Assessment of Collateral Flow in Patients with Carotid Stenosis Using Random Vessel-Encoded Arterial Spin-Labeling: Comparison with Digital Subtraction Angiography.

BACKGROUND AND PURPOSE: Collateral circulation plays an important role in steno-occlusive internal carotid artery disease (ICAD) to reduce the risk of stroke. We aimed to investigate the utility of planning-free random vessel-encoded arterial spin-labeling (rVE-ASL) in assessing collateral flows in patients with ICAD. MATERIALS AND METHODS: Forty patients with ICAD were prospectively recruited. The presence and extent of collateral flow were assessed and compared between rVE-ASL and DSA by using Contingency (C) and Cramer V (V) coefficients. The differences in flow territory alterations stratified by stenosis ratio and symptoms, respectively, were compared between symptomatic (n = 19) and asymptomatic (n = 21) patients by using the Fisher exact test. RESULTS: Good agreement was observed between rVE-ASL and DSA in assessing collateral flow (C = 0.762, V = 0.833, both P < .001). Patients with ICA stenosis of ≥90% were more likely to have flow alterations (P < .001). Symptomatic patients showed a higher prevalence of flow alterations in the territory of the MCA on the same side of ICAD (63.2%), compared with asymptomatic patients (23.8%, P = .012), while the flow alterations in the territory of anterior cerebral artery did not differ (P = .442). The collateral flow to MCA territory was developed primarily from the contralateral internal carotid artery (70.6%) and vertebrobasilar artery to a lesser extent (47.1%). CONCLUSIONS: rVE-ASL provides comparable information with DSA on the assessment of collateral flow. The flow alterations in the MCA territory may be attributed to symptomatic ICAD.

Cost-effectiveness of endovascular treatment after 6-24 h in ischaemic stroke patients with collateral flow on CT-angiography: A model-based economic evaluation of the MR CLEAN-LATE trial.

BACKGROUND: The MR CLEAN-LATE trial has shown that patient selection for endovascular treatment (EVT) in the late window (6-24 h after onset or last-seen-well) based on the presence of collateral flow on CT-angiography is safe and effective. We aimed to assess the cost-effectiveness of late-window collateral-based EVT-selection compared to best medical management (BMM) over a lifetime horizon (until 95 years of age). MATERIALS AND METHODS: A model-based economic evaluation was performed from a societal perspective in The Netherlands. A decision tree was combined with a state-transition (Markov) model. Health states were defined by the modified Rankin Scale (mRS). Initial probabilities at 3-months post-stroke were based on MR CLEAN-LATE data. Transition probabilities were derived from previous literature. Information on short- and long-term resource use and utilities was obtained from a study using MR CLEAN-LATE and cross-sectional data. All costs are expressed in 2022 euros. Costs and quality-adjusted life years (QALYs) were discounted at a rate of 4% and 1.5%, respectively. The effect of parameter uncertainty was assessed using probabilistic sensitivity analysis (PSA). RESULTS: On average, the EVT strategy cost €159,592 (95% CI: €140,830-€180,154) and generated 3.46 QALYs (95% CI: 3.04-3.90) per patient, whereas the costs and QALYs associated with BMM were €149,935 (95% CI: €130,841-€171,776) and 2.88 (95% CI: 2.48-3.29), respectively. The incremental cost-effectiveness ratio per QALY and the incremental net monetary benefit were €16,442 and €19,710, respectively. At a cost-effectiveness threshold of €50,000/QALY, EVT was cost-effective in 87% of replications. DISCUSSION AND CONCLUSION: Collateral-based selection for late-window EVT is likely cost-effective from a societal perspective in The Netherlands.

