Insights into multilevel tissue-level collateral status using ColorViz maps from dual data sources in acute ischemic cerebrovascular diseases: A STARD-compliant retrospective study.

This study aims to explore the utility of ColorViz mapping from dual data sources for assessing arterial collateral circulation and predicting cerebral tissue-level collateral (TLC) in patients with acute ischemic cerebrovascular diseases. A retrospective study was conducted at a single center on a cohort of 79 patients diagnosed with acute ischemic cerebrovascular diseases between November 2021 and April 2022, who had undergone both multi-phase CT angiography (mCTA) and computed tomography perfusion (CTP). The quality of images and arterial collateral status depicted on ColorViz maps from dual data-sets (mCTA and CTP) were assessed using a "5-point scale" and a "10-point scale," respectively. The status of TLC was evaluated by analyzing multilevel hypoperfusion volume and the hypoperfusion intensity ratio (HIR). The Spearman correlation coefficient was employed to examine the association between arterial collateral status derived from dual data sources and TLC. Receiver operating characteristic curve analysis was used to determine the diagnostic efficacy in detecting large vessel occlusive acute ischemic stroke (LVO-AIS). The ColorViz maps derived from dual data sources facilitated comparable image quality, with over 95% of cases meeting diagnostic criteria, for the evaluation of arterial level collateral circulation. Patients with robust arterial collateral circulation, as determined by dual data sources, were more likely to exhibit favorable TLC status, as evidenced by reductions in hypoperfusion volume (Tmax > 4 seconds, Tmax > 6 seconds, Tmax > 8 seconds, and Tmax > 10 seconds, P < .05) and HIR (Tmax > 6 seconds/4 seconds, Tmax > 8 seconds/4 seconds, Tmax > 10 seconds/4 seconds, and Tmax > 8 seconds/6 seconds, P < .05). The sensitivity and specificity in detecting LVO-AIS was 60.00% and 97.73% for mCTA source maps, while 74.29% and 72.73% for CTP source maps (P > .05 based on De-Long test). In conclusion, this study indicates that ColorViz maps derived from both data sources are equally important in evaluating arterial collateral circulation and enhancing diagnostic efficiency in patients with LVO-AIS, as well as offering insights into the TLC status based on hypoperfusion volume and HIR.

The Complement System Is Essential for Arteriogenesis by Enhancing Sterile Inflammation as a Relevant Step in Collateral Artery Growth.

Arteriogenesis is an inflammatory driven mechanism, describing the growth of a natural bypass from pre-existing collateral arteries to compensate for an occluded artery. The complement system component C3 is a potent natural inflammatory activator. Here, we investigated its impact on the process of collateral artery growth using C3-deficient (C3 -/-) and wildtype control mice in a murine hindlimb model of arteriogenesis. Induction of arteriogenesis by unilateral femoral artery ligation resulted in decreased perfusion recovery in C3 -/- mice on day 7 as shown by Laser Doppler imaging. Immunofluorescence staining revealed a reduced vascular cell proliferation in C3 -/- mice. Gene expression analysis displayed a significant reduction in monocyte chemoattractant protein-1 (MCP-1) expression in C3 -/- mice. Interestingly, 3 days after induction of arteriogenesis, the number of macrophages (CD68+) recruited to growing collaterals was not affected by C3 deficiency. However, a significant reduction in inflammatory M1-like polarized macrophages (CD68+/MRC1-) was noted. Forced mast cell activation by Compound 48/80 as well as exogenous MCP-1 application rescued the number of M1-like polarized macrophages along with perfusion recovery in C3 -/- mice. In summary, this study demonstrates that complement C3 influences arteriogenesis by mediating MCP-1 expression, which is essential for the induction and enhancement of sterile inflammation.

Comment on "Route patterns of the collateral venous pathway in patients with tumors invading the superior sagittal sinus: an angiographic study and clinical applications".

This commentary critiques the study "Route patterns of the collateral venous pathway in patients with tumors invading the superior sagittal sinus" by Pawit Jirawisan et al., highlighting its limitations in discussing parafalcine venous collaterals, reliance on invasive imaging modalities, and lack of structured assessments. It suggests improvements by incorporating alternative imaging techniques, acknowledging crucial venous structures, and providing grading systems for surgical decision-making.

