Publications by authors named "Maarten G Lansberg"

152 Publications

Predicting Infarct Core From Computed Tomography Perfusion in Acute Ischemia With Machine Learning: Lessons From the ISLES Challenge.

Stroke 2021 May 7:STROKEAHA120030696. Epub 2021 May 7.

Department of Radiology, Stanford University, CA (G.Z.).

Background And Purpose: The ISLES challenge (Ischemic Stroke Lesion Segmentation) enables globally diverse teams to compete to develop advanced tools for stroke lesion analysis with machine learning. Detection of irreversibly damaged tissue on computed tomography perfusion (CTP) is often necessary to determine eligibility for late-time-window thrombectomy. Therefore, the aim of ISLES-2018 was to segment infarcted tissue on CTP based on diffusion-weighted imaging as a reference standard.

Methods: The data, from 4 centers, consisted of 103 cases of acute anterior circulation large artery occlusion stroke who underwent diffusion-weighted imaging rapidly after CTP. Diffusion-weighted imaging lesion segmentation was performed manually and acted as a reference standard. The data were separated into 63 cases for training and 40 for testing, upon which quality metrics (dice score coefficient, Hausdorff distance, absolute lesion volume difference, etc) were computed to rank methods based on their overall performance.

Results: Twenty-four different teams participated in the challenge. Median time to CTP was 185 minutes (interquartile range, 180-238), the time between CTP and magnetic resonance imaging was 36 minutes (interquartile range, 25-79), and the median infarct lesion size was 15.2 mL (interquartile range, 5.7-45). The best performance for Dice score coefficient and absolute volume difference were 0.51 and 10.1 mL, respectively, from different teams. Based on the ranking criteria, the top team's algorithm demonstrated for average Dice score coefficient and average absolute volume difference 0.51 and 10.2 mL, respectively, outperforming the conventional threshold-based method (dice score coefficient, 0.3; volume difference, 15.3). Diverse algorithms were used, almost all based on deep learning, with top-ranked approaches making use of the raw perfusion data as well as methods to synthetically generate complementary information to boost prediction performance.

Conclusions: Machine learning methods may predict infarcted tissue from CTP with improved accuracy compared with threshold-based methods used in clinical routine. This dataset will remain public and can be used to test improvement in algorithms over time.
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http://dx.doi.org/10.1161/STROKEAHA.120.030696DOI Listing
May 2021

Association of Venous Outflow Profiles and Successful Vessel Reperfusion After Thrombectomy.

Neurology 2021 May 5. Epub 2021 May 5.

Department of Neuroimaging and Neurointerventions, Stanford University, Stanford, CA, USA

Objective: Robust arterial collaterals are associated with successful reperfusion after thrombectomy treatment of acute ischemic stroke due to large vessel occlusion (AIS-LVO). Excellent venous outflow (VO) reflects excellent tissue perfusion and collateral status in AIS-LVO patients. To determine whether favorable VO profiles assessed on pre-treatment CT angiography (CTA) images correlate with successful vessel reperfusion after thrombectomy in AIS-LVO patients.

Methods: Multicenter retrospective cohort study of consecutive AIS-LVO patients treated by thrombectomy. Baseline CTA was used to assess collateral status (Tan scale) and VO using the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcome was excellent vessel reperfusion status (modified Thrombolysis In Cerebral Infarction [TICI] 2c-3). Secondary outcome was good functional outcome defined as 0-2 on the Modified Ranking Scale (mRS) after 90 days.

Results: 565 patients met inclusion criteria. Multivariable logistic regression analysis showed that favorable VO (OR= 2.10 [95% CI 1.39-3.16]; p<0.001) was associated with excellent vessel reperfusion during thrombectomy, regardless of good CTA collateral status (OR= 0.87 [95%CI 0.58-1.34]; p=0.48). A favorable VO profile (OR= 8.9 [95%CI 5.3-14.9]; p<0.001) and excellent vessel reperfusion status (OR = 2.7 [95%CI 1.7-4.4]; p<0.001) were independently associated with good functional outcome adjusted for age, sex, glucose, tPA administration, good CTA collateral status and presentation NIHSS.

Conclusion: A favorable VO profile is associated with reperfusion success and good functional outcomes in patients with AIS-LVO treated by endovascular thrombectomy.
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http://dx.doi.org/10.1212/WNL.0000000000012106DOI Listing
May 2021

A dynamic simulation framework for CT perfusion in stroke assessment built from first principles.

Med Phys 2021 Apr 20. Epub 2021 Apr 20.

Departments of Bioengineering and Radiology, Stanford University, Stanford, CA, 94305, USA.

Purpose: Physicians utilize cerebral perfusion maps (e.g., cerebral blood flow, cerebral blood volume, transit time) to prescribe the plan of care for stroke patients. Variability in scanning techniques and post-processing software can result in differences between these perfusion maps. To determine which techniques are acceptable for clinical care, it is important to validate the accuracy and reproducibility of the perfusion maps. Validation using clinical data is challenging due to the lack of a gold standard to assess cerebral perfusion and the impracticality of scanning patients multiple times with different scanning techniques. In contrast, simulated data from a realistic digital phantom of the cerebral perfusion in acute stroke patients would enable studies to optimize and validate the scanning and post-processing techniques.

