Intravenous tPA (Tissue-Type Plasminogen Activator) Correlates With Favorable Venous Outflow Profiles in Acute Ischemic Stroke.

BACKGROUND: Intravenous tPA (tissue-type plasminogen activator) is often administered before endovascular thrombectomy (EVT). Recent studies have questioned whether tPA is necessary given the high rates of arterial recanalization achieved by EVT, but whether tPA impacts venous outflow (VO) is unknown. We investigated whether tPA improves VO profiles on baseline computed tomography (CT) angiography (CTA) images before EVT. METHODS: Retrospective multicenter cohort study of patients with acute ischemic stroke due to large vessel occlusion undergoing EVT triage. Included patients underwent CT, CTA, and CT perfusion before EVT. VO profiles were determined by opacification of the vein of Labbé, sphenoparietal sinus, and superficial middle cerebral vein on CTA as 0, not visible; 1, moderate opacification; and 2, full. Pial arterial collaterals were graded on CTA, and tissue-level collaterals were assessed on CT perfusion using the hypoperfusion intensity ratio. Clinical and demographic data were determined from the electronic medical record. Using multivariable regression analysis, we determined the correlation between tPA administration and favorable VO profiles. RESULTS: Seven hundred seventeen patients met inclusion criteria. Three hundred sixty-five patients received tPA (tPA+), while 352 patients were not treated with tPA (tPA-). Fewer tPA+ patients had atrial fibrillation (n=128 [35%] versus n=156 [44%]; P=0.012) and anticoagulants/antiplatelet treatment before acute ischemic stroke due to large vessel occlusion onset (n=130 [36%] versus n=178 [52%]; P<0.001) compared with tPA- patients. One hundred eighty-five patients (51%) in the tPA+ and 100 patients (28%) in the tPA- group exhibited favorable VO (P<0.001). Multivariable regression analysis showed that tPA administration was a strong independent predictor of favorable VO profiles (OR, 2.6 [95% CI, 1.7-4.0]; P<0.001) after control for favorable pial arterial CTA collaterals, favorable tissue-level collaterals on CT perfusion, age, presentation National Institutes of Health Stroke Scale, antiplatelet/anticoagulant treatment, history of atrial fibrillation and time from symptom onset to imaging. CONCLUSIONS: In patients with acute ischemic stroke due to large vessel occlusion undergoing thrombectomy triage, tPA administration was strongly associated with the presence of favorable VO profiles.

Cerebral Hypoperfusion Intensity Ratio Is Linked to Progressive Early Edema Formation.

The hypoperfusion intensity ratio (HIR) is associated with collateral status and reflects the impaired microperfusion of brain tissue in patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). As a deterioration in cerebral blood flow is associated with brain edema, we aimed to investigate whether HIR is correlated with the early edema progression rate (EPR) determined by the ischemic net water uptake (NWU) in a multicenter retrospective analysis of AIS-LVO patients anticipated for thrombectomy treatment. HIR was automatically calculated as the ratio of time-to-maximum (TMax) > 10 s/(TMax) > 6 s. HIRs < 0.4 were regarded as favorable (HIR+) and ≥0.4 as unfavorable (HIR−). Quantitative ischemic lesion NWU was delineated on baseline NCCT images and EPR was calculated as the ratio of NWU/time from symptom onset to imaging. Multivariable regression analysis was used to assess the association of HIR with EPR. This study included 731 patients. HIR+ patients exhibited a reduced median NWU upon admission CT (4% (IQR: 2.1−7.6) versus 8.2% (6−10.4); p < 0.001) and less median EPR (0.016%/h (IQR: 0.007−0.04) versus 0.044%/h (IQR: 0.021−0.089; p < 0.001) compared to HIR− patients. Multivariable regression showed that HIR+ (ß: 0.53, SE: 0.02; p = 0.003) and presentation of the National Institutes of Health Stroke Scale (ß: 0.2, SE: 0.0006; p = 0.001) were independently associated with EPR. In conclusion, favorable HIR was associated with lower early edema progression and decreased ischemic edema formation on baseline NCCT.

