Collateral flow and pulsatility during large vessel occlusions: insights from a quantitative in vitro study.

Acute ischemic stroke caused by large vessel occlusions is being increasingly treated with neurovascular interventions. The hemodynamics within the collateral system of the circle of Willis (CoW) hemodynamics play a fundamental role in therapy success. However, transient in vivo data on pathological collateral flow during large vessel occlusions are not available. Moreover, there are no flow models that accurately simulate the hemodynamic conditions in the CoW during large vessel occlusions. We used a circulatory loop to generate highly reproducible cerebrovascular-like flows and pressures and used non-invasive flow visualization and high-resolution flow and pressure measurements to acquire detailed, time-dependent hemodynamics inside an anatomical phantom of the CoW. After calibrating a physiological reference case, we induced occlusions in the 1. middle cerebral artery, 2. terminal carotid artery, and 3. basilar artery; and measured the left posterior communicating artery flow. Mean arterial pressure and pulse pressure remained unchanged in the different occlusion cases compared to the physiological reference case, while total cerebral flow decreased by up to 19%. In all three occlusion cases, reversed flow was found in the left posterior communicating artery compared to the reference case with different flow magnitudes and pulsatility index values. The experimental results were compared with clinical findings, demonstrating the capability of this realistic cerebrovascular flow setup. This novel cerebrovascular flow setup opens the possibility for investigating different topics of neurovascular interventions under various clinical conditions in controlled preclinical laboratory studies.

Transcoronary Gradients of Mechanosensitive MicroRNAs as Predictors of Collateral Development in Chronic Total Occlusion.

Background and Objectives: In this present study, we investigated the impact of mechanosensitive microRNAs (mechano-miRs) on the collateral development in 126 chronic total occlusion (CTO) patients, selected from 810 undergoing angiography. Materials and Methods: We quantified the collateral blood supply using the collateral flow index (CFI) and assessed the transcoronary mechano-miR gradients. Results: The patients with favorable collaterals had higher CFI values (0.45 ± 0.02) than those with poor collaterals (0.38 ± 0.03, p < 0.001). Significant differences in transcoronary gradients were found for miR-10a, miR-19a, miR-21, miR-23b, miR-26a, miR-92a, miR-126, miR-130a, miR-663, and let7d (p < 0.05). miR-26a and miR-21 showed strong positive correlations with the CFI (r = 0.715 and r = 0.663, respectively), while let7d and miR-663 were negatively correlated (r = -0.684 and r = -0.604, respectively). The correlations between cytokine gradients and mechano-miR gradients were also significant, including Transforming Growth Factor Beta with miR-126 (r = 0.673, p < 0.001) and Vascular Endothelial Growth Factor with miR-10a (r = 0.602, p = 0.002). A regression analysis highlighted the hemoglobin level, smoking, beta-blocker use, miR-26a, and miR-663 as significant CFI determinants, indicating their roles in modulating the collateral vessel development. Conclusions: These findings suggest mechanosensitive microRNAs as predictive biomarkers for collateral circulation, offering new therapeutic perspectives for CTO patients.

Systemic-to-pulmonary collateral flow associations with antegrade pulmonary flow in single ventricle patients: insights from cardiac magnetic resonance imaging.