Methods: We describe a complete framework to simulate CT perfusion studies for stroke assessment. We begin by expanding the XCAT brain phantom to enable spatially varying contrast agent dynamics and incorporate a realistic model of the dynamics in the cerebral vasculature derived from first principles. A dynamic CT simulator utilizes the time-concentration curves to define the contrast agent concentration in the object at each time point and generates CT perfusion images compatible with commercially available post-processing software. We also generate ground truth perfusion maps to which the maps generated by post-processing software can be compared.

Results: We demonstrate a dynamic CT perfusion study of a simulated patient with an ischemic stroke and the resulting perfusion maps generated by post-processing software. We include a visual comparison between the computer-generated perfusion maps and the ground truth perfusion maps. The framework is highly tunable; users can modify the perfusion properties (e.g., occlusion location, CBF, CBV, and MTT), scanner specifications (e.g., focal spot size and detector configuration), scanning protocol (e.g., kVp and mAs), and reconstruction parameters (e.g., slice thickness and reconstruction filter).

Conclusions: This framework provides realistic test data with the underlying ground truth that enables a robust assessment of CT perfusion techniques and post-processing methods for stroke assessment.
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http://dx.doi.org/10.1002/mp.14887DOI Listing
April 2021

Venous Outflow Profiles Are Linked to Cerebral Edema Formation at Noncontrast Head CT after Treatment in Acute Ischemic Stroke Regardless of Collateral Vessel Status at CT Angiography.

Radiology 2021 Apr 6:203651. Epub 2021 Apr 6.

From the Department of Radiology (T.D.F., R.K., G.K., M.P.M., M.W., J.J.H.) and Department of Neurology and Neurological Sciences (S.C., M.M., M.G.L., G.W.A.), Stanford University School of Medicine, 300 Pasteur Dr, Room S047, Stanford, CA 94305; and Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (L.M., G.B., F.F., J.F.).

Background Ischemic lesion net water uptake (NWU) at noncontrast head CT enables quantification of cerebral edema in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Purpose To assess whether favorable venous outflow (VO) profiles at CT angiography are associated with reduced NWU and good functional outcomes in patients with AIS due to LVO. Materials and Methods This multicenter retrospective cohort study evaluated consecutive patients with AIS due to LVO who underwent thrombectomy triage between January 2013 and December 2019. Arterial collateral vessel status (Tan scale) and venous output were measured at CT angiography. Venous outflow was graded with use of the cortical vein opacification score, which quantifies opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein. Favorable VO was regarded as a score of 3-6 and unfavorable VO as a score of 0-2. NWU was determined at follow-up noncontrast CT. Multivariable regression analyses were performed to determine the association between favorable VO profiles and NWU after treatment and good functional outcome (modified Rankin Scale, ≤2). Results A total of 580 patients were included. Of the 580 patients, 231 had favorable VO (104 women; median age, 73 years [interquartile range {IQR}, 62-81 years]) and 349 had unfavorable VO (190 women; median age, 77 years [IQR, 66-84 years]). Compared with patients with unfavorable VO, those with favorable VO exhibited lower baseline National Institutes of Health Stroke Scale score (median, 12.5 [IQR, 7-17] vs 17 [IQR, 13-21]), higher Alberta Stroke Program Early CT Score (median, 9 [IQR, 7-10] vs 7 [IQR, 6-8]), and less NWU after treatment (median, 7% [IQR, 4.6%-11.5%] vs 17.9% [IQR, 12.3%-22.2%]). In a multivariable regression analysis, NWU mean difference between patients with unfavorable VO and those with favorable VO was 6.1% (95% CI: 4.9, 7.3; < .001) regardless of arterial CT angiography collateral vessel status (b coefficient, 0.72 [95% CI: -0.59, 2.03; = .28]). Favorable VO (odds ratio [OR]: 4.1 [95% CI: 2.2, 7.7]; < .001) and reduced NWU after treatment (OR: 0.77 [95% CI: 0.73, 0.83]; < .001) were independently associated with good functional outcomes. Conclusion Favorable venous outflow (VO) correlated with reduced ischemic net water uptake (NWU) after treatment. Reduced NWU and favorable VO were associated with good functional outcomes regardless of CT angiography arterial collateral vessel status. © RSNA, 2021
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http://dx.doi.org/10.1148/radiol.2021203651DOI Listing
April 2021

Home-based Virtual Reality Therapy for Hand Recovery After Stroke.

PM R 2021 Mar 26. Epub 2021 Mar 26.

Stanford Stroke Center, Stanford University School of Medicine, Stanford, California, USA.

Introduction: Many stroke survivors suffer from arm and hand weakness, but there are only limited efficacious options for arm therapy available.

Objective: To assess the feasibility of unsupervised home-based use of a virtual reality device (Smart Glove) for hand rehabilitation post stroke.

Design: Prospective single-arm study consisting of a 2-week run-in phase with no device use followed by an 8-week intervention period.

Setting: Participants were recruited at the Stanford Neuroscience Outpatient Clinic.

Participants: Twenty chronic stroke patients with upper extremity impairment.

Interventions: Participants were instructed to use the Smart Glove 50 minutes per day, 5 days per week for 8 weeks.

Main Outcome Measures: We measured (1) compliance, (2) patients' impression of the intervention, and (3) efficacy measures including the upper extremity Fugl-Meyer (UE-FM), the Jebsen-Taylor hand function test (JTHFT) and the Stroke Impact Scale (SIS).

