Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial.

BACKGROUND: Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke. METHODS: In this multicentre, randomised, open-label, blinded-outcome trial in Europe and Canada, we recruited patients with stroke due to large vessel occlusion confirmed with CT or magnetic resonance angiography admitted to endovascular centres. Patients were randomly assigned (1:1) via a centralised web server using a deterministic minimisation method to receive stent-retriever thrombectomy alone or intravenous alteplase plus stent-retriever thrombectomy. In both groups, thrombectomy was initiated as fast as possible with any commercially available Solitaire stent-retriever revascularisation device (Medtronic, Irvine, CA, USA). In the combined treatment group, intravenous alteplase (0·9 mg/kg bodyweight, maximum dose 90 mg per patient) was administered as early as possible after randomisation for 60 min with 10% of the calculated dose given as an initial bolus. Personnel assessing the primary outcome were masked to group allocation; patients and treating physicians were not. The primary binary outcome was a score of 2 or less on the modified Rankin scale at 90 days. We assessed the non-inferiority of thrombectomy alone versus intravenous alteplase plus thrombectomy in all randomly assigned and consenting patients using the one-sided lower 95% confidence limit of the Mantel-Haenszel risk difference, with a prespecified non-inferiority margin of 12%. The main safety endpoint was symptomatic intracranial haemorrhage assessed in all randomly assigned and consenting participants. This trial is registered with ClinicalTrials.gov, NCT03192332, and is closed to new participants. FINDINGS: Between Nov 29, 2017, and May 7, 2021, 5215 patients were screened and 423 were randomly assigned, of whom 408 (201 thrombectomy alone, 207 intravenous alteplase plus thrombectomy) were included in the primary efficacy analysis. A modified Rankin scale score of 0-2 at 90 days was reached by 114 (57%) of 201 patients assigned to thrombectomy alone and 135 (65%) of 207 patients assigned to intravenous alteplase plus thrombectomy (adjusted risk difference -7·3%, 95% CI -16·6 to 2·1, lower limit of one-sided 95% CI -15·1%, crossing the non-inferiority margin of -12%). Symptomatic intracranial haemorrhage occurred in five (2%) of 201 patients undergoing thrombectomy alone and seven (3%) of 202 patients receiving intravenous alteplase plus thrombectomy (risk difference -1·0%, 95% CI -4·8 to 2·7). Successful reperfusion was less common in patients assigned to thrombectomy alone (182 [91%] of 201 vs 199 [96%] of 207, risk difference -5·1%, 95% CI -10·2 to 0·0, p=0·047). INTERPRETATION: Thrombectomy alone was not shown to be non-inferior to intravenous alteplase plus thrombectomy and resulted in decreased reperfusion rates. These results do not support omitting intravenous alteplase before thrombectomy in eligible patients. FUNDING: Medtronic and University Hospital Bern.

Sex Differences in Functional Outcomes Following Endovascular Treatment for Acute Ischemic Stroke.

BACKGROUND: Sex disparities have been reported across many aspects of acute ischemic stroke (AIS) care; however, there is a relative paucity of research examining sex differences in outcomes following endovascular treatment (EVT). Some studies report worse functional independence for females following EVT. Few, if any of these studies account for differences in age, baseline function, and comorbidity burden. This retrospective cohort study aimed to assess for sex differences in functional outcomes following EVT by comparing 90-day modified Rankin Scale (mRS) of males and females while controlling for baseline function and comorbidity burden. METHODS: Baseline demographic and clinical data, and stroke severity were compared for 230 consecutive patients undergoing EVT for AIS between October 2014 and July 2019 at a tertiary stroke centre in Toronto, Canada. Effect of sex on likelihood of functional independence post-EVT was assessed using regression analysis with and without correction for age, baseline mRS, and Charlson Comorbidity Index (CCI). RESULTS: Females undergoing EVT for AIS were older (75 ± 13 vs. 66 ± 15, p < 0.0001), with worse clinical and functional baselines. Unadjusted, males were more functionally independent (90-day mRS < 3) [OR = 1.831, 95%CI 1.082-3.098]. After controlling for age, baseline mRS and CCI, there was no difference between groups [OR 1.21, 95%CI 0.61-2.37]. CONCLUSIONS: This study provides evidence that prior findings of sex disparities in function after EVT may be accounted for by differences in age, baseline clinical status and functional independence between males and females when a comprehensive measure of comorbidity burden is utilized.

