Final Infarct Volume Research Articles

Agreement of three CT perfusion software packages in patients with acute ischemic stroke: A comparison with RAPID

PurposeTo compare ischemic core volume (ICV) and penumbra volume (PV) measured by MIStar, F-STROKE, and Syngo.via with that measured by RAPID in acute ischemic stroke (AIS), and their concordance in selecting patients for endovascular thrombectomy (EVT). MethodsComputed tomography perfusion (CTP) data were processed with four software packages. Bland–Altman analysis and intraclass correlation coefficient (ICC) were performed to evaluate their agreement in quantifying ICV and PV. Kappa test was conducted to assess consistency in the selection of EVT candidates. The correlation between predicted ICV and segmented final infarct volume (FIV) on follow-up images was investigated. ResultsA total of 91 patients were retrospectively included. F-STROKE had the best consistency with RAPID (ICV: ICC = 0.97; PV: ICC = 0.84) and Syngo.via had the worst consistency (ICV: ICC = 0.77; PV: ICC = 0.66). F-STROKE had the narrowest limits of agreements both in ICV (−27.02, 24.40 mL) and PV (−85.59, 101.80 mL). When selecting EVT candidates, MIStar (kappa = 0.71–0.88) and F-STROKE (kappa = 0.84–0.90) had good to excellent consistency with RAPID, while Syngo.via had poor consistency (kappa = 0.20–0.41). ICV predicted by MIStar was correlated strongest with FIV (r = 0.77). ConclusionsF-STROKE is most consistent with RAPID in quantitative ICV and PV. F-STROKE and MIStar exhibit similar EVT candidate selection to RAPID. Syngo.via, for its part, seems to have overestimated ICV and underestimated PV, leading to an overly restrictive selection of EVT candidates.

Safety and efficacy of periprocedural antithrombotics in patients with successful reperfusion after endovascular stroke treatment

ObjectivesWe aimed to evaluate whether the overall harmful effect of periprocedural treatment with aspirin or heparin during endovascular stroke treatment is different in patients with a successful reperfusion after the procedure. Materials and methodsWe performed a post-hoc analysis of the MR CLEAN-MED trial, including adult patients with a large vessel occlusion in the anterior circulation eligible for endovascular treatment (EVT). In this trial, patients were randomized for periprocedural intravenous treatment with aspirin or no aspirin (1:1 ratio), and for moderate-dose unfractionated heparin, low-dose unfractionated heparin or no unfractionated heparin (1:1:1 ratio). We tested for interaction between the post-EVT extended thrombolysis in cerebral infarction (eTICI) score and treatment with periprocedural medication with multivariable regression analyses. The primary outcome was the modified Rankin Scale score at 90 days. Secondary outcomes were final infarct volume, intracranial hemorrhage, and symptomatic intracranial hemorrhage. ResultsOf 534 included patients, 93 (17%) had a post-EVT eTICI score of 0-2a, 115 (22%) a score of 2b, 73 (14%) a score of 2c, and 253 (47%) a score of 3. For both aspirin and heparin, we found no interaction between post-EVT eTICI score and treatment on the modified Rankin Scale score (p=0.76 and p=0.47, respectively). We found an interaction between post-EVT eTICI score and treatment with heparin on the final infarct volume (p=0.01). Of note, this interaction showed a biologically implausible distribution over the subgroups. ConclusionsThe overall harmful effect of periprocedural aspirin and unfractionated heparin is not different in patients with a successful reperfusion after EVT.

Comparison of automated ASPECTS, large vessel occlusion detection and CTP analysis provided by Brainomix and RapidAI in patients with suspected ischaemic stroke

