wall shear stress gradients (WSSG) that are correlated with differences in cell morphology and cellular protein localization. Cells in higher WSS regions align better with the flow and display strong Notch1-extracellular domain (ECD) polarization, while, under low WSS, differences in WSSG due to curvature change were associated with less alignment and attenuation of Notch1-ECD polarization in ECs of the corresponding regions. These proof-of-concept results highlight the use of engineered cellularized aneurysm models for connecting computational fluid dynamics to the underlying endothelial biology that mediates disease.

Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

The ability of magnetic resonance black blood vessel wall imaging to evaluate blunt cerebrovascular injury following acute trauma.

BACKGROUND AND PURPOSE: Blunt cerebrovascular injury (BCVI) is associated with a significant risk of ischemic stroke when left untreated. Cross-sectional imaging is vital to early BCVI diagnosis and treatment; however, conventional luminal vessel imaging is limited in its ability to evaluate for vessel wall pathology. The purpose of this study is to evaluate the ability of vessel wall magnetic resonance imaging (VWI) to detect and evaluate BCVI in acutely injured trauma patients relative to neck computed tomographic angiography (CTA). MATERIALS AND METHODS: Trauma patients with suspected BCVI on initial neck CTA were prospectively recruited for VWI evaluation. Two neuroradiologists blinded to patient clinical history and CTA findings evaluated each artery independently on VWI and noted the presence and grade of BCVI. These results were subsequently compared to neck CTA findings relative to expert clinical consensus review. Interrater reliability of VWI for detecting BCVI was evaluated using a weighted Cohen κ-statistic. RESULTS: Ten trauma patients (40 cervical arteries) were prospectively evaluated using both CTA and VWI. Out of 18 vascular lesions identified as suspicious for BCVI on CTA, six lesions were determined to represent true BCVI by expert consensus review. There was almost perfect agreement between VWI and expert consensus regarding the presence and grade of BCVI (κ=0.82). This agreement increased when considering only low grade BCVI. There was only fair agreement between CTA and expert clinical consensus (κ=0.36). This agreement decreased when considering only low grade BCVI. CONCLUSIONS: VWI can potentially accurately identify and evaluate BCVI in acutely injured trauma patients with excellent inter-rater reliability.

Thrombus-associated microbiota in acute ischemic stroke patients.

Background: Despite a reduction in stroke incidence and age-standardized death rates, stroke remains a leading cause of death and disability worldwide. Significant interest in recent years has focused on the microbiota-host interaction because accumulating evidence has revealed myriad ways in which bacteria may contribute to risk of stroke and adverse outcomes after stroke. The emergence of endovascular thrombectomy as a treatment provides a unique opportunity to utilize thrombus retrieved from cerebral arteries to fill knowledge gaps about the influence of bacteria on stroke pathophysiology. While bacterial signatures have been confirmed in cerebral thrombi, the exact nature of the pathogenesis has not been established. Methods: Thrombi were obtained from a cohort of adult ischemic stroke patients during standard of care thrombectomy. After DNA extraction and quantification, thrombi underwent 16S rRNA amplicon-based metagenomic sequencing, followed by bioinformatics processing. Taxonomic identification of bacterial colonies isolated on Agar plates from plated suspension was performed using DNA extraction and full length 16S Sanger sequencing. Results: A broad diversity of bacterial signatures was identified in specimens, primarily of cariogenic origin. Conclusion: In this small study, we demonstrate proof of concept and technical feasibility for amplicon-based metagenomic sequencing of arterial thrombi and briefly discuss preliminary findings, challenges, and near-term translational opportunities for thrombus genomics.

Mobile Smartphone-Based Digital Pupillometry Curves in the Diagnosis of Traumatic Brain Injury.

Objective: The pupillary light reflex (PLR) and the pupillary diameter over time (the PLR curve) is an important biomarker of neurological disease, especially in the diagnosis of traumatic brain injury (TBI). We investigated whether PLR curves generated by a novel smartphone pupillometer application could be easily and accurately interpreted to aid in the diagnosis of TBI. Methods: A total of 120 PLR curves from 42 healthy subjects and six patients with TBI were generated by PupilScreen. Eleven clinician raters, including one group of physicians and one group of neurocritical care nurses, classified 48 randomly selected normal and abnormal PLR curves without prior training or instruction. Rater accuracy, sensitivity, specificity, and interrater reliability were calculated. Results: Clinician raters demonstrated 93% accuracy, 94% sensitivity, 92% specificity, 92% positive predictive value, and 93% negative predictive value in identifying normal and abnormal PLR curves. There was high within-group reliability (k = 0.85) and high interrater reliability (K = 0.75). Conclusion: The PupilScreen smartphone application-based pupillometer produced PLR curves for clinical provider interpretation that led to accurate classification of normal and abnormal PLR data. Interrater reliability was greater than previous studies of manual pupillometry. This technology may be a good alternative to the use of subjective manual penlight pupillometry or digital pupillometry.

