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Introduction: Repeat imaging when regional and remote stroke patients arrive at a comprehensive stroke center (CSC) can delay endovascular thrombectomy (EVT). We examined which clinical and imaging parameters predict infarct progression and perfusion core growth during transport. Methods: We included patients recruited from 2017 to 2023 in a prospective database who were transferred from remote sites with large vessel occlusion, had CT perfusion imaging at the primary stroke center (PSC), and had repeat CT on arrival at the CSC demonstrating persistent occlusion. The key imaging characteristics were perfusion core change (rCBF < 30%) and ASPECTS change. Multiple and ordinal logistic regression analyses were used to assess the relationship between background clinical and imaging variables and the CT-perfusion core and ASPECTS on arrival. DEFUSE 3 criteria (ASPECTS ≥ 6, perfusion core < 70 mL) were used to define "favorable imaging." Results: In 90 patients with CT perfusion at both PSC and CSC and persistent occlusion, the median time from onset to PSC presentation was 279 min (IQR 143–702). The median time from PSC presentation to CSC arrival was 243.5 min (IQR 186–335), and the median distance traveled was 186.5 km (IQR 101–258). Lower baseline ASPECTS (per point) was associated with a 7 mL increase (95%CI 2–11 mL) in perfusion core between scans (p = 0.004). The time from onset, the time between PSC and CSC, and the distance traveled were not significantly associated with either ASPECTS or perfusion core growth during transport. In total, 11 out of 78 patients (14%) had deterioration of initially favorable imaging profiles during transport. Conclusion: Perfusion core growth during transport was uncommon and most strongly associated with lower ASPECTS at the PSC. Initially, favorable PSC imaging May predict whether repeat imaging is necessary at the CSC. [ABSTRACT FROM AUTHOR]

IntroductionRepeat imaging when regional and remote stroke patients arrive at a comprehensive stroke center (CSC) can delay endovascular thrombectomy (EVT). We examined which clinical and imaging parameters predict infarct progression and perfusion core growth during transport.MethodsWe included patients recruited from 2017 to 2023 in a prospective database who were transferred from remote sites with large vessel occlusion, had CT perfusion imaging at the primary stroke center (PSC), and had repeat CT on arrival at the CSC demonstrating persistent occlusion. The key imaging characteristics were perfusion core change (rCBF < 30%) and ASPECTS change. Multiple and ordinal logistic regression analyses were used to assess the relationship between background clinical and imaging variables and the CT-perfusion core and ASPECTS on arrival. DEFUSE 3 criteria (ASPECTS ≥ 6, perfusion core < 70 mL) were used to define “favorable imaging.”ResultsIn 90 patients with CT perfusion at both PSC and CSC and persistent occlusion, the median time from onset to PSC presentation was 279 min (IQR 143–702). The median time from PSC presentation to CSC arrival was 243.5 min (IQR 186–335), and the median distance traveled was 186.5 km (IQR 101–258). Lower baseline ASPECTS (per point) was associated with a 7 mL increase (95%CI 2–11 mL) in perfusion core between scans (p = 0.004). The time from onset, the time between PSC and CSC, and the distance traveled were not significantly associated with either ASPECTS or perfusion core growth during transport. In total, 11 out of 78 patients (14%) had deterioration of initially favorable imaging profiles during transport.ConclusionPerfusion core growth during transport was uncommon and most strongly associated with lower ASPECTS at the PSC. Initially, favorable PSC imaging May predict whether repeat imaging is necessary at the CSC.

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. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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. [ABSTRACT FROM AUTHOR]

Abstract Background Failed aortofemoral and femoropopliteal bypass grafts in the lower extremity artery usually result in acute limb ischemia. Endovascular treatment and surgical revascularization have been reported for limb salvage. Case presentation A 72-year-old Japanese man was admitted with acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Endovascular treatment with balloon angioplasty, thrombectomy, and stent implantation in the long chronic total occlusion from the right common iliac artery to the superficial femoral artery did not result in efficient flow due to thrombus transfer from a failed aortofemoral bypass graft. However, a rescue femorofemoral bypass (the left femoral to the right deep femoral artery) improved his symptoms, and implanted in-stent flow was gradually recovered. Lower extremity angiography performed 5 months later confirmed the patency of the iliofemoral in-stent flow. However, the femorofemoral bypass graft was unfortunately occluded due to the progression of left external iliac artery stenosis. The patency of the iliofemoral in-stent flow was confirmed at 1 year by ultrasonography. Conclusions Improvement of the deep femoral artery flow plays an important role in the treatment of acute limb ischemia due to failed aortofemoral and femoropopliteal bypass grafts. Thus, increased collateral circulation to the periphery through the deep femoral artery dissolved the remaining in-stent thrombus in the iliofemoral artery.