ObjectivesThe ischaemic core and penumbra volumes derived from CTP aid the selection of patients with an arterial occlusion for mechanical thrombectomy. Different post-processing software packages may give different CTP outputs, potentially causing variable patient selection for mechanical thrombectomy. The study aims were, firstly, to assess the correlation in CTP outputs from software packages provided by Brainomix and RapidAI. Secondly, the correlation between automated ASPECTS and neuroradiologist-derived ASPECTS and accuracy in detecting large vessel occlusion was assessed. Materials and MethodsThis retrospective study included patients undergoing CTP for suspected anterior circulation large vessel occlusion. Pearson's correlation coefficient was used for testing the correlation in CTP outputs, ASPECTS/automated ASPECTS, and—in those with complete or near complete occlusion—final infarct volume. Diagnostic statistics were calculated for large vessel occlusion detection. ResultsCorrelation was high for ischaemic core and penumbra volumes (0.862 and 0.832, respectively) but lower for the mismatch ratio (0.477). Agreement in mechanical thrombectomy eligibility was achieved in 85% of cases (46/54). Correlation between ischaemic core and final infarct volume was higher for Brainomix (0.757) than for RapidAI (0.595). The correlation between ASPECTS and automated ASPECTS (0.738 and 0.659) and the accuracy of detecting large vessel occlusion (77% and 71%) was higher for Brainomix than for RapidAI. ConclusionThere was high correlation between the CTP output from Brainomix and RapidAI. However, there was a difference in MT eligibility in 15% of cases, which highlights that the decision regarding MT should not be based on imaging parameters alone.

Optimizing the Definition of Ischemic Core in CT Perfusion: Influence of Infarct Growth and Tissue-Specific Thresholds.

CTP allows estimating ischemic core in patients with acute stroke. However, these estimations have limited accuracy compared with MR imaging. We studied the effect of applying WM- and GM-specific thresholds and analyzed the infarct growth from baseline imaging to reperfusion. This was a single-center cohort of consecutive patients (n = 113) with witnessed strokes due to proximal carotid territory occlusions with baseline CT perfusion, complete reperfusion, and follow-up DWI. We segmented GM and WM, coregistered CTP with DWI, and compared the accuracy of the different predictions for each voxel on DWI through receiver operating characteristic analysis. We assessed the yield of different relative CBF thresholds to predict the final infarct volume and an estimated infarct growth-corrected volume (subtracting the infarct growth from baseline imaging to complete reperfusion) for a single relative CBF threshold and GM- and WM-specific thresholds. The fixed threshold underestimated lesions in GM and overestimated them in WM. Double GM- and WM-specific thresholds of relative CBF were superior to fixed thresholds in predicting infarcted voxels. The closest estimations of the infarct on DWI were based on a relative CBF of 25% for a single threshold, 35% for GM, and 20% for WM, and they decreased when correcting for infarct growth: 20% for a single threshold, 25% for GM, and 15% for WM. The combination of 25% for GM and 15% for WM yielded the best prediction. GM- and WM-specific thresholds result in different estimations of ischemic core in CTP and increase the global accuracy. More restrictive thresholds better estimate the actual extent of the infarcted tissue.

Effect of an individualized versus standard blood pressure management during mechanical thrombectomy for anterior ischemic stroke: the DETERMINE randomized controlled trial

BackgroundHypotension and blood pressure (BP) variability during endovascular therapy (EVT) for acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO) is associated with worse outcomes. However, the optimal BP threshold during EVT is still unknown given the lack of randomized controlled evidence. We designed the DETERMINE trial to assess whether an individualized BP management during EVT could achieve better functional outcomes compared to a standard BP management.MethodsThe DETERMINE trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial (PROBE design). AIS patients with a proximal anterior LVO are randomly assigned, in a 1:1 ratio, to an experimental arm in which mean arterial pressure (MAP) is maintained within 10% of the first MAP measured before EVT, or a control arm in which systolic BP (SBP) is maintained within 140–180 mm Hg until reperfusion is achieved or artery closure in case of EVT failure. The primary outcome is the rate of favorable functional outcomes, defined by a modified Rankin Scale (mRS) between 0 and 2 at 90 days. Secondary outcomes include excellent outcome and ordinal analysis of the mRS at 90 days, early neurological improvement at 24 h (National Institutes of Health Stroke Scale), final infarct volume, symptomatic intracranial hemorrhage rates, and all-cause mortality at 90 days. Overall, 432 patients will be included.DiscussionDETERMINE will assess the clinical relevance of an individualized BP management before reperfusion compared to the one size fits all approach currently recommended by international guidelines.Trial registrationClinicalTrials.gov, NCT04352296. Registered on 20th April 2020.