Favourable arterial, tissue-level and venous collaterals correlate with early neurological improvement after successful thrombectomy treatment of acute ischaemic stroke.

BACKGROUND AND PURPOSE: Early neurological improvement (ENI) after thrombectomy is associated with better long-term outcomes in patients with acute ischaemic stroke due to large vessel occlusion (AIS-LVO). Whether cerebral collaterals influence the likelihood of ENI is poorly described. We hypothesised that favourable collateral perfusion at the arterial, tissue-level and venous outflow (VO) levels is associated with ENI after thrombectomy. MATERIALS AND METHODS: Multicentre retrospective study of patients with AIS-LVO treated by thrombectomy. Tissue-level collaterals (TLC) were measured on cerebral perfusion studies by the hypoperfusion intensity ratio. VO and pial arterial collaterals (PAC) were determined by the Cortical Vein Opacification Score and the modified Tan scale on CT angiography, respectively. ENI was defined as improvement of ≥8 points or a National Institutes of Health Stroke Scale score of 0 hour or 1 24 hours after treatment. Multivariable regression analyses were used to determine the association of collateral biomarkers with ENI and good functional outcomes (modified Rankin Scale 0-2). RESULTS: 646 patients met inclusion criteria. Favourable PAC (OR: 1.9, CI 1.2 to 3.1; p=0.01), favourable VO (OR: 3.3, CI 2.1 to 5.1; p<0.001) and successful reperfusion (OR: 3.1, CI 1.7 to 5.8; p<0.001) were associated with ENI, but favourable TLC were not (p=0.431). Good functional outcomes at 90-days were associated with favourable TLC (OR: 2.2, CI 1.4 to 3.6; p=0.001), VO (OR: 5.7, CI 3.5 to 9.3; p<0.001) and ENI (OR: 5.7, CI 3.3 to 9.8; p<0.001), but not PAC status (p=0.647). CONCLUSION: Favourable PAC and VO were associated with ENI after thrombectomy. Favourable TLC predicted longer term functional recovery after thrombectomy, but the impact of TLC on ENI is strongly dependent on vessel reperfusion.

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

BACKGROUND AND PURPOSE: 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 radiological outcomes. MATERIALS AND METHODS: Multicenter retrospective cohort study of acute stroke patients undergoing thrombectomy triage. CCC was determined by quantifying pial arterial collaterals, tissue-level collaterals, and venous outflow. Pial arterial collaterals were determined by CT angiography, tissue-level collaterals were assessed on CT perfusion. Venous outflow was assessed on CT angiography using the cortical vein opacification score. 3 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 functional independence (modified Rankin Scale: 0-2) at 90-days. Secondary outcome was final infarct volume. RESULTS: 647 patients met inclusion criteria: 176 CCC+, 345 CCC mixed and 126 CCC-. Multivariable ordinal logistic regression showed that CCC+ predicted good functional outcomes (OR=18.9 [95% CI 8-44.5]; p<0.001) compared to CCC- and CCCmixed patients. CCCmixed patients likely had better functional outcomes compared to CCC- patients (OR=2.5 [95% CI 1.2-5.4]; p=0.014). Quantile regression analysis (50th percentile) showed that CCC+ (ß: -78.5, 95% CI -96.0- -61.1; p<0.001) and CCCmixed (ß: -64.0, 95% CI -82.4- -45.6; p<0.001) profiles were associated with considerably lower final infarct volumes compared to CCC- profiles. CONCLUSION: Comprehensive assessment of the collateral blood flow cascade in acute stroke patients is a strong predictor of clinical and radiological outcomes in patients treated by thrombectomy.

Venous outflow profiles are associated with early edema progression in ischemic stroke.

