Arterial Recanalization During Interhospital Transfer for Thrombectomy.

BACKGROUND: Patients with acute ischemic stroke harboring a large vessel occlusion admitted to nonendovascular-capable centers often require interhospital transfer for thrombectomy. We evaluated the incidence and predictors of arterial recanalization during transfer, as well as the relationship between interhospital recanalization and clinical outcomes. METHODS: We analyzed data from 2 cohorts of patients with an anterior circulation large vessel occlusion transferred for consideration of thrombectomy to a comprehensive center, with arterial imaging at the referring hospital and on comprehensive stroke center arrival. Interhospital recanalization was determined by comparison of the baseline and posttransfer arterial imaging and was defined as revised arterial occlusive lesion (rAOL) score 2b to 3. Pretransfer variables independently associated with interhospital recanalization were studied using multivariable logistic regression analysis. RESULTS: Of the 520 included patients (Montpellier, France, n=237; Stanford, United States, n=283), 111 (21%) experienced interhospital recanalization (partial [rAOL=2b] in 77% and complete [rAOL=3] in 23%). Pretransfer variables independently associated with recanalization were intravenous thrombolysis (adjusted odds ratio, 6.8 [95% CI, 4.0-11.6]), more distal occlusions (intracranial carotid occlusion as reference: adjusted odds ratio, 2.0 [95% CI, 0.9-4.5] for proximal first segment of the middle cerebral artery, 5.1 [95% CI, 2.3-11.5] for distal first segment of the middle cerebral artery, and 5.0 [95% CI, 2.1-11.8] for second segment of the middle cerebral artery), and smaller clot burden (clot burden score 0-4 as reference: adjusted odds ratio, 3.4 [95% CI, 1.5-7.6] for 5-7 and 5.6 [95% CI, 2.4-12.7] for 8-9). Recanalization on arrival at the comprehensive center was associated with less interhospital infarct growth (rAOL, 0-2a: 11.6 mL; rAOL, 2b: 2.2 mL; rAOL, 3: 0.6 mL; Ptrend<0.001) and greater interhospital National Institutes of Health Stroke Scale score improvement (0 versus -5 versus -6; Ptrend<0.001). Interhospital recanalization was associated with reduced 3-month disability (adjusted common odds ratio, 2.51 [95% CI, 1.68-3.77]) with greater benefit from complete than partial recanalization. CONCLUSIONS: Recanalization is frequently observed during interhospital transfer for thrombectomy and is strongly associated with favorable outcomes, even when partial. Broadening thrombolysis indications in primary centers, and developing therapies that increase recanalization during transfer, will likely improve clinical outcomes.

Clinical change during inter-hospital transfer for thrombectomy: Incidence, associated factors, and relationship with outcome.

BACKGROUND: Patients with acute ischemic stroke with a large vessel occlusion (LVO) admitted to non endovascular-capable centers often require inter-hospital transfer for thrombectomy. We aimed to describe the incidence of substantial clinical change during transfer, the factors associated with clinical change, and its relationship with 3-month outcome. METHODS: We analyzed data from two cohorts of acute stroke patients transferred for thrombectomy to a comprehensive center (Stanford, USA, November 2019 to January 2023; Montpellier, France, January 2015 to January 2017), regardless of whether thrombectomy was eventually attempted. Patients were included if they had evidence of an LVO at the referring hospital and had a National Institute of Health Stroke Scale (NIHSS) score documented before and immediately after transfer. Inter-hospital clinical change was categorized as improvement (⩾4 points and ⩾25% decrease between the NIHSS score in the referring hospital and upon comprehensive center arrival), deterioration (⩾4 points and ⩾25% increase), or stability (neither improvement nor deterioration). The stable group was considered as the reference and was compared to the improvement or deterioration groups separately. RESULTS: A total of 504 patients were included, of whom 22% experienced inter-hospital improvement, 14% deterioration, and 64% were stable. Pre-transfer variables independently associated with clinical improvement were intravenous thrombolysis use, more distal occlusions, and lower serum glucose; variables associated with deterioration included more proximal occlusions and higher serum glucose. On post-transfer imaging, clinical improvement was associated with arterial recanalization and smaller infarct growth and deterioration with larger infarct growth. As compared to stable patients, those with clinical improvement had better 3-month functional outcome (adjusted common odds ratio (cOR) = 2.43; 95% confidence interval (CI) = 1.59-3.71; p < 0.001), while those with deterioration had worse outcome (adjusted cOR = 0.60; 95% CI = 0.37-0.98; p = 0.044). CONCLUSION: Substantial inter-hospital clinical changes are frequently observed in LVO-related ischemic strokes, with significant impact on functional outcome. There is a need to develop treatments that improves the clinical status during transfer. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection.