Collateral assessment on magnetic resonance imaging/angiography up to 30 hours after stroke onset.

PURPOSE: We aimed to validate hyperintense vessel sign (HVS) on FLAIR imaging or posterior cerebral artery (PCA) laterality on MR angiography beyond 4.5 hours after stroke onset. MATERIALS AND METHODS: Data from acute ischemic stroke patients with internal carotid or middle cerebral artery occlusion who underwent CT perfusion imaging at baseline, follow-up MR perfusion imaging and angiography within 30 hours after stroke, without effective recanalization on follow-up imaging, were analysed retrospectively. Patients were separately classified as high or low HVS (>5 or ≤5 slices of HVS), and PCA laterality positive or negative group. We compared core and penumbra volumes at follow-up imaging and neurological outcomes between high or low HVS group, and between PCA laterality positive or negative group. RESULTS: Of 49 patients analyzed, four patients with artifacts were excluded and 45 were classified into high (n = 23) or low (n = 22) HVS group. High group had a smaller core volume (median 32 ml versus 109 ml, p = 0.004), larger penumbra volume at follow-up (68 ml versus 0 ml, p = 0.001), and better outcomes (modified Rankin Scale at three months, 3 versus 5, p = 0.03). For PCA laterality analysis, 1 patient with previously occluded PCA was excluded and 48 patients were classified as positive (n = 22) or negative (n = 26). Positive group had larger core volume (116 ml versus 37 ml), and no significant differences in penumbral volumes or outcomes. CONCLUSION: Prominent HVS in later time was associated with small core volume, persistent penumbra volume and favorable outcomes.

Association between ischaemic stroke aetiology and leptomeningeal collateral status: a retrospective cohort study.

INTRODUCTION: There is limited understanding of the pathomechanistic relationship between leptomeningeal collateral formation and ischaemic stroke aetiology. We aimed to assess the association of leptomeningeal collateral status and ischaemic stroke aetiology, using the widely recognised "Trial of Org 10172 in Acute Stroke Treatment" (TOAST) classification categorising strokes into five distinct aetiologies. METHODS: Retrospective study of consecutively admitted adult ischaemic stroke patients at a Swiss stroke centre. Leptomeningeal collateral status was assessed on admission with single-phase CT-angiographies using a validated 4-point score. Patients were categorised into large-artery atherosclerosis (LAA), cardioembolic (CE), small-vessel disease (SVD) and cryptogenic (CG) according to the TOAST classification. We performed ordinal and binary (poor [collaterals filling ≤50% of the occluded territory] vs good [collaterals filling >50% of the occluded territory] collateralisation) logistic regression to evaluate the impact of TOAST aetiology on collateral status. RESULTS: Among 191 patients, LAA patients had better collateral status compared to non-LAA aetiology (LAA: 2 vs CE: 2 vs SVD: 3 vs CG: 2, pLAA vs non-LAA = 0.04). In weighted multivariate logistic regression, LAA and SVD independently predicted better collateral status (binary models [adjusted odds ratio; aOR]: LAA: 3.72 [1.21-11.44] and SVD: 4.19 [1.21-14.52]; ordinal models [adjusted common odds ratio; acOR]: LAA: 2.26 [95% CI: 1.23-4.15] and SVD: 1.94 [1.03-3.66]), while CE predicted worse collateral status (binary models [aOR]: CE: 0.17 [0.07-0.41]; ordinal models [acOR]: CE: 0.24 [0.11-0.51]). CONCLUSION: The aetiology of ischaemic stroke is associated with leptomeningeal collateral status on single-phase CT-angiography, with LAA and SVD predicting better and CE predicting worse collateral status.

Route patterns of the collateral venous pathway in patients with tumors invading the superior sagittal sinus: an angiographic study and clinical applications.