Purpose: In the palliated single ventricle anomalies, a considerable amount of the aortic flow may be absorbed by the systemic-pulmonary collateral flow (SPCF), which can be noninvasively assessed by cardiac magnetic resonance (CMR). The aims of this study were to (1) identify factors associated with SCPF in pediatric single ventricle patients, and (2) establish a cutoff values indicating an association between SCPF and a reduction in antegrade pulmonary flow. Methods: A retrospective single-tertiary-center cohort study included 158 consecutive CMR studies of patients with a single ventricle. In the uni- and multivariable analysis, SPCF was presented as a percentage of the total pulmonary venous flow (SPCF%PV). The minimal clinically important difference in QP/QS ratios was estimated as ≥0.50, and an optimal cutoff value was defined using the receiver operating characteristic (ROC) curve. Results: SPCF%PV was significantly smaller in the post-total cavopulmonary connection (TCPC) group than in the pre-TCPC patients (p < 0.001). The patient's higher age and a higher antegrade pulmonary flow were associated with a lower SPCF%PV. A negative weak association was observed between the SPCF%PV and systemic saturation (r = -0.39, p < 0.001). SPCF%PV did not associate with ventricular volumes nor ejection fraction. The SPCF%PV was significantly smaller in patients that were palliated primarily with a pulmonary artery banding compared to those palliated with a BT-shunt (p = 0.002) or RV-PA- shunt (p = 0.044). In the ROC analysis, for pre-TCPC patient's, a cutoff of SPCF%PV 42% yielded a sensitivity of 100% and specificity of 80% for significantly reduced antegrade pulmonary flow (AUC 0.97). In the post-TCPC group, the optimal SPCF%PV cutoff was 34% (sensitivity 100%, specificity 98%, AUC 0.99). Conclusion: SPCF results in a considerable left-to-right shunt, which subsequently diminishes spontaneously after TCPC. Our findings indicated that for pre-TCPC patients, an SPCF%PV threshold of 42% (sensitivity 100%, specificity 80%), and for the post-TCPC group, a threshold of 34% (sensitivity 100%, specificity 98%) were effective in identifying reduced antegrade pulmonary flow.

Impact of coronary hyperemia on collateral flow correction of coronary microvascular resistance indices.

Recently, a novel method to estimate wedge pressure (Pw)-corrected minimal microvascular resistance (MR) was introduced. However, this method has not been validated since, and there are some theoretical concerns regarding the impact of different physiological conditions on the derivation of Pw measurements. This study sought to validate the recently introduced method to estimate Pw-corrected MR in a Doppler-derived study population and to evaluate the impact of different physiological conditions on the Pw measurements and the derivation of Pw-corrected MR. The method to derive "estimated" hyperemic microvascular resistance (HMR) without the need for Pw measurements was validated by estimating the coronary fractional flow reserve (FFRcor) from myocardial fractional flow reserve (FFRmyo) in a Doppler-derived study population (N = 53). From these patients, 24 had hyperemic Pw measurements available for the evaluation of hyperemic conditions on the derivation of Pw and its effect on the derivation of both "true" (with measured Pw) and "estimated" Pw-corrected HMR. Nonhyperemic Pw differed significantly from Pw measured in hyperemic conditions (26 ± 14 vs. 35 ± 14 mmHg, respectively, P < 0.005). Nevertheless, there was a strong linear relationship between FFRcor and FFRmyo in nonhyperemic conditions (R2 = 0.91, P < 0.005), as well as in hyperemic conditions (R2 = 0.87, P < 0.005). There was a strong linear relationship between "true" HMR and "estimated" HMR using either nonhyperemic (R2 = 0.86, P < 0.005) or hyperemic conditions (R2 = 0.85, P < 0.005) for correction. In contrast to a modest agreement between nonhyperemic Pw-corrected HMR and apparent HMR (R2 = 0.67, P < 0.005), hyperemic Pw-corrected HMR showed a strong agreement with apparent HMR (R2 = 0.88, P < 0.005). We validated the calculation method for Pw-corrected MR in a Doppler velocity-derived population. In addition, we found a significant impact of hyperemic conditions on the measurement of Pw and the derivation of Pw-corrected HMR.NEW & NOTEWORTHY The following are what is known: 1) wedge-pressure correction is often considered for the derivation of indices of minimal microvascular resistance, and 2) the Yong method for calculating wedge pressure-corrected index of microvascular resistance (IMR) without balloon inflation has never been validated in a Doppler-derived population and has not been tested under different physiological conditions. This study 1) adds validation for the Yong method for calculated wedge-pressure correction in a Doppler-derived study population and 2) shows significant influence of the physiological conditions on the derivation of coronary wedge pressure.

Cerebral Blood Flow, Brain Injury, and Aortic-Pulmonary Collateral Flow After the Fontan Operation.

