A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Quantitative analysis of thrombus migration before mechanical thrombectomy: Determinants and relationship with procedural and clinical outcomes.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS) and a large vessel occlusion (LVO), thrombus migration (T-Mig) is a common phenomenon before mechanical thrombectomy (MT), revealed by pre-treatment imaging. Previous works have used qualitative scales to define T-Mig. The aim of this study was to evaluate the determinants and impact of quantitatively assessed T-Mig on procedural characteristics and clinical outcome. METHODS: Consecutive patients with AIS due to LVO treated by MT at a reference academic hospital were analysed. Distance between vessel origin and beginning of the thrombus on MRI (3D-time-of-flight and/or contrast-enhanced magnetic-resonance-angiography) and digital-substracted-angiography (DSA) were measured in millimeters using a curve tool. Thrombus migration was defined quantitatively as ∆TD calculated as the difference between pre-MT-DSA and MRI thrombus location. ∆TD was rated as significant if above 5mm. RESULTS: A total of 267 patients were included (mean age 70±12 years; 46% females) were analyzed. Amongst them, 65 (24.3%) experienced any degree of T-Mig. T-Mig was found to be associated with iv-tPA administration prior to thrombectomy (ß-estimate 2.52; 95% CI [1.25-3.79]; p<0.001), fewer device passes during thrombectomy (1.22±1.31 vs 1.66±0.99; p<0.05), and shorter pre-treatment thrombi (ß-estimate -0.1millimeter; 95% CI [-0.27-0.07]; p<0.05). There was no association between T-Mig and a favourable outcome (defined by a 0-to-2 modified-Rankin-Scale at 3months, adjusted OR: 2.16 [0.93 - 5.02]; p=0.06) CONCLUSION: Thrombus migration happens in almost a fourth of our study sample, and its quantitative extent was associated with iv-tPA administration prior to MT, but not with clinical outcome.

Stroke Imaging Selection Modality and Endovascular Therapy Outcomes in the Early and Extended Time Windows.

BACKGROUND AND PURPOSE: Advanced imaging has been increasingly used for patient selection in endovascular stroke therapy. The impact of imaging selection modality on endovascular stroke therapy clinical outcomes in extended time window remains to be defined. We aimed to study this relationship and compare it to that noted in early-treated patients. METHODS: Patients from a prospective multicentric registry (n=2008) with occlusions involving the intracranial internal carotid or the M1- or M2-segments of the middle cerebral arteries, premorbid modified Rankin Scale score 0 to 2 and time to treatment 0 to 24 hours were categorized according to treatment times within the early (0-6 hour) or extended (6-24 hour) window as well as imaging modality with noncontrast computed tomography (NCCT)±CT angiography (CTA) or NCCT±CTA and CT perfusion (CTP). The association between imaging modality and 90-day modified Rankin Scale, analyzed in ordinal (modified Rankin Scale shift) and dichotomized (functional independence, modified Rankin Scale score 0-2) manner, was evaluated and compared within and across the extended and early windows. RESULTS: In the early window, 332 patients were selected with NCCT±CTA alone while 373 also underwent CTP. After adjusting for identifiable confounders, there were no significant differences in terms of 90-day functional disability (ordinal shift: adjusted odd ratio [aOR], 0.936 [95% CI, 0.709-1.238], P=0.644) or independence (aOR, 1.178 [95% CI, 0.833-1.666], P=0.355) across the CTP and NCCT±CTA groups. In the extended window, 67 patients were selected with NCCT±CTA alone while 180 also underwent CTP. No significant differences in 90-day functional disability (aOR, 0.983 [95% CI, 0.81-1.662], P=0.949) or independence (aOR, 0.640 [95% CI, 0.318-1.289], P=0.212) were seen across the CTP and NCCT±CTA groups. There was no interaction between the treatment time window (0-6 versus 6-24 hours) and CT selection modality (CTP versus NCCT±CTA) in terms of functional disability at 90 days (P=0.45). CONCLUSIONS: CTP acquisition was not associated with better outcomes in patients treated in the early or extended time windows. While confirmatory data is needed, our data suggests that extended window endovascular stroke therapy may remain beneficial even in the absence of advanced imaging.

Quantitative evaluation of WEB shape modification: A five-year follow-up study.