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. [ABSTRACT FROM AUTHOR]

BackgroundCollateral 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.MethodsA 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).ResultsWomen 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).ConclusionWomen 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.

A 59-year-old man presented with angina. Coronary angiography revealed an occlusion in the proximal left anterior descending artery (LAD), the distal segment of which was supplied by the collateral flow of a coronary-pulmonary arterial fistula (CPAF), originating from the right coronary artery and left sinus of Valsalva. Myocardial scintigraphy revealed ischemia in the anteroseptal region. Coronary artery bypass surgery was performed on the LAD, and the CPAF drains were closed. The CPAF may serve as collateral circulation. Even when CPAF serves as collateral circulation, open surgery could be indicated if the collateral flow is insufficient and the structure is complicated., (@ 2024 The Editorial Committee of Annals of Vascular Diseases.)

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 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.

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. [ABSTRACT FROM AUTHOR]

The association between baseline perfusion measures and clinical outcomes in patients with acute small subcortical infarcts (SSIs) has not been studied in detail. Post-processed acute perfusion CT and follow-up diffusion-weighted imaging of 71 patients with SSIs were accurately co-registered. Relative perfusion values were calculated from the perfusion values of the infarct lesion divided by those of the mirrored contralateral area. The association between perfusion measures with clinical outcomes and the interaction with intravenous thrombolysis were studied. Additionally, the perfusion measures for patients having perfusion CT before and after thrombolysis were compared. Higher contralateral hemispheric cerebral blood flow (CBF) was the only independent predictor of an excellent clinical outcome (modified Rankin Scale of 0-1) at 3 months (OR = 1.3, 95% CI 1.1–1.4, P = 0.001) amongst all the perfusion parameters, and had a significant interaction with thrombolysis (P = 0.04). Patients who had perfusion CT after thrombolysis demonstrated a better perfusion profile (relative CBF ≥1) than those who had perfusion CT before thrombolysis (After:45.5%, Before:21.1%, P = 0.03). This study implies that for patients with SSIs, hemispheric CBF is a predictor of clinical outcome and has an influence on the effect of intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

The brain vasculature has been increasingly recognized as a key player that directs brain development, regulates homeostasis, and contributes to pathological processes. Following ischemic stroke, the reduction of blood flow elicits a cascade of changes and leads to vascular remodeling. However, the temporal profile of vascular changes after stroke is not well understood. Growing evidence suggests that the early phase of cerebral blood volume (CBV) increase is likely due to the improvement in collateral flow, also known as arteriogenesis, whereas the late phase of CBV increase is attributed to the surge of angiogenesis. Arteriogenesis is triggered by shear fluid stress followed by activation of endothelium and inflammatory processes, while angiogenesis induces a number of pro-angiogenic factors and circulating endothelial progenitor cells (EPCs). The status of collaterals in acute stroke has been shown to have several prognostic implications, while the causal relationship between angiogenesis and improved functional recovery has yet to be established in patients. A number of interventions aimed at enhancing cerebral blood flow including increasing collateral recruitment are under clinical investigation. Transplantation of EPCs to improve angiogenesis is also underway. Knowledge in the underlying physiological mechanisms for improved arteriogenesis and angiogenesis shall lead to more effective therapies for ischemic stroke.

