Modeling cerebrovascular responses to assess the impact of the collateral circulation following middle cerebral artery occlusion.

OBJECTIVE: An improved understanding of the role of the leptomeningeal collateral circulation in blood flow compensation following middle cerebral artery (MCA) occlusion can contribute to more effective treatment development for ischemic stroke. The present study introduces a model of the cerebral circulation to predict cerebral blood flow and tissue oxygenation following MCA occlusion. METHODS: The model incorporates flow regulation mechanisms based on changes in pressure, shear stress, and metabolic demand. Oxygen saturation in cerebral vessels and tissue is calculated using a Krogh cylinder model. The model is used to assess the effects of changes in oxygen demand and arterial pressure on cerebral blood flow and oxygenation after MCA occlusion. RESULTS: An increase from five to 11 leptomeningeal collateral vessels was shown to increase the oxygen saturation in the region distal to the occlusion by nearly 100%. Post-occlusion, the model also predicted a loss of autoregulation and a decrease in flow to the ischemic territory as oxygen demand was increased; these results were consistent with data from experiments that induced cerebral ischemia. CONCLUSIONS: This study highlights the importance of leptomeningeal collaterals following MCA occlusion and reinforces the idea that lower oxygen demand and higher arterial pressure improve conditions of flow and oxygenation.

Hemoglobin in large vessel occlusion: Look further than collaterals.

BACKGROUND: Abnormal hemoglobin (Hb) levels lead to poorer outcomes in ischemic stroke, though the mechanisms remain elusive. We aimed to study the role of Hb on imaging and clinical outcomes, namely on collaterals as it is a known mediator of infarct growth. METHODS: Retrospective cohort study of patients with large vessel occlusion ischemic stroke admitted to our center. Demographics, clinical and imaging variables were collected, particularly baseline hemoglobin, presence of anemia and collateral score. Collaterals were scored from 0 to 3 and defined as poor if 0-1. Multivariable analyses were performed for collateral score and clinical outcomes (3-month mortality and good prognosis). RESULTS: We included 811 patients, 215 (26.5 %) with anemia. Patients with anemia were older, had more comorbidities and more severe strokes. Hemoglobin levels and anemia were not associated with collateral score (OR 0.97, 95 % CI 0.89-1.05, p = 0.414 and OR 0.89, 95 % CI 0.64-1.24, p = 0.487, respectively) nor with poor collaterals (OR 0.96, 95 % CI 0.88-1.05, p = 0.398 and OR 0.86, 95 % CI 0.60-1.23, p = 0.406, respectively). Hb levels were associated with 3-month mortality (OR 0.85, 95 % CI 0.76-0.96, p = 0.008). CONCLUSION: Hemoglobin or anemia were not found to be associated with collateral status. Our results raise further questions regarding the pathophysiology of anemia and outcomes in ischemic stroke, highlighting the need for future research.

Correlation between triglyceride glucose index and collateral circulation formation in patients with chronic total occlusion of coronary arteries in different glucose metabolic states.

BACKGROUND: To investigate the correlation between triglyceride glucose index (TyG) and collateral circulation in patients with chronic total occlusion (CTO) of coronary arteries in different glucose metabolic states. METHODS: A total of 681 patients who underwent coronary angiography between January 2020 and December 2021 to determine the presence of CTO lesions in at least one major coronary artery were retrospectively included in this study. Patients were categorized into a group with poor collateral circulation formation (Rentrop grade 0-1, n = 205) and a group with good collateral circulation formation (Rentrop grade 2-3, n = 476) according to the Rentrop scale. They were also categorized according to their glucose metabolism status: normal glucose regulation (NGR) (n = 139), prediabetes mellitus (Pre-DM) (n = 218), and diabetes mellitus (DM) (n = 324). Correlation between TyG index and collateral circulation formation was analyzed by logistic regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Among patients with CTO, TyG index was significantly higher in the group with poor collateral circulation formation than in the group with good collateral circulation formation. Logistic regression analysis showed that TyG index was an independent risk factor for poor collateral circulation formation (OR 5.104, 95% CI 3.323-7.839, P < 0.001). The accuracy of TyG index in predicting collateral circulation formation was evaluated by the ROC curve, which had an area under the curve of 0.779 (95% CI 0.738-0.820, P < 0.001). The restrictive cubic spline curves showed that the risk of poor collateral circulation formation in the Pre-DM and DM groups was initially flat and finally increased rapidly, except for the NGR group. TyG index was significantly associated with an increased risk of poor collateral circulation formation in the Pre-DM and DM groups. CONCLUSIONS: TyG index was significantly associated with the risk of poor collateral circulation formation in patients with CTO, especially those with Pre-DM and DM.