BACKGROUND AND PURPOSE: Web shape modification (WSM) has previously been associated with aneurysm recurrence. We report here our five-year experience of WEB device use with a quantitative approach of the WSM phenomenon. METHODS: From July 2012 to July 2017, 50 patients with 51 unruptured aneurysms treated with the WEB device have been prospectively enrolled in our data base and retrospectively analyzed. An independent "core lab" evaluated anatomical results and potential WSM in DSA follow-up. We defined the WSM ratio (WSMr) as a relative index between the height and the width of the device in working projections which gave an evaluation of the device deformation over the time. RESULTS: During the total follow-up period, WSM was observed in 35/48 aneurysms (72.9%). Adequate occlusion rates were 87.0% and 92.6% with and without WSM respectively (P = 0.65). 30 out the 35 (85.7%) shape modifications were already noticed at short-term follow-up (6-month DSA). 33 patients had 2 DSA controls and WSMr measurements were available in 24 patients: 18 (75%) with WSM and 6 (25%) without WSM. In the group with WSM, WSMr values were 0.80 in post-embolization, 0.52 at the first DSA angiogram and 0.42 at the second DSA angiogram. CONCLUSION: WEB shape modification was observed in more than half of cases but with no influence regarding adequate occlusion rate. This quantitative approach of WSM highlights that this phenomenon appears to be early and progressive over time. This supports the hypothesis that WSM could be more probably related to aneurysm healing rather than external compression.

Thrombus Length Predicts Lack of Post-Thrombolysis Early Recanalization in Minor Stroke With Large Vessel Occlusion.

Background and Purpose- Whether bridging therapy, that is, intravenous thrombolysis [IVT] followed by mechanical thrombectomy, is beneficial as compared with IVT alone in minor stroke (National Institutes of Health Stroke Scale ≤5) with large vessel occlusion is unknown and should be tested in randomized trials. To help select the most appropriate candidates for such trials, we aimed to identify strong predictors of lack of post-IVT early recanalization (ER)-a surrogate marker of poor outcome. Methods- From a large multicenter French registry of patients with large vessel occlusion referred for thrombectomy immediately after IVT start between 2015 and 2017, we extracted 97 minor strokes with ER evaluated on first angiographic run or noninvasive imaging ≤3 hours from IVT start. Thrombus length was measured using the susceptibility vessel sign on T2* imaging. Results- Median National Institutes of Health Stroke Scale was 3 (interquartile range, 2-4), and occlusion sites were proximal (intracranial carotid or M1) and distal (M2) in 50% and 50% of patients, respectively. On pre-IVT MRI, median length of susceptibility vessel sign (visible in 90%) was 9.2 mm (interquartile range, 7.4-13.3). ER was present in 34% of patients, and susceptibility vessel sign length was the only clinical or radiological variable associated with no-ER after stepwise variable selection into a multivariable model (odds ratio, 1.53 per 1-mm increase; 95% CI, 1.21-1.92; P<0.001). The C statistic of susceptibility vessel sign length for no-ER prediction was 0.82 (95% CI, 0.73-0.92), and the optimal cutoff (Youden) was 9 mm. Sensitivity and specificity of this cutoff for no-ER were 67.8% (95% CI, 55.9-79.7) and 84.6% (95% CI, 70.7-98.5), respectively. Conclusions- ER was frequent in this cohort of IVT-treated minor stroke patients with large vessel occlusion considered for thrombectomy, and thrombus length was a powerful independent predictor of no-ER. These findings may help design randomized trials aiming to test bridging therapy versus IVT alone in this population.

Primary Results of the Multicenter ARISE II Study (Analysis of Revascularization in Ischemic Stroke With EmboTrap).

BACKGROUND AND PURPOSE: EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke secondary to large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy compared with established stent retrievers. METHODS: ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0-2) and all-cause mortality at 90 days. RESULTS: Between October 2015 and February 2017, 227 patients were enrolled and treated with the EmboTrap device. The primary efficacy end point (mTICI ≥2b within 3 passes) was achieved in 80.2% (95% confidence interval, 74%-85% versus 56% performance goal criterion; P value, <0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was achieved in 76%, and mTICI ≥2b was 92.5%. The rate of first pass (mTICI ≥2b following a single pass) was 51.5%. The primary safety end point composite rate of symptomatic intracerebral hemorrhage or serious adverse device effects was 5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%, respectively. CONCLUSIONS: The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02488915.

Post-Thrombolysis Recanalization in Stroke Referrals for Thrombectomy: Incidence, Predictors, and Prediction Scores.