Background: The main cause of mortality in patients with atherosclerosis of aorta and peripheral arteries of the lower extremities is ischemic heart disease. The presence of peripheral artery atherosclerosis suggests a high probability of simultaneous coronary involvement. To reduce the risk of cardiac complications, these patients are offered myocardial revascularization as the first step of the intervention; however, the choice of a conduit for coronary artery bypass in these patients remains challenging.Case report: A 58-year old man with combined coronary artery stenoses, high occlusion of the aorta and common iliac arteries underwent autoarterial myocardial revascularization with the right internal thoracic artery (ITA) and left radial artery ("off pump”). In the early postoperative period, significant progression of the right leg ischemia was observed, related to partitioning of the main collateral flow between the right ITA and the inferior epigastric artery, that had contributed to blood supply to the right lower extremity. Taking into account the lack of efficacy of medical treatment and progression of the leg ischemia, at day 4 postoperatively the patient underwent resection of the infrarenal aorta with aortobifemoral bypass grafting and restoration of blood supply to the lower extremities and resolution of ischemia.Conclusion: ITA has been recognized as the conduit of choice for surgical treatment of ischemic heart disease; however, its use may result in significant progression of ischemia. When choosing a conduit, ITA at the side of less ischemic lower extremity is preferred. ITA imaging by computed tomography-angiography or by selective ITA angiography can be helpful for assessment of the ITA significance at the side of less ischemic leg. Also, the appearance of retrograde flow in the inferior epigastric artery at Doppler ultrasound examination can be a conditional valuable criterion.

Cerebral hemodynamics in the presence of cerebrovascular occlusive disease (CVOD) are influenced by the anatomy of the intracranial arteries, the degree of stenosis, the patency of collateral pathways, and the condition of the cerebral microvasculature. Accurate characterization of cerebral hemodynamics is a challenging problem. In this work, we present a strategy to quantify cerebral hemodynamics using computational fluid dynamics (CFD) in combination with arterial spin labeling MRI (ASL). First, we calibrated patient-specific CFD outflow boundary conditions using ASL-derived flow splits in the Circle of Willis. Following, we validated the calibrated CFD model by evaluating the fractional blood supply from the main neck arteries to the vascular territories using Lagrangian particle tracking and comparing the results against vessel-selective ASL (VS-ASL). Finally, the feasibility and capability of our proposed method were demonstrated in two patients with CVOD and a healthy control subject. We showed that the calibrated CFD model accurately reproduced the fractional blood supply to the vascular territories, as obtained from VS-ASL. The two patients revealed significant differences in pressure drop over the stenosis, collateral flow, and resistance of the distal vasculature, despite similar degrees of clinical stenosis severity. Our results demonstrated the advantages of a patient-specific CFD analysis for assessing the hemodynamic impact of stenosis.

BackgroundCurrently, intensive lipid lowering is recommended in patients with atherosclerotic ischemic stroke or transient ischemic attack. However, the role of statin in cardioembolic stroke is unclear. We investigated the association of statin with pretreatment collateral status in cardioembolic stroke.MethodsA collaborative study from two stroke centers in distinct geographic regions included consecutive patients with acute middle cerebral artery (MCA) infarction due to atrial fibrillation (AF) who underwent cerebral angiography. The relationship between pretreatment collateral grade and the use/dose of statin at stroke onset was assessed. The angiographic collateral grade was evaluated according to the ASITN/SIR Collateral Flow Grading System.ResultsNinety-eight patients (76 statin-naïve, 22 statin users) were included. Compared with statin-naïve patients, statin users were older and more frequently had hypertension, hyperlipidemia and coronary heart disease. Excellent collaterals (grade 3-4) were more frequently observed in statin users (11 patients, 50%) than in statin-naïve patients (21 patients, 27.6%; p = 0.049). The use of atorvastatin 10 mg equivalent or higher doses of statin was associated with excellent collaterals (p for trend = 0.025). In multiple regression analysis, prestroke statin use was independently associated with excellent collaterals (odds ratio, 7.841; 95% confidence interval, CI, 1.96-31.363; p = 0.004).ConclusionsPremorbid use of statin in AF patients is associated with excellent collateral flow. Although most statin trials excluded patients with cardioembolic stroke, our data suggests the possibility that statin may be beneficial in AF-related stroke