Chronic occlusion of the superior sagittal sinus (SSS) by tumors in the midsagittal region causes the collateral venous pathway (CVP). Understanding common patterns of CVP is helpful in reducing surgical complications. This study aimed to investigate the CVP found in patients with SSS-invading tumors, and to provide information on the prevention of operative venous complications. From January 2015 to December 2022, this retrospective study collected patients with tumors that invaded the SSS and underwent digital subtraction angiography of intracranial vessels. Data collected included sex, age, tumor pathology, tumor location along the SSS, tumor side, degree of obstruction of the SSS, types and route patterns of the CVP, and the distance between the tumor and the diploic vein (DV). Twenty patients (6 males, 14 females) were recruited. The prevalence of CVP types was 90% for DV, 35% for end-to-end anastomosis of superficial cortical vein, 15% for meningeal vein, and 20% for other types of CVP. The pteriofrontoparietal and occipitoparietal diploic routes were found on the cerebral hemisphere contralateral to the tumor significantly more than in the cerebral hemisphere ipsilateral to the tumor. Of all patients with presence of collateral DV, 61% had a very close (less than 1 cm) distance between the nearest DV and tumor attachment in the SSS. DV in the cerebral hemisphere contralateral to the tumor was the most common type of CVP found in patients with tumor-induced SSS obstruction. Most of the collateral DV was located very close to the SSS tumor attachment. Neurosurgeons should realize these findings when planning a craniotomy.

Relative Cerebral Blood Flow as an Indirect Imaging Surrogate in Patients With Anterior Circulation Large Vessel Occlusion and Association of Baseline Characteristics With Poor Collateral Status.

BACKGROUND: In acute ischemic stroke (AIS), collateral status (CS) is an important predictor of favorable outcomes in patients with AIS. Among quantitative cerebral perfusion parameters, relative cerebral blood flow (rCBF) is considered an accurate perfusion-based indicator of CS. This study investigated the relationship between admission laboratory values, baseline characteristics, and CS as assessed by rCBF in patients with AIS-large vessel occlusion. METHODS AND RESULTS: In this retrospective multicenter study, consecutive patients presenting with AIS secondary to anterior circulation large vessel occlusion who underwent pretreatment computed tomography perfusion were included. The computed tomography perfusion data processed by RAPID (IschemaView, Menlo Park, CA) generated the rCBF. Binary logistic regression models assessed the relationship between patients' baseline characteristics, admission laboratory values, and poor CS. The primary outcome measure was the presence of poor CS, which was defined as rCBF <38% at a lesion size ≥27 mL. Between January 2017 and September 2022, there were 221 consecutive patients with AIS-large vessel occlusion included in our study (mean age 67.0±15.8 years, 119 men [53.8%]). Logistic regression showed that male sex (odds ratio [OR], 2.98 [1.59-5.59]; P=0.001), chronic kidney disease (OR, 5.18 [2.44-11.0]; P<0.001), admission National Institutes of Health Stroke Scale score ≥12 (OR, 5.17 [2.36-11.36]; P<0.001), and systolic blood pressure <140 (OR, 2.00 [1.07-3.76]; P=0.030) were associated with poor CS. CONCLUSIONS: Higher stroke severity on admission with National Institutes of Health Stroke Scale score ≥12, systolic blood pressure <140, chronic kidney disease, and male sex are statistically significantly associated with poor CS in patients with AIS due to anterior circulation large vessel occlusion as defined by rCBF <38%.

Hypoperfusion Intensity Ratio as an Indirect Imaging Surrogate in Patients With Anterior Circulation Large-Vessel Occlusion and Association of Baseline Characteristics With Poor Collateral Status.