Background and Purpose­Whether all acute stroke patients with large vessel occlusion need to undergo intravenous thrombolysis before mechanical thrombectomy (MT) is debated as (1) the incidence of post-thrombolysis early recanalization (ER) is still unclear; (2) thrombolysis may be harmful in patients unlikely to recanalize; and, conversely, (3) transfer for MT may be unnecessary in patients highly likely to recanalize. Here, we determined the incidence and predictors of post-thrombolysis ER in patients referred for MT and derive ER prediction scores for trial design. Methods­Registries from 4 MT-capable centers gathering patients referred for MT and thrombolyzed either on site (mothership) or in a non MT-capable center (drip-and-ship) after magnetic resonance­ or computed tomography­based imaging between 2015 and 2017. ER was identified on either first angiographic run or noninvasive imaging. In the magnetic resonance imaging subsample, thrombus length was determined on T2*-based susceptibility vessel sign. Independent predictors of no- ER were identified using multivariable logistic regression models, and scores were developed according to the magnitude of regression coefficients. Similar registries from 4 additional MT-capable centers were used as validation cohort. Results­In the derivation cohort (N=633), ER incidence was ≈20%. In patients with susceptibility vessel sign (n=498), no-ER was independently predicted by long thrombus, proximal occlusion, and mothership paradigm. A 6-point score derived from these variables showed strong discriminative power for no-ER (C statistic, 0.854) and was replicated in the validation cohort (n=353; C statistic, 0.888). A second score derived from the whole sample (including negative T2* or computed tomography­based imaging) also showed good discriminative power and was similarly validated. Highest grades on both scores predicted no-ER with >90% specificity, whereas low grades did not reliably predict ER. Conclusions­The substantial ER rate underlines the benefits derived from thrombolysis in bridging populations. Both prediction scores afforded high specificity for no-ER, but not for ER, which has implications for trial design.

Wall shear stress distribution of small aneurysms prone to rupture: a case-control study.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage after intracranial aneurysm rupture remains a serious condition. We performed a case-control study to evaluate the use of computed hemodynamics to detect cerebral aneurysms prone to rupture. METHODS: Four patients with incidental aneurysms that ultimately ruptured (cases) were studied after initially being included in a prospective database including their 3-dimensional imaging before rupture. Ruptures were located in different arterial segments: M1 segment of the middle cerebral artery; basilar tip; posterior inferior cerebellar artery; and anterior communicating artery. For each case, 5 controls matched by location and size were randomly selected. An empirical cumulative distribution function of aneurysm wall shear stress percentiles was evaluated for every case and used to define a critical prone-to-rupture range. Univariate logistic regression analysis was then used to assess the individual risk of rupture. RESULTS: A cumulative wall shear stress distribution characterizing a hemodynamic prone-to-rupture range for small-sized aneurysms was identified and fitted independent of the location. Sensitivity and specificity of the preliminary tests were 90% and 93%, respectively. CONCLUSIONS: The wall shear stress cumulative probability function may be a potential predictor of small-sized aneurysm rupture.

Modification of Woven Endo-Bridge After Intracranial Aneurysm Treatment: A Methodology for Three-Dimensional Analysis of Shape and Relative Position Changes.

During follow-up of patients treated with WEB devices, shape changes have been observed. The quantitative three-dimensional measurement of the WEB shape modification (WSM) would offer useful information to be studied in association with the anatomical results and try to better understand mechanisms implicated in this modification phenomenon. We present a methodology to quantify the morphology and position of the WEB device in relation to the vascular anatomy. Three-dimensional rotational angiography (3DRA) images of seven aneurysms patients treated with WEBs were used, which also accompanied by a post-treatment 3DRA image and a follow-up 3DRA image. The device was manually segmented, obtaining the 3D models after treatment and at the follow-up. Volume, surface area, height, maximum diameter and WSM ratio of both surfaces were calculated. Position changes were evaluated measuring WEB axis and relative position between post-treatment and follow-up. Changes in WEB volume and surface area were observed with a mean modification of - 5.04 % ( ± 14.19 ) and - 1.68 % ( ± 8.29 ) , respectively. The positional variables also showed differences, mean change of device axis direction was 26.25 % ( ± 24.09 ) and mean change of distance l b was 5.87 % ( ± 10.59 ) . Inter-observer and intra-observer variability analyses did not show differences (ANOVA p > 0.05 ). This methodology allows quantifying the morphological and position changes suffered by the WEB device after treatment, offering new information to be studied in relation to the occurrence of WEB shape modification.