BACKGROUND: In patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO), development of extensive early ischemic brain edema is associated with poor functional outcomes, despite timely treatment. Robust cortical venous outflow (VO) profiles correlate with favorable tissue perfusion. We hypothesized that favorable VO profiles (VO+) correlate with a reduced early edema progression rate (EPR) and good functional outcomes. METHODS: Multicenter, retrospective analysis to investigate AIS-LVO patients treated by mechanical thrombectomy between May 2013 and December 2020. Baseline computed tomography angiography (CTA) was used to determine VO using the cortical vein opacification score (COVES); VO+ was defined as COVES ⩾ 3 and unfavorable as COVES ⩽ 2. EPR was determined as the ratio of net water uptake (NWU) on baseline non-contrast CT and time from symptom onset to admission imaging. Multivariable regression analysis was performed to assess primary (EPR) and secondary outcome (good functional outcomes defined as 0-2 points on the modified Rankin scale). RESULTS: A total of 728 patients were included. Primary outcome analysis showed VO+ (ß: -0.03, SE: 0.009, p = 0.002), lower presentation National Institutes of Health Stroke Scale (NIHSS; ß: 0.002, SE: 0.001, p = 0.002), and decreased time from onset to admission imaging (ß: -0.00002, SE: 0.00004, p < 0.001) were independently associated with reduced EPR. VO+ also predicted good functional outcomes (odds ratio (OR): 5.07, 95% CI: 2.839-9.039, p < 0.001), while controlling for presentation NIHSS, time from onset to imaging, general vessel reperfusion, baseline Alberta Stroke Program Early CT Score, infarct core volume, EPR, and favorable arterial collaterals. CONCLUSIONS: Favorable VO profiles were associated with slower infarct edema progression and good long-term functional outcomes as well as better neurological status and ischemic brain alterations at admission.

Cerebral venous outflow profiles are associated with the first pass effect in endovascular thrombectomy.

BACKGROUND: Recent studies found that favorable venous outflow (VO) profiles are associated with higher reperfusion rates after mechanical thrombectomy (MT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Fewer retrieval attempts and first-pass revascularization during MT lead to better functional outcomes. OBJECTIVE: To examine the hypothesis that favorable VO profiles assessed on baseline CT angiography (CTA) images correlate with successful vessel reperfusion after the first retrieval attempt and fewer retrieval attempts. METHODS: A multicenter retrospective cohort study of patients with AIS-LVO treated by MT. Baseline CTA was used to determine the cortical vein opacification score (COVES). Favorable VO was defined as COVES ≥3. Primary outcomes were successful with excellent vessel reperfusion status, defined as Thrombolysis in Cerebral Infarction (TICI) 2b/3 and 2c/3 after first retrieval attempt. RESULTS: 617 patients were included in this study, of whom 205 (33.2%) had first pass reperfusion. In univariate analysis, ordinal COVES (p=0.011) values were significantly higher in patients with first pass than in those with non-first pass reperfusion, while the number of patients exhibiting favorable pial arterial collaterals using the Maas scale on CTA did not differ (p=0.243). In multivariable logistic regression analysis, higher COVES were independently associated with TICI 2b/3 (OR=1.25, 95% CI 1.1 to 1.42; p=0.001) and TICI 2c/3 (OR=1.2, 95% CI 1.04 to 1.36; p=0.011) reperfusion after one retrieval attempt, controlling for penumbra volume and time from symptom onset to vessel reperfusion. CONCLUSIONS: Favorable VO, classified as higher COVES, is independently associated with successful and excellent first pass reperfusion in patients with AIS-LVO treated by endovascular thrombectomy.

Distinct intra-arterial clot localization affects tissue-level collaterals and venous outflow profiles.