Clopidogrel hyper-response increases peripheral hemorrhagic complications without increasing intracranial complications in endovascular aneurysm treatments requiring dual antiplatelet therapy.

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the VerifyNow P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU ≤ 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU ≥ 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (≤60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs ≥ 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (≤15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hypo-responders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.

Hybrid microcatheter angioplasty for refractory cerebral vasospasm.

Cerebral vasospasm is a significant cause of morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (aSAH). Intra-arterial chemical and mechanical angioplasty, performed alone or in combination, have been shown to ameliorate cerebral vasospasm and improve patient outcomes. Few options exist for patients who fail these traditional endovascular tactics. We propose a hybrid microcatheter technique that combines the mechanical benefit of transient high pressure induced by microcatheter fluid bolus with a low-dose vasodilator infusion. Five patients with moderate to severe symptomatic vasospasm who failed medical and traditional endovascular management were treated using a hybrid microcatheter technique. All angioplasty procedures were technically successful, and the degree of vasospasm improved following angioplasty. There were no complications related to the cerebral angioplasty procedures. None of the patients required repeat endovascular intervention. Hybrid microcatheter angioplasty may be a useful complement to mechanical or pharmacological techniques in the endovascular management of intractable cerebral vasospasm after aSAH.

Procedure for infusion of autologous mitochondria through the carotid artery in porcine brain. / Procedimiento para la infusión de mitocondrias autólogas por la arteria carótida en el cerebro porcino.

Mitochondria are complex organelles that play a critical role within the cell; mitochondrial dysfunction can result in significant cell damage or death. Previous studies have demonstrated the promising therapeutic effects of autologous mitochondria transplantation into ischemic cardiac tissue; however, few studies have examined the in vivo effects of mitochondria infusion into the brain. The aim of this study is to report a procedure for carotid infusion of autologous mitochondria into porcine brains. By using this infusion technique, we propose that a selective and minimally invasive administration is feasible and may provide benefits in the treatment of various central nervous system disorders.

Las mitocondrias son organelas complejas que desempeñan un papel fundamental en la célula, la disfunción mitocondrial puede ocasionar daños celulares significativos o la muerte. Estudios previos han demostrado los prometedores efectos terapéuticos del trasplante de mitocondrias autólogas a un tejido cardiaco isquémico, sin embargo, pocos estudios han evaluado los efectos in vivo de la infusión de mitocondrias en el cerebro. El presente trabajo tiene como objetivo dar a conocer el procedimiento para la infusión vía carótida de mitocondrias autólogas en cerebros porcinos. Mediante esta técnica de infusión, proponemos que una administración selectiva y mínimamente invasiva es factible y puede proporcionar beneficios en el tratamiento de diversas patologías del sistema nervioso central.

Computed tomography angiography findings predictive of post-intervention vasospasm in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To evaluate the association of CT/CT angiography (CTA) findings and clinical characteristics with subsequent vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS-: Consecutive presentation CTA head exams in patients with aSAH between January 2005 and June 2015 were retrospectively evaluated for intracranial arterial calcification, undulation and non-calcified stenosis. Additional variables including modified Fisher Scale (mFS), Glasgow Coma Scale (GCS) and neurological exam status were reviewed. Associations of CTA findings with the incidence of angiographic vasospasm were assessed with multivariate logistic regression models using the least absolute shrinkage and selection operator machine-learning algorithm. Model performance was summarized using c-index with bootstrap optimism-adjustment. RESULTS: Intracranial arterial calcification, seen in 51.7% of 195 total patients, was protective against vasospasm (OR-0.6; 95% CI-0.52-0.67; p = 0.009), while arterial undulation (24%) was associated with subsequent vasospasm (OR-2.6; 95% CI-1.3-5.1; p = 0.007). Non-calcified intracranial arterial stenosis (5%) was associated with subsequent vasospasm, (OR-4.7; 95% CI-1.0-22.8; p = 0.054). Least absolute shrinkage and selection operator selected all three CTA findings as predictors in a multivariate model for vasospasm in addition to clinical factors, which demonstrated superior predictive performance (c-index-0.74; 95% CI-0.69-0.82) compared to a model based on mFS and clinical factors only (c-index-0.66; 95% CI-0.57-0.75; p = 0.010 for the difference). CONCLUSION: Presentation CTA findings combined with clinical factors may better predict the development of vasospasm in patients with aSAH compared to current prognostic models alone. ADVANCES IN KNOWLEDGE: The combination of initial CT/CTA and clinical findings better predict development of vasospasm after aSAH. This can lead to better markers for use in future clinical trials to develop vasospasm preventative treatments and potentially provide better targets for early aggressive treatment.