Intraoperative angiography reloaded: a new hybrid operating theater for combined endovascular and surgical treatment of cerebral arteriovenous malformations: a pilot study on 25 patients.

BACKGROUND: Multimodality treatment suites for patients with cerebral arteriovenous malformations (AVM) have recently become available. This study was designed to evaluate feasibility, safety and impact on treatment of a new intraoperative flat-panel (FP) based integrated surgical and imaging suite for combined endovascular and surgical treatment of cerebral AVM. METHODS: Twenty-five patients with AVMs to treat with combined endovascular and surgical interventions were prospectively enrolled in this consecutive case series. The hybrid suite allows combined endovascular and surgical approaches with intraoperative scanner-like imaging (XperCT®) and intraoperative 3D rotational angiography (3D-RA). The impact of intraoperative multimodal imaging on feasibility, workflow of combined interventions, surgery, and unexpected imaging findings were analyzed. RESULTS: Twenty-five patients (mean age 38 ± 18.6 year) with a median Spetzler-Martin grade 2 AVM (range 1-4) underwent combined endovascular and surgical procedures. Sixteen patients presented with a ruptured AVM and nine with an unruptured AVM. In 16 % (n = 4) of cases, intraoperative imaging visualized AVM remnants ≤3 mm and allowed for completion of the resections in the same sessions. Complete resection was confirmed in all n = 16 patients who had follow-up angiography one year after surgery so far. All diagnostic and therapeutical steps, including angiographic control, were performed without having to move the patients CONCLUSION: The hybrid neurointerventional suite was shown to be a safe and useful setup which allowed for unconstrained combined microsurgical and neuroradiological workflow. It reduces the need for extraoperative angiographic controls and subsequent potential surgical revisions a second time, as small AVM remnants can be detected with high security.

Comparative Study of Automated Algorithms for Brain Arteriovenous Malformation Nidus Extent Identification Using 3DRA.

PURPOSE: When performing a brain arteriovenous malformation (bAVMs) intervention, computer-assisted analysis of bAVMs can aid clinicians in planning precise therapeutic alternatives. Therefore, we aim to assess currently available methods for bAVMs nidus extent identification over 3DRA. To this end, we establish a unified framework to contrast them over the same dataset, fully automatising the workflows. MATERIALS AND METHODS: We retrospectively collected contrast-enhanced 3DRA scans of patients with bAVMs. A segmentation network was used to automatically acquire the brain vessels segmentation for each case. We applied the nidus extent identification algorithms over each of the segmentations, computing overlap measurements against manual nidus delineations. RESULTS: We evaluated the methods over a private dataset with 22 3DRA scans of individuals with bAVMs. The best-performing alternatives resulted in [Formula: see text] and [Formula: see text] dice coefficient values. CONCLUSIONS: The mathematical morphology-based approach showed higher robustness through inter-case variability. The skeleton-based approach leverages the skeleton topomorphology characteristics, while being highly sensitive to anatomical variations and the skeletonisation method employed. Overall, nidus extent identification algorithms are also limited by the quality of the raw volume, as the consequent imprecise vessel segmentation will hinder their results. Performance of the available alternatives remains subpar. This analysis allows for a better understanding of the current limitations.

A multiscale computational framework to evaluate flow alterations during mechanical thrombectomy for treatment of ischaemic stroke.

The treatment of ischaemic stroke increasingly relies upon endovascular procedures known as mechanical thrombectomy (MT), which consists in capturing and removing the clot with a catheter-guided stent while at the same time applying external aspiration with the aim of reducing haemodynamic loads during retrieval. However, uniform consensus on procedural parameters such as the use of balloon guide catheters (BGC) to provide proximal flow control, or the position of the aspiration catheter is still lacking. Ultimately the decision is left to the clinician performing the operation, and it is difficult to predict how these treatment options might influence clinical outcome. In this study we present a multiscale computational framework to simulate MT procedures. The developed framework can provide quantitative assessment of clinically relevant quantities such as flow in the retrieval path and can be used to find the optimal procedural parameters that are most likely to result in a favorable clinical outcome. The results show the advantage of using BGC during MT and indicate small differences between positioning the aspiration catheter in proximal or distal locations. The framework has significant potential for future expansions and applications to other surgical treatments.