Results: Of 20 subjects, 7 (35%) met target compliance of 40 days use, and 6 (30%) used the device for 20-39 days. Eighty-five percent of subjects were satisfied with the therapy, with 80% reporting improvement in hand function. During the run-in phase there were no improvements in hand function. During the intervention, patients improved by a mean of 26.6 ± 48.8 seconds on the JTHFT (P = 0.03), by 16.1 ± 15.3 points on the hand-domain of the SIS (P < 0.01) and there was a trend towards improvement on the UE-FM (2.2 ± 5.5 points, P = 0.10).

Conclusions: Unsupervised use of the Smart Glove in the home environment may improve hand/arm function in subacute/chronic stroke patients. A randomized controlled trial is needed to confirm these results. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/pmrj.12598DOI Listing
March 2021

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

Int J Stroke 2021 Apr 20:17474930211005740. Epub 2021 Apr 20.

Department of Neurosciences, Drexel Neurosciences Institute, Philadelphia, PA, USA.

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  > 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),  < 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.
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http://dx.doi.org/10.1177/17474930211005740DOI Listing
April 2021

Favorable Venous Outflow Profiles Correlate With Favorable Tissue-Level Collaterals and Clinical Outcome.

Stroke 2021 May 8;52(5):1761-1767. Epub 2021 Mar 8.

Department of Radiology (T.D.F., R.K., G.M.K., M.P.M., M.W., J.J.H.), Stanford University School of Medicine, CA.

Background And Purpose: Patients with acute ischemic stroke due to large vessel occlusion and favorable tissue-level collaterals (TLCs) likely have robust cortical venous outflow (VO). We hypothesized that favorable VO predicts robust TLC and good clinical outcomes.

Methods: Multicenter retrospective cohort study of consecutive acute ischemic stroke due to large vessel occlusion patients who underwent thrombectomy triage. Included patients had interpretable prethrombectomy computed tomography, computed tomography angiography, and cerebral perfusion imaging. TLCs were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (volume ratio of brain tissue with [Tmax >10 s/Tmax >6 s]). VO was determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on computed tomography angiography as 0, not visible; 1, moderate opacification; and 2, full. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analyses, we determined the association between VO and (1) favorable TLC status (defined as hypoperfusion intensity ratio ≤0.4) and (2) good functional outcome (modified Rankin Scale score, 0-2).

Results: Six hundred forty-nine patients met inclusion criteria. Patients with favorable VO were younger (median age, 72 [interquartile range (IQR), 62-80] versus 77 [IQR, 66-84] years), had a lower baseline National Institutes of Health Stroke Scale (median, 12 [IQR, 7-17] versus 19 [IQR, 13-20]), and had a higher Alberta Stroke Program Early Computed Tomography Score (median, 9 [IQR, 7-10] versus 7 [IQR, 6-9]). Favorable VO strongly predicted favorable TLC (odds ratio, 4.5 [95% CI, 3.1-6.5]; <0.001) in an adjusted regression analysis. Favorable VO also predicted good clinical outcome (odds ratio, 10 [95% CI, 6.2-16.0]; <0.001), while controlling for favorable TLC, age, glucose, baseline National Institutes of Health Stroke Scale, and good vessel reperfusion status.

Conclusions: In this selective retrospective cohort study of acute ischemic stroke due to large vessel occlusion patients undergoing thrombectomy triage, favorable VO profiles correlated with favorable TLC and were associated with good functional outcomes after treatment. Future prospective studies should independently validate our findings.
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http://dx.doi.org/10.1161/STROKEAHA.120.032242DOI Listing
May 2021

Impact of Clot Shape on Successful M1 Endovascular Reperfusion.

Front Neurol 2021 1;12:642877. Epub 2021 Feb 1.

Interventional and Diagnostic Neuroradiology, Stanford Medical Center, Stanford, CA, United States.

The susceptibility-vessel-sign (SVS) allows thrombus visualization, length estimation and composition, and it may impact reperfusion during mechanical thrombectomy (MT). SVS can also describe thrombus shape in the occluded artery: in the straight M1-segment (S-shaped), or in an angulated/traversing a bifurcation segment (A-shaped). We determined whether SVS clot shape influenced reperfusion and outcomes after MT for proximal middle-cerebral-artery (M1) occlusions. Between May 2015 and March 2018, consecutive patients who underwent MT at one comprehensive stroke center and who had a baseline MRI with a T2 sequence were included. Clinical, procedural and radiographic data, including clot shape on SVS [angulated/bifurcation (A-SVS) vs. straight (S-SVS)] and length were assessed. Primary outcome was successful reperfusion (TICI 2b-3). Secondary outcome were MT complication rates, MT reperfusion time, and clinical outcome at 90-days. Predictors of outcome were assessed with univariate and multivariate analyses. A total of 62 patients were included. 56% (35/62) had an A-SVS. Clots were significantly longer in the A-SVS group (19 mm vs. 8 mm = 0.0002). Groups were otherwise well-matched with regard to baseline characteristics. There was a significantly lower rate of successful reperfusion in the A-SVS cohort (83%) compared to the S-SVS cohort (96%) in multivariable analysis [OR 0.04 (95% CI, 0.002-0.58), = 0.02]. There was no significant difference in long term clinical outcome between groups. Clot shape as determined on T2 imaging, in patients presenting with M1 occlusion appears to be a predictor of successful reperfusion after MT. Angulated and bifurcating clots are associated with poorer rates of successful reperfusion.
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http://dx.doi.org/10.3389/fneur.2021.642877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882685PMC
February 2021

Quality of Life in Physical, Social, and Cognitive Domains Improves With Endovascular Therapy in the DEFUSE 3 Trial.

Stroke 2021 Apr 18;52(4):1185-1191. Epub 2021 Feb 18.