Patients with a single ventricle develop aortopulmonary collaterals (APCs) whose flow has been shown to be inversely proportional to cerebral blood flow (CBF) in a previous cross-sectional study. Longitudinal CBF and APC flow in patients with Fontan physiology adjusting for brain injury (BI) has never been reported. Decreased CBF and BI may adversely impact neurodevelopment. A prospective longitudinal cohort of 27 patients with Fontan physiology (aged 10 ± 1.9 years, 74% male) underwent cardiac and brain magnetic resonance imaging 3 to 9 months and 6.0 ± 1.86 years after Fontan operation to measure the CBF and APC flow and to reassess the BI (focal BI, generalized insult, and hemorrhage). CBF was measured using jugular venous flow and APC flow was measured by the difference between aortic flow and caval return. Multivariate modeling was used to assess the relation between the change in APC flow and BI. A strong inverse relation was found between CBF/aortic flow change and APC flow/aortic flow and APC flow/body surface area change (R2 = 0.70 and 0.72 respectively, p <0.02). Overall, the CBF decreased by 9 ± 11% and the APC flow decreased by 0.73 ± 0.67 l/min/m2. The evolution of CBF and APC flow were significantly and inversely related when adjusting for time since Fontan operation, gender, and BI on the multivariate modeling. Every unit increase in APC flow change was associated with an 8% decrease in CBF change. In conclusion, CBF and APC flow change are inversely related across serial imaging, adjusting for time from Fontan operation, gender, and BI. CBF and APC aortic flow decrease over a 6-year period. This may adversely impact neurodevelopment. Because APCs can be embolized, this may be a modifiable risk factor. Clinical trials numbers: NCT02135081 and NCT02919956.

Immediate recruitment of dormant coronary collaterals can provide more than half of normal resting perfusion during coronary occlusion in patients with coronary artery disease.

BACKGROUND: Dormant coronary collaterals are highly prevalent and clinically beneficial in cases of coronary occlusion. However, the magnitude of myocardial perfusion provided by immediate coronary collateral recruitment during acute occlusion is unknown. We aimed to quantify collateral myocardial perfusion during balloon occlusion in patients with coronary artery disease (CAD). METHODS: Patients without angiographically visible collaterals undergoing elective percutaneous transluminal coronary angioplasty (PTCA) to a single epicardial vessel underwent two scans with 99mTc-sestamibi myocardial perfusion single-photon emission computed tomography (SPECT). All subjects underwent at least three minutes of angiographically verified complete balloon occlusion, at which time an intravenous injection of the radiotracer was administered, followed by SPECT imaging. A second radiotracer injection followed by SPECT imaging was performed 24 h after PTCA. RESULTS: The study included 22 patients (median [interquartile range] age 68 [54-72] years. The perfusion defect extent was 19 [11-38] % of the LV, and the collateral perfusion at rest was 64 [58-67]% of normal. CONCLUSION: This is the first study to describe the magnitude of short-term changes in coronary microvascular collateral perfusion in patients with CAD. On average, despite coronary occlusion and an absence of angiographically visible collateral vessels, collaterals provided more than half of the normal perfusion.

Association Between Cerebral Angiography and Asymmetrical Cortical and Deep/Medullary Vein Signs on T2 Star Magnetic Resonance Imaging in Patients with Hyperacute Horizontal Segment of the Middle Cerebral Artery Occlusion.