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).

Endovascular Thrombectomy Treatment Effect in Direct vs Transferred Patients With Large Ischemic Strokes: A Prespecified Analysis of the SELECT2 Trial.

Importance: Patients with large ischemic core stroke have poor clinical outcomes and are frequently not considered for interfacility transfer for endovascular thrombectomy (EVT). Objective: To assess EVT treatment effects in transferred vs directly presenting patients and to evaluate the association between transfer times and neuroimaging changes with EVT clinical outcomes. Design, Setting, and Participants: This prespecified secondary analysis of the SELECT2 trial, which evaluated EVT vs medical management (MM) in patients with large ischemic stroke, evaluated adults aged 18 to 85 years with acute ischemic stroke due to occlusion of the internal carotid or middle cerebral artery (M1 segment) as well as an Alberta Stroke Program Early CT Score (ASPECTS) of 3 to 5, core of 50 mL or greater on imaging, or both. Patients were enrolled between October 2019 and September 2022 from 31 EVT-capable centers in the US, Canada, Europe, Australia, and New Zealand. Data were analyzed from August 2023 to January 2024. Interventions: EVT vs MM. Main Outcomes and Measures: Functional outcome, defined as modified Rankin Scale (mRS) score at 90 days with blinded adjudication. Results: A total of 958 patients were screened and 606 patients were excluded. Of 352 enrolled patients, 145 (41.2%) were female, and the median (IQR) age was 66.5 (58-75) years. A total of 211 patients (59.9%) were transfers, while 141 (40.1%) presented directly. The median (IQR) transfer time was 178 (136-230) minutes. The median (IQR) ASPECTS decreased from the referring hospital (5 [4-7]) to an EVT-capable center (4 [3-5]). Thrombectomy treatment effect was observed in both directly presenting patients (adjusted generalized odds ratio [OR], 2.01; 95% CI, 1.42-2.86) and transferred patients (adjusted generalized OR, 1.50; 95% CI, 1.11-2.03) without heterogeneity (P for interaction = .14). Treatment effect point estimates favored EVT among 82 transferred patients with a referral hospital ASPECTS of 5 or less (44 received EVT; adjusted generalized OR, 1.52; 95% CI, 0.89-2.58). ASPECTS loss was associated with numerically worse EVT outcomes (adjusted generalized OR per 1-ASPECTS point loss, 0.89; 95% CI, 0.77-1.02). EVT treatment effect estimates were lower in patients with transfer times of 3 hours or more (adjusted generalized OR, 1.15; 95% CI, 0.73-1.80). Conclusions and Relevance: Both directly presenting and transferred patients with large ischemic stroke in the SELECT2 trial benefited from EVT, including those with low ASPECTS at referring hospitals. However, the association of EVT with better functional outcomes was numerically better in patients presenting directly to EVT-capable centers. Prolonged transfer times and evolution of ischemic change were associated with worse EVT outcomes. These findings emphasize the need for rapid identification of patients suitable for transfer and expedited transport. Trial Registration: ClinicalTrials.gov Identifier: NCT03876457.

Random expert sampling for deep learning segmentation of acute ischemic stroke on non-contrast CT.

BACKGROUND: Outlining acutely infarcted tissue on non-contrast CT is a challenging task for which human inter-reader agreement is limited. We explored two different methods for training a supervised deep learning algorithm: one that used a segmentation defined by majority vote among experts and another that trained randomly on separate individual expert segmentations. METHODS: The data set consisted of 260 non-contrast CT studies in 233 patients with acute ischemic stroke recruited from the multicenter DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. Additional external validation was performed using 33 patients with matched stroke onset times from the University Hospital Lausanne. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. The median of volume, overlap, and distance segmentation metrics were determined for agreement in lesion segmentations between (1) three experts, (2) the majority model and each expert, and (3) the random model and each expert. The two sided Wilcoxon signed rank test was used to compare performances (1) to 2) and (1) to (3). We further compared volumes with the 24 hour follow-up diffusion weighted imaging (DWI, final infarct core) and correlations with clinical outcome (modified Rankin Scale (mRS) at 90 days) with the Spearman method. RESULTS: The random model outperformed the inter-expert agreement ((1) to (2)) and the majority model ((1) to (3)) (dice 0.51±0.04 vs 0.36±0.05 (P<0.0001) vs 0.45±0.05 (P<0.0001)). The random model predicted volume correlated with clinical outcome (0.19, P<0.05), whereas the median expert volume and majority model volume did not. There was no significant difference when comparing the volume correlations between random model, median expert volume, and majority model to 24 hour follow-up DWI volume (P>0.05, n=51). CONCLUSION: The random model for ischemic injury delineation on non-contrast CT surpassed the inter-expert agreement ((1) to (2)) and the performance of the majority model ((1) to (3)). We showed that the random model volumetric measures of the model were consistent with 24 hour follow-up DWI.