Stanford Stroke Center, Palo Alto, CA (M.M., S.C., S.K., G.W.A., M.G.L.).

Background And Purpose: The DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) randomized clinical trial demonstrated the efficacy of endovascular therapy in treating ischemic stroke 6 to 16 hours after onset, resulting in better functional outcomes than standard medical therapy alone. The objective of this secondary analysis is to analyze the effect of late-window endovascular treatment of ischemic stroke on quality of life (QoL) outcomes.

Methods: Patients (n=182) who presented between 6 and 16 hours after they were last known to be well with acute anterior circulation ischemic stroke were randomized to endovascular thrombectomy plus standard medical therapy or standard medical therapy alone and followed-up through 90 days poststroke. QoL at day 90 was assessed with the QoL in Neurological Disorders measurement tool.

Results: Of the 146 subjects alive at day 90, 136 (95%) filled out QoL in Neurological Disorders short forms. Patients treated with endovascular therapy had better QoL scores in each domain: mobility, social participation, cognitive function, and depression (<0.01 for all). Variables other than endovascular therapy that were independently associated with better QoL included lower baseline National Institutes of Health Stroke Scale, younger age, and male sex. The degree to which the modified Rankin Scale captures differences in QoL between patients varied by domain; the modified Rankin Scale score accounted for a high proportion of the variability in mobility (Rs=0.82), a moderate proportion in social participation (Rs=0.62), and a low proportion in cognition (Rs=0.31) and depression (Rs=0.19).

Conclusions: Patients treated with endovascular therapy 6 to 16 hours after stroke have better QoL than patients treated with medical therapy alone, including better mobility, more social participation, superior cognition, and less depression. The modified Rankin Scale fails to capture patients' outcomes in cognition and depression, which should therefore be assessed with dedicated QoL tools. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02586415.
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http://dx.doi.org/10.1161/STROKEAHA.120.031490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987886PMC
April 2021

The Utility of Domain-Specific End Points in Acute Stroke Trials.

Stroke 2021 Mar 10;52(3):1154-1161. Epub 2021 Feb 10.

Division of Clinical Research, The National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (S.J.).

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http://dx.doi.org/10.1161/STROKEAHA.120.031939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902441PMC
March 2021

Perfusion imaging-based tissue-level collaterals predict ischemic lesion net water uptake in patients with acute ischemic stroke and large vessel occlusion.

J Cereb Blood Flow Metab 2021 Feb 8:271678X21992200. Epub 2021 Feb 8.

Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.

Ischemic lesion Net Water Uptake (NWU) quantifies cerebral edema formation and likely correlates with the microvascular perfusion status of patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We hypothesized that favorable tissue-level collaterals (TLC) predict less NWU and good functional outcomes. We performed a retrospective multicenter analysis of AIS-LVO patients who underwent thrombectomy triage. TLC were measured on cerebral perfusion studies using the hypoperfusion intensity ratio (HIR; volume ratio of brain tissue with [Tmax > 10 sec/Tmax > 6 sec]); favorable TLC were regarded as HIR 0.4. NWU was determined using a quantitative densitometry approach on follow-up CT. Primary outcome was NWU. Secondary outcome was a good functional outcome (modified Rankin Scale [mRS] 0-2).580 patients met inclusion criteria. Favorable TLC ( 0.65; p < 0.001) predicted smaller NWU after treatment. Favorable TLC (OR: 2.35, [95% CI: 1.31-4.21]; p < 0.001), and decreased NWU (OR: 0.75, [95% CI: 0.70-0.79]; p < 0.001) predicted good functional outcome, while controlling for age, glucose, CTA collaterals, baseline NIHSS and good vessel reperfusion status.We conclude that favorable TLC predict less ischemic lesion NWU after treatment in AIS-LVO patients. Favorable TLC and decreased NWU were independent predictors of good functional outcome.
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http://dx.doi.org/10.1177/0271678X21992200DOI Listing
February 2021

Effect of Oxygen Extraction (Brush-Sign) on Baseline Core Infarct Depends on Collaterals (HIR).

Front Neurol 2020 6;11:618765. Epub 2021 Jan 6.

Interventional and Diagnostic Neuroradiology, Stanford Medical Center, Palo Alto, CA, United States.

Baseline-core-infarct volume is a critical factor in patient selection and outcome in acute ischemic stroke (AIS) before mechanical thrombectomy (MT). We determined whether oxygen extraction efficiency and arterial collaterals, two different physiologic components of the cerebral ischemic cascade, interacted to modulate baseline-core-infarct volume in patients with AIS-LVO undergoing MT triage. Between January 2015 and March 2018, consecutive patients with an AIS and M1 occlusion considered for MT with a baseline MRI and perfusion-imaging were included. Variables such as baseline-core-infarct volume [mL], arterial collaterals (HIR: TMax > 10 s volume/TMax > 6 s), high oxygen extraction (HOE, presence of the brush-sign on T2) were assessed. A linear-regression was used to test the interaction of HOE and HIR with baseline-core-infarct volume, after including potential confounding variables. We included 103 patients. Median age was 70 (58-78), and 63% were female. Median baseline-core-infarct volume was 32 ml (IQR 8-74.5). Seventy six patients (74%) had HOE. In a multivariate analysis both favorable HIR collaterals ( = 0.02) and HOE ( = 0.038) were associated with lower baseline-core-infarct volume. However, HOE significantly interacted with HIR ( = 0.01) to predict baseline-core-infarct volume, favorable collaterals (low HIR) with HOE was associated with small baseline-core-infarct whereas patients with poor collaterals (high HIR) and HOE had large baseline-core-infarct. While HOE under effective collateral blood-flow has the lowest baseline-core-infarct volume of all patients, the protective effect of HOE reverses under poor collateral blood-flow and may be a maladaptive response to ischemic stroke as measured by core infarctions in AIS-LVO patients undergoing MT triage.
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http://dx.doi.org/10.3389/fneur.2020.618765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815586PMC
January 2021

Renal Safety of Multimodal Brain Imaging Followed by Endovascular Therapy.