BNP on Admission Combined with Imaging Markers of Multimodal CT to Predict the Risk of Cardioembolic Stroke.

Background The aim of the study was to find the potential roles of B-type natriuretic peptide (BNP) and imaging markers on distinguishing cardioembolic (CE) stroke from non-CE stroke, so as to provide useful information for making individualized endovascular treatment (EVT) plan for the patients with acute ischemic stroke (AIS). Methods The patients with unilateral anterior circulation large vessel occlusion who underwent EVT between March 2016 and December 2021 were analyzed in this study, retrospectively. The risk factors, laboratory test indicators, imaging parameters, and other factors were compared between the CE group and non-CE group. Logistic regression was used to analyze the risk factors of CE stroke. ROC curves were used to assess the values of different parameters on distinguishing CE stroke from non-CE stroke. The relationships between BNP and imaging parameters were assessed using the Spearman correlation analysis. Results 160 patients were enrolled in the study and divided into the CE group (n = 66) and non-CE group (n = 94). BNP (odds ratio (OR) = 1.004; 95% CI, 1.001-1.009; p = 0.038), MMR (OR = 0.736; 95% CI, 0.573-0.945; p = 0.016), NIHSS (OR = 1.150; 95% CI, 1.022-1.294; p = 0.020), and AF (OR = 556.968; 95% CI, 51.739-5995.765; p < 0.001) were the independent predictive factors of CE stroke. The area under the curve (AUC) of BNP and mismatch ratio (MMR) were 0.846 (95% CI (0.780-0.898), p < 0.001) and 0.636 (95% CI (0.633-0.779), p < 0.001), respectively. The cut-off value of BNP was 249.23 pg/mL with the sensitivity of 74.24% and the specificity of 82.98%. BNP combined with MMR improved the predictive value for CE stroke. The AUC of the combination was 0.858 with the sensitivity of 84.85% and the specificity of 73.40%. BNP was correlated with 4D CTA collateral score, MMR, clot burden score, final infarct volume, infarct core volume, and ischemic penumbra volume (all, p < 0.05). Conclusion BNP on admission combined with MMR is valuable for the risk prediction of CE stroke, which will promote the further screening of the high-risk patients with CE stroke and provide more diagnostic information for clinicians.

Reader Response: Clinical Outcome After Endovascular Treatment in Patients With Active Cancer and Ischemic Stroke: A MR CLEAN Registry Substudy.

We thank the authors for their contribution to an improved understanding of efficacy and complications of endovascular treatment (EVT) in patients with active malignancy.1 The findings of the study that patients with active cancer experienced worse outcomes after EVT, even with favorable prestroke function and technical success, is in agreement with data from the ESCAPE and ESCAPE-NA1 trials of EVT. In both these trials, we found that experiencing comorbid cancer was strongly associated with poor functional outcomes according to the modified Rankin scale score in patients at 90 days, despite achieving small final infarct volumes after EVT.2,3 While these data can help us adjust our expectations regarding post-EVT outcomes in patients with cancer, it remains challenging to identify a subset of these patients for whom EVT would be definitively futile, or even harmful, to justify withholding acute therapy—assuming they are otherwise eligible. In our clinical experience, we have found that treatment decisions become especially complex when the acute stroke evaluation unexpectedly uncovers a potential malignancy, such as an intracranial metastasis. Shared decision-making strategies have proven helpful in such settings, making the uncertain variables clear to the patient or their proxies.4

Differences in Automated Perfusion Software: Do They Matter Clinically?

Differences in Automated Perfusion Software: Do They Matter Clinically?