Background Unloading the left ventricle and delaying reperfusion reduces infarct size in preclinical models of acute myocardial infarction. We hypothesized that a potential explanation for this effect is that left ventricular (LV) unloading before reperfusion increases collateral blood flow to ischemic myocardium. Methods and Results Acute myocardial infarction was induced by balloon occlusion of the left anterior descending artery for 120 minutes in adult swine, followed by reperfusion for 180 minutes. After 90 minutes of occlusion, animals were assigned to 30 minutes of continued occlusion (n=6) or to 30 minutes of support with either an Impella CP (n=4) or venoarterial extracorporeal membrane oxygenation (n=5) with persistent occlusion. The primary end point was measures of microcirculatory blood flow including the collateral flow index (CFI) during left anterior descending artery occlusion as (Pw−RA)/(Pa−RA), where Pa, Pw, and RA are aortic, coronary wedge, and right atrial pressure, respectively. Infarct size was quantified using triphenyltetrazolium chloride. Compared with continued occlusion, Impella, not venoarterial extracorporeal membrane oxygenation, reduced infarct size relative to the area at risk. Before reperfusion, Impella reduced LV stroke work by 25% and increased the CFI by 75%, but venoarterial extracorporeal membrane oxygenation did not. Among all groups, the change in CFI between 90 and 120 minutes correlated inversely with the change in LV stroke work (r2=0.44, P=0.01) and infarct size (r2=0.41, P=0.02). Conclusions We report for the first time that 30 minutes of LV unloading during coronary occlusion increases the CFI, which correlates inversely with LV stroke work and infarct size. Venoarterial extracorporeal membrane oxygenation failed to increase the CFI and did not reduce infarct size.

Background: Collateral circulation in ischemic stroke patients plays an important role in infarct evolution und assessing patients' eligibility for endovascular treatment. By means of dynamic susceptibility contrast MRI, we aimed to investigate the effects of reperfusion, recanalization, and collateral flow on clinical and imaging outcomes after stroke.Methods: Retrospective analysis of 184 patients enrolled into the prospective observational 1000Plus study (clinicaltrials.org NCT00715533). Inclusion criteria were vessel occlusion on baseline MR-angiography, imaging within 24 h after stroke onset and follow-up perfusion imaging. Baseline Higashida score using subtracted dynamic MR perfusion source images was used to quantify collateral flow. The influence of these variables, and their interaction with vessel recanalization, on clinical and imaging outcomes was assessed using robust linear regression.Results: Ninety-eight patients (53.3%) showed vessel recanalization. Higashida score (p = 0.002), and recanalization (p = 0.0004) were independently associated with reperfusion. However, we found no evidence that the association between Higashida score and reperfusion relied on recanalization status (p = 0.2). NIHSS on admission (p < 0.0001) and recanalization (p = 0.001) were independently associated with long-term outcome at 3 months, however, Higashida score (p = 0.228) was not.Conclusion: Higashida score and recanalization were independently associated with reperfusion, but the association between recanalization and reperfusion was similar regardless of collateral flow quality. Recanalization was associated with long-term outcome. DSC-based measures of collateral flow were not associated with long-term outcome, possibly due to the complex dynamic nature of collateral recruitment, timing of imaging and the employed post-processing.

Background: Collateral circulation in ischemic stroke patients plays an important role in infarct evolution und assessing patients' eligibility for endovascular treatment. By means of dynamic susceptibility contrast MRI, we aimed to investigate the effects of reperfusion, recanalization, and collateral flow on clinical and imaging outcomes after stroke. Methods: Retrospective analysis of 184 patients enrolled into the prospective observational 1000Plus study (clinicaltrials.org NCT00715533). Inclusion criteria were vessel occlusion on baseline MR-angiography, imaging within 24 h after stroke onset and follow-up perfusion imaging. Baseline Higashida score using subtracted dynamic MR perfusion source images was used to quantify collateral flow. The influence of these variables, and their interaction with vessel recanalization, on clinical and imaging outcomes was assessed using robust linear regression. Results: Ninety-eight patients (53.3%) showed vessel recanalization. Higashida score (p = 0.002), and recanalization (p = 0.0004) were independently associated with reperfusion. However, we found no evidence that the association between Higashida score and reperfusion relied on recanalization status (p = 0.2). NIHSS on admission (p < 0.0001) and recanalization (p = 0.001) were independently associated with long-term outcome at 3 months, however, Higashida score (p = 0.228) was not. Conclusion: Higashida score and recanalization were independently associated with reperfusion, but the association between recanalization and reperfusion was similar regardless of collateral flow quality. Recanalization was associated with long-term outcome. DSC-based measures of collateral flow were not associated with long-term outcome, possibly due to the complex dynamic nature of collateral recruitment, timing of imaging and the employed post-processing. [ABSTRACT FROM AUTHOR]