Stroke 2021 01 30;52(1):313-316. Epub 2020 Nov 30.

Stanford Stroke Center (M.M., S.K., M.G.L., G.W.A.), Stanford University School of Medicine, CA.

Background And Purpose: Contrast-enhanced noninvasive angiography and perfusion imaging are recommended to identify eligible patients for endovascular therapy (EVT) in extended time windows (>6 hours or wake-up). If eligible, additional intraarterial contrast exposure will occur during EVT. We aimed to study the renal safety in the DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) population, selected with contrast-enhanced multimodal Imaging and randomized to EVT versus medical management.

Methods: In the randomized DEFUSE 3 trial population, we compared changes in serum creatinine between baseline (before randomization) and 24 hours later. The primary outcome was the relative change in creatinine level between baseline and 24 hours in the EVT versus medical arm. The secondary outcome was a comparison between computed tomography (CT) versus magnetic resonance imaging selection in the EVT arm. The safety outcome was a comparison of the proportion of patients with criteria for contrast-associated kidney injury in the EVT versus medical arm and a comparison between CT versus magnetic resonance imaging selection in the EVT arm.

Results: In the DEFUSE 3 population (n=182, age 69±13, 51% female), mean creatinine decreased from a baseline of 0.98±0.33 mg/dL to 0.88±0.28 mg/dL at 24 hours (<0.001). There was no difference in change between treatment groups: relative to baseline, there was a 6.3% reduction in the EVT group versus 9.2% in the medical group, =0.294. Absolute decrease -0.08±0.18 in EVT versus -0.12±0.18 in medical, =0.135; Among patients treated with EVT, there was no difference in 24-hour creatinine level changes between patients who were selected with CT angiography/CT perfusion (-0.08±0.18) versus magnetic resonance imaging (-0.07±0.19), =0.808 or 6.8% reduction versus 4.8%, =0.696. In the EVT arm, contrast-associated kidney injury was encountered in 4 out of 91 (4.4%) versus 2/90 (2.2%) in the medical arm =0.682. In the EVT arm, contrast-associated kidney injury was evenly distributed between magnetic resonance imaging (1/22, 4.6%) versus CT 3 out of 69 (4.4%), =1.0.

Conclusions: Perfusion imaging before EVT was not associated with evidence of decline in renal function. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.
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http://dx.doi.org/10.1161/STROKEAHA.120.030816DOI Listing
January 2021

Effect of Sex on Clinical Outcome and Imaging after Endovascular Treatment of Large-Vessel Ischemic Stroke.

J Stroke Cerebrovasc Dis 2021 Feb 21;30(2):105468. Epub 2020 Nov 21.

Stanford Stroke Center, Stanford, United States.

Background And Purpose: It is unclear if sex differences explain some of the variability in the outcomes of stroke patients who undergo endovascular treatment (EVT). In this study we assess the effect of sex on radiological and functional outcomes in EVT-treated acute stroke patients and determine if differences in baseline perfusion status between men and women might account for differences in outcomes.

Methods: We included patients from the CRISP (Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke) study, a prospective cohort study of acute stroke patients who underwent EVT up to 18 hours after last seen well. We designed ordinal regression and univariable and multivariable regression models to examine the association between sex and infarct growth, final infarct volume and 90-day mRS score.

Results: We included 198 patients. At baseline, women had smaller perfusion lesions, more often had a target mismatch perfusion profile, and had better collateral perfusion. Women experienced less ischemic core growth (median 15 mL vs. 29 mL, p < 0.01) and had smaller final infarct volumes (median 26 mL vs. 50 mL, p < 0.01). Female sex was associated with a favorable shift on the modified Rankin Scale (adjusted cOR 1.79 [1.04 - 3.08; p = 0.04]) and lower odds of severe disability or death (adjusted OR 0.29 [0.10 - 0.81]; p = 0.02).

Conclusions: The results suggest that women have better collaterals and, therefore, more often exhibit a favorable imaging profile on baseline imaging, experience less lesion growth, and have better clinical outcomes following endovascular therapy.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856002PMC
February 2021

Hypoperfusion Intensity Ratio Predicts Malignant Edema and Functional Outcome in Large-Vessel Occlusive Stroke with Poor Revascularization.

Neurocrit Care 2020 Nov 16. Epub 2020 Nov 16.

Department of Neurology, Division of Vascular Neurology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.

Background And Objective: Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a < 80 mL ischemic core who do not achieve complete reperfusion.

Methods: We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct < 80 mL, a T > 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6-48 h after the pre-ET perfusion scan.

Results: Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p < 0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was ≥ 0.54 (OR 14.7, 95% CI 2.4-78.0, p = 0.003). HIR was also associated with 3-month mRS (HIR ≥ 0.54 for mRS of 3-6: OR 10.8, 95% CI 1.9-44.0, p = 0.02).