Poor Cortical Venous Opacification on Baseline Computed Tomography Angiography Predicts Parenchymal Hemorrhage After Thrombectomy

Background Although the association between cortical venous opacification (VO) and clinical outcomes has been shown in previous studies, little is known about the relationship between parenchymal hemorrhage (PH) and VO in patients with acute stroke. We aimed to determine whether cortical VO assessed on computed tomography angiography correlates with the risk of PH following endovascular treatment. Methods This is a post hoc analysis of the ESCAPE NA‐1 (Efficacy and Safety of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial. Control‐arm patients with adequate venous assessment on computed tomography angiography were included. Any PH and symptomatic intracranial hemorrhage were compared between patients with poor VO (cortical vein opacification score&lt;3) versus good opacification (cortical vein opacification score≥3). The relationships with unfavorable functional outcome (90‐day modified Rankin scale 3–6) and 24‐hour infarct volume were assessed. Multivariable logistic and linear regressions were performed. Results Among the 545 patients that met the inclusion criteria, 55 (10.2%) had PH and 21 (3.9%) had symptomatic intracranial hemorrhage. Poor VO was observed in 286 (52.5%) patients (median age, 71 years; 51.4% women). PH was more frequent in the patients with poor VO compared with good VO: 43 of 283 (15.2%) versus 12 of 257 (4.7%) (adjusted odds ratio, 3.43; [95% CI, 1.66–7.10]). Symptomatic intracranial hemorrhage was not significantly higher in the poor versus good opacification groups: 14 of 283 (5.0%) versus 7 of 257 (2.7%). Poor opacification was a predictor of unfavorable functional outcome (adjusted odds ratio, 3.01; [95% CI, 1.95–4.64]; P &lt;0.001), and larger final infarct volume (adjusted B 0.74; [95% CI, 0.45–1.03]; P &lt;0.001). Conclusions Poor VO on computed tomography angiography is strongly associated with an increased risk of PH and worse clinical outcomes after endovascular treatment, and therefore it may be used as a tool for risk stratification in patients with stroke.

ASPECTS as a clinical outcome marker for MCA infarction treated with thrombolytic therapy: Non-contrast CT versus CTA source images

Background &amp; Objective: Computed tomography angiography (CTA) in acute stroke has been widely used to demonstrate arterial occlusion. Alberta Stroke Program Early CT Score (ASPECTS) is used to detect early ischemic signs in non-contrast computed tomography (NCCT) in the middle cerebral artery region. We hypothesized that computed tomography angiography source image (CTA-SI) is superior to NCCT in predicting final infarct volume, 24 hour National Institutes of Health Stroke Scale (NIHSS) score and 90-day clinical outcome. Methods: Patients who had an acute ischemic stroke due to middle cerebral artery (MCA) occlusion and treated with tissue plasminogen activator (tPA) were retrospectively evaluated. ASPECTS was evaluated by two experienced stroke neurologists in acute NCCT, CTA-SI, and follow up imaging. The final ASPECTS was compared with the mean baseline ASPECTS of NCCT and CTA-SI. The relation of both scores with 24-hour NIHSS and clinical outcome was compared. The Modified Rankin Scale (mRS) was utilized to evaluate the 90-day outcomes. mRS score of 0-2 was considered a “good outcome”. Results: Fifty-three patients were evaluated. We observed a significant relation among CTA-SI ASPECTS and after treatment 24hr ASPECTS (y= -3.9 + 1.4 x; 95% CI, -7.6 to -0.2) (y= -26.04 + 3.5 x; CI, -41 to -10). The median baseline 24-hr NHISS was 6 (0 - 22). We found a better correlation between CTA-SI ASPECTS and 24-hr NHISS (y= 363.06 + -37.03 x; CI, -148 to 864) than between NCCT ASPECTS and 24h NHISS (y=529.80 + -62.55 x; CI, 180 - 829). Median 90 days mRS score was 2 (0 - 6). According to Deming regression analysis, the CTA-SI ASPECTS (y= 76.10 + -7.69 x; 95% CI, -36 to 188) was more consistent with the 90 day mRS compared to NCCT ASPECTS (y=149.86 + -17.67 x; 95% CI, 23 - 267) CTA-SI was superior in predicting 24hr NIHSS and day 90 mRS compared to NCCT ASPECTS. Conclusion: Prediction of CTA-SI ASPECTs is better than NCCT ASPECTs at 24hr NIHSS, 3-month mRS and final infarct size in acute ischemic stroke patients treated with tPA.

