A novel angiographic method to estimate arterial blood flow rates using contrast reflux: Effect of injection parameters.

BACKGROUND: Contrast reflux, which is the retrograde movement of contrast against flow direction, is commonly observed during angiography. Despite a vast body of literature on angiography, the hemodynamic factors affecting contrast reflux have not been studied. Numerous methods have been developed to extract flow from angiography, but the reliability of these methods is not yet sufficient to be of routine clinical use. PURPOSE: To evaluate the effect of baseline blood flow rates and injection conditions on the extent of contrast reflux. To estimate arterial flow rates based on measurement of contrast reflux length. MATERIALS AND METHODS: Iodinated contrast was injected into an idealized tube as well as a physiologically accurate model of the cervico-cerebral vasculature. A total of 194 high-speed angiograms were acquired under varying "blood" flow rates and injection conditions (catheter size, injection rate, and injection time). The length of contrast reflux was compared to the input variables and to dimensionless fluid dynamics parameters at the catheter-tip. Arterial blood flow rates were estimated using contrast reflux length as well as a traditional transit-time method and compared to measured flow rates. RESULTS: Contrast reflux lengths were significantly affected by contrast injection rate (p < 0.0001), baseline blood flow rate (p = 0.0004), and catheter size (p = 0.04), but not by contrast injection time (p = 0.4). Reflux lengths were found to be correlated to dimensionless fluid dynamics parameters by an exponential function (R2  = 0.6-0.99). When considering the entire dataset in unison, flow estimation errors with the reflux-length method (39% ± 33%) were significantly higher (p = 0.003) than the transit-time method (33% ± 36%). However, when subgrouped by catheter, the error with the reflux-length method was substantially reduced and was significantly lower (14% ± 14%, p < 0.0001) than the transit-time method. CONCLUSION: Results show correlations between contrast reflux length and baseline hemodynamic parameters that have not been reported previously. Clinically relevant blood flow rate estimation is feasible by simple measurement of reflux length. In vivo and clinical studies are required to confirm these correlations and to refine the methodology of estimating blood flow by reflux.

Technical Success and Early Efficacy in 851 Patients with Saccular Intracranial Aneurysms: A Subset Analysis of SMART, a Prospective, Multicenter Registry Assessing the Embolization of Neurovascular Lesions using the Penumbra SMART COIL System.

OBJECTIVE: The Prospective, Multicenter Registry Assessing the Embolization of Neurovascular Lesions Using the Penumbra SMART COIL® System (SMART) is the largest prospective, multicenter, postmarket registry established to gather real-world experience on Penumbra (Alameda, USA) SMART COIL System, PC400, and POD embolization coils. The goal of this study is to report the technical success and efficacy of SMART COIL System coils in treating saccular intracranial aneurysms. METHODS: This subgroup analysis from the SMART registry included patients with saccular intracranial aneurysms treated using ≥75% SMART COIL System or PC400 coils. Baseline and procedural data, angiographic data, and clinical outcomes were collected. Predictors of catheter kickout, packing density, and postprocedural angiographic outcome were analyzed using multivariable regression models in saccular aneurysm cases. RESULTS: Between June 2016 and August 2018, the SMART registry enrolled 995 patients at 68 sites, of which 851 of 995 (85.5%) were treated for saccular aneurysms (mean age, 59.9 years). Aneurysms had a mean size of 6.8 mm, were wide neck in 63.1%, and ruptured in 31.0% of patients. Mean aneurysm packing density was 32.3%. Postprocedural Raymond-Roy Occlusion Classification (RROC) I-II was achieved in 80.3% of patients; smaller aneurysms, non-wide-neck aneurysms, and high packing density were predictive of RROC I-II. Overall, mean fluoroscopic time was 43.4 minutes, rate of reaccess attempts because of catheter kickout was 6.2%, and mean procedure time was 83.2 minutes. CONCLUSIONS: SMART COIL System coils achieved good technical success and adequate occlusion in treating saccular intracranial aneurysms in a real-world setting.