Perfusion Collateral Index versus Hypoperfusion Intensity Ratio in Assessment of Collaterals in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Perfusion-based collateral indices such as the perfusion collateral index and the hypoperfusion intensity ratio have shown promise in the assessment of collaterals in patients with acute ischemic stroke. We aimed to compare the diagnostic performance of the perfusion collateral index and the hypoperfusion intensity ratio in collateral assessment compared with angiographic collaterals and outcome measures, including final infarct volume, infarct growth, and functional independence. MATERIALS AND METHODS: Consecutive patients with acute ischemic stroke with anterior circulation proximal arterial occlusion who underwent endovascular thrombectomy and had pre- and posttreatment MRI were included. Using pretreatment MR perfusion, we calculated the perfusion collateral index and the hypoperfusion intensity ratio for each patient. The angiographic collaterals obtained from DSA were dichotomized to sufficient (American Society of Interventional and Therapeutic Neuroradiology [ASITN] scale 3-4) versus insufficient (ASITN scale 0-2). The association of collateral status determined by the perfusion collateral index and the hypoperfusion intensity ratio was assessed against angiographic collaterals and outcome measures. RESULTS: A total of 98 patients met the inclusion criteria. Perfusion collateral index values were significantly higher in patients with sufficient angiographic collaterals (P < .001), while there was no significant (P = .46) difference in hypoperfusion intensity ratio values. Among patients with good (mRS 0-2) versus poor (mRS 3-6) functional outcome, the perfusion collateral index of ≥ 62 was present in 72% versus 31% (P = .003), while the hypoperfusion intensity ratio of ≤0.4 was present in 69% versus 56% (P = .52). The perfusion collateral index and the hypoperfusion intensity ratio were both significantly predictive of final infarct volume, but only the perfusion collateral index was significantly (P = .03) associated with infarct growth. CONCLUSIONS: Results show that the perfusion collateral index outperforms the hypoperfusion intensity ratio in the assessment of collateral status, infarct growth, and determination of functional outcomes.

ASSESSMENT OF CORONARY COLLATERAL CIRCULATION PREDICTORS AMONG PATIENTS WITH ACUTE CORONARY SYNDROME IN POPULATION GEORGIA.

Coronary collateral circulation (CCC) has been shown to have a prognostic role in acute myocardial infarction (MI). We aimed to identify factors associated with CCC development in patients with acute myocardial ischemia. In the present analysis, 673 consecutive patients aged 27 - 94 years (64.7±11.48) with acute coronary syndrome (ACS), who underwent coronary angiography within the first 24 hours after symptom onset were included. Baseline data, including sex, age, cardiovascular risk factors, medication, antecedent angina, prior coronary revascularization, EF%, blood pressure levels were obtained from patient medical records. The study individuals were divided into two groups: patients with Rentrop grade 0 to 1 were classified as the poor collateral group (456 patients), and the patients with grade 2 to 3 - as the good collateral group (217 patients). Prevalence of good collaterals of 32% was found. Odds of good collateral circulation increases with higher eosinophil count - OR=17.36 (95% CI: 3.25-92.86); history of MI (OR=1.76; 95% CI:1.13-2.75); multivessel disease - OR=9.78 (95% CI: 5.65-16.96); culprit vessel stenosis - OR=3.91 (95% CI: 2.35-6.52); presence of angina pectoris > 5 years - OR=5.55 (95% CI:2.66-11.57) and decreases with high N/L- OR=0.37 (95% CI:0.31-0.45) and male gender - OR=0.44 (95% CI:0.29-0.67). High N/L is a predictor of poor collateral circulation, with 68.4 sensitivity and 72.8% specificity (cutoff: 2.73*109). Relative chance of good collateral circulation increases with the higher number of eosinophils, presence of angina pectoris with duration of more than 5 years, history of past myocardial infarction, culprit vessel stenosis, multivessel disease, and reduces if patient is male and has high N/L ratio. Peripheral blood parameters may serve as an additional simple risk assessment tool in ACS patients.

Clinical significance of CT angiographic assessment of collateral circulation combined with serum NLRP1 levels in ischemic stroke patients.