Conclusions: Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.
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http://dx.doi.org/10.1007/s12028-020-01152-6DOI Listing
November 2020

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

J Neurointerv Surg 2020 Nov 13. Epub 2020 Nov 13.

Department of Radiology, University Hospital Munich, Munich, Germany.

Background: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts.

Methods: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials.

Results: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively.

Conclusions: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results.

Clinical Trial Registration: NCT02446587.
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http://dx.doi.org/10.1136/neurintsurg-2020-016766DOI Listing
November 2020

The Effect of Hyperglycemia on Infarct Growth after Reperfusion: An Analysis of the DEFUSE 3 trial.

J Stroke Cerebrovasc Dis 2021 Jan 6;30(1):105380. Epub 2020 Nov 6.

Department of Neurology, University of Utah Medical Center, Salt Lake City, UT, United States. Electronic address:

Background And Purpose: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied.

Materials And Methods: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core.

Results: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03).

Conclusion: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736545PMC
January 2021

A longitudinal study of the post-stroke immune response and cognitive functioning: the StrokeCog study protocol.

BMC Neurol 2020 Aug 26;20(1):313. Epub 2020 Aug 26.

Department of Neurology and Neurological Sciences, Stanford University Medical Center, 213 Quarry Rd, Palo Alto, CA, 94305, USA.

Background: Stroke increases the risk of cognitive impairment even several years after the stroke event. The exact mechanisms of post-stroke cognitive decline are unclear, but the immunological response to stroke might play a role. The aims of the StrokeCog study are to examine the associations between immunological responses and long-term post-stroke cognitive trajectories in individuals with ischemic stroke.

Methods: StrokeCog is a single-center, prospective, observational, cohort study. Starting 6-12 months after stroke, comprehensive neuropsychological assessment, plasma and serum, and psychosocial variables will be collected at up to 4 annual visits. Single cell sequencing of peripheral blood monocytes and plasma proteomics will be conducted. The primary outcome will be the change in global and domain-specific neuropsychological performance across annual evaluations. To explain the differences in cognitive change amongst participants, we will examine the relationships between comprehensive immunological measures and these cognitive trajectories. It is anticipated that 210 participants will be enrolled during the first 3 years of this 4-year study. Accounting for attrition, an anticipated final sample size of 158 participants with an average of 3 annual study visits will be available at the completion of the study. Power analyses indicate that this sample size will provide 90% power to detect an average cognitive change of at least 0.23 standard deviations in either direction.

Discussion: StrokeCog will provide novel insight into the relationships between immune events and cognitive change late after stroke.
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http://dx.doi.org/10.1186/s12883-020-01897-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448308PMC
August 2020

Perioperative Stroke Risk Reduction in Patients With Patent Foramen Ovale.

JAMA Neurol 2020 Dec;77(12):1479-1480

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California.

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http://dx.doi.org/10.1001/jamaneurol.2020.2619DOI Listing
December 2020

Natalizumab in acute ischemic stroke (ACTION II): A randomized, placebo-controlled trial.

Neurology 2020 08 26;95(8):e1091-e1104. Epub 2020 Jun 26.

From Columbia University (M.S.V.E.), New York, NY; Imperial College London (R.V.), UK; Alfried-Krupp Krankenhaus (R.V.), Essen, Germany; Vall d'Hebron Research Institute (VHIR) (J.M.), Barcelona; Institute of Biomedicine of Seville (IBiS) Stroke Programme (J.M.), Spain; University of Texas (S.C.J.), Austin; Massachusetts General Hospital (A.B.S.), Boston; University of Washington (K.B.), Seattle; Stanford University Medical Center (M.G.L.), Stanford Stroke Center, CA; and Biogen (W.T., R.K., J.E.), Cambridge, MA.

Objective: We evaluated the effect of 2 doses of natalizumab on functional outcomes in patients with acute ischemic stroke (AIS).

Methods: In this double-blind phase 2b trial, patients with AIS aged 18-80 years with NIH Stroke Scale scores of 5-23 from 53 US and European sites were randomized 1:1:1 to receive a single dose of 300 or 600 mg IV natalizumab or placebo, with randomization stratified by treatment window (≤9 or >9 to ≤24 hours from patient's last known normal state). The primary endpoint was a composite measure of excellent outcome (modified Rankin Scale score ≤1 and Barthel Index score ≥95) at day 90 assessed in all patients receiving a full dose. Sample size was estimated from a Bayesian model; values were not used for hypothesis testing.

Results: An excellent outcome was less likely with natalizumab than with placebo (natalizumab 300 or 600 mg odds ratio 0.60; 95% confidence interval 0.39-0.93). There was no effect modification by time to treatment or use of thrombolysis/thrombectomy. For natalizumab 300 mg, 600 mg, or placebo, there were no differences in incidence of adverse events (90.0%, 92.1%, and 92.3%, respectively), serious adverse events (25.6%, 32.6%, and 20.9%, respectively), or deaths (6.7%, 4.5%, and 5.5%, respectively).

Conclusions: Natalizumab administered ≤24 hours after AIS did not improve patient outcomes.

Clinicaltrialsgov Identifier: NCT02730455 CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with AIS, an excellent outcome was less likely in patients treated with natalizumab than with placebo.
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http://dx.doi.org/10.1212/WNL.0000000000010038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668547PMC
August 2020

What predicts poor outcome after successful thrombectomy in late time windows?

J Neurointerv Surg 2021 May 17;13(5):421-425. Epub 2020 Jun 17.

Department of Neurology, Stanford University, Stanford, California, USA.