BACKGROUND: When treating acute ischemic stroke patients, evaluation of collateral flow to the ischemic area is essential. Blood-oxygen-level-dependent imaging, including T2 star (T2∗), can identify elevated deoxyhemoglobin levels, reflecting an increase in the oxygen extraction fraction. Prominent veins on T2∗ represent increased deoxyhemoglobin and cerebral blood volume. This study compared asymmetrical vein signs (AVSs) on T2∗ and digital subtraction angiography findings during mechanical thrombectomy (MT) in patients with hyperacute middle cerebral artery occlusion. METHODS: Clinical and imaging data of 41 patients with occlusion of the horizontal segment of the middle cerebral artery who underwent MT were collected. Patients were divided into 2 groups based on angiographic occlusion sites as: proximal and distal to the lenticulostriate artery (LSA). AVSs on T2∗ were divided into asymmetrical cortical vein sign (cortical AVS) and asymmetrical deep/medullary vein sign (deep/medullary AVS), and were compared with the findings of intraoperative digital subtraction angiography. RESULTS: Twenty-seven patients had AVSs. Cortical AVS was the only parameter with a significant association with poor angiographic collateral supply. In terms of occlusion site, deep/medullary AVS was the only parameter with a significant association with occlusion proximal to the LSA. CONCLUSIONS: In patients with occlusion of the horizontal segment of the middle cerebral artery, presence of the cortical AVS on T2∗ suggests a poor angiographic collateral supply, while presence of the deep/medullary AVS suggests impaired blood flow to the basal ganglia through LSAs. Both these signs contribute to poor outcomes in patients undergoing MT.

A deep learning approach to predict collateral flow in stroke patients using radiomic features from perfusion images.

Collateral circulation results from specialized anastomotic channels which are capable of providing oxygenated blood to regions with compromised blood flow caused by arterial obstruction. The quality of collateral circulation has been established as a key factor in determining the likelihood of a favorable clinical outcome and goes a long way to determining the choice of a stroke care model. Though many imaging and grading methods exist for quantifying collateral blood flow, the actual grading is mostly done through manual inspection. This approach is associated with a number of challenges. First, it is time-consuming. Second, there is a high tendency for bias and inconsistency in the final grade assigned to a patient depending on the experience level of the clinician. We present a multi-stage deep learning approach to predict collateral flow grading in stroke patients based on radiomic features extracted from MR perfusion data. First, we formulate a region of interest detection task as a reinforcement learning problem and train a deep learning network to automatically detect the occluded region within the 3D MR perfusion volumes. Second, we extract radiomic features from the obtained region of interest through local image descriptors and denoising auto-encoders. Finally, we apply a convolutional neural network and other machine learning classifiers to the extracted radiomic features to automatically predict the collateral flow grading of the given patient volume as one of three severity classes - no flow (0), moderate flow (1), and good flow (2). Results from our experiments show an overall accuracy of 72% in the three-class prediction task. With an inter-observer agreement of 16% and a maximum intra-observer agreement of 74% in a similar experiment, our automated deep learning approach demonstrates a performance comparable to expert grading, is faster than visual inspection, and eliminates the problem of grading bias.

Under (back) pressure: Better collateral flow may facilitate clot removal in ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Collateral status may facilitate clot removal and affect rates of successful reperfusion following endovascular therapy (EVT) for acute ischemic stroke (AIS). METHODS: Following the PRISMA guidelines, a systematic literature review of the English language literature was conducted using PubMed, Scopus, Web of Science, and Embase. Papers which focused on collateral status and patients treated with EVT for AIS were included in our analysis. Outcomes of interest included collateral score grading, rates of successful reperfusion defined as thrombolysis in cerebral infarction (TICI) score 2b-3 and onset to revascularization time. We calculated pooled odds ratio (OR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) based on collateral status. RESULTS: 16 studies, with 6073 patients, were included in our analysis. Among the included studies, there were six different collateral grading scales, which were dichotomized into "good to moderate" and "poor" collaterals. Odds of successful reperfusion were significantly higher among patients with good to moderate collateral circulation compared to those with poor collaterals (OR = 1.61; 95% CI = 1.24 to 2.09; P-value < 0.001); however, there was heterogeneity among included studies (I2 = 5 4%; P-value = 0.008). Onset to revascularization time was comparable between patients with good to moderate collateral circulation compared to those with poor collaterals (MD = 3.91 min; 95% CI = -8.71 to 16.53; P-value = 0.544); however, there was heterogeneity among included studies (I2= 60%; P-value = 0.014). CONCLUSIONS: The presence of good collaterals may increase the odds of achieving successful reperfusion following EVT for AIS. Improved collateral flow was associated with improved angiographic outcomes, although future work is needed to determine if a causal relationship exists.

A magnetic resonance imaging-based computational analysis of cerebral hemodynamics in patients with carotid artery stenosis.