A Clinical and Imaging Fused Deep Learning Model Matches Expert Clinician Prediction of 90-Day Stroke Outcomes.

BACKGROUND AND PURPOSE: Predicting long-term clinical outcome in acute ischemic stroke is beneficial for prognosis, clinical trial design, resource management, and patient expectations. This study used a deep learning-based predictive model (DLPD) to predict 90-day mRS outcomes and compared its predictions with those made by physicians. MATERIALS AND METHODS: A previously developed DLPD that incorporated DWI and clinical data from the acute period was used to predict 90-day mRS outcomes in 80 consecutive patients with acute ischemic stroke from a single-center registry. We assessed the predictions of the model alongside those of 5 physicians (2 stroke neurologists and 3 neuroradiologists provided with the same imaging and clinical information). The primary analysis was the agreement between the ordinal mRS predictions of the model or physician and the ground truth using the Gwet Agreement Coefficient. We also evaluated the ability to identify unfavorable outcomes (mRS >2) using the area under the curve, sensitivity, and specificity. Noninferiority analyses were undertaken using limits of 0.1 for the Gwet Agreement Coefficient and 0.05 for the area under the curve analysis. The accuracy of prediction was also assessed using the mean absolute error for prediction, percentage of predictions ±1 categories away from the ground truth (±1 accuracy [ACC]), and percentage of exact predictions (ACC). RESULTS: To predict the specific mRS score, the DLPD yielded a Gwet Agreement Coefficient score of 0.79 (95% CI, 0.71-0.86), surpassing the physicians' score of 0.76 (95% CI, 0.67-0.84), and was noninferior to the readers (P < .001). For identifying unfavorable outcome, the model achieved an area under the curve of 0.81 (95% CI, 0.72-0.89), again noninferior to the readers' area under the curve of 0.79 (95% CI, 0.69-0.87) (P < .005). The mean absolute error, ±1ACC, and ACC were 0.89, 81%, and 36% for the DLPD. CONCLUSIONS: A deep learning method using acute clinical and imaging data for long-term functional outcome prediction in patients with acute ischemic stroke, the DLPD, was noninferior to that of clinical readers.

Endovascular thrombectomy plus medical care versus medical care alone for large ischaemic stroke: 1-year outcomes of the SELECT2 trial.

BACKGROUND: Multiple randomised trials have shown efficacy and safety of endovascular thrombectomy in patients with large ischaemic stroke. The aim of this study was to evaluate long-term (ie, at 1 year) evidence of benefit of thrombectomy for these patients. METHODS: SELECT2 was a phase 3, open-label, international, randomised controlled trial with blinded endpoint assessment, conducted at 31 hospitals in the USA, Canada, Spain, Switzerland, Australia, and New Zealand. Patients aged 18-85 years with ischaemic stroke due to proximal occlusion of the internal carotid artery or of the first segment of the middle cerebral artery, showing large ischaemic core on non-contrast CT (Alberta Stroke Program Early Computed Tomographic Score of 3-5 [range 0-10, with lower values indicating larger infarctions]) or measuring 50 mL or more on CT perfusion and MRI, were randomly assigned, within 24 h of ischaemic stroke onset, to thrombectomy plus medical care or to medical care alone. The primary outcome for this analysis was the ordinal modified Rankin Scale (range 0-6, with higher scores indicating greater disability) at 1-year follow-up in an intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT03876457) and is completed. FINDINGS: The trial was terminated early for efficacy at the 90-day follow-up after 352 patients had been randomly assigned (178 to thrombectomy and 174 to medical care only) between Oct 11, 2019, and Sept 9, 2022. Thrombectomy significantly improved the 1-year modified Rankin Scale score distribution versus medical care alone (Wilcoxon-Mann-Whitney probability of superiority 0·59 [95% CI 0·53-0·64]; p=0·0019; generalised odds ratio 1·43 [95% CI 1·14-1·78]). At the 1-year follow-up, 77 (45%) of 170 patients receiving thrombectomy had died, compared with 83 (52%) of 159 patients receiving medical care only (1-year mortality relative risk 0·89 [95% CI 0·71-1·11]). INTERPRETATION: In patients with ischaemic stroke due to a proximal occlusion and large core, thrombectomy plus medical care provided a significant functional outcome benefit compared with medical care alone at 1-year follow-up. FUNDING: Stryker Neurovascular.

Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (ß estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

Insole Pressure Sensors to Assess Post-Stroke Gait.

OBJECTIVE: To confirm that the simplified insole does not affect the gait speed and to identify objective sensor-based gait parameters that correlate strongly with existing clinical gait assessment scales. METHODS: Ten participants with gait impairment due to hemiplegic stroke were enrolled in this study. Pairs of insoles with four pressure sensors on each side were manufactured and placed in each shoe. Data were extracted during the 10-Meter Walk Test. Several sensor-derived parameters (for example stance time, heel_on-to-toe_peak time, and toe_peak pressure) were calculated and correlated with gait speed and lower extremity Fugl-Meyer (F-M) score. RESULTS: The insole pressure sensor did not affect gait, as indicated by a strong correlation (ρ=0.988) and high agreement (ICC=0.924) between the gait speeds with and without the insole. The parameters that correlated most strongly with highest ß coefficients against the clinical measures were stance time of the non-hemiplegic leg (ß=-0.87 with F-M and ß=-0.95 with gait speed) and heel_on-to-toe_peak time of the non-hemiplegic leg (ß=-0.86 with F-M and -0.94 with gait speed). CONCLUSION: Stance time of the non-hemiparetic leg correlates most strongly with clinical measures and can be assessed using a non-obtrusive insole pressure sensor that does not affect gait function. These results suggest that an insole pressure sensor, which is applicable in a home environment, may be useful as a clinical endpoint in post-stroke gait therapy trials.

Early neurological deterioration in patients with acute ischemic stroke is linked to unfavorable cerebral venous outflow.

INTRODUCTION: Early neurological deterioration (END) is associated with poor outcomes in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Causes of END after mechanical thrombectomy (MT) include unsuccessful recanalization and reperfusion hemorrhages. However, little is known about END excluding the aforementioned causes. We aimed to investigate factors associated with unexplained END (ENDunexplained) with regard to the cerebral collateral status. PATIENTS AND METHODS: Multicenter retrospective study of AIS-LVO patients with successful MT (mTICI 2b-3). On admission CT angiography (CTA), pial arterial collaterals and venous outflow (VO) were assessed using the modified Tan-Scale and the Cortical Vein Opacification Score (COVES), respectively. ENDunexplained was defined as an increase in NIHSS score of ⩾ 4 within the first 24 hours after MT without parenchymal hemorrhage on follow-up imaging. Multivariable regression analyses were performed to examine factors of ENDunexplained and unfavorable functional outcome (modified Rankin Scale score 3-6). RESULTS: A total of 620 patients met the inclusion criteria. ENDunexplained occurred in 10% of patients. While there was no significant difference in pial arterial collaterals, patients with ENDunexplained exhibited more often unfavorable VO (81% vs. 53%; P < 0.001). Unfavorable VO (aOR [95% CI]; 2.56 [1.02-6.40]; P = 0.045) was an independent predictor of ENDunexplained. ENDunexplained was independently associated with unfavorable functional outcomes at 90 days (aOR [95% CI]; 6.25 [2.06-18.94]; P = 0.001). DISCUSSION AND CONCLUSION: Unfavorable VO on admission CTA was associated with ENDunexplained. ENDunexplained was independently linked to unfavorable functional outcomes at 90 days. Identifying AIS-LVO patients at risk of ENDunexplained may help to select patients for intensified monitoring and guide to optimal treatment regimes.

Priorities for Advancements in Neuroimaging in the Diagnostic Workup of Acute Stroke.

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes.

Semiautomated Detection of Early Infarct Signs on Noncontrast CT Improves Interrater Agreement.