A Rational Approach to Meshing Cerebral Venous Geometries for High-Fidelity Computational Fluid Dynamics.

Computational fluid dynamics (CFD) of cerebral venous flows has become popular owing to the possibility of using local hemodynamics and hemoacoustics to help diagnose and plan treatments for venous diseases of the brain. Lumen geometries in low-pressure cerebral veins are different from those in cerebral arteries, often exhibiting fenestrations and flattened or triangular cross section, in addition to constrictions and expansions. These can challenge conventional size-based volume meshing strategies, and the ability to resolve nonlaminar flows. Here we present a novel strategy leveraging estimation of length scales that could be present if flow were to become transitional or turbulent. Starting from the lumen geometry and flow rate boundary conditions, centerlines are used to determine local hydraulic diameters and cross-sectional mean velocities, from which flow length scales are approximated using conventional definitions of local Kolmogorov and Taylor microscales. By inspection of these scales, a user specifies minimum and maximum mesh edge lengths, which are then distributed along the model in proportion to the approximated local Taylor length scales. We demonstrate in three representative cases that this strategy avoids some of the pitfalls of conventional size-based strategies. An exemplary CFD mesh-refinement study shows convergence of high-frequency flow instabilities even starting from relatively coarse edge lengths near the lower bounds of the approximated Taylor length scales. Rational consideration of the length scales in a possibly nonlaminar flow may thus provide a useful and replicable baseline for denovo meshing of complicated or unfamiliar venous lumen geometries.

Histological composition of retrieved emboli in acute ischemic stroke is independent of pre-thrombectomy alteplase use.

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.

Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct.

BACKGROUND: The effect of endovascular thrombectomy that is performed more than 6 hours after the onset of ischemic stroke is uncertain. Patients with a clinical deficit that is disproportionately severe relative to the infarct volume may benefit from late thrombectomy. METHODS: We enrolled patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery who had last been known to be well 6 to 24 hours earlier and who had a mismatch between the severity of the clinical deficit and the infarct volume, with mismatch criteria defined according to age (<80 years or ≥80 years). Patients were randomly assigned to thrombectomy plus standard care (the thrombectomy group) or to standard care alone (the control group). The coprimary end points were the mean score for disability on the utility-weighted modified Rankin scale (which ranges from 0 [death] to 10 [no symptoms or disability]) and the rate of functional independence (a score of 0, 1, or 2 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating more severe disability) at 90 days. RESULTS: A total of 206 patients were enrolled; 107 were assigned to the thrombectomy group and 99 to the control group. At 31 months, enrollment in the trial was stopped because of the results of a prespecified interim analysis. The mean score on the utility-weighted modified Rankin scale at 90 days was 5.5 in the thrombectomy group as compared with 3.4 in the control group (adjusted difference [Bayesian analysis], 2.0 points; 95% credible interval, 1.1 to 3.0; posterior probability of superiority, >0.999), and the rate of functional independence at 90 days was 49% in the thrombectomy group as compared with 13% in the control group (adjusted difference, 33 percentage points; 95% credible interval, 24 to 44; posterior probability of superiority, >0.999). The rate of symptomatic intracranial hemorrhage did not differ significantly between the two groups (6% in the thrombectomy group and 3% in the control group, P=0.50), nor did 90-day mortality (19% and 18%, respectively; P=1.00). CONCLUSIONS: Among patients with acute stroke who had last been known to be well 6 to 24 hours earlier and who had a mismatch between clinical deficit and infarct, outcomes for disability at 90 days were better with thrombectomy plus standard care than with standard care alone. (Funded by Stryker Neurovascular; DAWN ClinicalTrials.gov number, NCT02142283 .).

Coexistence of large conventional and planar spin Hall effect with long spin diffusion length in a low-symmetry semimetal at room temperature.