BACKGROUND: Collateral status (CS) plays a crucial role in infarct growth rate, risk of postthrombectomy hemorrhage, and overall clinical outcomes in patients with acute ischemic stroke (AIS) secondary to anterior circulation large-vessel occlusions (LVOs). Hypoperfusion intensity ratio has been previously validated as an indirect noninvasive pretreatment imaging biomarker of CS. In addition to imaging, derangements in admission laboratory findings can also influence outcomes in patients with AIS-LVO. Therefore, our study aims to assess the relationship between admission laboratory findings, baseline characteristics, and CS, as assessed by hypoperfusion intensity ratio in patients with AIS-LVO. METHODS AND RESULTS: In this retrospective study, consecutive patients presenting with AIS secondary to anterior circulation LVO who underwent pretreatment computed tomography perfusion were included. The computed tomography perfusion data processed by RAPID (Ischema View, Menlo Park, CA) generated the hypoperfusion intensity ratio. Binary logistic regression models were used to assess the relationship between patients' baseline characteristics, admission laboratory findings, and poor CS. A total of 221 consecutive patients with AIS-LVO between January 2017 and September 2022 were included in our study (mean±SD age, 67.0±15.8 years; 119 men [53.8%]). Multivariable logistic regression showed that patients with AIS caused by cardioembolic and cryptogenic causes (adjusted odds ratio [OR], 2.67; 95% CI, 1.20-5.97; P=0.016), those who presented with admission National Institutes of Health Stroke Scale score ≥12 (adjusted OR, 3.12; 95% CI, 1.61-6.04; P=0.001), and male patients (adjusted OR, 2.06; 95% CI, 1.13-3.77; P=0.018) were associated with poor CS. CONCLUSIONS: Stroke caused by cardioembolic or cryptogenic causes, admission National Institutes of Health Stroke Scale score of ≥12, and male sex were associated with poor CS, as defined by hypoperfusion intensity ratio in the patients with AIS-LVO.

Association between the pan-immune-inflammation value and coronary collateral circulation in chronic total coronary occlusive patients.

BACKGROUND: Inflammation and immunity play important roles in the formation of coronary collateral circulation (CCC). The pan-immune-inflammation value (PIV) is a novel marker for evaluating systemic inflammation and immunity. The study aimed to investigate the association between the PIV and CCC formation in patients with chronic total occlusion (CTO). METHODS: This retrospective study enrolled 1150 patients who were diagnosed with CTO through coronary angiographic (CAG) examinations from January 2013 to December 2021 in China. The Cohen-Rentrop criteria were used to catagorize CCC formation: good CCC formation (Rentrop grade 2-3) and poor CCC formation group (Rentrop grade 0-1). Based on the tertiles of the PIV, all patients were classified into three groups as follows: P1 group, PIV ≤ 237.56; P2 group, 237.56< PIV ≤ 575.18; and P3 group, PIV > 575.18. RESULTS: A significant relationship between the PIV and the formation of CCC was observed in our study. Utilizing multivariate logistic regression and adjusting for confounding factors, the PIV emerged as an independent risk factor for poor CCC formation. Notably, the restricted cubic splines revealed a dose-response relationship between the PIV and risk of poor CCC formation. In terms of predictive accuracy, the area under the ROC curve (AUC) for PIV in anticipating poor CCC formation was 0.618 (95% CI: 0.584-0.651, P < 0.001). Furthermore, the net reclassification index (NRI) and integrated discrimination index (IDI) for PIV, concerning the prediction of poor CCC formation, were found to be 0.272 (95% CI: 0.142-0.352, P < 0.001) and 0.051 (95% CI: 0.037-0.065, P < 0.001), respectively. It's noteworthy that both the NRI and IDI values were higher for PIV compared to other inflammatory biomarkers, suggesting its superiority in predictive capacity. CONCLUSIONS: PIV was associated with the formation of CCC. Notably, PIV exhibited potential as a predictor for poor CCC formation and showcased superior predictive performance compared to other complete blood count-based inflammatory biomarkers.

A retrospective study: Long term prognosis in adults with PA-VSD-MAPCAs.