BACKGROUND: Acute ischemic infarct identification on noncontrast computed tomography (NCCT) is highly variable between raters. A semiautomated method for segmentation of acute ischemic lesions on NCCT may improve interrater reliability. METHODS: Patients with successful endovascular reperfusion from the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) were included. We created relative NCCT (rNCCT) color-gradient overlays by comparing the density of a voxel on NCCT to the homologous region in the contralateral hemisphere. Regions with a relative hypodensity of at least 5% were visualized. We coregistered baseline and follow-up images. Two neuroradiologists and 6 nonradiologists segmented the acute ischemic lesion on the baseline scans with 2 methods: (1) manually outlining hypodense regions on the NCCT (unassisted segmentation) and (2) manually excluding areas deemed outside of the ischemic lesion on the rNCCT color map (rNCCT-assisted segmentation). Voxelwise interrater agreement was quantified using the Dice similarity coefficient and volumetric agreement between raters with the detection index (DI), defined as the true positive volume minus the false positive volume. RESULTS: From a total of 92, we included 61 patients. Median age was 59 (64-77), and 57% were female. Stroke onset was known in 39%. Onset to NCCT was median, 8.5 hours (7-11) and median 10 hours (8.4-11.5) in patients with known and unknown onset, respectively. Compared with unassisted NCCT segmentation, rNCCT-assisted segmentation increased the Dice similarity coefficient by >50% for neuroradiologists (Dice similarity coefficient, 0.38 versus 0.83; P<0.001) and nonradiologists (Dice similarity coefficient, 0.14 versus 0.84; P<0.001), and improved the DI among nonradiologists (mean improvement, 5.8 mL [95% CI, 3.1-8.5] mL, P<0.001) but not among neuroradiologists. CONCLUSIONS: The high variability of manual segmentations of the acute ischemic lesion on NCCT is greatly reduced using semiautomated rNCCT. The rNCCT map may therefore aid acute infarct detection and provide more reliable infarct estimates for clinicians with less experience.

Brain edema growth after thrombectomy is associated with comprehensive collateral blood flow.

BACKGROUND: We determined whether a comprehensive assessment of cerebral collateral blood flow is associated with ischemic lesion edema growth in patients successfully treated by thrombectomy. METHODS: This was a multicenter retrospective study of ischemic stroke patients who underwent thrombectomy treatment of large vessel occlusions. Collateral status was determined using the cerebral collateral cascade (CCC) model, which comprises three components: arterial collaterals (Tan Scale) and venous outflow profiles (Cortical Vein Opacification Score) on CT angiography, and tissue-level collaterals (hypoperfusion intensity ratio) on CT perfusion. Quantitative ischemic lesion net water uptake (NWU) was used to determine edema growth between admission and follow-up non-contrast head CT (ΔNWU). Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and venous outflow), CCC- (poor pial collaterals, tissue-level collaterals, and venous outflow), and CCCmixed (remainder of patients). Primary outcome was ischemic lesion edema growth (ΔNWU). Multivariable regression models were used to assess the primary and secondary outcomes. RESULTS: 538 patients were included. 157 patients had CCC+, 274 patients CCCmixed, and 107 patients CCC- profiles. Multivariable regression analysis showed that compared with patients with CCC+ profiles, CCC- (ß 1.99, 95% CI 0.68 to 3.30, P=0.003) and CCC mixed (ß 1.65, 95% CI 0.75 to 2.56, P<0.001) profiles were associated with greater ischemic lesion edema growth (ΔNWU) after successful thrombectomy treatment. ΔNWU (OR 0.74, 95% CI 0.68 to 0.8, P<0.001) and CCC+ (OR 13.39, 95% CI 4.88 to 36.76, P<0.001) were independently associated with functional independence. CONCLUSION: A comprehensive assessment of cerebral collaterals using the CCC model is strongly associated with edema growth and functional independence in acute stroke patients successfully treated by endovascular thrombectomy.

Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters.

BACKGROUND: Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters. METHODS: We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass. RESULTS: The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min). CONCLUSION: BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

Larger ischemic cores and poor collaterals among large vessel occlusions presenting in the late evening.

BACKGROUND: Components critical to cerebral perfusion have been noted to oscillate over a 24-h cycle. We previously reported that ischemic core volume has a diurnal relationship with stroke onset time when examined as dichotomized epochs (i.e. Day, Evening, Night) in a cohort of over 1,500 large vessel occlusion (LVO) patients. In this follow-up analysis, our goal was to explore if there is a sinusoidal relationship between ischemic core, collateral status (as measured by HIR), and stroke onset time. METHODS: We retrospectively examined collection of LVO patients with baseline perfusion imaging performed within 24 h of stroke onset from four international comprehensive stroke centers. Both ischemic core volume and HIR, were utilized as the primary radiographic parameters. To evaluate for differences in these parameters over a continuous 24-h cycle, we conducted a sinusoidal regression analysis after linearly regressing out the confounders age and time to imaging. RESULTS: A total of 1506 LVO cases were included, with a median ischemic core volume of 13.0 cc (IQR: 0.0-42.0) and median HIR of 0.4 (IQR: 0.2-0.6). Ischemic core volume varied by stroke onset time in the unadjusted (p = 0.001) and adjusted (p = 0.003) sinusoidal regression analysis with a peak in core volume around 7:45PM. HIR similarly varied by stroke onset time in the unadjusted (p = 0.004) and adjusted (p = 0.002) models with a peak in HIR values at around 8:18PM. CONCLUSION: The results suggest that critical factors to the development of the ischemic core vary by stroke onset time and peak around 8PM. When placed in the context of prior studies, strongly suggest a diurnal component to the development of the ischemic core.