The spin Hall effect (SHE) is usually observed as a bulk effect in high-symmetry crystals with substantial spin-orbit coupling (SOC), where the symmetric spin-orbit field imposes a widely encountered trade-off between spin Hall angle (θSH) and spin diffusion length (Lsf), and spin polarization, spin current and charge current are constrained to be mutually orthogonal. Here, we report a large θSH of 0.32 accompanied by a long Lsf of 2.2 µm at room temperature in a low-symmetry few-layered semimetal MoTe2, thus identifying it as an excellent candidate for simultaneous spin generation, transport and detection. In addition, we report that longitudinal spin current with out-of-plane polarization can be generated by both transverse and vertical charge current, due to the conventional and a newly observed planar SHE, respectively. Our study suggests that manipulation of crystalline symmetries and strong SOC opens access to new charge-spin interconversion configurations and spin-orbit torques for spintronic applications.

Liver Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin Deficiency Caused by the Pi*ZZ Mutation.

BACKGROUND & AIMS: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD. METHODS: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant. RESULTS: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion. CONCLUSIONS: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940.

Flow diversion for treatment of intracranial aneurysms: Mechanism and implications.

Flow diverters are new generation stents that have recently garnered a large amount of interest for use in treatment of intracranial aneurysms. Flow diverters reduce blood flow into the aneurysm, with redirection along the path of the parent vessel. Flow stagnation into the aneurysm and neck coverage with subsequent endothelialization are the important synergistic mechanisms by which the therapy acts. Several studies have examined the mechanisms by which flow diverters subsequently lead to aneurysm occlusion. This review aims to provide a general overview of the flow diverters and their mechanism of action and potential implications. ANN NEUROL 2019;85:793-800.

Canted Persistent Spin Texture and Quantum Spin Hall Effect in WTe_{2}.

We report an unconventional quantum spin Hall phase in the monolayer WTe_{2}, which exhibits hitherto unknown features in other topological materials. The low symmetry of the structure induces a canted spin texture in the yz plane, which dictates the spin polarization of topologically protected boundary states. Additionally, the spin Hall conductivity gets quantized (2e^{2}/h) with a spin quantization axis parallel to the canting direction. These findings are based on large-scale quantum simulations of the spin Hall conductivity tensor and nonlocal resistances in multiprobe geometries using a realistic tight-binding model elaborated from first-principle methods. The observation of this canted quantum spin Hall effect, related to the formation of topological edge states with nontrivial spin polarization, demands for specific experimental design and suggests interesting alternatives for manipulating spin information in topological materials.

Comparison of multimodal CT scan protocols used for decision-making on mechanical thrombectomy in acute ischemic stroke.

PURPOSE: Different CT-based protocols are being used in acute ischemic stroke. We aimed to assess the added value of delayed-phase CT angiography (CTA) and CT perfusion (CTP) to a basic protocol using non-contrast computerized tomography (NCCT) with arterial-phase CTA in patient selection for mechanical thrombectomy. METHODS: We retrospectively included consecutive acute ischemic stroke patients with a symptomatic intracranial arterial occlusion between January 2015 and November 2016 who underwent NCCT, arterial and delayed-phase CTA, and CTP. These imaging studies were grouped into five protocols: (1) NCCT and arterial-phase CTA; (2) NCCT, arterial-phase CTA, and CTP; (3) NCCT, arterial- and delayed-phase CTA; (4) NCCT, arterial- and delayed-phase CTA, and CTP; and (5) NCCT and delayed-phase CTA. Two interventional neuro-radiologists independently decided on mechanical thrombectomy for each patient based on the protocols. They reached consensus for discrepant decisions. We assessed the raters' confidence level, inter-rater agreement, and compared treatment decisions for the different protocols. RESULTS: We included 73 patients (44% male, mean age 74). The inter-rater agreement was substantial for protocols with three or more modalities (Ò¡ = 0.613-0.704) and moderate for two-modality protocols (Ò¡ = 0.506-0.529). The highest agreement and confidence level was achieved for the combination of NCCT, arterial-phase CTA, and CTP. Adding CTP to NCCT and arterial-phase CTA resulted in a 10% increase of recommendations for mechanical thrombectomy and adding delayed-phase CTA resulted in a 4% increase. These management changes did not reach statistical significance (p = 0.07; p = 0.25, respectively). CONCLUSION: Adding CTP and/or a delayed-phase CTA to NCCT with arterial-phase CTA improves the decision-maker's confidence level and creates a trend towards a lower threshold for mechanical thrombectomy.