Background: Thrombectomy for acute ischemic stroke treatment leads to improved outcomes, but many patients do not achieve a good outcome despite successful reperfusion. We determined predictors of poor outcome after successful thrombectomy (TICI 2b-3) with an emphasis on modifiable factors.

Methods: Patients from the randomized DEFUSE 3 trial who underwent thrombectomy with TICI 2b-3 revascularization were included. Primary outcome was a poor outcome at 90 days (modified Rankin Scale score 3-6).

Results: 70 patients were included. Poor outcome patients were older (73.5 vs 66.5 years; P=0.01), more likely to be female (68% vs 39%; P=0.02), had higher NIHSS scores (20 vs 13; P<0.001), and had poor cerebral perfusion collaterals (hypoperfusion intensity ratio) (median 0.45 vs 0.38; P=0.03). Following thrombectomy, poor outcome patients had larger 24 hour' core infarctions (median 59.5 vs 29.9 mL; P=0.01), more core infarction growth (median 33.6 vs 13.4 mL; P<0.001), and more mild (65% vs 50%; P=0.02) and severe (18% vs 0%; P=0.01) reperfusion hemorrhage. In a logistic regression analysis, the presence of any reperfusion hemorrhage (OR 3.3 [95% CI, 1.67 to 5]; P=0.001), age (OR 1.1 [95% CI, 1.03 to 1.11], P=0.004), higher NIHSS (OR 1.25 [95% CI, 1.07 to 1.41], P=0.002), and time from imaging to femoral artery puncture (OR 5 [95% CI, 1.16 to 16.67], P=0.03) independently predicted poor outcomes.

Conclusions: In late time windows, both mild and severe reperfusion hemorrhage were associated with poor outcomes. Older age, higher NIHSS, and increased time from imaging to arterial puncture were also associated with poor outcomes despite successful revascularization.

Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02586415.
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http://dx.doi.org/10.1136/neurintsurg-2020-016125DOI Listing
May 2021

Collateral status contributes to differences between observed and predicted 24-h infarct volumes in DEFUSE 3.

J Cereb Blood Flow Metab 2020 10 19;40(10):1966-1974. Epub 2020 May 19.

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.

We previously demonstrated that in the DEFUSE 3 trial, the union of the baseline core and the 24-h Tmax > 6 s perfusion lesion predicts the infarct volume at 24 h. Presently, we assessed if collateral robustness measured by the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index accounts for the variance in these predictions. DEFUSE 3 patients underwent MRI/CT perfusion imaging at baseline and 24 h post-randomization. We compared baseline and follow-up HIR and CBV index across subgroups stratified by differences between predicted and observed 24-h infarct volumes. Of 123 eligible patients, 34 with 24-h infarcts larger than predicted had less favorable collaterals at baseline (HIR 0.43 vs. 0.32,  = 0.006; CBV Index 0.78 vs. 0.85,  = 0.001) and 24 h (HIR 0.56 vs. 0.07,  = 0.004; CBV Index 0.47 vs. 0.73,  = 0.006) compared to 71 patients with more accurate infarct volume prediction. Eighteen patients with 24-h infarcts smaller than predicted had similar baseline collateral scores but more favorable 24-h CBV indices (0.81 vs. 0.73,  = 0.040). Overall, patients with 24-h infarcts larger than predicted had evidence of less favorable baseline collaterals that fail within 24 h, while patients with 24-h infarcts smaller than predicted typically had favorable collaterals that persisted for 24 h.
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http://dx.doi.org/10.1177/0271678X20918816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786839PMC
October 2020

Sex Differences in Oral Anticoagulation and Outcomes of Stroke and Intracranial Bleeding in Newly Diagnosed Atrial Fibrillation.

J Am Heart Assoc 2020 05 12;9(10):e015689. Epub 2020 May 12.

VA Palo Alto Healthcare System Palo Alto CA.

Background Female sex is an independent predictor of stroke in patients with atrial fibrillation (AF). Older data suggest undertreatment with anticoagulation among women compared with men. However, it is unknown if novel therapies and updated guidelines have impacted sex differences in AF treatment and outcomes. Methods and Results We performed a retrospective cohort study of 2.3 million women and men with a new diagnosis of AF and CHADS-VASc ≥2 from Marketscan US commercial claims data from 2008 to 2015 to determine whether women with AF remain undertreated and whether this difference mediates observed differences in outcomes. There were 358 649 patients with newly diagnosed AF (43% women). Compared with men, women were older, with higher CHADS-VASc scores, and higher comorbidity burden (<0.0001 for all). Oral anticoagulation-eligible women with CHADS-VASc scores ≥2 were more likely to not receive anticoagulation (50.0% women versus 43.9% men). Women, compared with men, had a higher risk of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% CI, 1.21-1.32; <0.0001) and hospitalization (aHR, 1.06; 95% CI, 1.05-1.07, <0.0001) but had a lower risk of intracranial bleeding (aHR, 0.91; 95% CI, 0.83-0.99, =0.03). In mediation analysis, nonreceipt of oral anticoagulation partially mediated the observed increased risk of stroke and decreased risk of intracranial bleeding in women. Conclusions In the care of newly diagnosed AF in the United States, women, compared with men, are less likely to receive oral anticoagulation. This appears to mediate the increased risk of both stroke and hospitalization but also appears to mediate lower observed intracranial bleeding risk.
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http://dx.doi.org/10.1161/JAHA.120.015689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660841PMC
May 2020

Tilt-Corrected Region Boundaries May Enhance the Alberta Stroke Program Early Computed Tomography Score for Less Experienced Raters.