Factors Associated With Fast Early Infarct Growth in Patients With Acute Ischemic Stroke With a Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: The optimal methods for predicting early infarct growth rate (EIGR) in acute ischemic stroke with a large vessel occlusion (LVO) have not been established. We aimed to study the factors associated with EIGR, with a focus on the collateral circulation as assessed by the hypoperfusion intensity ratio (HIR) on perfusion imaging, and determine whether the associations found are consistent across imaging modalities. METHODS: Retrospective multicenter international study including patients with anterior circulation LVO-related acute stroke with witnessed stroke onset and baseline perfusion imaging (MRI or CT) performed within 24 hours from symptom onset. To avoid selection bias, patients were selected from (1) the prospective registries of 4 comprehensive stroke centers with systematic use of perfusion imaging and including both thrombectomy-treated and untreated patients and (2) 1 prospective thrombectomy study where perfusion imaging was acquired per protocol, but treatment decisions were made blinded to the results. EIGR was defined as infarct volume on baseline imaging divided by onset-to-imaging time and fast progressors as EIGR ≥10 mL/h. The HIR, defined as the proportion of time-to-maximum (Tmax) >6 second with Tmax >10 second volume, was measured on perfusion imaging using RAPID software. The factors independently associated with fast progression were studied using multivariable logistic regression models, with separate analyses for CT- and MRI-assessed patients. RESULTS: Overall, 1,127 patients were included (CT, n = 471; MRI, n = 656). Median age was 74 years (interquartile range [IQR] 62-83), 52% were male, median NIH Stroke Scale was 16 (IQR 9-21), median HIR was 0.42 (IQR 0.26-0.58), and 415 (37%) were fast progressors. The HIR was the primary factor associated with fast progression, with very similar results across imaging modalities: The proportion of fast progressors was 4% in the first HIR quartile (i.e., excellent collaterals), ∼15% in the second, ∼50% in the third, and ∼77% in the fourth (p < 0.001 for each imaging modality). Fast progression was independently associated with poor 3-month functional outcome in both the CT and MRI cohorts (p < 0.001 and p = 0.030, respectively). DISCUSSION: The HIR is the primary factor associated with fast infarct progression, regardless of imaging modality. These results have implication for neuroprotection trial design, as well as informing triage decisions at primary stroke centers.

USE-Evaluator: Performance metrics for medical image segmentation models supervised by uncertain, small or empty reference annotations in neuroimaging.

Performance metrics for medical image segmentation models are used to measure the agreement between the reference annotation and the predicted segmentation. Usually, overlap metrics, such as the Dice, are used as a metric to evaluate the performance of these models in order for results to be comparable. However, there is a mismatch between the distributions of cases and the difficulty level of segmentation tasks in public data sets compared to clinical practice. Common metrics used to assess performance fail to capture the impact of this mismatch, particularly when dealing with datasets in clinical settings that involve challenging segmentation tasks, pathologies with low signal, and reference annotations that are uncertain, small, or empty. Limitations of common metrics may result in ineffective machine learning research in designing and optimizing models. To effectively evaluate the clinical value of such models, it is essential to consider factors such as the uncertainty associated with reference annotations, the ability to accurately measure performance regardless of the size of the reference annotation volume, and the classification of cases where reference annotations are empty. We study how uncertain, small, and empty reference annotations influence the value of metrics on a stroke in-house data set regardless of the model. We examine metrics behavior on the predictions of a standard deep learning framework in order to identify suitable metrics in such a setting. We compare our results to the BRATS 2019 and Spinal Cord public data sets. We show how uncertain, small, or empty reference annotations require a rethinking of the evaluation. The evaluation code was released to encourage further analysis of this topic https://github.com/SophieOstmeier/UncertainSmallEmpty.git.