Management of asymptomatic carotid artery stenosis (CAS) relies on measuring the percentage of stenosis. The aim of this study was to investigate the impact of CAS on cerebral hemodynamics using magnetic resonance imaging (MRI)-informed computational fluid dynamics (CFD) and to provide novel hemodynamic metrics that may improve the understanding of stroke risk. CFD analysis was performed in two patients with similar degrees of asymptomatic high-grade CAS. Three-dimensional anatomical-based computational models of cervical and cerebral blood flow were constructed and calibrated patient-specifically using phase-contrast MRI flow and arterial spin labeling perfusion data. Differences in cerebral hemodynamics were assessed in preoperative and postoperative models. Preoperatively, patient 1 demonstrated large flow and pressure reductions in the stenosed internal carotid artery, while patient 2 demonstrated only minor reductions. Patient 1 exhibited a large amount of flow compensation between hemispheres (80.31%), whereas patient 2 exhibited only a small amount of collateral flow (20.05%). There were significant differences in the mean pressure gradient over the stenosis between patients preoperatively (26.3 vs. 1.8 mmHg). Carotid endarterectomy resulted in only minor hemodynamic changes in patient 2. MRI-informed CFD analysis of two patients with similar clinical classifications of stenosis revealed significant differences in hemodynamics which were not apparent from anatomical assessment alone. Moreover, revascularization of CAS might not always result in hemodynamic improvements. Further studies are needed to investigate the clinical impact of hemodynamic differences and how they pertain to stroke risk and clinical management.

Ischemic Lesion Growth in Patients with a Persistent Target Mismatch After Large Vessel Occlusion.

BACKGROUND: Failure to reperfuse a cerebral occlusion resulting in a persistent penumbral pattern has not been fully described. METHODS: We retrospectively reviewed patients with anterior large vessel occlusion who did not receive reperfusion, and underwent repeated perfusion imaging, with baseline imaging < 6 h after onset and follow-up scans from 16-168 h. A persistent target mismatch (PTM) was defined as core volume of < 100 mL, mismatch ratio > 1.2, and mismatch volume > 10 mL on follow-up imaging. Patients were divided into PTM or non-PTM groups. Ischemic core and penumbral volumes were compared between baseline and follow-up imaging between the two groups, and collateral flow status assessed using CT perfusion collateral index. RESULTS: A total of 25 patients (14 PTM and 11 non-PTM) were enrolled in the study. Median core volumes increased slightly in the PTM group, from 22 to 36 ml. There was a much greater increase in the non-PTM group, from 57 to 190 ml. Penumbral volumes were stable in the PTM group from a median of 79 ml at baseline to 88 ml at follow-up, whereas penumbra was reduced in the non-PTM group, from 120 to 0 ml. Collateral flow status was also better in the PTM group and the median collateral index was 33% compared with 44% in the non-PTM group (p = 0.043). CONCLUSION: Multiple patients were identified with limited core growth and large penumbra (persistent target mismatch) > 16 h after stroke onset, likely due to more favorable collateral flow.

Quantification of systemic-to-pulmonary collateral flow in univentricular physiology with 4D flow MRI.