Anomalous Quantum Metal in a 2D Crystalline Superconductor with Electronic Phase Nonuniformity.

The details of the superconducting to quantum metal transition (SQMT) at T = 0 are an open problem that invokes great interest in the nature of this exotic and unexpected ground state (Ephron et al., 1996; Mason and Kapitulnik, 1999; Chervenak and Valles, 2000). However, the SQMT was not yet investigated in a crystalline 2D superconductor with coexisting and fluctuating quantum orders. Here, we report the observation of a SQMT in 2D ion-gel-gated 1T-TiSe2 (Li et al., 2016) driven by a magnetic field. A field-induced crossover between Bose quantum metal and vortex quantum creeping with an increasing field is observed. We discuss the interplay between superconducting and CDW fluctuations (discommensurations) and their relation to the anomalous quantum metal (AQM) phase. From our findings, gate-tunable 1T-TiSe2 emerges as a privileged platform to scrutinize, in a controlled way, the details of the SQMT, the role of coexisting fluctuating orders and, ultimately, to obtain a deeper understanding of the fate of superconductivity in strictly two-dimensional crystals near zero temperature.

Sex Differences in Outcome After Endovascular Stroke Therapy for Acute Ischemic Stroke.

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.

How patient specific are patient-specific computational models of cerebral aneurysms? An overview of sources of error and variability.

Computational modeling of cerebral aneurysms, derived from clinical 3D angiography, has become widespread over the past 15 years. While such "image-based" or "patient-specific" models have shown promise for the assessment of rupture risk, much debate remains about their reliability in light of necessary modeling assumptions and incomplete or uncertain model input parameters derived from the clinic. The aims of this review were to walk through the various steps of this so-called patient-specific modeling pipeline and to highlight evidence supporting those steps that we can or cannot rely on. The relative importance of the different sources of error and variability on hemodynamic predictions is summarized, with recommendations to standardize for those that can be avoided and to pay closer attention those to that cannot.

Impact of Hyperglycemia According to the Collateral Status on Outcomes in Mechanical Thrombectomy.

Background and Purpose- Understanding the influence of hyperglycemia on outcomes in terms of the pretreatment collateral status might contribute to the achievement of case-specific glucose management in acute ischemic stroke. We sought to investigate whether the glucose level can influence the pretreatment collateral status and functional outcomes of endovascular thrombectomy in acute ischemic stroke and whether the impact of hyperglycemia on outcomes can be modified by the pretreatment collateral status. Methods- We analyzed the Triple-S database, which includes individual patient data pooled from 3 prospective Solitaire stent retriever studies (SWIFT [Solitaire With the Intention for Thrombectomy], SWIFT PRIME [SWIFT as Primary Endovascular Treatment], and STAR [Solitaire Flow Restoration Thrombectomy for Acute Revascularization]). Patients were eligible if they had acute ischemic stroke with moderate to severe neurological deficits, harbored angiographically confirmed large vessel occlusion, and were treatable by endovascular thrombectomy within 8 hours of onset. Pretreatment catheter angiograms were scored for collateral grades by a core imaging laboratory. The main outcome was 3-month good outcome (modified Rankin Scale score of 0-2). Results- Angiographic data on collaterals were available in 309 patients (age, 67±12 years; glucose, 131±55 mg/dL). Overall, the glucose level at presentation was not associated with pretreatment collateral status but was significantly lower in patients with a good outcome at 90 days (124 versus 140 mg/dL). Collateral grades modified the effect of glucose on good outcomes at 90 days ( Pint=0.03). Among patients with poor collaterals (collateral grades, 0-2), higher glucose levels did not alter the outcome, whereas among patients with good collaterals (3-4), higher glucose levels reduced the likelihood of a good outcome at 90 days (per 10 mg/dL increase: odds ratio, 0.81; 95% CI, 0.69-0.95). Conclusions- Our study revealed that higher glucose levels reduce the likelihood of a good outcome among patients with good collaterals, but their effects on the outcome are less significant for patients with poor collaterals. The results suggest that good collaterals at presentation may be targets for more intensive glucose control and future studies relating to glucose management.

Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.