This research aimed to combine serum NLR-pyrin domain containing 1 (NLRP1) levels and collateral circulation to assess ischemic stroke patients and predict the prognoses of the patients. This present prospective observational study enrolled 196 ischemic stroke patients. All patients underwent CTA as well as digital subtraction angiography (DSA) to assess collateral circulation by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR). In addition, we collected serum samples from 100 patients with carotid atherosclerosis as controls. The serum NLRP1, tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1ß and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). The age, BMI, sex, smoke condition, diastolic blood pressure, systolic blood pressure, National Institutes of Health Stroke Scores (NIHSS), modified Rankin Scale (mRS) scores, imaging indicators and the levels of triglyceride, total cholesterol (TC), low-density leptin cholesterol (LDLC), high-density leptin cholesterol of all subjects were recorded. All data used SPSS 18.0 to statistical analyses. The serum levels of NLRP1 were remarkably enhanced in the ischemic stroke patients compared with the carotid atherosclerosis patients. The NIHSS score, the mRS score after 90 days and the levels of NLRP1, CRP, TNF-α IL-6 and IL-1ß of ischemic stroke patients in the ASITN/SIR grade 0 to 2 group were remarkably elevated than the ischemic stroke patients in ASITN/SIR grade 3 to 4 group. Spearman analysis supported that a positive correlation existed among the NLRP1, CRP, IL-6, TNF-α, and IL-1ß levels. The NIHSS score, infarct volume and the levels of NLRP1, IL-6, TNF-α, and IL-1ß of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than the ischemic stroke patients in the mRS score ≤ 2 group. ASITN/SIR grade and NLRP1 could be potential diagnostic biomarkers of poor prognosis of ischemic stroke patients. It was found that NLRP1, ASITN/SIR grade, infarct volume, NIHSS, IL-6, and IL-1ß were the risk factors for bad prognosis of ischemic stroke patients. This study showed that the serum NLRP1 levels were remarkably decreased in ischemic stroke patients. In addition, the serum NLRP1 levels and ASITN/SIR grade could predict the prognosis of ischemic stroke patients.

MRI for collateral assessment pre-thrombectomy and association with outcome: a systematic review and meta-analysis.

PURPOSE: Various neuroimaging methods exist to assess the collateral circulation in stroke patients but much of the evidence is based on computed tomography. Our aim was to review the evidence for using magnetic resonance imaging for collateral status evaluation pre-thrombectomy and assess the impact of these methods on functional independence. METHODS: We systematically reviewed EMBASE and MEDLINE for studies that evaluated baseline collaterals using MRI pre-thrombectomy and conducted a meta-analysis to express the relationship between good collaterals (defined variably as the presence [good] vs absence [poor] or quality [ordinal scores binarized as good-moderate vs poor] of collaterals) and functional independence (modified Rankin score mRS≤2) at 90 days. Outcome data were presented as relative risk (RR, 95% confidence interval, 95%CI). We assessed for study heterogeneity, publication bias, and conducted subgroup analyses of different MRI methods and affected arterial territories. RESULTS: From 497 studies identified, we included 24 (1957 patients) for the qualitative synthesis, and 6 (479 patients) for the metanalysis. Good pre-thrombectomy collaterals were significantly associated with favorable outcome at 90 days (RR=1.91, 95%CI=1.36-2.68], p= 0.0002) with no difference between MRI methods and affected arterial territory subgroups. There was no evidence of statistical heterogeneity (I2=25%) among studies but there was evidence of publication bias. CONCLUSION: In stroke patients treated with thrombectomy, good pre-treatment collaterals assessed using MRI are associated with double the rate of functional independence. However, we found evidence that relevant MR methods are heterogenous and under-reported. Greater standardization and clinical validation of MRI for collateral evaluation pre-thrombectomy are required.

A Deep Learning-Based Automatic Collateral Assessment in Patients with Acute Ischemic Stroke.