PURPOSE: Systemic-to-pulmonary collateral flow is a well-recognised phenomenon in patients with single ventricle physiology, but remains difficult to quantify. The aim was to compare the reported formula's that have been used for calculation of systemic-to-pulmonary-collateral flow to assess their consistency and to quantify systemic-to-pulmonary collateral flow in patients with a Glenn and/or Fontan circulation using four-dimensional flow MRI (4D flow MR). METHODS: Retrospective case-control study of Glenn and Fontan patients who had a 4D flow MR study. Flows were measured at the ascending aorta, left and right pulmonary arteries, left and right pulmonary veins, and both caval veins. Systemic-to-pulmonary collateral flow was calculated using two formulas: 1) pulmonary veins - pulmonary arteries and 2) ascending aorta - caval veins. Anatomical identification of collaterals was performed using the 4D MR image set. RESULTS: Fourteen patients (n = 11 Fontan, n = 3 Glenn) were included (age 26 [22-30] years). Systemic-to-pulmonary collateral flow was significantly higher in the patients than the controls (n = 10, age 31.2 [15.1-38.4] years) with both formulas: 0.28 [0.09-0.5] versus 0.04 [-0.66-0.21] l/min/m2 (p = 0.036, formula 1) and 0.67 [0.24-0.88] versus -0.07 [-0.16-0.08] l/min/m2 (p < 0.001, formula 2). In patients, systemic-to-pulmonary collateral flow differed significantly between formulas 1 and 2 (13% versus 26% of aortic flow, p = 0.038). In seven patients, veno-venous collaterals were detected and no aortopulmonary collaterals were visualised. CONCLUSION: 4D flow MR is able to detect increased systemic-to-pulmonary collateral flow and visualise collaterals vessels in Glenn and Fontan patients. However, the amount of systemic-to-pulmonary collateral flow varies with the formula employed. Therefore, further research is necessary before it could be applied in clinical care.

CT vascular territory mapping: a novel method to identify large vessel occlusion collateral.

INTRODUCTION: This descriptive study explores typical patterns of vascular territory mapping (VTM) in ischaemic stroke patients with proximal vessel occlusion. VTM is a novel process using CT perfusion that can identify the source and extent of collateral blood flow in patients with vessel occlusion. It functions by determining which vessel provides dominant blood flow to a brain voxel. METHODS: A total of 167 consecutive patients were analysed from INSPIRE (International Stroke Perfusion Imaging Registry) with their CT perfusion reprocessed through VTM software. We explored the typical territory maps generated by this software relating to common large vessel occlusion location sites (ACA/MCA/PCA). RESULTS/CONCLUSION: In the presence of occlusion, VTM demonstrated a reciprocal increase in collateral vessel territories.

Poor collateral flow with severe hypoperfusion explains worse outcome in acute stroke patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with poorer functional outcomes in acute stroke patients. It has been hypothesized that this is due to poor collateral recruitment. AIMS: This study aimed to investigate the relationship between AF and collaterals with outcome in thrombectomy patients. METHODS: This retrospective cohort study identified 1036 acute ischemic patients from the INternational Stroke Perfusion Imaging REgistry. The cohort was divided into two groups: 432 with AF and 604 without AF. Patients were stratified by collateral grades as good, moderate, and poor. Within each collateral grade, the prediction of AF versus No AF for good outcome (3-month modified Rankin Scale of 0-2) was determined. Then, within each collateral grade, perfusion was compared between those with and without AF. RESULTS: AF was negatively associated with good outcome in patients with poor collaterals (26.7% vs 51.2% for AF vs No AF, odds ratio = 0.32 (95% confidence interval = 0.22-0.50), p < 0.001), but not in patients with good (50.9% vs 58.1% for AF vs No AF, odds ratio = 0.75 (0.46-1.23), p = 0.249) or moderate collaterals (43.6% vs 50.9% for AF vs No AF, odds ratio = 0.75 (0.47-1.18), p = 0.214). AF was associated with severe hypoperfusion only in patients with poor collateral flow (54.0 vs 35.5 mL for AF vs No AF, p < 0.001). CONCLUSIONS: AF-related stroke is associated with more severe hypoperfusion and worse outcome in those with poor collaterals.

Evaluating cell viability, capillary perfusion, and collateral tortuosity in an ex vivo mouse intestine fluidics model.