The SMART Registry: Long-Term Results on the Utility of the Penumbra SMART COIL System for Treatment of Intracranial Aneurysms and Other Malformations.

Introduction: Penumbra SMART COIL® (SMART) System is a novel generation embolic coil with varying stiffness. The study purpose was to report real-world usage of the SMART System in patients with intracranial aneurysms (ICA) and non-aneurysm vascular lesions. Materials and Methods: The SMART Registry is a post-market, prospective, multicenter registry requiring ≥75% Penumbra Coils, including SMART, PC400, and/or POD coils. The primary efficacy endpoint was retreatment rate at 1-year and the primary safety endpoint was the procedural device-related serious adverse event rate. Results: Between June 2016 and August 2018, 995 patients (mean age 59.6 years, 72.1% female) were enrolled at 68 sites in the U.S. and Canada. Target lesions were intracranial aneurysms in 91.0% of patients; 63.5% were wide-neck and 31.8% were ruptured. Adjunctive devices were used in 55.2% of patients. Mean packing density was 32.3%. Procedural device-related serious adverse events occurred in 2.6% of patients. The rate of immediate post-procedure adequate occlusion was 97.1% in aneurysms and the rate of complete occlusion was 85.2% in non-aneurysms. At 1-year, the retreatment rate was 6.8%, Raymond Roy Occlusion Classification (RROC) I or II was 90.0% for aneurysms, and Modified Rankin Scale (mRS) 0-2 was achieved in 83.1% of all patients. Predictors of 1-year for RROC III or retreatment (incomplete occlusion) were rupture status (P < 0.0001), balloon-assisted coiling (P = 0.0354), aneurysm size (P = 0.0071), and RROC III immediate post-procedure (P = 0.0086) in a model that also included bifurcation aneurysm (P = 0.7788). Predictors of aneurysm retreatment at 1-year was rupture status (P < 0.0001). Conclusions: Lesions treated with SMART System coils achieved low long-term retreatment rates. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT02729740.

An in vitro study of pressure increases during contrast injections in diagnostic cerebral angiography.

BACKGROUND: During diagnostic cerebral angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows. One potential, and serious complication is the re-rupture of aneurysms due to these injections. The goals of this in vitro study were to evaluate the effect of injection conditions on intraneurysmal pressure changes during angiography. METHODS: A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a physiologically accurate flow pump. Contrast injections were performed under different conditions (carotid or vertebral vessel imaging, catheter diameter, injection rate, injection time, and arterial blood flow rate) and the pressure in each aneurysm was recorded before and during each injection. The effect of injection conditions on percentage increase in aneurysm pressures was statistically assessed. Additionally, the effect of the distance between the aneurysm and the catheter-tip on aneurysmal pressures was assessed. RESULTS: Mean intraneurysmal pressures during injection (84.5 ± 10.8 mmHg) were significantly higher than pre-injection pressures (80.4 ± 10.6 mmHg, p < 0.0001). Only 3 of the 5 conditions - carotid injections, higher injection rates, and smaller catheter diameters - significantly increased intraneurysmal pressures. The catheter-tip distance showed no correlation to pressure increases. CONCLUSIONS: Increasing contrast injection rates and decreasing catheter diameters are correlated to intraneurysmal pressure increases during angiography irrespective of the distance to the catheter tip. Future in vivo studies are required to confirm these findings and determine whether the amplitude of pressure increases with commonly used injection rates can be clinically detrimental.

Stent-assisted coiling of cerebral aneurysms: multi-center analysis of radiographic and clinical outcomes in 659 patients.