Middle Meningeal Artery Embolization for Chronic Subdural Hematoma: A Multi-Center Experience of 154 Consecutive Embolizations.

BACKGROUND: Middle meningeal artery (MMA) embolization has emerged as a promising treatment for chronic subdural hematoma (cSDH). OBJECTIVE: To determine the safety and efficacy of MMA embolization. METHODS: Consecutive patients who underwent MMA embolization for cSDH (primary treatment or recurrence after conventional surgery) at 15 centers were included. Clinical details and follow-up were collected prospectively. Primary clinical and radiographic outcomes were the proportion of patients requiring additional surgical treatment within 90 d after index treatment and proportion with > 50% cSDH thickness reduction on follow-up computed tomography imaging within 90 d. National Institute of Health Stroke Scale and modified Rankin Scale were also clinical outcomes. RESULTS: A total of 138 patients were included (mean age: 69.8, 29% female). A total of 15 patients underwent bilateral interventions for 154 total embolizations (66.7% primary treatment). At presentation, 30.4% and 23.9% of patients were on antiplatelet and anticoagulation therapy, respectively. Median admission cSDH thickness was 14 mm. A total of 46.1% of embolizations were performed under general anesthesia, and 97.4% of procedures were successfully completed. A total of 70.2% of embolizations used particles, and 25.3% used liquid embolics with no significant outcome difference between embolization materials (P > .05). On last follow-up (mean 94.9 d), median cSDH thickness was 4 mm (71% median thickness reduction). A total of 70.8% of patients had >50% improvement on imaging (31.9% improved clinically), and 9 patients (6.5%) required further cSDH treatment. There were 16 complications with 9 (6.5%) because of continued hematoma expansion. Mortality rate was 4.4%, mostly unrelated to the index procedure but because of underlying comorbidities. CONCLUSION: MMA embolization may provide a safe and efficacious minimally invasive alternative to conventional surgical techniques.

Lower complication rates associated with transradial versus transfemoral flow diverting stent placement.

BACKGROUND: Currently, there are no large-scale studies in the neurointerventional literature comparing safety between transradial (TRA) and transfemoral (TFA) approaches for flow diversion procedures. This study aims to assess complication rates in a large multicenter registry for TRA versus TFA flow diversion. METHODS: We retrospectively analyzed flow diversion cases for cerebral aneurysms from 14 institutions from 2010 to 2019. Pooled analysis of proportions was calculated using weighted analysis with 95% CI to account for results from multiple centers. Access site complication rate and overall complication rate were compared between the two approaches. RESULTS: A total of 2,285 patients who underwent flow diversion were analyzed, with 134 (5.86%) treated with TRA and 2151 (94.14%) via TFA. The two groups shared similar patient and aneurysm characteristics. Crossover from TRA to TFA was documented in 12 (8.63%) patients. There were no access site complications in the TRA group. There was a significantly higher access site complication rate in the TFA cohort as compared with TRA (2.48%, 95% CI 2.40% to 2.57%, vs 0%; p=0.039). One death resulted from a femoral access site complication. The overall complications rate was also higher in the TFA group (9.02%, 95% CI 8.15% to 9.89%) compared with the TRA group (3.73%, 95% CI 3.13% to 4.28%; p=0.035). CONCLUSION: TRA may be a safer approach for flow diversion to treat cerebral aneurysms at a wide range of locations. Both access site complication rate and overall complication rate were lower for TRA flow diversion compared with TFA in this large series.

Left transradial access for cerebral angiography.

INTRODUCTION: Transradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions. METHODS: A retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time. RESULTS: Nineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications. CONCLUSIONS: Left transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access.

Predictors of preoperative endovascular embolization of meningiomas: subanalysis of anatomic location and arterial supply.