This study aimed to develop a supervised deep learning (DL) model for grading collateral status from dynamic susceptibility contrast magnetic resonance perfusion (DSC-MRP) images from patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) and compare its performance against experts' manual grading. Among consecutive LVO-AIS at three medical center sites, DSC-MRP data were processed to generate collateral flow maps consisting of arterial, capillary, and venous phases. With the use of expert readings as a reference, a DL model was developed to analyze collateral status with output classified into good and poor grades. The resulting model was externally validated in a later-collected population from one medical center site. The model was trained on 255 patients and externally validated on 72 patients. In the all-site internal validation population, DL grading of good collateral probability yielded a c statistic of 0.91; in the external validation population, the c statistic was 0.85. In the external validation population, there was moderate agreement between the experts' grades and DL grades (kappa = 0.53, 95% CI = 0.32-0.73, p < 0.0001). Day 7 infarct growth volume was higher in DL-graded poor collateral group than good collateral group patients (median volume [26 mL vs. 6 mL], p = 0.01) in patients with successful reperfusion (modified treatment in cerebral infarction (mTICI) = 2b-3). In all patients with a 90-day modified Rankin Scale (mRS) score, there was a shift to more favorable outcomes in the good collateral group, with a common odds ratio of 2.99 (95% CI = 1.89-4.76, p < 0.0001). The DL-based collateral grading was in good agreement with expert manual grading in both development and validation populations. After exclusion of patients with large infarct volume, early reperfusion is more likely to benefit patients with the poor collateral flow, and the DL method has the potential to aid the assessment of collateral status.

Collateral Capacity Assessment : Robustness and Interobserver Agreement of Two Grading Scales and Agreement with Quantitative Scoring.

BACKGROUND AND PURPOSE: Intracranial collateral capacity is conducive to imply parenchymal perfusion of affected territory after acute vessel occlusion. The Tan collateral score is commonly used to assess the intracranial collateral capacity; however, this score is coarsely grained and interobserver agreement is low, which reduces prognostic value and clinical utility. We introduce and evaluate an alternative extended Tan score based on the conventional Tan scale and assess the agreement with a quantitative score. METHODS: We included 100 consecutive patients with a proven acute single large vessel occlusion of the proximal anterior circulation. Collaterals were graded with the conventional and extended Tan score and an automated quantitative score. The extended Tan score is a finer 6­scale manual score based on the conventional 4­point Tan scale. The quantitative score is calculated by an automatic software package (StrokeViewer). Interobserver agreement of the manual scores was assessed with the weighted kappa. The Spearman correlation coefficient was calculated to determine the agreement between the manual and automated collateral scores. RESULTS: The interobserver agreement was higher for the extended score than for the conventional score with a weighted kappa of 0.70 and 0.65, respectively. For the extended and conventional score, the Spearman correlation coefficient for the agreement with the automated score was 0.78 and 0.76, respectively. CONCLUSION: Because of the good interobserver agreement and good agreement with quantitative assessment, the extended collateral score is a strong candidate to improve prognostic value of collateral assessment and implementation in clinical practice.

Automatic assessment of collaterals physiology in chronic total occlusions by means of artificial intelligence.

BACKGROUND: Assessment of collaterals physiology in chronic total occlusions (CTO) currently requires dedicated devices, adds complexity, and increases the cost of the intervention. This study sought to derive collaterals physiology from flow velocity changes (ΔV) in donor arteries, calculated with artificial intelligence- aided angiography. METHODS: Angiographies with successful percutaneous coronary intervention (PCI) in 2 centers were retro- spectively analyzed. CTO collaterals were angiographically evaluated according to Rentrop and collateral connections (CC) classifications. Flow velocities in the primary and secondary collateral donor arteries (PCDA, SCDA) were automatically computed pre and post PCI, based on a novel deep-learning model to extract the length/time curve of the coronary filling in angiography. Parameters of collaterals physiology, Δcollateral-flow (Δfcoll) and Δcollateral-flow-index (ΔCFI), were derived from the ΔV pre-post. RESULTS: The analysis was feasible in 105 out of 130 patients. Flow velocity in the PCDA significantly decreased after CTO-PCI, proportionally to the angiographic collateral grading (Rentrop 1: 0.02 ± 0.01 m/s; Rentrop 2: 0.04 ± 0.01 m/s; Rentrop 3: 0.07 ± 0.02 m/s; p < 0.001; CC0: 0.01 ± 0.01 m/s; CC1: 0.04 ± ± 0.02 m/s; CC2: 0.06 ± 0.02 m/s; p < 0.001). Δfcoll and ΔCFI paralleled ΔV. SCDA also showed a greater reduction in flow velocity if its collateral channels were CC1 vs. CC0 (0.03 ± 0.01 vs. 0.01 ± 0.01 m/s; p < 0.001). For each individual patient, ΔV was more pronounced in the PCDA than in the SCDA. CONCLUSIONS: Automatic assessment of collaterals physiology in CTO is feasible, based on a deeplearning model analyzing the filling of the donor vessels in angiography. The changes in collateral flow with this novel method are quantitatively proportional to the angiographic grading of the collaterals.