BACKGROUND: Pulmonary Atresia, Ventricular Deptal Defect, and Major Aortopulmonary Collateral Arteries (PA-VSD-MAPCAs) is a congenital cyanotic heart defect with poor prognosis. Due to its complex and highly variable anatomy, the best treatment plan is not clear. We aimed (1) to investigate the survival of PA-VSD-MAPCAs patients according to the underlying original anatomy and treatment strategy, and (2) to evaluate life expectancy between patients with or without severe hypoplastic native pulmonary arteries (NPAs) after surgical versus non-surgical treatment. METHODS: A prospectively established database of 169 PA-VSD-MAPCAs patients treated and followed up at University Hospitals Leuven was accessed. Patients were divided into three groups according to the treatment strategy. Kaplan-Meier survival curves were plotted, and Log Rank tests were used for comparison. RESULTS: The overall mean survival for patients with PA-VSD-MAPCAs was 38.5 years (95%-CI: 33.1-43.9). Patients with complete intracardiac repair had the longest mean survival of 43.8 years (95%-CI: 38.1-49.6) versus the other groups (p < 0.001). A longer mean event-free survival time was found in patients with normal, well-developed NPAs (p = 0.047). Finally, patients with poorly developed or absent NPAs had worse survival rates when a surgical approach was followed. Systemic-pulmonary shunt placement or unifocalisation had limited effect on prognosis in the absence of total repair (p = 0.167). CONCLUSIONS: Patients with PA-VSD-MAPCAs who underwent complete intracardiac repair and/or with well-developed native pulmonary arteries had the best prognosis. Our analyzed data suggest that incomplete surgical repair resulted in survival rates comparable to those seen with a non-surgical approach.

Predictive value of early serum ACSL4 and ASITN/SIR grade for motor function recovery in patients with post-ischemic stroke lower limb neurological sequelae after modified constraint-induced movement therapy.

BACKGROUND: Ischemic stroke accounts for over 85 % of all stroke types. Acyl-CoA synthetase long chain family member 4 (ACSL4) is considered to promote myocardial and cerebral ischaemia/ reperfusion. However, up to now, no study focused on the role of ACSL4 in patients with post-stroke lower limb neurological sequelae. OBJECTIVE: The present study aimed to investigate the predictive value of ACSL4 and collateral circulation for lower limb neurological sequelae of ischemic stroke patients after modified constraint-induced movement therapy (mCIMT). METHODS: This is a prospective cohort study which included 99 ischemic stroke patients with lower limb neurological sequelae who were admitted to our hospital during January 2021 to December 2022. All patients received mCIMT after the admission. Collateral circulation was evaluated by digital subtraction angiography (DSA) and graded by the American Society of Interventional and Therapeutic Neuroradiology/ Society of Interventional Radiology (ASITN/SIR) grading system. Enzyme linked immunosorbent assay (ELISA) was used to detect serum ACSL4. Basic characteristics were collected and lower limb motor function was measured by Fugl-Meyer score (FMS), modified Ashworth score (MAS) and Brunnstrom stage, as well as timed up and go (TUG) test, ten-Meter walk test (10MWT), and six-minute walk test (6MWT) before and after treatment. RESULTS: Serum ACSL4 and percentage of patients with ASITN/SIR 0-1 decreased significantly after treatment compared with the values before treatment. Patients with higher baseline serum ACSL4 values at admission showed significantly lower FMS scores, higher TUG and 10MWT, as well as lower 6MWT. Patients with ASITN/SIR grade 0-1 at admission only showed significantly higher TUG and 10MWT, as well as lower 6MWT. Receiver operating characteristic (ROC) curves showed ACSL4 and ASITN/SIR grade could be used to predict the prognosis. Logistic regression found only national institutes of health stroke scores (NIHSS) was the independent risk factor for post-treatment motor impairment after mCIMT. CONCLUSION: Higher levels of ACSL4 and ASITN/SIR 0-1 are associated with poor recovery of motor functions of patients with post-stroke sequelae after mCIMT.

Association between the atherogenic index of plasma and coronary collateral circulation in patients with chronic total occlusion.