BACKGROUND AND PURPOSE: Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC), and venous outflow (VO) profiles and their impact on good functional outcomes. METHODS: We conducted a multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline computed tomographic angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal first segment of the middle cerebral artery [M1]) and distal vessel occlusion (DVO; distal M1 and M2), and to assess collateral scores. TLC were assessed on computed tomographic perfusion data using the hypoperfusion intensity ratio. VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC; secondary outcome was the modified Rankin Scale after 90 days. RESULTS: A total of 649 patients met inclusion criteria. Of these, 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariate ordinal logistic regression showed that DVO predicted favorable TLC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24-2.52, p = 0.002) and favorable VO (OR = 7.2, 95% CI = 5.2-11.9, p < 0.001). DVO (OR = 3.4, 95% CI = 2.1-5.6, p < 0.001), favorable VO (OR = 6.4, 95% CI = 3.8-10.6, p < 0.001), and favorable TLC (OR = 3.2, 95% CI = 2-5.3, p < 0.001), but not CTA collaterals (OR = 1.07, 95% CI = 0.60-1.91, p = 0.813), were predictors of good functional outcome. CONCLUSIONS: DVO in AIS-LVO patients correlates with favorable TLC and VO profiles, which are associated with good functional outcome.

Corrigendum: Neoplastic and Non-neoplastic Acute Intracerebral Hemorrhage in CT Brain Scans: Machine Learning-Based Prediction Using Radiomic Image Features.

[This corrects the article DOI: 10.3389/fneur.2020.00285.].

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

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.

Impact of intravenous alteplase on sub-angiographic emboli in high-resolution diffusion-weighted imaging following successful thrombectomy.

OBJECTIVE: Thrombus microfragmentation causing peripheral emboli (PE) during mechanical thrombectomy (MT) may modulate treatment effects, even in cases with successful reperfusion. This study aims to investigate whether intravenous alteplase is of potential benefit in reducing PE after successful MT. METHODS: Patients from a prospective study treated at a tertiary care stroke center between 08/2017 and 12/2019 were analyzed. The main inclusion criterion was successful reperfusion after MT (defined as expanded thrombolysis in cerebral infarction (eTICI) scale ≥ 2b50) of large vessel occlusion anterior circulation stroke. All patients received a high-resolution diffusion-weighted imaging (DWI) follow-up 24 h after MT for PE detection. Patients were grouped as "direct MT" (no alteplase) or as MT plus additional intravenous alteplase. The number and volume of ischemic core lesions and PE were then quantified and analyzed. RESULTS: Fifty-six patients were prospectively enrolled. Additional intravenous alteplase was administered in 46.3% (26/56). There were no statistically significant differences of PE compared by groups of direct MT and additional intravenous alteplase administration regarding mean numbers (12.1, 95% CI 8.6-15.5 vs. 11.1, 95% CI 7.0-15.1; p = 0.701), and median volume (0.70 mL, IQR 0.21-1.55 vs. 0.39 mL, IQR 0.10-1.62; p = 0.554). In uni- and multivariable linear regression analysis, higher eTICI scores were significantly associated with reduced PE, while the administration of alteplase was neither associated with numbers nor volume of peripheral emboli. Additional alteplase did not alter reperfusion success. CONCLUSIONS: Intravenous alteplase neither affects the number nor volume of sub-angiographic DWI-PE after successful endovascular reperfusion. In the light of currently running randomized trials, further studies are warranted to validate these findings. KEY POINTS: • Thrombus microfragmentation during endovascular stroke treatment may cause peripheral emboli that are only detectable on diffusion-weighted imaging and may directly compromise treatment effects. • In this prospective study, the application of intravenous alteplase did not influence the occurrence of peripheral emboli detected on high-resolution diffusion-weighted imaging. • A higher degree of recanalization was associated with a reduced number and volume of peripheral emboli and better functional outcome, while contrariwise, peripheral emboli did not modify the effect of recanalization on modified Rankin Scale scores at day 90.

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.