BACKGROUND: Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, less than 40% regain functional independence when treated with intravenous tissue plasminogen activator (t-PA) alone. Thrombectomy with the use of a stent retriever, in addition to intravenous t-PA, increases reperfusion rates and may improve long-term functional outcome. METHODS: We randomly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone (control group) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset (intervention group). Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions. The primary outcome was the severity of global disability at 90 days, as assessed by means of the modified Rankin scale (with scores ranging from 0 [no symptoms] to 6 [death]). RESULTS: The study was stopped early because of efficacy. At 39 centers, 196 patients underwent randomization (98 patients in each group). In the intervention group, the median time from qualifying imaging to groin puncture was 57 minutes, and the rate of substantial reperfusion at the end of the procedure was 88%. Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale (P<0.001). The rate of functional independence (modified Rankin scale score, 0 to 2) was higher in the intervention group than in the control group (60% vs. 35%, P<0.001). There were no significant between-group differences in 90-day mortality (9% vs. 12%, P=0.50) or symptomatic intracranial hemorrhage (0% vs. 3%, P=0.12). CONCLUSIONS: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME ClinicalTrials.gov number, NCT01657461.).

3D phase contrast MRI: Partial volume correction for robust blood flow quantification in small intracranial vessels.

PURPOSE: Recent advances in 3D-PCMRI (phase contrast MRI) sequences allow for measuring the complex hemodynamics in cerebral arteries. However, the small size of these vessels vs spatial resolution can lead to non-negligible partial volume artifacts, which must be taken into account when computing blood flow rates. For this purpose, we combined the velocity information provided by 3D-PCMRI with vessel geometry measured with 3DTOF (time of flight MRI) or 3DRA (3D rotational angiography) to correct the partial volume effects in flow rate assessments. METHODS: The proposed methodology was first tested in vitro on cylindrical and patient specific vessels subject to fully controlled pulsatile flows. Both 2D- and 3D-PCMRI measurements using various spatial resolutions ranging from 20 to 1.3 voxels per vessel diameter were analyzed and compared with flowmeter baseline. Second, 3DTOF, 2D- and 3D-PCMRI measurements were performed in vivo on 35 patients harboring internal carotid artery (ICA) aneurysms indicated for endovascular treatments requiring 3DRA imaging. RESULTS: The in vitro 2D- and 3D-PCMRI mean flow rates assessed with partial volume correction showed very low sensitivity to the acquisition resolution above ≈2 voxels per vessel diameter while uncorrected flow rates deviated critically when decreasing the spatial resolution. 3D-PCMRI flow rates measured in vivo in ICA agreed very well with 2D-PCMRI data and a good flow conservation was observed at the C7 bifurcation. Globally, partial volume correction led to 10-15% lower flow rates than uncorrected values as those reported in most of the published studies on intracranial flows. CONCLUSION: Partial volume correction may improve the accuracy of PCMRI flow rate measurements especially in small vessels such as intracranial arteries. Magn Reson Med 79:129-140, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Reproduction of the Charge Density Wave Phase Diagram in 1T-TiSe_{2} Exposes its Excitonic Character.

Recent experiments suggest that excitonic degrees of freedom play an important role in precipitating the charge density wave (CDW) transition in 1T-TiSe_{2}. Through systematic calculations of the electronic and phonon spectrum based on density functional perturbation theory, we show that the predicted critical doping of the CDW phase overshoots the experimental value by 1 order of magnitude. In contrast, an independent self-consistent many-body calculation of the excitonic order parameter and renormalized band structure is able to capture the experimental phase diagram in extremely good qualitative and quantitative agreement. This demonstrates that electron-electron interactions and the excitonic instability arising from direct electron-hole coupling are pivotal to accurately describe the nature of the CDW in this system. This has important implications to understand the emergence of superconductivity within the CDW phase of this and related systems.

Quantized Transport, Strain-Induced Perfectly Conducting Modes, and Valley Filtering on Shape-Optimized Graphene Corbino Devices.