INTRODUCTION: The endovascular stent-assisted coiling approach for the treatment of cerebral aneurysms is evolving rapidly with the availability of new stent devices. It remains unknown how each type of stent affects the safety and efficacy of the stent-coiling procedure. METHODS: This study compared the outcomes of endovascular coiling of cerebral aneurysms using Neuroform (NEU), Enterprise (EP), and Low-profile Visualized Intraluminal Support (LVIS) stents. Patient characteristics, treatment details and angiographic results using the Raymond-Roy grade scale (RRGS), and procedural complications were analyzed in our study. RESULTS: Our study included 659 patients with 670 cerebral aneurysms treated with stent-assisted coiling (NEU, n=182; EP, n=158; LVIS, n=330) that were retrospectively collected from six academic centers. Patient characteristics included mean age 56.3±12.1 years old, female prevalence 73.9%, and aneurysm rupture on initial presentation of 18.8%. We found differences in complete occlusion on baseline imaging, defined as RRGS I, among the three stents: LVIS 64.4%, 210/326; NEU 56.2%, 95/169; EP 47.6%, 68/143; P=0.008. The difference of complete occlusion on 10.5 months (mean) and 8 months (median) angiographic follow-up remained significant: LVIS 84%, 251/299; NEU 78%, 117/150; EP 67%, 83/123; P=0.004. There were 7% (47/670) intra-procedural complications and 11.5% (73/632) post-procedural-related complications in our cohort. Furthermore, procedure-related complications were higher in the braided-stents vs laser-cut, P=0.002. CONCLUSIONS: There was a great variability in techniques and choice of stent type for stent-assisted coiling among the participating centers. The type of stent was associated with immediate and long-term angiographic outcomes. Randomized prospective trials comparing the different types of stents are warranted.

Angiographic assessment of the efficacy of flow diverter treatment for cerebral aneurysms.

BACKGROUND: The recent growth of neuro-endovascular treatment has rekindled interest in the use of angiographic techniques for flow assessment. Aneurysm treatment with flow diverters is particularly amenable to such analysis. We analyze contrast time-density curves - recorded within aneurysms before (pre) and immediately after (post) flow diverter implantation to estimate six-month treatment outcomes. METHODS: Fifty-six patients with 65 aneurysms were treated with flow diverters at two institutions. A region of interest was drawn around the aneurysm perimeter in image sequences taken both pre and post angiography, and the temporal variation in grayscale intensity within the aneurysm (time-density curve) was recorded. Eleven parameters were quantified from each time-density curve. Aneurysm occlusion status was recorded six months post treatment. The change in parameters from pre to post treatment was statistically evaluated between aneurysm occluded and non-occluded groups. RESULTS: Of the 11 parameters, eight were significantly different before and immediately after flow diversion. Considering the entire data set, none of the parameters was statistically different between the occluded and non-occluded groups. However, subgroup analyses showed that four variables were significantly different between the aneurysm occluded and non-occluded groups. The sensitivity of these variables to predict aneurysm occlusion at six months ranged from 60% to 89%, while the specificity ranged from 55% to 70%. CONCLUSIONS: Device-induced intra-aneurysmal flow alterations quantified by simple aneurysmal time-density curves can potentially be used to predict long-term outcomes of flow diversion. Large multi-center studies will be required to confirm these findings. Patient-to-patient variability in coagulation may need to be incorporated for clinically relevant predictive values.

Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial.