Stroke Severity and Early Ischemic Changes Predict Infarct Growth Rate and Clinical Outcomes in Patients With Large‐Vessel Occlusion

Background The infarct growth rate (IGR) measures ischemic stroke progression and varies among patients. Clinicoradiological phenotypes of IGR are poorly understood. We evaluated the association of presentation stroke severity and early ischemic changes with infarct progression in patients who underwent successful thrombectomy. Methods This is a retrospective cohort observational study of consecutive endovascular therapy patients with anterior circulation large‐vessel occlusion strokes and successful reperfusion (modified Thrombolysis in Cerebral Ischemia≥2b) from 2 comprehensive stroke centers. National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT [Computed Tomography] Score (ASPECTS) were scored at admission. IGR was defined as the final infarct volume after endovascular therapy divided by the time from stroke onset to successful reperfusion. We used the Youden J index to identify the optimal IGR cutoff to stratify fast and slow progressors. A multivariate logistic regression was used to identify variables associated with a fast IGR and clinical outcomes. Results A total of 212 patients were included in the study. The optimal IGR threshold was 3.2 mL/h, and 135 patients (63.6%) were classified as fast progressors. Presentation National Institutes of Health Stroke Scale score (odds ratio [OR], 1.12; 95% CI, 1.06–1.19) and ASPECTS (OR, 0.56; 95% CI, 0.41–0.73) were accurate predictors of a fast IGR after adjusting for significant confounders. For each 1‐point increase in National Institutes of Health Stroke Scale score at admission, the likelihood of being a fast progressor increased by 12%; for each 1‐point increase in ASPECTS, the likelihood of being a fast progressor decreased by 44%. In the early window (≤6 hours), all patients with ASPECTS &lt;7 were identified as fast progressors. Conclusions This study shows that National Institutes of Health Stroke Scale score and ASPECTS at presentation could predict fast versus slow IGR in patients receiving endovascular therapy.

Prognostic Accuracy of CTP Summary Maps in Patients with Large Vessel Occlusive Stroke and Poor Revascularization after Mechanical Thrombectomy-Comparison of Three Automated Perfusion Software Applications.

Background: Innovative automated perfusion software solutions offer support in the management of acute stroke by providing information about the infarct core and penumbra. While the performance of different software solutions has mainly been investigated in patients with successful recanalization, the prognostic accuracy of the hypoperfusion maps in cases of futile recanalization has hardly been validated. Methods: In 39 patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation and poor revascularization (thrombolysis in cerebral infarction (TICI) 0-2a) after mechanical thrombectomy (MT), hypoperfusion analysis was performed using three different automated perfusion software solutions (A: RAPID, B: Brainomix e-CTP, C: Syngo.via). The hypoperfusion volumes (HV) as Tmax > 6 s were compared with the final infarct volumes (FIV) on follow-up CT 36–48 h after futile recanalization. Bland–Altman analysis was applied to display the levels of agreement and to evaluate systematic differences. Based on the median hypoperfusion intensity ratio (HIR, volumetric ratio of tissue with a Tmax > 10 s and Tmax > 6 s) patients were dichotomized into high- and low-HIR groups. Subgroup analysis with favorable (<0.6) and unfavorable (≥0.6) HIR was performed with respect to the FIV. HIR was correlated to clinical baseline and outcome parameters using Pearson’s correlation. Results: Overall, there was good correlation without significant differences between the HVs and the FIVs with package A (r = 0.78, p < 0.001) being slightly superior to B and C. However, levels of agreement were very wide for all software applications in Bland-Altman analysis. In cases of large infarcts exceeding 150 mL the performance of the automated software solutions generally decreased. Subgroup analysis revealed the FIV to be generally underestimated in patients with HIR ≥ 0.6 (p < 0.05). In the subgroup with favorable HIR, however, there was a trend towards an overestimation of the FIV. Nevertheless, packages A and B showed good correlation between the HVs and FIVs without significant differences (p > 0.2), while only package C significantly overestimated the FIV (−54.6 ± 56.0 mL, p = 0.001). The rate of modified Rankin Scale (mRS) 0–3 after 3 months was significantly higher in favorable vs. unfavorable HIR (42.1% vs. 13.3%, p = 0.02). Lower HIR was associated with higher Alberta Stroke Program Early CT Score (ASPECTS) at presentation and on follow-up imaging, lower risk of malignant edema, and better outcome (p < 0.05). Conclusion: Overall, the performance of the automated perfusion software solutions to predict the FIV after futile recanalization is good, with decreasing accuracy in large infarcts exceeding 150 mL. However, depending on the HIR, FIV can be significantly over- and underestimated, with Syngo showing the widest range. Our results indicate that the HIR can serve as valuable parameter for outcome predictions and facilitate the decision whether or not to perform MT in delicate cases.