Outcome study of the Pipeline Vantage Embolization Device (second version) in unruptured (and ruptured) aneurysms (PEDVU(R) study).

BACKGROUND: The Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate safety and efficacy outcomes. Primary and secondary objectives were to determine outcomes for unruptured and ruptured cohorts, respectively. METHODS: In this multicenter retrospective and prospective study, we analyzed outcome data from eight centers using core laboratory assessments. We determined 30-day and ≥3-month mortality and morbidity rates, and 6- and 18-month radiographic aneurysm occlusion rates for procedures performed during the period July 2021-March 2023. RESULTS: We included 121 consecutive patients with 131 aneurysms. The adequate occlusion rate for the unruptured cohort at short-term and medium-term follow up, and also for the ruptured cohort at short-term follow up, was >90%. Two aneurysms (1.5%) underwent retreatment. When mortality attributed to a palliative case in the unruptured cohort, or subarachnoid hemorrhage in the ruptured cohort, was excluded then the overall major adverse event rate in respective cohorts was 7.5% and 23.5%, with 0% mortality rates for each. When all event causes were included on an intention-to-treat basis, the major adverse event rates in respective cohorts were 8.3% and 40.9%, with 0.9% and 22.7% mortality rates. CONCLUSIONS: For unruptured aneurysm treatment, the second PEDV version appears to have a superior efficacy and similar safety profile to previous-generation PEDs. These are acceptable outcomes in this pragmatic and non-industry-sponsored study. Analysis of ruptured aneurysm outcomes is limited by cohort size. Further prospective studies, particularly for ruptured aneurysms, are needed.

What is a Challenging Clot? : A DELPHI Consensus Statement from the CLOTS 7.0 Summit.

BACKGROUND: Predicting a challenging clot when performing mechanical thrombectomy in acute stroke can be difficult. One reason for this difficulty is a lack of agreement on how to precisely define these clots. We explored the opinions of stroke thrombectomy and clot research experts regarding challenging clots, defined as difficult to recanalize clots by endovascular approaches, and clot/patient features that may be indicative of such clots. METHODS: A modified DELPHI technique was used before and during the CLOTS 7.0 Summit, which included experts in thrombectomy and clot research from different specialties. The first round included open-ended questions and the second and final rounds each consisted of 30 closed-ended questions, 29 on various clinical and clot features, and 1 on number of passes before switching techniques. Consensus was defined as agreement ≥ 50%. Features with consensus and rated ≥ 3 out of 4 on the certainty scale were included in the definition of a challenging clot. RESULTS: Three DELPHI rounds were performed. Panelists achieved consensus on 16/30 questions, of which 8 were rated 3 or 4 on the certainty scale, namely white-colored clots (mean certainty score 3.1), calcified clots under histology (3.7) and imaging (3.7), stiff clots (3.0), sticky/adherent clots (3.1), hard clots (3.1), difficult to pass clots (3.1) and clots that are resistant to pulling (3.0). Most panelists considered switching endovascular treatment (EVT) techniques after 2-3 unsuccessful attempts. CONCLUSION: This DELPHI consensus identified 8 distinct features of a challenging clot. The varying degree of certainty amongst the panelists emphasizes the need for more pragmatic studies to enable accurate a priori identification of such occlusions prior to EVT.

CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS): 12-month angiographic results of a multicenter study.

BACKGROUND: The CLinical Assessment of WEB device in Ruptured aneurYSms (CLARYS) study has shown that the endovascular treatment of ruptured bifurcation aneurysms with the Woven EndoBridge (WEB) is safe and effective and provides protection against rebleeding at 1 month and 1 year. The 12-month angiographic follow-up is an important endpoint of the study. METHODS: The CLARYS study is a prospective multicenter study conducted in 13 European centers. The study enrolled 60 patients with 60 ruptured aneurysms of the anterior and posterior circulation. The study was conducted with an independent assessment of safety outcomes and imaging. RESULTS: Sixty patients with 60 ruptured bifurcation aneurysms to be treated with the WEB were included. Fifty-three aneurysms (88.3%) had a broad base with a dome to neck ratio <2 (mean 1.6). Of these, 46 patients were evaluated by an independent core laboratory with follow-up imaging performed at 12 months or before eventual retreatment. At 1 year, 19/46 aneurysms (41.3%) were completely occluded (Raymond-Roy grade I), 21/46 (45.7%) had a residual neck and 6/46 (13.0%) had residual aneurysm filling. Adequate occlusion was reported in 40/46 (87%) aneurysms. Six patients underwent target aneurysm retreatment. CONCLUSIONS: The CLARYS study has previously shown that the use of the WEB in the endovascular treatment of ruptured bifurcation aneurysms provides effective protection against rebleeding with a good safety profile. The angiographic occlusion rates at 1 year reported here are comparable to those already seen in previous multicenter studies which primarily included unruptured aneurysms.