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; P < .001) regardless of arterial CT angiography collateral vessel status (b coefficient, 0.72 [95% CI: -0.59, 2.03; P = .28]). Favorable VO (odds ratio [OR]: 4.1 [95% CI: 2.2, 7.7]; P < .001) and reduced NWU after treatment (OR: 0.77 [95% CI: 0.73, 0.83]; P < .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 Online supplemental material is available for this article.

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

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]; P<0.001) in an adjusted regression analysis. Favorable VO also predicted good clinical outcome (odds ratio, 10 [95% CI, 6.2-16.0]; P<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.

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

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 (ß: 4.23, SE: 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.

Automated Perfusion Calculations vs. Visual Scoring of Collaterals and CBV-ASPECTS : Has the Machine Surpassed the Eye?

PURPOSE: Use of automated perfusion software has gained importance for imaging of stroke patients for mechanical thrombectomy (MT). We aim to compare four perfusion software packages: 1) with respect to their association with 3­month functional outcome after successful reperfusion with MT in comparison to visual Cerebral Blood Volume - Alberta Stroke Program Early CT Score (CBV-ASPECTS) and collateral scoring and 2) with respect to their agreement in estimation of core and penumbra volume. METHODS: This retrospective, multicenter cohort study (2015-2019) analyzed data from 8 centers. We included patients who were functionally independent before and underwent successful MT of the middle cerebral artery. Primary outcome measurements were the relationship of core and penumbra volume calculated by each software, qualitative assessment of collaterals and CBV-APECTS with 3­month functional outcome and disability (modified Rankin scale >2). Quantitative differences between perfusion software measurements were also assessed. RESULTS: A total of 215 patients (57% women, median age 77 years) from 8 centers fulfilled the inclusion criteria. Multivariable analyses showed a significant association of RAPID core (common odds ratio, cOR 1.02; p = 0.015), CBV-ASPECTS (cOR 0.78; p = 0.007) and collaterals (cOR 0.78; p = 0.001) with 3­month functional outcome (shift analysis), while RAPID core (OR 1.02; p = 0.018), CBV-ASPECTS (OR 0.77; p = 0.024), collaterals (OR 0.78; p = 0.007) and OLEA core (OR 1.02; p = 0.029) were significantly associated with 3­month functional disability. Mean differences on core estimates between VEOcore and RAPID were 13.4 ml, between syngo.via and RAPID 30.0 ml and between OLEA and RAPID -3.2 ml. CONCLUSION: Collateral scoring, CBV-ASPECTS and RAPID were independently associated with functional outcome at 90 days. Core and Penumbra estimates using automated software packages varied significantly and should therefore be used with caution.

Neoplastic and Non-neoplastic Acute Intracerebral Hemorrhage in CT Brain Scans: Machine Learning-Based Prediction Using Radiomic Image Features.

Background: Early differentiation of neoplastic and non-neoplastic intracerebral hemorrhage (ICH) can be difficult in initial radiological evaluation, especially for extensive ICHs. The aim of this study was to evaluate the potential of a machine learning-based prediction of etiology for acute ICHs based on quantitative radiomic image features extracted from initial non-contrast-enhanced computed tomography (NECT) brain scans. Methods: The analysis included NECT brain scans from 77 patients with acute ICH (n = 50 non-neoplastic, n = 27 neoplastic). Radiomic features including shape, histogram, and texture markers were extracted from non-, wavelet-, and log-sigma-filtered images using regions of interest of ICH and perihematomal edema (PHE). Six thousand and ninety quantitative predictors were evaluated utilizing random forest algorithms with five-fold model-external cross-validation. Model stability was assessed through comparative analysis of 10 randomly drawn cross-validation sets. Classifier performance was compared with predictions of two radiologists employing the Matthews correlation coefficient (MCC). Results: The receiver operating characteristic (ROC) area under the curve (AUC) of the test sets for predicting neoplastic vs. non-neoplastic ICHs was 0.89 [95% CI (0.70; 0.99); P < 0.001], and specificities and sensitivities reached >80%. Compared to the radiologists' predictions, the machine learning algorithm yielded equal or superior results for all evaluated metrics. The MCC of the proposed algorithm at its optimal operating point (0.69) was significantly higher than the MCC of the radiologist readers (0.54); P = 0.01. Conclusion: Evaluating quantitative features of acute NECT images in a machine learning algorithm provided high discriminatory power in predicting non-neoplastic vs. neoplastic ICHs. Utilized in the clinical routine, the proposed approach could improve patient care at low risk and costs.