Design of the BEST‐II Randomized Clinical Trial

Background Prior observational studies indicate that lower systolic blood pressure (SBP) after successful endovascular treatment (EVT) is associated with better functional outcomes in patients with acute ischemic stroke. However, whether targeting SBP to levels below the guideline‐recommended target of ≤180 mm Hg is safe and efficacious remains to be determined. Methods The BEST (Blood Pressure After Endovascular Stroke Therapy)‐II trial (NCT04116112) is a pragmatic, phase 2, multisite, prospective, randomized, open‐label trial with blinded end‐point assessment designed to (1) compare the safety of lower SBP targets with higher SBP targets in successfully EVT‐treated patients with stroke and (2) inform the design and estimate the probability of success of a future phase 3 trial. A total of 120 patients with acute ischemic stroke who undergo successful EVT (final modified Thrombolysis in Cerebral Infarction score ≥2b) for intracranial internal carotid artery or M1 or M2 segment of the middle cerebral artery will be randomized to the SBP targets of ≤180, &lt;160, and &lt;140 mm Hg, to be maintained for 24 hours using intravenous nicardipine as the first‐line agent. We will assess the harm of decreased post‐EVT SBP by quantifying its linear relationship with multiple primary outcomes of final infarct volume on magnetic resonance imaging (or computed tomography) at 36 hours and utility‐weighted modified Rankin scale score at 90 days. The study is approved by the Institutional Review Boards of both participating institutions and the Data and Safety Monitoring Board. Results Enrollment in the BEST‐II trial began in January 2020, with 90 patients enrolled as of October 13, 2021. The trial is progressing ahead of target, with an anticipated enrollment completion date before January 2023. Conclusions The BEST‐II trial results will inform the stroke community of the safety of lower SBP targets in patients with acute ischemic stroke who are successfully treated with EVT and will demonstrate the feasibility of both achieving lower blood pressure targets as well as conducting an efficacy trial. Trial enrollment is on target despite the COVID‐19 pandemic. Clinical Trial Registration Information NCT04116112 ( https://clinicaltrials.gov/ct2/show/NCT04116112 )

The Cerebral Collateral Cascade: Comprehensive Blood Flow in Ischemic Stroke.

Robust cerebral collaterals are associated with favorable outcomes in patients with acute ischemic stroke due to large vessel occlusion treated by thrombectomy. However, collateral status assessment mostly relies on single imaging biomarkers and a more comprehensive holistic approach may provide deeper insights into the biology of collateral perfusion on medical imaging. Comprehensive collateralization is defined as blood flow of cerebral arteries through the brain tissue and into draining veins. We hypothesized that a comprehensive analysis of the cerebral collateral cascade (CCC) on an arterial, tissue, and venous level would predict clinical and radiologic outcomes. This was a multicenter retrospective cohort study of patients with acute stroke undergoing thrombectomy triage. CCC was determined by quantifying pial arterial collaterals, tissue-level collaterals, and venous outflow (VO). Pial arterial collaterals were determined by CT angiography; tissue-level collaterals were assessed on CT perfusion. VO was assessed on CT angiography using the cortical vein opacification score. Three groups were defined: CCC+ (good pial collaterals, tissue-level collaterals, and VO), CCC- (poor pial collaterals, tissue-level collaterals, and VO), and CCCmixed (the remainder of the patients). Primary outcome was functional independence (modified Rankin Scale score 0-2) at 90 days. Secondary outcome was final infarct volume. A total of 647 patients met inclusion criteria: 176 CCC+, 345 CCCmixed, and 126 CCC-. Multivariable ordinal logistic regression showed that CCC+ predicted good functional outcomes (odds ratio [OR] 18.9 [95% CI 8-44.5]; p < 0.001) compared with CCC- and CCCmixed. CCCmixed patients likely had better functional outcomes compared with CCC- patients (OR 2.5 [95% CI 1.2-5.4]; p = 0.014). Quantile regression analysis (50th percentile) showed that CCC+ (β -78.5, 95% CI -96.0 to -61.1; p < 0.001) and CCCmixed (β -64.0, 95% CI -82.4 to -45.6; p < 0.001) profiles were associated with considerably lower final infarct volumes compared with CCC- profiles. Comprehensive assessment of the collateral blood flow cascade in patients with acute stroke is a strong predictor of clinical and radiologic outcomes in patients treated by thrombectomy.