J Stroke Cerebrovasc Dis 2020 Jul 16;29(7):104820. Epub 2020 Apr 16.

Stanford Stroke Center, Stanford University School of Medicine, Palo Alto, California.

Background: The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to quantify early ischemic changes in the anterior circulation but has limited inter-rater reliability.

Aims: We investigated whether application of 3-dimensional boundaries outlining the ASPECTS regions improves inter-rater reliability and accuracy.

Methods: We included all patients from our DEFUSE 2 database who had a pretreatment noncontrast computed tomography scan (NCCT) of acceptable quality. Six raters (2 neuroradiologists, 2 vascular neurologists, and 2 neurology residents) scored ASPECTS of each NCCT without ("CT-native") and with the superimposed boundary template ("CT-template"). Gold-standard ASPECTS were generated by the 2 neuroradiologists through joint adjudication. Inter-rater reliability and accuracy were assessed using the intraclass correlation coefficient (ICC) for full-scale agreements and Gwet's AC1 for dichotomized (ASPECTS 0-6 vs 7-10) agreements.

Results: Eighty-two patients were included. Inter-rater reliability improved with higher training level for both CT-native (ICC = .15, .31, .54 for residents, neurologists, and radiologists, respectively) and CT-template (ICC = .18, .33, .56). Use of the boundary template improved correlation with the gold-standard for one resident on full-scale agreement (ICC increased from .01 to .31, P = .01) and another resident on dichotomized agreement (AC1 increased from .36 to .64, P = .01), but resulted in no difference for other raters. The template did not improve ICC between raters of the same training level.

Conclusions: Inter-rater reliability of ASPECTS improves with physician training level. Standardized display of ASPECTS region boundaries on NCCT does not improve inter-rater reliability but may improve accuracy for some less experienced raters.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282975PMC
July 2020

CT perfusion core and ASPECT score prediction of outcomes in DEFUSE 3.

Int J Stroke 2021 Apr 31;16(3):288-294. Epub 2020 Mar 31.

Department of Radiology and Neurosurgery, NeuroInterventional Radiology Section, Stanford University Medical Center, Stanford, CA, USA.

Background: The role of Alberta Stroke Program Early CT Score (ASPECTS) for thrombectomy patient selection and prognostication in late time windows is unknown.

Aims: We compared baseline ASPECTS and core infarction determined by CT perfusion (CTP) as predictors of clinical outcome in the Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE) 3 trial.

Methods: We included all DEFUSE 3 patients with baseline non-contrast CT and CTP imaging. ASPECTS and core infarction were determined by the DEFUSE 3 core laboratory. Primary outcome was functional independence (modified Rankin Scale (mRS) ≤2). Secondary outcomes included ordinal mRS shift at 90 days and final core infarction volume.

Results: Of the 142 patients, 85 patients (60%) had ASPECTS 8-10 and 57 (40%) had ASPECTS 5-7. Thirty-one patients (36%) with ASPECTS 8-10 and 11 patients (19%) with ASPECTS 5-7 were functionally independent at 90 days ( = 0.03). In the primary and secondary logistic regression analysis, there was no difference in ordinal mRS shift ( = 0.98) or functional independence (mRS ≤ 2;  = 0.36) at 90 days between ASPECTS 8-10 and ASPECTS 5-7 patients. Similarly, primary and secondary logistic regression analyses found no difference in ordinal mRS shift ( = 1.0) or functional independence (mRS ≤ 2;  = 0.87) at 90 days between patients with baseline small core ( < 50 ml) versus medium core (50-70 ml).

Conclusions: Higher ASPECTS (8-10) correlated with functional independence at 90 days in the DEFUSE trial. ASPECTS and core infarction volume did not modify the thrombectomy treatment effect, which indicates that patients with a target mismatch profile on perfusion imaging should undergo thrombectomy regardless of ASPECTS or core infarction volume in late time windows.
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http://dx.doi.org/10.1177/1747493020915141DOI Listing
April 2021

Comparison of Tmax values between full- and half-dose gadolinium perfusion studies.

J Cereb Blood Flow Metab 2021 Feb 24;41(2):336-341. Epub 2020 Mar 24.

Department of Radiology, University of Melbourne, Parkville, Australia.

AHA guidelines recommend use of perfusion imaging for patient selection in the 6-24 h window. Recently, the safety of gadolinium-based contrast agents for MR perfusion imaging has been questioned based on findings that gadolinium accumulates in brain tissue. Regulatory bodies have recommended to limit the use of gadolinium-based contrast agents where possible. Focusing specifically on the time to maximum of the tissue residue function (Tmax) parameter, used in DAWN and DEFUSE 3, we hypothesized that half-dose scans would yield a similar Tmax delay pattern to full-dose scans. We prospectively recruited 10 acute ischemic stroke patients imaged with two perfusion scans at their follow-up visit, one with a standard dose gadolinium followed by a half-dose injection a median of 7 min apart. The brain was parcellated into a grid of 3 × 3 regions and the mean of the difference in Tmax between the 3 × 3 regions on the half- and full-dose Tmax maps was 0.1 s (iqr 0.38 s). The fraction of brain tissue that differed by no more than ±1 s was 93.7%. In patients with normal or modest Tmax delays, half-dose gadolinium appears to provide comparable Tmax measurements to those of full-dose scans.
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http://dx.doi.org/10.1177/0271678X20914537DOI Listing
February 2021