Growth factor free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia.

Critical limb ischemia (CLI) occurs when blood flow is restricted through the arteries, resulting in ulcers, necrosis, and chronic wounds in the downstream extremities. The development of collateral arterioles (i.e. arteriogenesis), either by remodeling of pre-existing vascular networks or de novo growth of new vessels, can prevent or reverse ischemic damage, but it remains challenging to stimulate collateral arteriole development in a therapeutic context. Here, we show that a gelatin-based hydrogel, devoid of growth factors or encapsulated cells, promotes arteriogenesis and attenuates tissue damage in a murine CLI model. The gelatin hydrogel is functionalized with a peptide derived from the extracellular epitope of Type 1 cadherins. Mechanistically, these "GelCad" hydrogels promote arteriogenesis by recruiting smooth muscle cells to vessel structures in both ex vivo and in vivo assays. In a murine femoral artery ligation model of CLI, delivery of in situ crosslinking GelCad hydrogels was sufficient to restore limb perfusion and maintain tissue health for 14 days, whereas mice treated with gelatin hydrogels had extensive necrosis and autoamputated within 7 days. A small cohort of mice receiving the GelCad hydrogels were aged out to 5 months and exhibited no decline in tissue quality, indicating durability of the collateral arteriole networks. Overall, given the simplicity and off-the-shelf format of the GelCad hydrogel platform, we suggest it could have utility for CLI treatment and potentially other indications that would benefit from arteriole development.

A Deep Dive Into Retroesophageal Major Aortopulmonary Collateral Arteries.

Background: The anatomy of major aortopulmonary collateral arteries (MAPCAs) can be highly variable with regard to number, anatomic origin, course, and relationship to the native pulmonary arteries. Some MAPCAs travel behind the esophagus (retroesophageal) and bronchus before entering the lung parenchyma. The purpose of this paper was to review the anatomy, physiology, and surgical characteristics of retroesophageal MAPCAs. Methods: This manuscript summarizes the data from a series of three papers that have focused on the subject of retroesophageal MAPCAs from our institution over the past ten years. Results: Two-thirds of patients evaluated had a retroesophageal MAPCA identified at surgery. Retroesophageal major aortopulmonary collateral arteries (REMs) were more common with a left arch (77%) compared with a right arch (53%). Of all REMs evaluated, 83% were single supply, 13% were dual supply with an inadequate connection, and 4% were dual supply with an adequate connection. Based on these findings, 96% of retroesophageal MAPCAs were unifocalized. Follow-up catheterization was performed at a median of 17 months after surgery; 75% of unifocalized MAPCAs were widely patent, 20% were patent but stenotic, and 5% were occluded. Conclusions: The data demonstrate that retroesophageal MAPCAs are relatively common and almost always require unifocalization. At mid-term follow-up, 95% of unifocalized MAPCAs were found to be patent.

The effect of interarm blood pressure difference on coronary collateral flow in patients with ST-segment elevation myocardial infarction who had undergone primary percutaneous coronary intervention.

OBJECTIVE: In patients with acute myocardial infarction, coronary collateral circulation (CCC) is associated with reduced infarct size, preserved cardiac function, and decreased mortality. An interarm blood pressure difference (IABPD) is shown to be independently associated with cardiovascular and all-cause of mortality. We aimed to determine the effect of IABPD on coronary collateral flow in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (p-PCI). PATIENTS AND METHODS: We prospectively investigated 1,348 consecutive patients who were hospitalized for STEMI and underwent p-PCI. The Rentrop classification was used to assess CCC. According to this classification, we defined Rentrop 0 and 1 as poor CCC, and Rentrop 2 and 3 as good CCC. A 10 mm Hg difference is considered the upper limit of IABPD. RESULTS: Patients were divided into two groups according to the collateral circulation, 325 patients (24%) had good collateral, while 1,023 patients (76%) had poor collateral. IABPD was significantly higher in the poor collateral group (57 patients, 5.6%) than in the good collateral group (9 patients, 2.8%) (p=0.04). Pre-infarction angina and IABPD were identified as independent predictors of poor collateral (OR: 0.516, 95% CI 0.370-0.631, p=0.007; OR: 3.681, 95% CI: 1.773-7.461, p=0.01, respectively) in multivariate analysis. CONCLUSIONS: The IABPD was shown as an independent predictor of poor collateral circulation in patients with STEMI who underwent p-PC.