The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia.

BackgroundHypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume.MethodsA cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology.ResultsBetween group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm3 smaller in hypothermia-treated pigs (P = 0.04) and showed a similar, but non-significant reduction in MRI (P = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's r = 0.48 (p = 0.05) and r = −0.59 (p = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C.ConclusionsIn a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.

Characterizing Fast and Slow Progressors in Anterior Circulation Large Vessel Occlusion Strokes.

Infarct growth rate (IGR) in acute ischemic stroke is highly variable. We sought to evaluate impact of symptom-reperfusion time on outcomes in patients undergoing mechanical thrombectomy (MT). A prospectively maintained database from January,2012-August,2020 was reviewed. All patients with isolated MCA-M1 occlusion who achieved complete reperfusion(mTICI2C-3), had a witnessed symptom onset and follow-up MRI were included. IGR was calculated as final infarct volume (FIV)(ml)/symptom onset to reperfusion time(hours) and was dichotomized according to the median value into slow-(SP) versus fast-progressors (FP). The primary analysis aimed to evaluate the impact of symptom-reperfusion time on 90-day mRS in SP and FP. Secondary analysis was performed to identify predictors of IGR. A total of 137 patients were eligible for analysis. Mean age was 63 ± 15.4 years and median IGR was 5.13ml/hour. SP(n = 69) had higher median ASPECTS, lower median rCBF<30% lesion volume, higher proportion of favorable collaterals and hypoperfusion intensity ratio (HIR)<0.4, higher minimal mean arterial blood pressure before reperfusion, and lower rates of general anesthesia compared to FP(n = 68). Symptom-reperfusion time was comparable between both groups. SP had higher rates of 90-day mRS0-2(71.9%vs.38.9%,aOR;7.226,95%CI[2.431-21.482],p < 0.001) and lower median FIV. Symptom-reperfusion time was associated with 90-day mRS0-2 in FP (aOR;0.541,95%CI[0.309-0.946],p = 0.03) but not in SP (aOR;0.874,95%CI[0.742-1.056],p = 0.16). On multivariable analysis, high ASPECTS and favorable collaterals in the NCCT/CTA model, and low rCBF<30% and HIR<0.4 in the CTP model were independent predictors of SP. The impact of symptom-reperfusion time on outcomes significantly varies across slow-versus fast-progressors. ASPECTS, collateral score, rCBF<30%, and HIR define stroke progression profile.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

ObjectiveThe objective of this paper was to explore the utility of time to maximum concentration (Tmax)‐based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT).MethodsPatients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow‐up non‐contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90‐day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves.ResultsA total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95–0.97, p < 0.001). Tmax > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842–0.909). A Tmax > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73).InterpretationTmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878–888

Assessment of three MR perfusion software packages in predicting final infarct volume after mechanical thrombectomy

AimsTo evaluate the performance of three MR perfusion software packages (A: RAPID; B: OleaSphere; and C: Philips) in predicting final infarct volume (FIV).MethodsThis cohort study included patients treated with mechanical...

Falsely normal CT perfusion ischemic core readings are common and often associated with deep infarcts

BackgroundProper identification of infarct extent is crucial for thrombectomy and prognostication. We sought to study the frequency and topographic aspects of those cases in which CT perfusion (CTP) misses a...

Comparative analysis between 1-D, 2-D and 3-D carotid web quantification

BackgroundCarotid webs (CaW) are now recognized as a cause of ischemic stroke in young patients. The thromboembolic potential appears related to the CaW’s morphology and consequent impact on local flow...