Effect of Balloon Guide Catheter Utilization on the Incidence of Sub-angiographic Peripheral Emboli on High-Resolution DWI After Thrombectomy: A Prospective Observational Study.

Background: Thrombus fragmentation causing distal emboli is a feared complication during mechanical thrombectomy (MT). We aimed to investigate the impact of procedural parameters and thrombus properties on the incidence of peripheral emboli after MT for large vessel occlusions (LVO). Methods: We performed a prospective analysis of patients with LVO stroke successfully treated with MT, defined as a score of 2b, 2c, or 3 on the thrombolysis in cerebral infarction (TICI) scale. A follow-up MRI including high-resolution diffusion-weighted imaging (DWI) was performed within 24 h following MT. The primary endpoint was the number and volume of peripheral emboli, classified as punctuate DWI lesions distant to the diffusion-restricted core lesion. Further analysis included the influence of baseline characteristics, procedural and outcome parameters, and thrombus properties on peripheral emboli. Results: Thirty-seven patients with successful MT met the inclusion criteria. Use of a balloon guide catheter (BGC) and TICI were the only independent predictors for a reduced number of peripheral emboli. The use of a BGC led to a significant reduction in the number and volume of peripheral emboli, with a median number/volume of peripheral emboli of 4.5/287 µl (IQR 1.25-8.25/76-569 µl) vs. 12/938 µl (IQR 4-19/242-1,836 µl). In cases where BGC was not employed, the number of peripheral emboli increased with decreasing TICI scores. Conclusions: BGC-aided MT reduces the number of peripheral emboli in successful but incomplete reperfusion (TICI 2b and 2c). The effectiveness of this strategy therefore goes above and beyond that which can be demonstrated by the TICI score alone.

Sub-angiographic peripheral emboli in high resolution DWI after endovascular recanalization.

BACKGROUND AND AIM: To analyze the incidence of peripheral emboli after successful mechanical thrombectomy (MT) of intracranial large vessel occlusions (LVO). METHODS: We performed a prospective analysis of patients with intracranial LVO who underwent successful MT and received a 1.5 T MRI including diffusion-weighted imaging (DWI) in standard- and high-resolution as well as susceptibility-weighted imaging (SWI) on the day following the intervention. Reperfusion grade was assessed on post-thrombectomy digital subtraction angiography (DSA) using the expanded thrombolysis in cerebral infarction (eTICI) scale. Punctuate DWI lesions distal to the DWI core lesion were classified as peripheral emboli. DWI lesions outside the primary affected vascular territory were classified as emboli into new territories. Additionally, SWI and post-thrombectomy DSA were analyzed and correlated to findings on DWI. RESULTS: Twenty-eight patients undergoing successful MT met the inclusion criteria. In 26/28 patients (93%), a total of 324 embolic lesions were detected in DWI representing 2.1% of the cumulated ischemic core volume. 151 peripheral emboli were detected in standard-resolution DWI, 173 additional emboli were uncovered in high-resolution DWI. Eight out of nine patients with an eTICI 3 reperfusion had embolic lesions (29 DWI lesions). 9.6% (31/324) of peripheral emboli were observed in vascular territories not affected by the LVO. SWI lesions were observed in close proximity to 10.2% (33/324) of DWI lesions. CONCLUSIONS: Peripheral emboli are frequent after MT even after complete reperfusion. These emboli occur rather in the vascular territory of the occluded vessel than in other territories. A large proportion of peripheral emboli is only detected by high-resolution DWI.