BACKGROUND: Stent retriever thrombectomy of large-vessel occlusion results in better outcomes than medical therapy alone. Alternative thrombectomy strategies, particularly a direct aspiration as first pass technique, while promising, have not been rigorously assessed for clinical efficacy in randomised trials. We designed COMPASS to assess whether patients treated with aspiration as first pass have non-inferior functional outcomes to those treated with a stent retriever as first line. METHODS: We did a multicentre, randomised, open label, blinded outcome, core lab adjudicated non-inferiority trial at 15 sites (ten hospitals and four specialty clinics in the USA and one hospital in Canada). Eligible participants were patients presenting with acute ischaemic stroke from anterior circulation large-vessel occlusion within 6 h of onset and an Alberta Stroke Program Early CT Score of greater than 6. We randomly assigned participants (1:1) via a central web-based system without stratification to either direct aspiration first pass or stent retriever first line thrombectomy. Those assessing primary outcomes via clinical examinations were masked to group assignment as they were not involved in the procedures. Physicians were allowed to use adjunctive technology as was consistent with their standard of care. The null hypothesis for this study was that patients treated with aspiration as first pass achieve inferior outcomes compared with those treated with a stent retriever first line approach. The primary outcome was non-inferiority of clinical functional outcome at 90 days as measured by the percentage of patients achieving a modified Rankin Scale score of 0-2, analysed by intent to treat; non-inferiority was established with a margin of 0·15. All randomly assigned patients were included in the safety analyses. This trial is registered at ClinicalTrials.gov, number: NCT02466893. FINDINGS: Between June 1, 2015, and July 5, 2017, we assigned 270 patients to treatment: 134 to aspiration first pass and 136 to stent retriever first line. A modified Rankin score of 0-2 at 90 days was achieved by 69 patients (52%; 95% CI 43·8-60·3) in the aspiration group and 67 patients (50%; 41·6-57·4) in the stent retriever group, showing that aspiration as first pass was non-inferior to stent retriever first line (pnon-inferiority=0·0014). Intracranial haemorrhage occurred in 48 (36%) of 134 in the aspiration first pass group, and 46 (34%) of 135 in the stent retriever first line group. All-cause mortality at 3 months occurred in 30 patients (22%) in both groups. INTERPRETATION: A direct aspiration as first pass thrombectomy conferred non-inferior functional outcome at 90 days compared with stent retriever first line thrombectomy. This study supports the use of direct aspiration as an alternative to stent retriever as first-line therapy for stroke thrombectomy. FUNDING: Penumbra.

Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis.

Background and Purpose- Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods- This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ2 tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke. Results- Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory (P=0.14 for comparing the 3 groups, P=0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis (P=0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%). Conclusions- Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00576693.

In vitro measurement of the permeability of endovascular coils deployed in cerebral aneurysms.

BACKGROUND AND PURPOSE: Aneurysm recurrence is the primary limitation of endovascular coiling treatment for cerebral aneurysms. Coiling is currently quantified by a volumetric porosity measure called packing density (pd). Blood flow through a coil mass depends on the permeability of the coil mass, and not just its pd. The permeability of coil masses has not yet been quantified. Here we measure coil permeability with a traditional falling-head permeameter modified to incorporate idealized aneurysms. METHODS: Silicone replicas of idealized aneurysms were manufactured with three different aneurysm diameters (4, 5, and 8 mm). Four different coil types (Codman Trufill Orbit, Covidien Axium, Microvention Microplex 10, and Penumbra 400) were deployed into the aneurysms with a target pd of 35%. Coiled replicas were installed on a falling-head permeameter setup and the time taken for a column of fluid above the aneurysm to drop a certain height was recorded. Permeability of the samples was calculated based on a simple modification of the traditional permeameter equation to incorporate a spherical aneurysm. RESULTS: The targeted 35% pd was achieved for all samples (35%±1%, P=0.91). Coil permeabilities were significantly different from each other (P<0.001) at constant pd. Microplex 10 coils had the lowest permeability of all coil types. Data suggest a trend of increasing permeability with thicker coil wire diameter (not statistically significant). CONCLUSIONS: A simple in vitro setup was developed to measure the permeabilities of coil masses based on traditional permeametry. Coil permeability should be considered when evaluating the hemodynamic efficacy of coiling instead of just packing density. Coils made of thicker wires may be more permeable, and thus less effective, than coils made from thinner wires. Whether aneurysm recurrence is affected by coil wire diameter or permeability needs to be confirmed with clinical trials.

In vitro angiographic comparison of the flow-diversion performance of five neurovascular stents.