Dedifferentiation and Proliferation of Artery Endothelial Cells Drive Coronary Collateral Development in Mice.

BACKGROUND: Collateral arteries act as natural bypasses which reroute blood flow to ischemic regions and facilitate tissue regeneration. In an injured heart, neonatal artery endothelial cells orchestrate a systematic series of cellular events, which includes their outward migration, proliferation, and coalescence into fully functional collateral arteries. This process, called artery reassembly, aids complete cardiac regeneration in neonatal hearts but is absent in adults. The reason for this age-dependent disparity in artery cell response is completely unknown. In this study, we investigated if regenerative potential of coronary arteries is dictated by their ability to dedifferentiate. METHODS: Single-cell RNA sequencing of coronary endothelial cells was performed to identify differences in molecular profiles of neonatal and adult endothelial cells in mice. Findings from this in silico analyses were confirmed with in vivo experiments using genetic lineage tracing, whole organ immunostaining, confocal imaging, and cardiac functional assays in mice. RESULTS: Upon coronary occlusion, neonates showed a significant increase in actively cycling artery cells and expressed prominent dedifferentiation markers. Data from in silico pathway analyses and in vivo experiments suggested that upon myocardial infarction, cell cycle reentry of preexisting neonatal artery cells, the subsequent collateral artery formation, and recovery of cardiac function are dependent on arterial VegfR2 (vascular endothelial growth factor receptor-2). This subpopulation of dedifferentiated and proliferating artery cells was absent in nonregenerative postnatal day 7 or adult hearts. CONCLUSIONS: These data indicate that adult artery endothelial cells fail to drive collateral artery development due to their limited ability to dedifferentiate and proliferate.

[Variants of collateral cerebral circulation in moyamoya disease]. / Varianty kollateral'nogo krovoobrashcheniya golovnogo mozga pri bolezni moya-moya.

BACKGROUND: Moyamoya disease is a chronic progressive cerebrovascular disease with a complex pathophysiology and unique features of neoangiogenesis. These features are still known only to a few specialists, although they determine clinical course and outcomes of disease. OBJECTIVE: To determine the nature and degree of neoangiogenesis in restructuring the natural collateral circulation in patients with moyamoya disease and its effect on cerebral blood flow. The influence of collateral circulation on postoperative results and factors of its effectiveness will be analyzed in the 2nd part of the study. MATERIAL AND METHODS: The study included 65 patients with moyamoya disease who underwent preoperative selective direct angiography with separate contrast enhancement of both internal, external and vertebral arteries. We analyzed 130 hemispheres. Suzuki stage of disease, pathways of collateral circulation and their relationship with reduction of cerebral blood flow and clinical manifestations were assessed. Distal vessels of the middle cerebral artery (MCA) were additionally studied. RESULTS: Suzuki stage 3 was the most common (36 hemispheres, 38%). Leptomeningeal collaterals were the most common among intracranial collateral tracts (82 hemispheres, 66.1%). Extra-intracranial transdural collaterals were found in half of the cases (56 hemispheres). We observed certain changes in distal vessels of the MCA (hypoplasia of M3 branches) in 28 (20.9%) hemispheres. Suzuki stage of disease significantly determined degree of cerebral blood flow insufficiency, i.e. more severe perfusion deficit was observed at the later stages of disease. A well-developed system of leptomeningeal collaterals significantly reflected stages of compensation and subcompensation of cerebral blood flow according to perfusion data (χ2=20.394, p<0.001). CONCLUSION: Neoangiogenesis is a natural compensatory mechanism in moyamoya disease designed to maintain brain perfusion under reduced cerebral blood flow. Predominant intra-intracranial collaterals are associated with ischemic and hemorrhagic events. Timely restructuring on extra-intracranial ways of collateral circulation prevents adverse manifestations of disease. Assessment and understanding of collateral circulation in patients with moyamoya disease create the prerequisites for substantiating the method of surgical treatment.