BACKGROUND: The atherogenic index of plasma (AIP) is considered an independent risk factor for coronary artery disease (CAD). The present study investigated whether AIP correlates with the formation of coronary collateral circulation (CCC) in CAD patients with chronic total occlusion (CTO). METHODS: This retrospective study included 1093 CAD patients with CTO confirmed by coronary angiography from January 2020 to December 2020 at Beijing Anzhen Hospital. Based on the Rentrop scoring system, the patients were divided into the good CCC group and the poor CCC group. AIP was calculated by log (triglyceride/high-density lipoprotein cholesterol). Meanwhile, the study population was further divided into four groups according to the quartiles of AIP. RESULTS: Patients in the poor CCC group exhibited significantly higher AIP compared to those in the good CCC group (0.31 ± 0.27 vs. 0.14 ± 0.24, p < 0.001). Multivariate logistic regression analysis revealed an independent association between AIP and poor CCC, regardless of whether AIP was treated as a continuous or categorical variable (p < 0.001), after adjusting for confounding factors. Besides, this association remained consistent across most subgroups. The incorporation of AIP into the baseline model significantly enhanced the accuracy of identifying poor CCC [area under the curve (AUC): baseline model, 0.661 vs. baseline model + AIP, 0.721, p for comparison < 0.001]. CONCLUSIONS: Elevated AIP is independently associated with an increased risk of poor CCC in CAD patients with CTO, and AIP may improve the ability to identify poor CCC in clinical practice.

Transient formation of collaterals contributes to the restoration of the arterial tree during cardiac regeneration in neonatal mice.

Revascularization of ischemic myocardium following cardiac damage is an important step in cardiac regeneration. However, the mechanism of arteriogenesis has not been well described during cardiac regeneration. Here we investigated coronary artery remodeling and collateral growth during cardiac regeneration. Neonatal MI was induced by ligature of the left descending artery (LAD) in postnatal day (P) 1 or P7 pups from the Cx40-GFP mouse line and the arterial tree was reconstructed in 3D from images of cleared hearts collected at 1, 2, 4, 7 and 14 days after infarction. We show a rapid remodeling of the left coronary arterial tree induced by neonatal MI and the formation of numerous collateral arteries, which are transient in regenerating hearts after MI at P1 and persistent in non-regenerating hearts after MI at P7. This difference is accompanied by restoration of a perfused or a non-perfused LAD following MI at P1 or P7 respectively. Interestingly, collaterals ameliorate cardiac perfusion and drive LAD repair, and lineage tracing analysis demonstrates that the restoration of the LAD occurs by remodeling of pre-existing arterial cells independently of whether they originate in large arteries or arterioles. These results demonstrate that the restoration of the LAD artery during cardiac regeneration occurs by pruning as the rapidly forming collaterals that support perfusion of the disconnected lower LAD subsequently disappear on restoration of a unique LAD. These results highlight a rapid phase of arterial remodeling that plays an important role in vascular repair during cardiac regeneration.

Development and validation of a novel nomogram model predicting the unfavorable outcome based on NAR and collaterals status for patients with AIS.

INTRODUCTION: Stroke is a leading cause of disability and mortality globally. This study aimed to develop a prognostic nomogram based on neutrophil-to-albumin ratio (NAR) and collateral status in acute ischemic stroke (AIS) patients with anterior large vessel occlusion (LVO). MATERIAL & METHOD: 590 AIS patients with LVO assessed for regional leptomeningeal collateral (rLMC) were retrospectively enrolled, and randomly divided into a training set (n = 414) and a testing set (n = 176). Unfavorable functional outcome was defined as a modified Rankin scale (mRS) score of 3 to 6 at 3 months. We assessed the accuracy and clinical utility of the nomogram using calibration plots, area under the curve (AUC), decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). RESULTS: Both NAR and rLMC were independently associated with unfavorable outcome at 3 months (OR=8.96, p=0.0341; OR=0.89, p=0.0002, respectively). The developed nomogram (akaike information criterion (AIC)=398.77), which included NAR, rLMC and other factors, showed good performance (the AUC for the development and validation cohorts was 0.848 and 0.840 respectively) and improved the predictive value compared to a model without NAR and rLMC, according to an overall NRI of 3.27% (p=0.2401), overall IDI of 3.27% (p=0.2414), and a higher AUC (0.848 vs 0.831). CONCLUSIONS: NAR can serve as an independent predictor in AIS patients with anterior LVO, and the nomogram incorporating NAR and rLMC is reliable in predicting unfavorable outcome. Further studies with larger sample sizes are needed to validate and extend these findings.