Determining Clinically-Viable Biomarkers for Ischaemic Stroke Through a Mechanistic and Machine Learning Approach.

Assessment of distal cerebral perfusion after ischaemic stroke is currently only possible through expensive and time-consuming imaging procedures which require the injection of a contrast medium. Alternative approaches that could indicate earlier the impact of blood flow occlusion on distal cerebral perfusion are currently lacking. The aim of this study was to identify novel biomarkers suitable for clinical implementation using less invasive diagnostic techniques such as Transcranial Doppler (TCD). We used 1D modelling to simulate pre- and post-stroke velocity and flow wave propagation in a typical arterial network, and Sobol's sensitivity analysis, supported by the use of Gaussian process emulators, to identify biomarkers linked to cerebral perfusion. We showed that values of pulsatility index of the right anterior cerebral artery > 1.6 are associated with poor perfusion and may require immediate intervention. Three additional biomarkers with similar behaviour, all related to pulsatility indices, were identified. These results suggest that flow pulsatility measured at specific locations could be used to effectively estimate distal cerebral perfusion rates, and ultimately improve clinical diagnosis and management of ischaemic stroke.

Simulation of intra-saccular devices for pre-operative device size selection: Method and validation for sizing and porosity simulation.

Intra-saccular devices (ID) are novel braided devices used for complex intracranial aneurysms treatment. Treatment success is associated with correct device size selection. A technique that predicts the ID size within the aneurysm before intervention will provide a powerful computational tool to aid the interventionist during device selection. We present a method to calculate the device's final height, radial expansion and porosity within the patient's anatomy, which allows assessing different device sizes before treatment takes place. The proposed sizing technique was tested in-vitro and in real patient's geometries obtained from 3DRA angiographic images of 8 unruptured aneurysms previously treated with IDs. The obtained simulated height was compared to the real height, with a mean error of less than 0.28 mm (±0.44). The porosity calculation method was tested in-vitro with an error of 0.02 (±0.022). The results of both sizing and porosity experiments resemble well measures from real patients. This methodology could be used before treatment to provide the interventionist with additional information that allows selecting the device that best fits the patient's aneurysm to be treated.

Influence of time to endovascular stroke treatment on outcomes in the early versus extended window paradigms.

BACKGROUND: The effect of time from stroke onset to thrombectomy in the extended time window remains poorly characterized. AIM: We aimed to analyze the relationship between time to treatment and clinical outcomes in the early versus extended time windows. METHODS: Proximal anterior circulation occlusion patients from a multicentric prospective registry were categorized into early (≤6 h) or extended (>6-24 h) treatment window. Patients with baseline National Institutes of Health Stroke Scale (NIHSS) ≥ 10 and intracranial internal carotid artery or middle cerebral artery-M1-segment occlusion and pre-morbid modified Rankin scale (mRS) 0-1 ("DAWN-like" cohort) served as the population for the primary analysis. The relationship between time to treatment and 90-day mRS, analyzed in ordinal (mRS shift) and dichotomized (good outcome, mRS 0-2) fashion, was compared within and across the extended and early windows. RESULTS: A total of 1603 out of 2008 patients qualified. Despite longer time to treatment (9[7-13.9] vs. 3.4[2.5-4.3] h, p < 0.001), extended-window patients (n = 257) had similar rates of symptomatic intracranial hemorrhage (sICH; 0.8% vs. 1.7%, p = 0.293) and 90-day-mortality (10.5% vs. 9.6%, p = 0.714) with only slightly lower rates of 90-day good outcomes (50.4% vs. 57.6%, p = 0.047) versus early-window patients (n = 709). Time to treatment was associated with 90-day disability in both ordinal (adjusted odd ratio (aOR), ≥ 1-point mRS shift: 0.75; 95%CI [0.66-0.86], p < 0.001) and dichotomized (aOR, mRS 0-2: 0.73; 95%CI [0.62-0.86], p < 0.001) analyses in the early- but not in the extended-window (aOR, mRS shift: 0.96; 95%CI [0.90-1.02], p = 0.15; aOR, mRS0-2: 0.97; 95%CI [0.90-1.04], p = 0.41). Early-window patients had significantly lower 90-day functional disability (aOR, mRS shift: 1.533; 95%CI [1.138-2.065], p = 0.005) and a trend towards higher rates of good outcomes (aOR, mRS 0-2: 1.391; 95%CI [0.972-1.990], p = 0.071). CONCLUSIONS: The impact of time to thrombectomy on outcomes appears to be time dependent with a steep influence in the early followed by a less significant plateau in the extended window. However, every effort should be made to shorten treatment times regardless of ischemia duration.