Fetal posterior cerebral artery in pediatric and adult moyamoya disease: A single-center experience of 480 patients.

PURPOSE: In past pediatric and adult cohort studies of moyamoya disease, the fetal posterior cerebral artery has received less attention. Its relationship with the clinical manifestations and collateral circulation of moyamoya disease or ipsilateral cerebral hemispheres remains unclear. METHOD: We summarize the clinical features of patients with and without fetal posterior cerebral artery moyamoya disease from consecutive cases.We explored the relationship between fetal posterior cerebral arteries and collateral circulation in the ipsilateral cerebral hemispheres, as well as differences among different subgroups of patients.According to the morphology, the fetal posterior cerebral artery is divided into complete fetal posterior cerebral artery and partial fetal posterior cerebral artery. Clinical features were classified as: infarction,hemorrhage,and non-stroke in unilateral/bilateral cerebral hemispheres. Collateral circulation is divided into extracranial vascular compensation and leptomeningeal collateral circulation. Digital subtraction angiography and CT/MR were used to evaluate the blood flow status and clinical characteristics of patients with moyamoya disease. RESULT: A total of 960 cerebral hemispheres from 142 pediatric patients and 338 adult patients were included in the study. A total of 273 (56.9%) patients had 399 cerebral hemispheres (41.6%) with fetal posterior cerebral arteries. Adults with fetal posterior cerebral arteries had lower rates of infarction (24.6%vs37.3%, P =0.005) and were less likely to have bilateral stroke (8.4%vs11.5%, P =0.038). Cerebral hemispheres with fetal posterior cerebral artery were more likely to have anterior cerebral artery and middle cerebral artery stenosis and less likely to have occlusion (P =0.002, 0.001), and less likely to involve the posterior circulation (P < 0.001). The cerebral hemispheres of the fetal posterior cerebral artery had higher leptomeningeal collateral circulation scores. There are significant differences in extracranial vascular compensation between cerebral hemispheres with and without fetal posterior cerebral artery. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage (P =0.017). CONCLUSIONS: Our results suggest that fetal posterior cerebral artery is associated with infarct manifestations in pediatric and adult moyamoya disease. In the cerebral hemispheres, the fetal posterior cerebral artery is associated with ipsilateral hemispheric anterior and posterior circulation artery injury, extracranial vascular compensation, leptomeningeal collateral circulation compensation, and infarction. Adult patients with fetal posterior cerebral artery were more advanced in Suzuki stage.

Evaluation of Collateral Circulation in Patients with Acute Ischemic Stroke.

The cerebral collateral circulation is an increasingly important consideration in the management of acute ischemic stroke and is a key determinant of outcomes. Growing evidence has demonstrated that better collaterals can predict the rate of infarct progression, degree of recanalization, the likelihood of hemorrhagic transformation and various therapeutic opportunities. Collaterals can also identify those unlikely to respond to reperfusion therapies, helping to optimize resources. More randomized trials are needed to evaluate the risks and benefits of endovascular reperfusion with consideration of collateral status. This reviews our current understanding of the pathophysiologic mechanisms, effect on outcomes and strategies for improvement of the collateral system.

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.

Microvascular dysfunction associated with unfavorable venous outflow in acute ischemic stroke patients.

Unfavorable venous outflow (VO) is associated with cerebral edema, which represents microvascular dysfunction. This study estimated the relationship between VO and microvascular function in acute ischemic stroke patients. We retrospectively included 102 MCA/ICA occluded patients with anterior circulation infarction who underwent reperfusion therapy between July 2017 and April 2022. Unfavorable VO was defined as a cortical vein opacification score of 0-3 and favorable VO as that of 4-6. The clinical characteristics, collateral status, microvascular integrity, and outcomes were compared between patients with favorable and unfavorable VO. Multivariate analysis and receiver operator characteristic (ROC) analysis were used. The patients with unfavorable VO had higher extravascular-extracellular volume fraction (Ve) in the infarct core and a lower percentage of robust arterial collateral circulation. ROC analysis revealed that Ve in the infarct core predicts unfavorable VO (AUC = 0.67, sensitivity = 65.08%, specificity = 69.23%). The higher Ve in the infarct core (odds ratio = 1.011, 95% CI = 1.000-1.021, P = 0.046) and poor arterial collateral flow (odds ratio = 0.102, 95% CI = 0.032-0.327, P < 0.001) were independent predictors of unfavorable VO. This suggests that microvascular dysfunction may be one of the mechanisms underlying impaired VO.