Background: Anatomic variants of the circle of Willis (CW) are commonly observed in healthy subjects. Genetic and environmental factors influencing these variants remain unclear. Our aim was to assess the genetic and environmental background affecting variant CW phenotypes.Methods: A total of 122 adult healthy twins from the Hungarian Twin Registry (39 monozygotic (MZ) and 22 dizygotic (DZ) pairs, average age 49.7 ± 13.4 years) underwent Time-of-Flight magnetic resonance angiography and transcranial Doppler sonography. We investigated the anterior and posterior CW according to morphological categories. Prevalence and concordance rates of CW variants were calculated. MZ twins discordant for CW variants were analyzed for cardiovascular risk factors and altered blood flow.Results: Complete CW (45.0%) and bilaterally absent posterior communicating artery (PCoA) (22.5%) were the most prevalent variants in the anterior and posterior CW, respectively. There was no significant difference regarding the prevalence of variants across zygosity except for bilaterally hypoplastic PCoA (p = .02). DZ concordance was higher compared to MZ twins regarding morphological categories of the CW. Cardiovascular risk factors were not significantly associated with variant CW in MZ twins discordant to CW morphology. Flow parameters did not differ significantly among MZ twins discordant to CW variants.Conclusion: CW variants may not be determined by substantial genetic effects and are not influenced by altered blood flow in healthy individuals. Further investigations are needed to identify potential environmental factors affecting these variants. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The collateral circulation development is considered as a compensatory inherent mechanism to restore damaged blood perfusion after ischemia. We aimed to detect the collateral flow and the mean blood-flow velocities (mBFVs) level in the basilar trunk during or after cerebral hypoxia-ischemia in the mice brain and explore the effect of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. MATERIALS AND METHODS: C57BL/6J mice and the nNOS knockout (KO) mice were randomly divided into a sham-operated group (control) and the hypoxia-ischemia (HI) groups that were treated with the phosphate buffered solution (PBS) control or 7-nitroindazole (7-NI). Cortexes were harvested after the HI treatment for analysis of nNOS expression using Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Ultrasound imaging experiments were performed to detect the collateral flow and the mBFVs level in the basilar trunk. RESULTS: After cerebral HI, the cortical nNOS mRNA and protein levels increased markedly compared with the sham-operated control mice. Besides, 7-NI treatment had no effect on the blood flow in the sham-operated control mice. What's more, either the 7-NI pretreatment or the nNOS gene knockdown before the HI procedure could attenuate the brain injury by the increased collateral flow and the decreased mBFVs level in the basilar trunk. CONCLUSIONS: nNOS inhibition protected hypoxic- ischemic-induced mice brain damage by the increased collateral flow and the decreased mBFVs level in the basilar trunk. Therefore, the 7-NI administration may have potential utility for the treatment of HI injury in human beings. [ABSTRACT FROM AUTHOR]

Backgound and Purpose: Computerized tomography (CT) perfusion (or CTP) source images from CT scanners with small detector widths can be used to create a dynamic CT angiogram (CTA) similar to digital subtraction angiography (DSA). Because CTP studies use a single intravenous injection, all arterial territories enhance simultaneously, and individual arterial territories [i.e., anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA)] cannot be delineated. This limits the ability to assess collateral flow patterns on dynamic CTAs. The aim of this study was to devise and test a postprocessing method to selectively color-label the major arterial territories on dynamic CTA. Materials and Methods: We identified 22 acute-stroke patients who underwent CTP on a 320-slice CT scanner within 6 h from symptom onset. For each case, two investigators independently generated an arterial territory map from CTP bolus arrival maps using a semiautomated method. The volumes of the arterial territories were calculated for each map and the average relative difference between these volumes was calculated for each case as a measure of interrater agreement. Arterial territory maps were superimposed on the dynamic CTA to create a vessel-selective dynamic CTA with color-coding of the main arterial territories. Two experts rated the arterial territory maps and the color-coded CTAs for consistency with expected arterial territories on a 3-point scale (excellent, moderate, poor). Results: Arterial territory maps were generated for all 22 patients. The median difference in arterial territory volumes between investigators was 2.2% [interquartile range (IQR) 0.6-8.5%]. Based on expert review, the arterial territory maps and the vessel-selective dynamic CTAs showed excellent consistency with the expected arterial territories in 18 of 22 patients, moderate consistency in 2 patients, and poor consistency in another 2 patients. Conclusion: Using a novel postprocessing technique, arterial territory maps and dynamic CTAs with vessel-selective color-coding can be derived from a standard CTP scan. These maps may be used to noninvasively assess collateral flow in patients with acute stroke.