Clinical effectiveness of endovascular stroke treatment in the early and extended time windows.

BACKGROUND: The clinical efficacy of mechanical thrombectomy has been unequivocally demonstrated in multiple randomized clinical trials. However, these studies were performed in carefully selected centers and utilized strict inclusion criteria. AIM: We aimed to assess the clinical effectiveness of mechanical thrombectomy in a prospective registry. METHODS: A total of 2008 patients from 76 sites across 12 countries were enrolled in a prospective open-label mechanical thrombectomy registry. Patients were categorized into the corresponding cohorts of the SWIFT-Prime, DAWN, and DEFUSE 3 trials according to the basic demographic and clinical criteria without considering specific parenchymal imaging findings. Baseline and outcome variables were compared across the corresponding groups. RESULTS: As compared to the treated patients in the actual trials, registry-derived patients tended to be younger and had lower baseline ASPECTS. In addition, time to treatment was earlier and the use of intravenous tissue plasminogen activator (IV-tPA) and general anesthesia were higher in DAWN- and DEFUSE-3 registry derived patients versus their corresponding trials. Reperfusion rates were higher in the registry patients. The rates of 90-day good outcome (mRS0-2) in registry-derived patients were comparable to those of the patients treated in the corresponding randomized clinical trials (SWIFT-Prime, 64.5% vs. 60.2%; DAWN, 50.4% vs. 48.6%; Beyond-DAWN: 52.4% vs. 48.6%; DEFUSE 3, 52% vs. 44.6%, respectively; all P > 0.05). Registry-derived patients had significant less disability than the corresponding randomized clinical trial controls (ordinal modified Rankin Scale (mRS) shift odds ratio (OR), P < 0.05 for all). CONCLUSION: Our study provides favorable generalizability data for the safety and efficacy of thrombectomy in the "real-world" setting and supports that patients may be safely treated outside the constraints of randomized clinical trials.

Diversion-p64: results from an international, prospective, multicenter, single-arm post-market study to assess the safety and effectiveness of the p64 flow modulation device.

BACKGROUND: The use of flow diversion to treat intracranial aneurysms has increased in recent years. OBJECTIVE: To assess the safety and angiographic efficacy of the p64 flow modulation device. METHODS: Diversion-p64 is an international, prospective, multicenter, single-arm, study conducted at 26 centers. The p64 flow modulation device was used to treat anterior circulation aneurysms between December 2015 and January 2019. The primary safety endpoint was the incidence of major stroke or neurologic death at 3-6 months, with the primary efficacy endpoint being complete aneurysm occlusion (Raymond-Roy Occlusion Classification 1) on follow-up angiography. RESULTS: A total of 420 patients met the eligibility criteria and underwent treatment with the p64 flow modulation device (mean age 55±12.0 years, 86.2% female). Mean aneurysm dome width was 6.99±5.28 mm and neck width 4.47±2.28 mm. Mean number of devices implanted per patient was 1.06±0.47, with adjunctive coiling performed in 14.0% of the cases. At the second angiographic follow-up (mean 375±73 days), available for 343 patients (81.7%), complete aneurysm occlusion was seen in 287 (83.7%) patients. Safety data were available for 413 patients (98.3%) at the first follow-up (mean 145±43 days) with a composite morbidity/mortality rate of 2.42% (n=10). CONCLUSIONS: Diversion-p64 is the largest prospective study using the p64 flow modulation device. The results of this study demonstrate that the device has a high efficacy and carries a low rate of mortality and permanent morbidity.