Numerous disease conditions involve the sudden or progressive loss of blood flow. Perfusion restoration is vital for returning affected organs to full health. While a range of clinical interventions can successfully restore flow to downstream tissues, the microvascular responses after a loss-of-flow event can vary over time and may involve substantial microvessel instability. Increased insight into perfusion-mediated capillary stability and access-to-flow is therefore essential for advancing therapeutic reperfusion strategies and improving patient outcomes. To that end, we developed a tissue-based microvascular fluidics model to better understand (i) microvascular stability and access-to-flow over an acute time course post-ischemia, and (ii) collateral flow in vessels neighboring an occlusion site. We utilized murine intestinal tissue regions by catheterizing a feeder artery and introducing perfusate at physiologically comparable flow-rates. The cannulated vessel as well as a portion of the downstream vessels and associated intestinal tissue were cultured while constant perfusion conditions were maintained. An occlusion was introduced in a selected arterial segment, and changes in perfusion within areas receiving varying degrees of collateral flow were observed over time. To observe the microvascular response to perfusion changes, we incorporated (i) tissues harboring cell-reporter constructs, specifically Ng2-DsRed labeling of intestinal pericytes, and (ii) different types of fluorescent perfusates to quantify capillary access-to-flow at discrete time points. In our model, we found that perfusion tracers could enter capillaries within regions downstream of an occlusion upon the initial introduction of perfusion, but at 24 h tissue perfusion was severely decreased. However, live/dead cell discrimination revealed that the tissue overall did not experience significant cell death, including that of microvascular pericytes, even after 48 h. Our findings suggest that altered flow conditions may rapidly initiate cellular responses that reduce capillary access-to-flow, even in the absence of cellular deterioration or hypoxia. Overall, this ex vivo tissue-based microfluidics model may serve as a platform upon which a variety of follow-on studies may be conducted. It will thus enhance our understanding of microvessel stability and access-to-flow during an occlusive event and the role of collateral flow during normal and disrupted perfusion.

Modelling collateral flow and thrombus permeability during acute ischaemic stroke.

The presence of collaterals and high thrombus permeability are associated with good functional outcomes after an acute ischaemic stroke. We aim to understand the combined effect of the collaterals and thrombus permeability on cerebral blood flow during an acute ischaemic stroke. A cerebral blood flow model including the leptomeningeal collateral circulation is used to simulate cerebral blood flow during an acute ischaemic stroke. The collateral circulation is varied to capture the collateral scores: absent, poor, moderate and good. Measurements of the transit time, void fraction and thrombus length in acute ischaemic stroke patients are used to estimate thrombus permeability. Estimated thrombus permeability ranges between 10-7 and 10-4 mm2. Measured flow rates through the thrombus are small and the effect of a permeable thrombus on brain perfusion during stroke is small compared with the effect of collaterals. Our simulations suggest that the collaterals are a dominant factor in the resulting infarct volume after a stroke.

Role of collateral flow in infarct border zone extent and contractile function in patients with chronic coronary total occlusion.

PURPOSE: There is a paucity of data regarding the border zone parameters in patients with chronic coronary total occlusion (CTO). We investigated the border zone extent and contractile function and their associations with collateral flow. METHODS: CTO patients (n = 47) and sex- and age-matched volunteers (n = 15) were prospectively enrolled and underwent cardiac MRI examinations to acquire cine and late-gadolinium enhancement (LGE) images. Myocardial peak strain (PS) and the time to PS were determined at the segmental level and global level. Infarct, border zone, adjacent, and remote regions were defined according to the transmural extent of infarction (TEI) by LGE at each segment. Angiographic collateral flow was evaluated using the Rentrop grading system. RESULTS: CTO patients with well-developed collateral flow had a higher TEI in border zone regions compared to patients with poorly developed collateral flow (p = 0.02). Conversely, CTO patients with poorly developed collaterals showed a higher TEI in infarct regions (p < 0.01). Enhanced border function, characterized by greater PS and earlier time to PS, was noted in well-developed collaterals (all p < 0.05). In the multivariate linear analyses, the level of collateral flow was an independent predictor of the border zone extent (ß = 0.40, p = 0.02) and contractile function (radial: ß = -0.42, p = 0.02; circumferential: ß = 0.39, p = 0.02; and longitudinal: ß = 0.47, p < 0.01). CONCLUSIONS: In CTO patients, the presence of well-developed collateral flow was closely linked to a greater extent of LGE and contractile function in border zone regions. Our findings shed light on the cardiac MRI-based pathophysiological underpinning in border zone regions, which could offer complementary and prognostic information in clinical practice.