Background and purpose Data differentiating flow diversion properties of commercially available low- and high-porosity stents are limited. This in vitro study applies angiographic analysis of intra-aneurysmal flow to compare the flow-diversion performance of five neurovascular devices in idealized sidewall and bifurcation aneurysm models. Methods Five commercial devices (Enterprise, Neuroform, LVIS, FRED, and Pipeline) were implanted in silicone sidewall and bifurcation aneurysm models under physiological average flow of blood analog fluid. High-speed angiographic images were acquired pre- and post-device implantation and contrast concentration-time curves within the aneurysm were recorded. The curves were quantified with five parameters to assess changes in contrast transport, and thus aneurysm hemodynamics, due to each device. Results Inter-device flow-diversion performance was more easily distinguished in the sidewall model than the bifurcation model. There were no obvious overall statistical trends in the bifurcation parameters but the Pipeline performed marginally better than the other devices. In the sidewall geometry, overall evidence suggests that the LVIS performed better than the Neuroform and Enterprise. The Pipeline and FRED devices were statistically superior to the three stents and Pipeline was superior to FRED in all sidewall parameters evaluated. Conclusions Based on this specific set of experiments, lower-porosity flow diverters perform significantly better in reducing intra-aneurysmal flow activity than higher-porosity stents in sidewall-type geometries. The LVIS device is potentially a better flow diverter than the Neuroform and Enterprise devices, while the Pipeline is potentially better than the FRED.

Long-Term Clinical and Angiographic Outcomes Following Pipeline Embolization Device Treatment of Complex Internal Carotid Artery Aneurysms: Five-Year Results of the Pipeline for Uncoilable or Failed Aneurysms Trial.

BACKGROUND: Early and mid-term safety and efficacy of aneurysm treatment with the Pipeline Embolization Device (PED) has been well demonstrated in prior studies. OBJECTIVE: To present 5-yr follow-up for patients treated in the Pipeline for Uncoilable or Failed Aneurysms clinical trial. METHODS: In our prospective, multicenter trial, 109 complex internal carotid artery (ICA) aneurysms in 107 subjects were treated with the PED. Patients were followed per a standardized protocol at 180 d and 1, 3, and 5 yr. Aneurysm occlusion, in-stent stenosis, modified Rankin Scale scores, and complications were recorded. RESULTS: The primary endpoint of complete aneurysm occlusion at 180 d (73.6%) was previously reported. Aneurysm occlusion for those patients with angiographic follow-up progressively increased over time to 86.8% (79/91), 93.4% (71/76), and 95.2% (60/63) at 1, 3, and 5 yr, respectively. Six aneurysms (5.7%) were retreated. New serious device-related events at 1, 3, and 5 yr were noted in 1% (1/96), 3.5% (3/85), and 0% (0/81) of subjects. There were 4 (3.7%) reported deaths in our trial. Seventy-eight (96.3%) of 81 patients with 5-yr clinical follow-up had modified Rankin Scale scores ≤2. No delayed neurological deaths or hemorrhagic or ischemic cerebrovascular events were reported beyond 6 mo. No recanalization of a previously occluded aneurysm was observed. CONCLUSION: Our 5-yr findings demonstrate that PED is a safe and effective treatment for large and giant wide-necked aneurysms of the intracranial ICA, with high rates of complete occlusion and low rates of delayed adverse events.

Pipeline for uncoilable or failed aneurysms: 3-year follow-up results.

OBJECTIVE The long-term effectiveness of endovascular treatment of large and giant wide-neck aneurysms using traditional endovascular techniques has been disappointing, with high recanalization and re-treatment rates. Flow diversion with the Pipeline Embolization Device (PED) has been recently used as a stand-alone therapy for complex aneurysms, showing significant improvement in effectiveness while demonstrating a similar safety profile to stent-supported coil treatment. However, relatively little is known about its long-term safety and effectiveness. Here the authors report on the 3-year safety and effectiveness of flow diversion with the PED in a prospective cohort of patients with large and giant internal carotid artery aneurysms enrolled in the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. METHODS The PUFS trial is a prospective study of 107 patients with 109 aneurysms treated with the PED. Primary effectiveness and safety end points were demonstrated based on independently monitored 180-day clinical and angiographic data. Patients were enrolled in a long-term follow-up protocol including 1-, 3-, and 5-year clinical and imaging follow-up. In this paper, the authors report the midstudy (3-year) effectiveness and safety data. RESULTS At 3 years posttreatment, 74 subjects with 76 aneurysms underwent catheter angiography as required per protocol. Overall, complete angiographic aneurysm occlusion was observed in 71 of these 76 aneurysms (93.4% cure rate). Five aneurysms were re-treated, using either coils or additional PEDs, for failure to occlude, and 3 of these 5 were cured by the 3-year follow-up. Angiographic cure with one or two treatments of Pipeline embolization alone was therefore achieved in 92.1%. No recanalization of a previously completely occluded aneurysm was noted on the 3-year angiograms. There were 3 (2.6%) delayed device- or aneurysm-related serious adverse events, none of which led to permanent neurological sequelae. No major or minor late-onset hemorrhagic or ischemic cerebrovascular events or neurological deaths were observed in the 6-month through 3-year posttreatment period. Among 103 surviving patients, 85 underwent functional outcome assessment in which modified Rankin Scale scores of 0-1 were demonstrated in 80 subjects. CONCLUSIONS Pipeline embolization is safe and effective in the treatment of complex large and giant aneurysms of the intracranial internal carotid artery. Unlike more traditional endovascular treatments, flow diversion results in progressive vascular remodeling that leads to complete aneurysm obliteration over longer-term follow-up without delayed aneurysm recanalization and/or growth. Clinical trial registration no.: NCT00777088 (clinicaltrials.gov).

Hemodynamics of Flow Diverters.

Cerebral aneurysms are pathological focal evaginations of the arterial wall at and around the junctions of the circle of Willis. Their tenuous walls predispose aneurysms to leak or rupture leading to hemorrhagic strokes with high morbidity and mortality rates. The endovascular treatment of cerebral aneurysms currently includes the implantation of fine-mesh stents, called flow diverters, within the parent artery bearing the aneurysm. By mitigating flow velocities within the aneurysmal sac, the devices preferentially induce thrombus formation in the aneurysm within hours to days. In response to the foreign implant, an endothelialized arterial layer covers the luminal surface of the device over a period of days to months. Organization of the intraneurysmal thrombus leads to resorption and shrinkage of the aneurysm wall and contents, eventually leading to beneficial remodeling of the pathological site to a near-physiological state. The devices' primary function of reducing flow activity within aneurysms is corollary to their mesh structure. Complete specification of the device mesh structure, or alternately device permeability, necessarily involves the quantification of two variables commonly used to characterize porous media-mesh porosity and mesh pore density. We evaluated the flow alteration induced by five commercial neurovascular devices of varying porosity and pore density (stents: Neuroform, Enterprise, and LVIS; flow diverters: Pipeline and FRED) in an idealized sidewall aneurysm model. As can be expected in such a model, all devices substantially reduced intraneurysmal kinetic energy as compared to the nonstented case with the coarse-mesh stents inducing a 65-80% reduction whereas the fine-mesh flow diverters induced a near-complete flow stagnation (∼98% reduction). We also note a trend toward greater device efficacy (lower intraneurysmal flow) with decreasing device porosity and increasing device pore density. Several such flow studies have been and are being conducted in idealized as well as patient-derived geometries with the overarching goals of improving device design, facilitating treatment planning (what is the optimal device for a specific aneurysm), and predicting treatment outcome (will a specific aneurysm treated with a specific device successfully occlude over the long term). While the results are generally encouraging, there is poor standardization of study variables between different research groups, and any consensus will only be reached after standardized studies are conducted on collectively large datasets. Biochemical variables may have to be incorporated into these studies to maximize predictive values.