Objective: Ischaemic stroke is a leading cause of death and disability. Autoregulation and collateral blood flow through the circle of Willis both play a role in preventing tissue infarction. To investigate the interaction of these mechanisms a one-dimensional steady-state model of the cerebral arterial network was created. Methods: Structural variants of the circle of Willis that present particular risk of stroke were recreated by using a network model coupled with: 1) a steady-state physiological model of cerebral autoregulation; and 2) one wherein the cerebral vascular bed was modeled as a passive resistance. Simulations were performed in various conditions of internal carotid and vertebral artery occlusion. Results: Collateral flow alone is unable to ensure adequate blood flow ( >\text90\% normal flow) to the cerebral arteries in several common variants during internal carotid artery occlusion. However, compared to a passive model, cerebral autoregulation is better able to exploit available collateral flow and maintain flows within \text10\% of baseline. This is true for nearly all configurations. Conclusion: Hence, autoregulation is a crucial facilitator of collateral flow through the circle of Willis. Significance : Impairment of this response during ischemia will severely impact cerebral blood flows and tissue survival, and hence, autoregulation should be monitored in this situation. [ABSTRACT FROM PUBLISHER]

ABSTRACT Objective After arteriolar occlusion, collaterals enlarge and initially elevated WSS normalizes. While most previous studies focused on endpoints of such adaptive changes in larger collaterals, the present investigation aimed to continuously determine the relation between WSS and diameter in microvascular collaterals during adaptive reactions. Methods In Hamburger-Hamilton stage 40 CAMs, junction points between arteriolar segments were identified and the third upstream segment on one side was occluded. Intravital microscopy recordings were taken for 24 hours post-occlusion. Segment diameter and blood velocity were measured: WSS and capillary density were calculated. Results After occlusion, vascular diameters exhibited an immediate decrease, then increased with a time constant of 2.5 ± 0.8 hours and reached a plateau of up to 60% above baseline after about 7 hours. Vascular tone showed no significant change. WSS exhibited an immediate increase post-occlusion and linearly returned to baseline after about 12 hours. Local WSS change and diameter change rate showed similar patterns during the initial but not the later phase of post-occlusive adaptation. Conclusions CAM collaterals undergo fast structural remodeling within 24 hours post-occlusion. This remodeling might be driven by local WSS and by other regulators within the vascular network. [ABSTRACT FROM AUTHOR]

Background and Purpose: Transient ischemic attack may rarely reveal an intracranial artery occlusion. We analyzed acute magnetic resonance imaging (MRI) patterns and early outcome after reperfusion therapy in these cases.Method: Clinical and imaging data were taken retrospectively from our comprehensive stroke center registry. Two MRI patterns were determined. Pattern A: full mismatch with negative diffusion-weighted imaging (DWI) and perfusion defect. Pattern B: large mismatch with positive DWI and perfusion defect. MRI-derived collateral flow maps were automatically generated from the raw of dynamic susceptibility contrast MRI. Patients were treated either by recombinant tissue plasminogen activator (rtPA) alone or in combination with mechanical thrombectomy.Results: From October 1, 2010 to May 15, 2016, 1,019 patients were admitted and treated by t-PA within 4.5 hours of stroke onset of them; 14 had a transient ischemic attack (TIA) within the 6 hours preceding MRI. Perfusion imaging was performed in 11 patients. An arterial occlusion was found in all of them, 11 patients had a distal anterior circulation occlusion, whereas 3 patients (21%) had a proximal occlusion. According to MRI, 6 patients showed pattern A, whereas 5 patients had pattern B. Good collaterals were observed in 10 patients (6 patients with grade 3 and 4 patients with grade 4), whereas 1 patient had poor collaterals (grade 2). The day 1 National Institutes of Health Stroke Scale median was 0. Modified Rankin Scale median at 3 months was 0.Conclusion: TIAs may reveal acute intracranial artery occlusion. Acute MRI may able to assist in therapeutic decision. [ABSTRACT FROM AUTHOR]