Serial Lung Perfusion Scintigraphy After Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals.

BACKGROUND: In patients with tetralogy of Fallot and major aortopulmonary collaterals (MAPCAs), pulmonary blood supply is highly variable. Our approach to this condition emphasizes complete unifocalization of the pulmonary circulation, incorporating all lung segments and addressing stenoses out to the segmental level. Post-repair, we recommend serial lung perfusion scintigraphy (LPS) to assess short-term changes in pulmonary blood flow distribution. METHODS: We reviewed post-discharge and follow-up LPS performed through three years post-repair and analyzed serial changes in perfusion, risk factors for change, and the relationship between LPS parameters and pulmonary artery reintervention. RESULTS: Of 543 patients who had postoperative LPS results in our system, 317 (58%) had only a predischarge LPS available for review, while 226 had 1 (20%) or more (22%) follow-up scans within three years. Overall, pulmonary flow distribution prior to discharge was balanced, and there was minimal change over time; however, there was considerable patient-to-patient variation in both metrics. On multivariable mixed modeling, time after repair (P = .025), initial anatomy consisting of a ductus arteriosus to one lung (P < .001), and age at repair (P = .014) were associated with changes on serial LPS. Patients who had follow-up LPS were more likely to undergo pulmonary artery reintervention, but within that cohort, LPS parameters were not associated with reintervention risk. CONCLUSION: Serial LPS during the first year after MAPCAs repair is a noninvasive method of screening for significant post-repair pulmonary artery stenosis that occurs in a small but important minority of patients. In patients who received follow-up LPS beyond the perioperative period, there was minimal change over time in the population overall, but large changes in some patients and considerable variability. There was no statistical association between LPS findings and pulmonary artery reintervention.

The Roles of Bone Marrow-Derived Stem Cells in Coronary Collateral Growth Induced by Repetitive Ischemia.

Many clinical trials have attempted to use stem cells to treat ischemic heart diseases (IHD), but the benefits have been modest. Though coronary collaterals can be a "natural bypass" for IHD patients, the regulation of coronary collateral growth (CCG) and the role of endogenous stem cells in CCG are not fully understood. In this study, we used a bone marrow transplantation scheme to study the role of bone marrow stem cells (BMSCs) in a rat model of CCG. Transgenic GFP rats were used to trace BMSCs after transplantation; GFP bone marrow was harvested or sorted for bone marrow transplantation. After recovering from transplantation, the recipient rats underwent 10 days of repetitive ischemia (RI), with echocardiography before and after RI, to measure cardiac function and myocardial blood flow. At the end of RI, the rats were sacrificed for the collection of bone marrow for flow cytometry or heart tissue for imaging analysis. Our study shows that upon RI stimulation, BMSCs homed to the recipient rat hearts' collateral-dependent zone (CZ), proliferated, differentiated into endothelial cells, and engrafted in the vascular wall for collateral growth. These RI-induced collaterals improved coronary blood flow and cardiac function in the recipients' hearts during ischemia. Depletion of donor CD34+ BMSCs led to impaired CCG in the recipient rats, indicating that this cell population is essential to the process. Overall, these results show that BMSCs contribute to CCG and suggest that regulation of the function of BMSCs to promote CCG might be a potential therapeutic approach for IHD.

Collateral circulation predicts 3-month functional outcomes of subacute ischemic stroke patients: A study combining arterial spin labeling and MR angiography.

OBJECTIVE: Collateral circulation could help preserve the blood supply and protect penumbra in ischemic stroke (IS), critical for late-window therapeutic decisions and clinical outcomes. In this study, we aimed to investigate the prognostic value of two collateral indexes measured by arterial spin labeling (ASL) and MR angiography (MRA) in subacute IS patients. MATERIALS AND METHODS: Fifty-five subacute IS patients with large artery atherosclerosis were retrospectively collected. Arterial transit artifact (ATA) on ASL and good circulation (GC) on MRA were ranked as markers of leptomeningeal collaterals and fast collaterals, respectively. Volume and relative cerebral blood flow (rCBF) of infarct and hypoperfusion area were calculated. Stroke severity was determined by baseline- and discharge- National Institute of Hospital Stroke Scale (NIHSS). Functional independence (FI) was defined as 3-month modified Ranking Scale ≤2. Univariate analyses and multivariable logistic regression analyses were conducted to identify the independent predictors of FI. RESULTS: Thirty-eight patients (69.1 %) presented ATA and 29 (52.7 %) patients presented GC. Univariate analyses showed that baseline-NIHSS, discharge-NIHSS, rCBF of infarct, presence of ATA and GC were associated with FI (P < 0.05). After multivariable adjustment, ATA (adjusted Odds Ratio [OR]: 13.785, 95 % CI: 2.608-72.870, P = 0.002) and GC (adjusted OR: 8.317, 95 % CI: 1.629-42.454, P = 0.011) remained independent predictors of FI. Besides, patients with both ATA and GC had the highest frequencies of FI while patients with neither of them showed the lowest (94.7 % vs 14.3 %, P < 0.001), indicating a positive synergistic effect between ATA and GC. CONCLUSION: The combination of ASL and MRA simultaneously reflects leptomeningeal collaterals and fast collaterals, providing a useful method to predict functional outcomes of subacute IS patients.

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.

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

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

Myosteatosis as an independent predictor of short-term mortality in successfully reperfused acute ischemic stroke.

BACKGROUND AND PURPOSE: Poor clinical outcomes are still common in successfully reperfused acute ischemic stroke patients. The aim of our study was to assess the impact of sarcopenia and myosteatosis on neurological outcomes and mortality in successfully reperfused acute ischemic stroke patients. MATERIALS AND METHODS: We included in our retrospective observational study 166 consecutive patients who underwent technically successful mechanical thrombectomy for anterior circulation acute ischemic stroke between Jan 2016 and Dec 2019. ASPECTS and collateral score were assessed on pre-operative CT/CTA. Masseter muscles area and attenuation were measured on CTA images. Clinical and radiological variables were tested in multivariate logistic models to predict the probability of death and, among survivors, of incurring poor outcome. RESULTS: At admission, mean NIHSS was 19 (SD = 6.5), mean body mass index 25.5 (SD = 4.4) kg/m2, and mean ASPECTS 8.0 (SD = 1.9). Of all, 48.2% patients showed good collaterals, 38.5% intermediate collaterals, and 13.3% poor collaterals. Overall, 90 days mRS was ≤2 in 48.2% of the patients, 3-5 in 30.7%, and 6 in 21.1%. At multivariate logistic regression, age (OR = 1.08, p = 0.036), ASPECTS (OR = 0.59, p = 0.013), and masseter muscles attenuation (OR = 0.93, p = 0.010) were independent predictors of mortality, whereas sex (OR = 7.15, p = 0.043), age (OR = 1.05, p = 0.042), body mass index (OR = 1.35, p = 0.013), NIHSS (OR = 1.12, p = 0.012), and ASPECTS (OR = 0.64, p = 0.024) were independent predictors of poor neurological outcome (mRS 3-5). CONCLUSION: Beyond other well-known variables, low masseter attenuation, indicating myosteatosis, represents an independent negative prognostic factor for 90 days mortality in patients successfully reperfused after anterior circulation stroke.

Collateral Blood Flow and Ischemic Core Growth.

Treatment of a large vessel occlusion in the acute ischemic stroke setting focuses on vessel recanalization, and endovascular thrombectomy results in favorable outcomes in appropriate candidates. Expeditious treatment is imperative, but patients often present to institutions that do not have neurointerventional surgeons and need to be transferred to a comprehensive stroke center. These treatment delays are common, and it is important to identify factors that mitigate the progression of the ischemic core in order to maximize the preservation of salvageable brain tissue. Collateral blood flow is the strongest factor known to influence ischemic core growth, which includes the input arterial vessels, tissue-level vessels, and venous outflow. Collateral blood flow at these different levels may be imaged by specific imaging techniques that may also predict ischemic core growth during treatment delays and help identify patients who would benefit from transfer and endovascular therapy, as well as identify those patients in whom transfer may be futile. Here we review collateral blood flow and its relationship to ischemic core growth in stroke patients.

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.