The extreme mechanical resilience of graphene and the peculiar coupling it hosts between lattice and electronic degrees of freedom have spawned a strong impetus toward strain-engineered graphene where, on the one hand, strain augments the richness of its phenomenology and makes possible new concepts for electronic devices, and on the other hand, new and extreme physics might take place. Here, we demonstrate that the shape of substrates supporting graphene sheets can be optimized for approachable experiments where strain-induced pseudomagnetic fields (PMF) can be tailored by pressure for directionally selective electronic transmission and pinching-off of current flow down to the quantum channel limit. The Corbino-type layout explored here furthermore allows filtering of charge carriers according to valley and current direction, which can be used to inject or collect valley-polarized currents, thus realizing one of the basic elements required for valleytronics. Our results are based on a framework developed to realistically determine the combination of strain, external parameters, and geometry optimally compatible with the target spatial profile of a desired physical property-the PMF in this case. Characteristic conductance profiles are analyzed through quantum transport calculations on large graphene devices having the optimal shape.

Efficacy of Stent-Retriever Thrombectomy in Magnetic Resonance Imaging Versus Computed Tomographic Perfusion-Selected Patients in SWIFT PRIME Trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: The majority of patients enrolled in SWIFT PRIME trial (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) had computed tomographic perfusion (CTP) imaging before randomization; 34 patients were randomized after magnetic resonance imaging (MRI). METHODS: Patients with middle cerebral artery and distal carotid occlusions were randomized to treatment with tPA (tissue-type plasminogen activator) alone or tPA+stentriever thrombectomy. The primary outcome was the distribution of the modified Rankin Scale score at 90 days. Patients with the target mismatch profile for enrollment were identified on MRI and CTP. RESULTS: MRI selection was performed in 34 patients; CTP in 139 patients. Baseline National Institutes of Health Stroke Scale score was 17 in both groups. Target mismatch profile was present in 95% (MRI) versus 83% (CTP). A higher percentage of the MRI group was transferred from an outside hospital (P=0.02), and therefore, the time from stroke onset to randomization was longer in the MRI group (P=0.003). Time from emergency room arrival to randomization did not differ in CTP versus MRI-selected patients. Baseline ischemic core volumes were similar in both groups. Reperfusion rates (>90%/TICI [Thrombolysis in Cerebral Infarction] score 3) did not differ in the stentriever-treated patients in the MRI versus CTP groups. The primary efficacy analysis (90-day mRS score) demonstrated a statistically significant benefit in both subgroups (MRI, P=0.02; CTP, P=0.01). Infarct growth was reduced in the stentriever-treated group in both MRI and CTP groups. CONCLUSIONS: Time to randomization was significantly longer in MRI-selected patients; however, site arrival to randomization times were not prolonged, and the benefits of endovascular therapy were similar. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.

Cost-Effectiveness of Solitaire Stent Retriever Thrombectomy for Acute Ischemic Stroke: Results From the SWIFT-PRIME Trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke).

BACKGROUND AND PURPOSE: Clinical trials have demonstrated improved 90-day outcomes for patients with acute ischemic stroke treated with stent retriever thrombectomy plus tissue-type plasminogen activator (SST+tPA) compared with tPA. Previous studies suggested that this strategy may be cost-effective, but models were derived from pooled data and older assumptions. METHODS: In this prospective economic substudy conducted alongside the SWIFT-PRIME trial (Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke), in-trial costs were measured for patients using detailed medical resource utilization and hospital billing data. Utility weights were assessed at 30 and 90 days using the EuroQol-5 dimension questionnaire. Post-trial costs and life-expectancy were estimated for each surviving patient using a model based on trial data and inputs derived from a contemporary cohort of ischemic stroke survivors. RESULTS: Index hospitalization costs were $17 183 per patient higher for SST+tPA than for tPA ($45 761 versus $28 578; P<0.001), driven by initial procedure costs. Between discharge and 90 days, costs were $4904 per patient lower for SST+tPA than for tPA ($11 270 versus $16 174; P=0.014); total 90-day costs remained higher with SST+tPA ($57 031 versus $44 752; P<0.001). Higher utility values for SST+tPA led to higher in-trial quality-adjusted life years (0.131 versus 0.105; P=0.005). In lifetime projections, SST+tPA was associated with substantial gains in quality-adjusted life years (6.79 versus 5.05), cost savings of $23 203 per patient and was economically dominant when compared with tPA in 90% of bootstrap replicates. CONCLUSIONS: Among patients with acute ischemic stroke enrolled in the SWIFT-PRIME trial, SST increased initial treatment costs, but was projected to improve quality-adjusted life-expectancy and reduce healthcare costs over a lifetime horizon compared with tPA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657461.