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

BACKGROUND AND PURPOSE: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. METHODS: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. RESULTS: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. CONCLUSIONS: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Neuroophthalmological outcomes associated with use of the Pipeline Embolization Device: analysis of the PUFS trial results.

OBJECT: Neuroophthalmological morbidity is commonly associated with large and giant cavernous and supraclinoid internal carotid artery (ICA) aneurysms. The authors sought to evaluate the neuroophthalmological outcomes after treatment of these aneurysms with the Pipeline Embolization Device (PED). METHODS: The Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial was an international, multicenter prospective trial evaluating the safety and efficacy of the PED. All patients underwent complete neuroophthalmological examinations both before the PED procedure and at a 6-month follow-up. All examinations were performed for the purpose of this study and according to study criteria. RESULTS: In total, 108 patients were treated in the PUFS trial, 98 of whom had complete neuroophthalmological follow-up. Of the patients with complete follow-up, 39 (40%) presented with a neuroophthalmological baseline deficit that was presumed to be attributable to the aneurysm, and patients with these baseline deficits had significantly larger aneurysms. In 25 of these patients (64%), the baseline deficit showed at least some improvement 6 months after PED treatment, whereas in 1 patient (2.6%), the deficits only worsened. In 5 patients (5%), new deficits had developed at the 6-month follow-up, while in another 6 patients (6%), deficits that were not originally assumed to be related to the aneurysm had improved by that time. A history of diabetes was associated with failure of the baseline deficits to improve after the treatment. The aneurysm maximum diameter was significantly larger in patients with a new deficit or a worse baseline deficit at 6 months postprocedure. CONCLUSIONS: Patients treated with the PED for large and giant ICA aneurysms had excellent neuroophthalmological outcomes 6 months after the procedure, with deficits improving in most of the patients, very few deficits worsening, and few new deficits developing.

A meta-analysis of prospective randomized controlled trials evaluating endovascular therapies for acute ischemic stroke.

INTRODUCTION: A recent randomized controlled trial (RCT), the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), demonstrated better outcomes with endovascular treatment compared with medical therapy for acute ischemic stroke (AIS). However, previous trials have provided mixed results regarding the efficacy of endovascular treatment for AIS. A meta-analysis of all available trial data was performed to summarize the available evidence. METHODS: A literature search was performed to identify all prospective RCTs comparing endovascular therapies with medical management for AIS. Two datasets were created: (1) all patients randomized after confirmation of large vessel occlusion (LVO) (consistent with the contemporary standard of practice at the majority of centers); and (2) all patients with outcome data who underwent randomization regardless of qualifying vascular imaging. The pre-specified primary outcome measure was modified Rankin Scale score of 0-2 at 90 days. A fixed-effect model was used to determine significance. RESULTS: Five prospective RCTs comparing endovascular therapies with medical management were included in dataset 1 (1183 patients) and six were included in dataset 2 (1903 total patients). Endovascular therapies were associated with significantly improved outcomes compared with medical management (OR 1.67, 95% CI 1.29 to 1.16, p=0.0001) for patients with LVO (dataset 1). This benefit persisted when patients from all six RCTs were included, even in the absence of confirmation of LVO (OR 1.27, 95% CI 1.05 to 1.54, p=0.019; dataset 2). CONCLUSIONS: A meta-analysis of prospective RCTs comparing endovascular therapies with medical management demonstrates superior outcomes in patients randomized to endovascular therapy.

Evidence-based clinical practice for the neurointerventionalist.

The field of neurointerventional (NI) surgery has developed in the context of technologic innovation. Many treatments readily provided in 2014 would have been hard to imagine as recently as 10 years ago. The reality of present day NI care is that, while providers, payors, policy makers and patients rely on evidence to guide NI decision-making, the available data are often less robust than participants might desire. In this paper we will explore the fundamentals of evidence-based clinical practice.