Assessment of Primary Collateral Grades Based on the Integrity of Willis' Circle: Predicting the Prognosis of Acute Intracranial Internal Carotid Artery Occlusion Before Thrombectomy.

OBJECTIVE: Endovascular mechanical thrombectomy (EVMT) has shown significant efficacy in improving neurological functions in patients with intracranial internal carotid artery occlusion (IICAO), but its clinical outcomes are variable. We examined the relationship between favorable clinical outcomes after EVMT in IICAO and a set of predictors. METHODS: In this retrospective study, 189 patients with IICAO treated by EVMT at 3 centers from November 2015 to December 2020 were included and analyzed. Non-contrast computed tomography and computed tomography angiography were evaluated on admission. The morphology of IICAO was categorized into Ia, Ib, L, or T types, depending on the involvement of the posterior communicating artery origin, proximal anterior cerebral artery, and middle cerebral artery. The Willis' circle was categorized as integrated or compromised Willis' circle. In combination with the involvement of the IICAO and the integrity of Willis' circle, we used the primary collateral grade (PCG) to describe the presence of functional Willisian collaterals. Baseline data including demographics, characteristics, vascular risk factors, and initial National Institutes of Health Stroke Scale scores were collected. Hemorrhagic transformation was evaluated using the 24-hour non-contrast computed tomography after EVMT. Favorable outcomes based on modified Rankin scale, were defined as 0-2 at 90 days. RESULTS: A total of 189 patients were included (median age, 69 years; 126 male [66.7%]). 104 patients [55.0%] showed reperfusion after EVMT, but 72 patients [38.1%] achieved favorable outcomes at 90 days. The mortality rate of type Ib was significantly higher than that with type Ia (χ2 = 14.21, P = 0.001). The outcome with different structure of Willis' circle was not statistically different between the 2 groups. A multivariate logistic regression analysis showed that IICAO T-type (odds ratio, 0.028 [95% confidence interval: 0.323-3.829], P = 0.042) and PCG 2 (odds ratio 9.427[95% confidence interval:1.863-47.698], P = 0.007) were predictors of favorable outcomes. CONCLUSIONS: Evaluation of PCG by determining the type of IICAO and the integrity of Willis' circle may serve as a valuable indicator for the prognosis and as an essential reference for screening patients before EVMT.

Quantitative Collateral Assessment on CTP in the Prediction of Stroke Etiology.

BACKGROUND AND PURPOSE: Patients with stroke etiology of large-artery atherosclerosis were thought to have better collateral circulation compared with patients with other stroke etiologies. We aimed to investigate the association between stroke etiology and collateral circulation with a new quantitative collateral assessment method. MATERIALS AND METHODS: This retrospective study reviewed data from consecutive patients with proximal anterior artery occlusion who underwent CTP before reperfusion therapy. CBF maps were derived from CTP. A new indicator, maximum CBF of collateral vessels within the Sylvian fissure (cCBFmax), was applied to quantitatively assess the collateral status. The relationship between collateral status and stroke etiology was investigated. RESULTS: A total of 296 patients were finally analyzed. The median cCBFmax was significantly higher in patients with large-artery atherosclerosis than in those without it (92 [interquartile range, 65-123] mL/100 g/min versus 62 [interquartile range, 46-82] mL/100 g/min; P < .001). Multivariable analysis revealed that a higher cCBFmax score was independently associated with large-artery atherosclerosis etiology (OR, 1.010; 95% CI, 1.002-1.018; P = .017) after adjustment. The area under the curve, sensitivity, and specificity of the final model in predicting the etiology of large-artery atherosclerosis were 0.870, 89.7%, and 75.2%, respectively. CONCLUSIONS: Patients with large-artery atherosclerosis had a more adequate collateral perfusion supply with the new quantitative collateral assessment. The new quantitative collateral measurement might contribute to the prediction of stroke etiology in the acute clinical scenario for patients with acute ischemic stroke.

Assessment of the Relationship Between the Adropin Levels and the Coronary Collateral Circulation in Patients with Chronic Coronary Syndrome. / Avaliação da Relação entre Níveis de Adropina e Circulação Colateral Coronária em Pacientes com Síndrome Coronariana Crônica.

BACKGROUND: Coronary collateral circulation (CCC) provides an alternative blood flow to myocardial tissue exposed to ischemia and helps to preserve myocardial functions. Endothelial-derived nitric-oxide (NO) production and vascular endothelial growth factor (VEGF) have been suggested as the most important factors in the development of CCC. Adropin is a peptide hormone responsible for energy hemostasis, and is known for its positive effects on the endothelium through NO and VEGF. OBJECTIVE: The aim of this study is to investigate the association between adropin and the presence of CCC in patients with chronic coronary syndrome (CCS). METHODS: A total of 102 patients with CCS, who had complete occlusion of at least one major epicardial coronary artery, were included in the study and were divided into two groups: the group of patients (n:50) with poor CCC (Rentrop 0-1) and the group of patients (n:52) with good CCC (Rentrop 2-3). The level of significance adopted in the statistical analysis was 5%. RESULTS: Mean adropine levels were found as 210.83±17.76 pg/mL and 268.25±28.94 pg/mL in the poor and good CCC groups, respectively (p<0.001). Adropin levels proved to be positively correlated with neutrophil-to-lymphocyte ratios (r:0.17, p:0.04) and the rentrop scores (r:0.76, p<0.001), and negatively correlated with age (r:-0.23, p:0.01) and Gensini scores (r:-0.19, p:0.02). Adropin level is a strong independent predictor of good CCC development (OR:1.12, 95% CI:(1.06-1.18), p<0.001). CONCLUSION: This study suggests that adropin levels may be a possible factor associated with the presence of CCC in CCS patients.

FUNDAMENTO: A circulação colateral coronária (CCC) proporciona um fluxo sanguíneo alternativo a tecido miocárdico exposto a isquemia e ajuda a preservar as funções miocárdicas. A produção endotelial de óxido nítrico (NO) e o fator de crescimento endotelial vascular (VEGF) foram apontados como os fatores mais importantes no desenvolvimento da CCC. A adropina é um hormônio peptídeo responsável pela hemostasia energética, e é conhecida por seus efeitos positivos no endotélio por NO e VEGF. OBJETIVO: O objetivo deste estudo é investigar a associação entre adropina e a presença de CCC em pacientes com síndrome coronariana crônica (SCC). MÉTODOS: Um total de 102 pacientes com SCC, que tinham oclusão total de pelo menos 1 artéria coronária epicárdica importante, foram incluídos no estudo e foram divididos em dois grupos: o grupo de pacientes (n: 50) com CCC ruim (Rentrop 0-1) e o grupo de pacientes (n: 52) com CCC boa (Rentrop 2-3). O nível de significância adotado para a análise estatística foi 5%. RESULTADOS: Os níveis médios de adropina identificados foram 210,83±17,76 pg/mL e 268,25±28,94 pg/mL nos grupos com CCC ruim e boa, respectivamente (p<0,001). Detectou-se que os níveis de adropina têm correlação com as razões neutrófilo-linfócito (r: 0,17, p: 0,04) e com os escores de Rentrop (r: 0,76, p<0,001), e correlação negativa com idade (r: -0,23, p: 0,01) e com os escores Gensini (r: -0,19, p: 0,02). O nível de adropina é um preditor independente da boa evolução da CCC (RC: 1.12, IC 95%: (1,06­1,18), p<0,001). CONCLUSÃO: Este estudo sugere que os níveis de adropina podem ser um fator associado à de CCC em pacientes com SCC.

Impact of collateral flow on cost-effectiveness of endovascular thrombectomy.

OBJECTIVE: Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals. METHODS: A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed. RESULTS: EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0-2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%-8% more patients than medical management. CONCLUSIONS: EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

Independent Significance of Visual Assessment of Perfusion CT Maps in Anterior Circulation Stroke Patients Treated with Mechanical Thrombectomy.

BACKGROUND: In the absence of an automated software analysis, the role of computed tomography perfusion (CTP) in a real time clinical practice is not well established. We evaluated the clinical significance of a widely accessible and simple visual grading scale of CTP in the anterior circulation of acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: The single center consecutive CT investigations of AIS patients treated with MT in the anterior circulation have been evaluated retrospectively. ASPECT score and collateral circulation evaluation based on the Maas score were determined. Time to peak parametric maps, derived from CTP, were graded into four categories, from least to most favorable. The primary endpoint was functional outcome evaluated as modified Rankin Scale (mRS) ≤ 2 at 90 days after MT. RESULTS: We included 318 patients in the analysis; 142 (45%) patients had mRS ≤ 2 after 90 days, mortality rate was 24%. Higher CTP and Maas score were significantly correlated with better clinical outcome (Pearson χ2 25.0 and 37.7, respectively; p < 0.01). Collateral circulation and CTP grades were strongly interrelated (Pearson χ2 78.6; p < 0.01). The CTP grade demonstrated statistically significant independent correlation with the clinical outcome irrespective of the collateral circulation grade, ASPECT score and age (OR 2.5; p = 0.011). The correlation was more pronounced in patients with normal collateral circulation (OR 3.27; p = 0.029). CONCLUSION: We demonstrated that both visually graded CTP and collateral circulation grade strongly correlated with the clinical outcome of MT in the anterior circulation of AIS patients. Importantly, CTP correlated with the clinical outcome independent of the collateral circulation.

CT Perfusion collateral index in assessment of collaterals in acute ischemic stroke with delayed presentation: Comparison to single phase CTA.

BACKGROUND & PURPOSE: Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients. METHODS: ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS. RESULTS: A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p<0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003). CONCLUSION: CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

Automated Collateral Flow Assessment in Patients with Acute Ischemic Stroke Using Computed Tomography with Artificial Intelligence Algorithms.

BACKGROUND: Collateral circulation is associated with improved functional outcome in patients with large vessel occlusion acute ischemic stroke (AIS) who undergo reperfusion therapy. Assessment of collateral flow can be time consuming, subjective, and difficult because of complex neurovasculature. This study assessed the ability of multiple artificial intelligence algorithms in determining collateral flow of patients with AIS. METHODS: Two hundred patients with AIS between March 2019 and January 2020 were included in this retrospective study. Peak arterial computed tomography perfusion volumes were used to assess collateral scores. Neural networks were developed for dichotomized (≥50% or <50%) and multiclass (0% filling, 0%-50% filling, 50%-100% filling, or 100% filling) collateral scoring. Maximum intensity projections from axial and anteroposterior (AP) views were synthesized for each bone subtracted three-dimensional volume and used as network inputs separately and together, along with three-dimensional data. Training:testing:validation splits of 60:30:10 and 20 iterations of Monte Carlo cross-validation were used. Network performance was assessed using 95% confidence intervals of accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The axial and AP input combination provided the most accurate results for dichotomized classification: accuracy, 0.85 ± 0.01; sensitivity, 0.88 ± 0.02; specificity, 0.82 ± 0.03; PPV, 0.86 ± 0.02; and NPV, 0.83 ± 0.03. Similarly, the axial and AP input combination provided the best results for multiclass classification: accuracy, 0.80 ± 0.01; sensitivity, 0.64 ± 0.01; specificity, 0.85 ± 0.01; PPV, 0.65 ± 0.02; and NPV, 0.85 ± 0.01. CONCLUSIONS: This study reports one of the first artificial intelligence-based algorithms capable of accurately and efficiently assessing collateral flow of patients with AIS. This automated method for determining collateral filling could streamline clinical workflow, reduce bias, and aid in clinical decision making for determining reperfusion-eligible patients.

Rethinking the Collateral Vasculature Assessment in Acute Ischemic Stroke: The Comprehensive Collateral Cascade.

ABSTRACT: Occlusion of a cervical or cerebral artery results in disruption of blood flow to the brain and may result in irreversible infarction. Intracranial pial collaterals are a network of arteries that may preserve blood flow to otherwise critically hypoperfused brain areas until vessel recanalization is achieved. The robustness of these arterial collaterals is pivotal for the survivability of ischemic brain tissue and is associated with treatment success and long-term clinical outcome. More recently, the importance of venous outflow from ischemic brain tissue has been appreciated. Arterial collaterals and venous outflow are evaluated by neuroimaging parameters, and recent imaging advances have enabled a more comprehensive assessment of the entire collateral cascade in patients with acute ischemic stroke. Here we review novel imaging biomarkers for the assessment of arterial collaterals, tissue-level collateral blood flow, and venous outflow. We also summarize how a more comprehensive assessment of the cerebral blood flow leads to a better prediction of treatment efficacy and improved clinical outcomes.

Quantitative collateral assessment evaluated by cerebral blood volume measured by CT perfusion in patients with acute ischemic stroke.

OBJECTIVES: Collateral status (CS) is considered a predictor of clinical outcome after reperfusion therapy (RT) in patients with acute ischemic stroke (AIS). We proposed a quantitative assessment of CS using cerebral blood volume (CBV) measured by computed tomography perfusion (CTP) imaging. MATERIALS AND METHODS: This retrospective study was approved by the Institutional Review Board. Between February 2019 and September 2020, 60 patients with anterior circulation large-vessel occlusion who presented to our institution within 8 h after stroke onset were included. The ratio of the average CBV values in the affected middle cerebral artery (MCA) territories to the unaffected side was defined as the CBV ratio. CS was assessed by scores from previously reported qualitative scoring systems (Tan & regional leptomeningeal collateral (rLMC) scores). RESULTS: The CBV ratio was an independent factor contributing to a good functional outcome (P<0.01) and was significantly correlated with the Tan score (ρ=0.73, P<0.01) and the rLMC score (ρ=0.77, P<0.01). Among the patients with recanalization, the CBV ratio was a useful parameter that predicted both a good functional outcome (area under the receiver operating characteristic curve (AUC-ROC), 0.76; 95% CI, 0.55-0.89) and a good radiological outcome (AUC-ROC, 0.90; 95% CI, 0.72-0.97), and it was an independent predictor for good radiological outcome (OR: 4.38; 95% CI:1.29-14.82; P<0.01) in multivariate models. CONCLUSIONS: The CBV ratio is a suitable parameter for evaluating CS quantitatively for patients with AIS that can predict patient response to recanalization.

Comparison of methods between CT perfusion source images and CT angiography in collateral flow assessment.

BACKGROUND: The methods used for grading leptomeningeal collateral flow (LMF) on single-phase computed tomography angiography (CTA) are heterogeneous and limited by temporal resolution. PURPOSE: To compare the reliability of relative filling time delay (rFTD) on CT perfusion source images (CTP-SI) and the currently used single-phase CTA collateral assessment methods and evaluate their ability to predict clinical outcomes in acute ischemic stroke patients. MATERIAL AND METHODS: We analyzed consecutive middle cerebral artery or internal carotid artery occlusion patients who received multimodal CT before treatment and within 12 h of stroke symptom onset from October 2015 to December 2018. Patients were dichotomized using the 90-day mRS into good (0-1) versus adverse (2-6) outcomes. CTP-SI was used to identify the rFTD score. CTA images were reconstructed to assess collateral status using the collateral score (Cs) and region leptomeningeal collateral score (rLMCs). Two observers independently assessed images. RESULTS: The baseline characteristics (n = 54) were median age of 67 years and 68.5% of the participants were men. The baseline median NIHSS was 14. Good clinical outcomes were observed in 19 (35.2%) patients. The k value was higher for rFTDs (k = 0.779, P < 0.001) than Cs (k = 0.666, P < 0.001) and rLMCs (k = 0.763, P < 0.001). Higher rFTDs were correlated with lower rLMCs (Spearman's rho -0.68, P < 0.001) and Cs (rho -0.66, P < 0.001). In multivariate logistic regression, rFTD was associated with functional outcomes (P = 0.044). CONCLUSION: The rFTDs method is comparable to single-phase CTA-based assessments in assessing LMFs in acute ischemic stroke patients. Higher rFTDs is independently associated with adverse long-term functional outcomes.