Sex Differences in Collateral Circulation and Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

Background: Collateral circulation is known to lead to smaller infarct volume and better functional outcome after mechanical thrombectomy (MT), but studies examining sex differences in collateral circulation are scarce. The aim of this study was to investigate if collateral circulation has a different impact on outcome in women and men. Methods: A single-center retrospective study of 487 patients (230 men and 257 women) treated with MT for acute ischemic stroke in the anterior cerebral circulation. Collateral circulation was assessed on computed tomography angiography images. The outcome was evaluated at 90 days according to the modified Rankin Scale (mRS). Results: Women were older, median age 76 years (IQR 68-83) vs. 71 years (IQR 63-78). Stroke severity and time to recanalization were comparable. More women had moderate or good collaterals in 58.4 vs. 47.0% for men (p = 0.01). Among patients with moderate and good collaterals significantly more men (61%) were functionally independent (mRS 0-2) than women (41.5%) (p = < 0.01). This difference remained significant after correcting for age by linear weighting, 60.4 vs. 46.8% (p = 0.03). Conclusion: Women had better collateral flow but showed worse functional outcomes, while good collateral flow led to better outcomes in men, even after correcting for age. Further clinical studies on peri- and post-interventional care, factors affecting recovery after hospital discharge as well as basic research on the neurovascular unit are needed to find modifiable targets to improve clinical outcomes for women.

Association of collateral flow with clinical outcomes in patients with acute myocardial infarction.

Coronary collateral flow is an important prognostic marker in percutaneous coronary intervention (PCI) for chronic total occlusion. However, the role of collateral flow to the culprit lesion of acute myocardial infarction (AMI) has not been fully established yet. The purpose of this retrospective study was to examine the association between collateral flow and long-term clinical outcomes in patients with AMI. We included 937 patients with AMI, and divided those into the no-collateral group (n = 704) and the collateral group (n = 233) according to the presence or absence of collateral flow to the culprit lesion of AMI. The primary endpoint was the incidence of major adverse cardiac events (MACE), which was defined as a composite of all-cause death, non-fatal MI, re-admission for heart failure, and ischemia driven target vessel revascularization. The median follow-up duration was 473 days (Q1: 184 days- Q3: 1027 days), and a total of 263 MACE was observed during the study period. The incidence of MACE was significantly greater in the no-collateral group than in the collateral group (29.8% vs. 22.3%, p = 0.027). In the multivariate COX hazard model, the presence of collateral flow was inversely associated with MACE (HR 0.636, 95% CI 0.461-0.878, p = 0.006) after controlling multiple confounding factors. In conclusion, the presence of collateral flow to the culprit lesion of AMI was inversely associated with long-term adverse outcomes. Careful observation of collateral flow may be important in emergent coronary angiography to stratify a high-risk group among various patients with AMI.

Leukocytes in Cerebral Thrombus Respond to Large-Vessel Occlusion in a Time-Dependent Manner and the Association of NETs With Collateral Flow.

Thrombus components are dynamically influenced by local blood flow and blood immune cells. After a large-vessel occlusion stroke, changes in the cerebral thrombus are unclear. Here we assessed a total of 206 cerebral thrombi from patients with ischemic stroke undergoing endovascular thrombectomy. The thrombi were categorized by time to reperfusion of <4 h (T4), 4-8 h (T4-8), and >8 h (T8). The cellular compositions in thrombus were analyzed, and relevant clinical features were compared. Both white blood cells and neutrophils were increased and then decreased in thrombus with time to reperfusion, which were positively correlated with those in peripheral blood. The neutrophil extracellular trap (NET) content in thrombus was correlated with the degree of neurological impairment of patients. Moreover, with prolonged time to reperfusion, the patients showed a trend of better collateral grade, which was associated with a lower NET content in the thrombus. In conclusion, the present results reveal the relationship between time-related endovascular immune response and clinical symptoms post-stroke from the perspective of thrombus and peripheral blood. The time-related pathological changes of cerebral thrombus may not be the direct cause for the difficulty in thrombolysis and thrombectomy. A low NET content in thrombi indicates excellent collateral flow, which suggests that treatments targeting NETs in thrombi might be beneficial for early neurological protection.