INTRODUCTION: Endovascular embolization of intracranial meningiomas is commonly used as an adjunct to surgical resection. We sought to describe the anatomic locations and vascular supplies of meningiomas to identify characteristics predictive of successful preoperative endovascular embolization. METHODS: We conducted a retrospective review of 139 meningioma cases receiving cerebral angiograms for possible preoperative endovascular embolization at our institution between December 2000 and March 2017. The extent of embolization, arterial supply, anatomic location, and procedural complications were recorded for each case. Univariate and multivariate analyses were performed to identify tumor characteristics that predicted successful embolization. RESULTS: Of the total meningioma patients undergoing preoperative angiography, 78% (108/139) were successfully embolized, with a 2.8% periprocedural complication rate (3/108). Within the subset of patients with successful embolization, 31% (33/108) achieved complete angiographic embolization. Significant multivariate predictors of embolization (either partial or complete) were convexity/parasagittal locations (OR 5.15, 95% CI 0.93 to 28.54, p=0.060), meningohypophyseal trunk (MHT, OR 4.65, 95% CI 1.63 to 13.23, p=0.004), middle meningeal artery (MMA, OR 10.89, 95% CI 3.43 to 34.64, p<0.001), and ascending pharyngeal artery supply (APA, OR 9.96, 95% CI 1.88 to 52.73, p=0.007). Significant predictors for complete embolization were convexity/parasagittal locations (OR 4.79, 95% CI 1.66 to 13.84, p=0.004) and embolized APA supply (OR 6.94, 95% CI 1.90 to 25.39, p=0.003). Multiple arterial supply was a negative predictor of complete embolization (OR 0.38, 95% CI 0.15 to 0.98, p=0.05). CONCLUSIONS: Tumor characteristics can be used to predict the likelihood of preoperative meningioma embolization. Parasagittal and convexity meningiomas, and those with APA supply, are most likely to achieve complete angiographic embolization.

Platelet Dynamics and Hemodynamics of Cerebral Aneurysms Treated with Flow-Diverting Stents.

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy.

Flow Diversion for Treatment of Intracranial Aneurysms in Pediatric Patients: Multicenter Case Series.

BACKGROUND: Though the Pipeline Embolization Device (Medtronic) is approved for use in adults 22 yr and older, the high efficacy and long-term durability of the device is attractive for treatment of intracranial aneurysms in younger patients who often have aneurysms less amenable to traditional endovascular treatments. OBJECTIVE: To report technical, angiographic, and clinical outcomes in patients aged 21 or below undergoing flow-diversion treatment for intracranial aneurysms. METHODS: Retrospective review across 16 institutions identified 39 patients aged 21 or below undergoing 46 treatment sessions with Pipeline Embolization Device placement between 2012 and 2018. A total of 50 intracranial aneurysms were treated. Details regarding patient demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed in a multicenter database. RESULTS: A total of 70% of patients were male. Nonsaccular morphology was seen in half of identified aneurysms. Six aneurysms were giant, and five patients were treated acutely after ruptured presentation. Eight patients were younger than 10 yr of age. Complete aneurysm occlusion was seen in 74% of treated aneurysms. Three aneurysms (6%) were retreated. A total of 83% of patients had a modified Rankin Scale scores of ≤2 at last clinical follow-up. There were 2 early mortalities (4.3%) in the immediate postprocedure period because of rerupture of a treated ruptured aneurysm. No recanalization of a previously occluded aneurysm was observed. CONCLUSION: Flow-diversion treatment is a safe and effective treatment for intracranial aneurysms in patients younger than 22 yr. Rates of complete aneurysm occlusion and adverse events are comparable for rates seen in older patients.

Clinical outcomes and cost-effectiveness analysis for the treatment of basilar tip aneurysms.

BACKGROUND: Endovascular treatment of basilar tip aneurysms is less invasive than microsurgical clipping, but requires closer follow-up. OBJECTIVE: To characterize the additional costs associated with endovascular treatment of basilar tip aneurysms rather than microsurgical clipping. MATERIALS AND METHODS: We obtained clinical records and billing information for 141 basilar tip aneurysms treated with clip ligation (n=48) or endovascular embolization (n=93). Costs included direct and indirect costs associated with index hospitalization, as well as re-treatments, follow-up visits, imaging studies, rehabilitation, and disability. Effectiveness of treatment was quantified by converting functional outcomes (modified Rankin Scale (mRS) score) into quality-adjusted life-years (QALYs). Cost-effectiveness was performed using cost/QALY ratios. RESULTS: Average index hospitalization costs were significantly higher for patients with unruptured aneurysms treated with clip ligation ($71 400 ± $47 100) compared with coil embolization ($33 500 ± $22 600), balloon-assisted coiling ($26 200 ± $11 600), and stent-assisted coiling ($38 500 ± $20 900). Multivariate predictors for higher index hospitalization cost included vasospasm requiring endovascular intervention, placement of a ventriculoperitoneal shunt, longer length of stay, larger aneurysm neck and width, higher Hunt-Hess grade, and treatment-associated complications. At 1 year, endovascular treatment was associated with lower cost/QALY than clip ligation in unruptured aneurysms ($52 000/QALY vs $137 000/QALY, respectively, p=0.006), but comparable rates in ruptured aneurysms ($193 000/QALY vs $233 000/QALY, p=0.277). Multivariate predictors for higher cost/QALY included worse mRS score at discharge, procedural complications, and larger aneurysm width. CONCLUSIONS: Coil embolization of basilar tip aneurysms is associated with a lower cost/QALY. This effect is sustained during follow-up. Clinical condition at discharge is the most significant predictor of overall cost/QALY at 1 year.

Genetic correlates of wall shear stress in a patient-specific 3D-printed cerebral aneurysm model.

OBJECTIVES: To study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm. MATERIALS AND METHODS: A 3D-printed model of a cerebral aneurysm was created from a patient's angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations. RESULTS: The model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations. CONCLUSIONS: Creating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.

Reconstructing patient-specific cerebral aneurysm vasculature for in vitro investigations and treatment efficacy assessments.

Perianeurysmal hemodynamics play a vital role in the initiation, growth and rupture of intracranial aneurysms. In vitro investigations of aneurysmal hemodynamics are helpful to visualize and measure blood flow, and aiding surgical planning approaches. Improving in vitro model creation can improve the feasibility and accuracy of hemodynamic investigations and surgical planning, improving clinical value. In this study, in vitro models were created from three-dimensional rotational angiography (3DRA) of six patients harboring intracranial aneurysms using a multi-step process involving 3D printing, index of refraction matching and silicone casting that renders the models transparent for flow visualization. Each model was treated with the same commercially-available, patient-specific, endovascular devices (coils and/or stents). All models were scanned by synchrotron X-ray microtomography to obtain high-resolution imaging of the vessel lumen, aneurysmal sac and endovascular devices. Dimensional accuracy was compared by quantifying the differences between the microtomographic reconstructions of the fabricated phantoms and the original 3DRA obtained during patient treatment. True-scale in vitro flow phantoms were successfully created for all six patients. Optical transparency was verified by using an index of refraction matched working fluid that replicated the mechanical behavior of blood. Synchrotron imaging of vessel lumen, aneurysmal sac and endovascular devices was successfully obtained, and dimensional errors were found to be O(100 µm). The creation of dimensionally-accurate, optically-transparent flow phantoms of patient-specific intracranial aneurysms is feasible using 3D printing technology. Such models may enable in vitro investigations of aneurysmal hemodynamics to aid in treatment planning and outcome prediction to devise optimal patient-specific neurointerventional strategies.

Predictors of Recurrence, Progression, and Retreatment in Basilar Tip Aneurysms: A Location-Controlled Analysis.

BACKGROUND: Endovascular treatment of intracranial aneurysms is associated with higher rates of recurrence and retreatment, though contemporary rates and risk factors for basilar tip aneurysms (BTAs) are less well-described. OBJECTIVE: To characterize progression, retreatement, and retreated progression of BTAs treated with microsurgical or endovascular interventions. METHODS: We retrospectively reviewed records for 141 consecutive BTA patients. We included 158 anterior communicating artery (ACoA) and 118 middle cerebral artery (MCA) aneurysms as controls. Univariate and multivariate analyses were used to calculate rates of progression (recurrence of previously obliterated aneurysms and progression of known residual aneurysm dome or neck), retreatment, and retreated progression. Kaplan-Meier analysis was used to characterize 24-mo event rates for primary outcome prediction. RESULTS: Of 141 BTA patients, 62.4% were ruptured and 37.6% were unruptured. Average radiographical follow-up was 33 mo. Among ruptured aneurysms treated with clipping, there were 2 rehemorrhages due to recurrence (6.1%), and none in any other cohorts. Overall rates of progression (28.9%), retreatment (28.9%), and retreated progression (24.7%) were not significantly different between surgical and endovascular subgroups, though ruptured aneurysms had higher event rates. Multivariate modeling confirmed rupture status (P = .003, hazard ratio = 0.14) and aneurysm dome width (P = .005, hazard ratio = 1.23) as independent predictors of progression requiring retreatment. In a separate multivariate analysis with ACoA and MCA aneurysms, basilar tip location was an independent predictor of progression, retreatment, and retreated progression. CONCLUSION: BTAs have higher rates of progression and retreated progression than other aneurysm locations, independent of treatment modality. Rupture status and dome width are risk factors for progression requiring retreatment.