Hemorrhage After Endovascular Recanalization in Acute Stroke: Lesion Extent, Collaterals and Degree of Ischemic Water Uptake Mediate Tissue Vulnerability.

Background and Purpose: Intracranial hemorrhage (ICH) remains a major complication of endovascular treatment (ET) in acute stroke. The aim of this study was to identify clinical and imaging predictors for ICH in patients with acute ischemic stroke undergoing successful ET. Methods: We performed a retrospective analysis of patients with large vessel occlusion in the anterior circulation who underwent successful ET at our university medical center between 2015 and 2018. ICH was diagnosed on non-enhanced CT and a binary outcome was defined: ICH occurrence in the immediate post-interventional phase within 12-36 h (yes/no). The impacts of clinical, radiological, and interventional parameters on outcome were assessed in logistic regression models. Results: One hundred and seven patients fulfilled the inclusion criteria. 37 (34.6%) showed an ICH of which 7 (6.5%) patients were diagnosed as symptomatic and 30 (28.04%) as asymptomatic. Multivariable regression analyses identified a lower ASPECTS (adjusted odds ratio (OR) 1.95, 95%CI: 1.4-3.63, P = 0.037), low collateral score (adjusted OR 0.12, 95%CI: 0.03-0.49, P = 0.003) and high Net Water Uptake (NWU) (adjusted OR 1.56, 95%CI: 2.34-1.03, P = 0.007) as independent predictors of ICH after successful ET. Conclusions: CT-based quantitative NWU, ASPECTS, and collateral score mediate tissue vulnerability and are reliable independent predictors of a bleeding event after successful ET. This imaging-based prediction model might be useful for early stratification of patients at high risk of a bleeding event after ET, especially with low ASPECTS.

Adaptive immunity and IL-17A are not involved in the progression of chronic kidney disease after 5/6 nephrectomy in mice.

BACKGROUND AND PURPOSE: The adaptive immune response and IL-17A contribute to renal damage in several experimental models of renal injury. EXPERIMENTAL APPROACH: To evaluate the role of the adaptive immune response, 5/6 nephrectomy was performed in wildtype DBA/1J mice and in recombination-activating gene-1 (RAG-1) deficient mice that lack B and T-cells. To assess the role of IL-17A, we carried out 5/6 nephrectomy in IL-17A deficient mice. Flow cytometric analysis, immunohistochemistry and RT-PCR were used. KEY RESULTS: Infiltration of CD3+ T-cells in the remnant kidney was increased after 5/6 nephrectomy in wildtype mice, along with a robust induction of IL-17A production in CD4+ T and γδ T-cells. After 5/6 nephrectomy, wildtype mice developed albuminuria in the nephrotic range over 10 weeks. This was accompanied by severe glomerular sclerosis and tubulointerstitial injury, and as well as renal mRNA expression of markers of inflammation and fibrosis (the chemokine CCL2, plasminogen activator inhibitor-1; PAI-1 and neutrophil gelatinase-associated lipocalin; NGAL). Unexpectedly, RAG-1 deficient mice and IL-17A deficient mice developed renal injury, similar to that in wildtype mice. No differences were found for albuminuria, glomerular sclerosis, tubulointerstitial injury and mRNA expression of CCL2, PAI-1 and NGAL. Mortality did not differ between the three groups. CONCLUSIONS AND IMPLICATIONS: Numbers of CD3+ T-cells and IL-17A+ lymphocytes infiltrating the kidney were increased after 5/6 nephrectomy. In contrast to other experimental models of renal injury, genetic deficiency of the adaptive immune system or of IL-17A did not attenuate induction or progression of chronic kidney disease after 5/6 nephrectomy. LINKED ARTICLES: This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc.