Collateral Flow Research Articles

Perfusion Defects and Collateral Flow Patterns in Acute Small Subcortical Infarction: a 4D Dynamic MRI Study

The hemodynamic changes of acute small subcortical infarction (SSI) are not well understood. We evaluate the hemodynamic changes and collaterals in acute SSI using perfusion magnetic resonance imaging (MRI). A total of 103 patients with acute SSI in penetrating artery territories were recruited and underwent MRI within 24 h of stroke onset. Using 4D dynamic perfusion MRI, they were divided into three patterns: 25 (24%) with normal perfusion, 31 (30%) with compensated perfusion, and 47 (46%) with hypoperfusion. The development of anterograde or retrograde collaterals was also evaluated. Patients with hypoperfusion pattern had the highest rate of early neurological deterioration (32%, p = 0.007), the largest initial and final infarction volumes (p < 0.001 and p = 0.029), the lowest relative cerebral blood flow (0.63, p < 0.001), and the lowest rate of anterograde and retrograde collaterals (19%, p < 0.001; 66%, p = 0.002). The anterograde collaterals were associated with higher relative cerebral blood volume (0.91 vs. 0.77; p = 0.024) and a higher rate of deep cerebral microbleeds (48 vs. 21%; p = 0.028), whereas retrograde collaterals were associated with higher systolic and diastolic blood pressure (p = 0.031 and 0.020), smaller initial infarction volume (0.81 vs. 1.34 ml, p = 0.031), and a higher rate of lobar cerebral microbleeds (30 vs. 0%; p = 0.013). Both anterograde and retrograde collaterals may play a critical role in maintaining cerebral perfusion and can have an impact on patient clinical outcomes. Further studies are warranted to verify these findings and to investigate effective treatments.

Habitual exercise provides better prognosis for cardiac arrest with coronary artery disease

Abstract Background Although regular physical activity has beneficial cardiovascular effects, exercise can trigger sudden cardiac arrest (SCA). Coronary artery disease (CAD) was identified as the most common cause of an exercise-related out-of-hospital cardiac arrest (OHCA). Regular exercise has been reported to reduce the risk of plaque rupture in animal studies and basic research. Therefore, we compared the coronary artery findings in CAD-OHCA patients with and without habitual exercise. There have been few reports on whether regular exercise changes the prognosis in OHCA due to CAD (CAD-OHCA). We investigated the association between the better clinical outcome and the regular exercise in patients with CAD-OHCA. Methods This is a single-center retrospective analysis from 2006 to 2019. The consecutive 397 patients with OHCA due to myocardial ischemia underwent coronary angiography (CAG). After excluding 73 patients with vasospastic angina, the remaining 324 patients with CAD were enrolled in this study. We divided these patients into two groups according to whether they were habitually exercising (Exercise group: N=37) or not/unknown (Non-Exercise group: N=287). Clinical outcome was a 30-day survival with minimal neurologic impairment represented by a Glasgow-Pittsburgh Cerebral Performance Categories Scale value 1 or 2. Results The patients in the Exercise Group were significantly younger (exercise vs. non-exercise, 57±12 vs. 64±12 years; P&amp;lt;0.01) than those in the non-exercise group. The Exercise group had a lower incidence of diabetes mellitus (22% vs. 42%; P=0.02) and a higher incidence of dyslipidemia (81% vs. 62%; P=0.02) than the non-exercise group. The time from collapse to cardiopulmonary resuscitation (1.4±4.0 vs. 3.0±4.8min) and from collapse to return of spontaneous circulation (11.9±10.0 vs. 28.0±25.3min) were shorter in Exercise group (all p&amp;lt;0.05). The ST-segment elevation was recorded on electrocardiography in fewer of the Exercise group (22% vs. 63%; P&amp;lt;0.01). The finding of culprit lesion in the coronary arteries on arrival resulted significant differences between the 2groups (good collateral and/or TIMI3 flow: 62% vs. 25%, the plaque rupture and/or thrombus: 22% vs. 73%) (all p&amp;lt;0.01) (Figure 1). Kaplan-Meier curve showed Exercise group has better neurological outcome at 30days compared than Non-Exercise (95% vs 51%; P&amp;lt;0.001, log-rank test) (Figure 2). Multivariable Cox proportional hazards models revealed that a habitual exercise was one of the predictors of a good neurological outcome (HR 0.21, 95% CI 0.05–0.92; P=0.039). Conclusions The patients with habitual exercise had less plaque rupture, less coronary thrombosis than non-exercise. The patients with regular exercise had better clinical outcomes than non-exercise after CAD-OHCA. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Tokyo Metropolitan Goverment Figure 1. Findings of the culprit lesion in coronar arteriesFigure 2. Kaplan-Meier analysis

Extracardiac coronary steal induced by upper limb hyperemia: a feature of internal mammary artery arteriogenesis

Abstract Introduction Function of naturally existing internal mammary artery (IMA)-to-coronary artery anastomoses has been shown by augmented blood supply to the coronary collateral circulation in response to IMA occlusion. Theoretically, this functional connection is invertible and can cause coronary steal, the verification of whose hypothesis would provide alternate proof to the mentioned functional evidence. Method This was a prospective observational study including 40 patients with chronic coronary syndrome and IMA occlusion, and 40 propensity score matched controls (placebo group) without IMA occlusion. Primary study endpoint was the inter-group difference in coronary collateral function (i.e., collateral flow index, CFI) as obtained at 30, 45 and 60 seconds following a proximal coronary artery balloon occlusion. CFI is the ratio between simultaneous mean coronary occlusive pressure divided by mean aortic pressure both subtracted by central venous pressure. To provoke a steal phenomenon, upper limb hyperemia was induced by upper arm blood pressure cuff deflation following a 5-minute supra-systolic inflation ipsilateral to the sensor-wired coronary artery with release immediately after the first CFI measurement. Results Between the first and the second CFI-measurement, CFI change (i.e., CFI@45s minus CFI@30s) was absent in the verum group while there was CFI recruitment in the placebo group: 0.000±0.023 and +0.009±0.013, respectively; p=0.032. Conclusion Among patients with artificial IMA occlusion, induction of ipsilateral upper limb hyperemia provokes extracardiac coronary steal as expressed by temporarily absent collateral recruitment as it normally takes place without upper limb hyperemia. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Sciences Foundation

Initial experience of subcutaneous nitroglycerin for distal transradial access in neurointerventions.

Background: Transradial access (TRA) for diagnostic and interventional neuroendovascular procedures has gained significant popularity in recent years due to its improved safety profile and appeal to patients compared with transfemoral access. However, risks of TRA include hand ischemia in cases of poor ulnar collateral circulation and inability to cannulate the radial artery due to its relatively small diameter. By accessing the radial artery distal to the superficial palmar arch where ulnar collateral blood flow arises, in the anatomic snuffbox, the risk of hand ischemia is theoretically eliminated. The use of subcutaneous nitroglycerin and lidocaine to improve rates of success in radial artery access has been reported in the cardiac literature, however, has yet to be described for neurointerventional procedures. We discuss our technique and report our initial experience using subcutaneous nitroglycerin and lidocaine cocktail for access to the distal transradial artery in a variety of neuroendovascular procedures.Methods: A retrospective review of our institution’s database of neurointerventional and diagnostic procedures performed using dTRA was conducted, and 64 patients were identified between February and December 2020. Patient demographics, clinical data, procedural details, and radiographic information were collected and analyzed.Results: A total of 64 patients underwent neurointerventional procedures using the subcutaneous injection for dTRA access. The procedures performed included diagnostic cerebral angiograms (n = 47), stent and balloon assisted aneurysm coiling (n = 5), flow diversion (n = 2), intra-saccular device placement (n = 1), mechanical thrombectomy (n = 1), tumor embolization (n = 1), middle meningeal artery embolization (n = 2), extracranial carotid stent placement (n = 2), and arteriovenous malformation embolization (n = 3). While no complications of hand ischemia were appreciated, the access site conversion rate was 3.1%; 2 cases required a switch to femoral artery access due to proximal vessel tortuosity and aortic anatomical variations, and not due to access site complication. Furthermore, on repeat angiograms by the same proceduralist, distal TRA (dTRA) was successful in 100% of the cases.Conclusion: dTRA using subcutaneous nitroglycerin and lidocaine is a safe and effective method for neurointerventional and diagnostic procedures.

Investigation of the Pressure and Flow Dynamics during Aspiration Thrombectomy: A Mathematical Modelling Study

Aspiration thrombectomy is a life-saving interventional procedure to remove a blood clot from the brain of stroke patients. The pressure and blood flow dynamics during this procedure are crucial in determining the clinical outcomes. A mathematical model based on Hagen-Poiseuille law of fluid flow in a tube is adapted to simulate the pressure and fluid flow characteristics in an in vitro model of an occluded and unoccluded cerebrovascular network that mimics a poor (unilateral) and good (symmetrical) collateral flow within the Circle of Willis. The results show that in the absence of an occlusion, the pressure and pressure drop are higher in the symmetrical network compared to that in the unilateral network. This is due to the additional limb in the symmetrical network that must be supplied, which is absent in the unilateral network. In the presence of an occlusion, the flow reduces in the obstructed vessel, the collateral flow, overall pressure and pressure drop increases in both systems, but is higher for the symmetrical network. The results compare qualitatively with those observed in in vitro studies and with clinical observations. The theoretical framework lays the foundation for more advanced models for the pressure and blood flow dynamics towards clinical applicability.

THROMBECTOMY FOR ACUTE EMBOLIC STROKE FOLLOWING HEART SURGERY

Introduction Acute ischaemic stroke occurs in approximately 1-10% of patients undergoing cardiac surgery and can markedly impair recovery (1). Thrombolysis carries an unacceptably high risk of haemorrhage in the early postoperative period after heart surgery. Mechanical thrombectomy is becoming an increasingly preferred alternative to treat ischaemic strokes, and unlike thrombolysis, is not contraindicated in the early postoperative period. We report a patient who had witnessed onset of ischaemic stroke in the early postoperative period after aortic valve replacement (AVR) and coronary artery bypass grafting (CABG) surgery and was treated with mechanical thrombectomy. Discussion An 81-year-old male patient underwent elective tissue AVR and CABG (internal mammary to left anterior descending coronary artery) surgery. Surgery was uncomplicated and following weaning from mechanical ventilation, the patient's trachea was extubated on the evening of surgery. His recovery progressed uneventfully and on the day after surgery, he was moved to a high dependency unit. On the morning of the second post-operative day, the patient had a witnessed rapid deterioration in conscious level, becoming unresponsive with a divergent gaze. Urgent plain CT scan of the brain showed hyperattenuation of the left middle cerebral artery (MCA) territory consistent with acute thrombosis. The patient was granted emergency funding for a mechanical thrombectomy and was transported to the regional neurology hospital. A mechanical thrombectomy was performed successfully, with digital subtraction angiography (DSA) confirming complete occlusion of the left MCA with poor collateral cross flow. The patient failed to recover neurological function and died approximately 24 hours later. Mechanical thrombectomy is now a well-established treatment for acute ischaemic stroke. There are clear advantages with regard to functional outcome for patients undergoing mechanical thrombectomy versus best available medical therapies such as thrombolysis (2). A recent systematic review of acute ischaemic stroke post cardiac surgery showed that 50% of patients who underwent endovascular mechanical thrombectomy had a full or good neurological recovery, 36% had moderate recovery and 14% had little improvement (1). Factors that may have led to a poor outcome in this patient's case included the delay in hospital transfer, the poor cerebral cross blood flow noted on DSA and extensive comorbidities. In conclusion, although there are many reports of mechanical thrombectomy being associated with a good neurological outcome from acute ischaemic stroke associated with cardiac surgery, outcome may not be improved if there is underlying cerebrovascular disease and intervention is delayed.

Carotid Artery-Cavernous Segment Injury during an Endoscopic Endonasal Surgery: A Case Report and Literature Review of the Overlooked Option for Surgical Trapping in the Hyperacute Phase.

Internal carotid artery (ICA) injury is a catastrophic complication of endoscopic endonasal surgery (EES). However, its standard management, emergent endovascular treatment, may not always be available, and the transnasal approach may be insufficient to achieve hemostasis.A 44-year-old woman with pituitary adenoma underwent EES complicated with the ICA cavernous segment injury (CSI). In urgent intraoperative angiogram, a good collateral flow from the contralateral carotid circulation was observed. Due to the unavailability of intraoperative embolization, emergent surgical trapping was performed by combined transcranial and cervical approach. The patient recovered but later developed a giant cavernous pseudoaneurysm. During the pseudoaneurysm embolization, ICA was directly accessed via a 1.7-F puncture hole using a bare microcatheter technique. Then, both the aneurysm and parent artery were obliterated with coils. At the 4-year follow-up, the patient was asymptomatic without a residual tumor. To our knowledge, this is the first case of ICA–CSI during EES successfully treated with ICA trapping as a lifesaving urgent surgery that achieved a complete recovery after a pseudoaneurysm embolization. Although several studies reported that EES-related ICA–CSIs with percutaneous carotid artery access, neither our surgical salvage technique nor our carotid access and tract embolization techniques were previously described.

Hemodynamic Disturbances in Posterior Circulation Stroke: 4D Flow Magnetic Resonance Imaging Added to Computed Tomography Angiography.

Objective: A clinically feasible, non-invasive method to quantify blood flow, hemodynamics, and collateral flow in the vertebrobasilar arterial tree is missing. The objective of this study was to evaluate the feasibility of quantifying blood flow and blood flow patterns using 4D flow magnetic resonance imaging (MRI) in consecutive patients after an ischemic stroke in the posterior circulation. We also explore if 4D-flow, analyzed in conjunction with computed tomography angiography (CTA), has potential as a diagnostic tool in posterior circulation stroke.Methods: Twenty-five patients (mean age 62 years; eight women) with acute ischemic stroke in the posterior circulation were investigated. At admission, all patients were examined with CTA followed by MRI (4D flow MRI and diffusion-weighted sequences) at median 4 days after the presenting event. Based on the classification of Caplan, patients were divided into proximal/middle (n = 16) and distal territory infarcts (n = 9). Absolute and relative blood flow rates were calculated for internal carotid arteries (ICA), vertebral arteries (VA), basilar artery (BA), posterior cerebral arteries (P1 and P2), and the posterior communicating arteries (Pcom). In a control group consisting of healthy elderly, the 90th and 10th percentiles of flow were calculated in order to define normal, increased, or decreased blood flow in each artery. “Major hemodynamic disturbance” was defined as low BA flow and either low P2 flow or high Pcom flow. Various minor hemodynamic disturbances were also defined. Blood flow rates were compared between groups. In addition, a comprehensive analysis of each patient’s blood flow profile was performed by assessing relative blood flow rates in each artery in conjunction with findings from CTA.Results: There was no difference in total cerebral blood flow between patients and controls [604 ± 117 ml/min vs. 587 ± 169 ml/min (mean ± SD), p = 0.39] or in total inflow to the posterior circulation (i.e., the sum of total VA and Pcom flows, 159 ± 63 ml/min vs. 164 ± 52 ml/min, p = 0.98). In individual arteries, there were no significant differences between patients and controls in absolute or relative flow. However, patients had larger interindividual relative flow variance in BA, P1, and P2 (p = 0.01, <0.01, and 0.02, respectively). Out of the 16 patients that had proximal/middle territory infarcts, nine had CTA findings in VA and/or BA generating five with major hemodynamic disturbance identified with 4D flow MRI. For those without CTA findings, seven had no or minor 4D flow MRI hemodynamic disturbance. Among nine patients with distal territory infarcts, one had major hemodynamic disturbances, while the remaining had minor disturbances.Conclusion: 4D flow MRI contributed to the identification of the patients who had major hemodynamic disturbances from the vascular pathologies revealed on CTA. We thus conclude that 4D flow MRI could add valuable hemodynamic information when used in conjunction with CTA.

Parallel VBX Stents For Complex Common Iliac Aneurysm Treatment in Patients Ineligible for Iliac Branch Endoprosthesis

Endovascular treatment of common iliac aneurysms (CIAs) has evolved, with the iliac branch endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz) allowing for treatment of CIA aneurysms with preservation of flow to the external iliac artery (EIA) and internal iliac artery (IIA). The hypogastric artery is critical for collateral flow to the spinal cord, perfusion to the pelvis and buttocks, and the avoidance of impotence. We offer a novel approach using parallel VBX grafts in the CIA, EIA, and IIA to seal iliac aneurysms and preserve flow to both vessels. Patients with a CIA aneurysm with abdominal aortic aneurysms or short CIA landing zones for endovascular aneurysm repair were identified. The patients were not candidates for IBE therapy or had had contraindication to hypogastric embolization. Measurements of the CIA, EIA, and IIA were performed using three-dimensional reconstructive software and centerline imaging studies. To determine the combined sizing of the VBX stents, the CIA diameter was divided by 0.7 to achieve an adequate seal of the two VBX stents (a 15-mm CIA stent requires the combined diameters of the EIA and IIA stents to be >21.5 mm; Fig). The patients were scheduled for follow-up at 1, 3, and 6 months with arterial duplex ultrasound or computed tomography angiography. A total of six patients had undergone complex endovascular double barrel stenting of the CIA, EIA, and IIA. The pathologic indications included type Ib endoleak from prior endovascular aneurysm repair, an iliac aneurysm, and a short common iliac artery for the seal. Seven VBX stents were deployed in the EIA, and seven VBX stents were deployed in the IIA. At the 1-month postoperative follow-up examination, 100% of the VBX stents had demonstrated primary patency without evidence of an endoleak. At 3 months of follow-up, 100% of the EIA VBX stent and 100% of the IIA VBX stent were patent without an endoleak or migration. One patient had died (three VBX stents total) secondary to nonvascular pathology. The use of double barrel VBX grafts is a safe and effective method to treat CIA pathology with preservation of flow to the EIA and IIA. Further long-term follow-up is required to continue to assess for endoleaks, stent migration, and other complications. The limitations of the present study included the small sample size, single-center experience, and limited follow-up.

Robert's Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157.

We redefined Robert’s prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert’s model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.

Occult blood flow patterns distal to an occluded artery in acute ischemic stroke

Residual blood flow distal to an arterial occlusion in patients with acute ischemic stroke (AIS) is associated with favorable patient outcome. Both collateral flow and thrombus permeability may contribute to such residual flow. We propose a method for discriminating between these two mechanisms, based on determining the direction of flow in multiple branches distal to the occluding thrombus using dynamic Computed Tomography Angiography (dynamic CTA). We analyzed dynamic CTA data of 30 AIS patients and present patient-specific cases that identify typical blood flow patterns and velocities. We distinguished patterns with anterograde (N = 10), retrograde (N = 9), and both flow directions (N = 11), with a large variability in velocities for each flow pattern. The observed flow patterns reflect the interplay between permeability and collaterals. The presented method characterizes distal flow and provides a tool to study patient-specific distal tissue perfusion.

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

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

Clinical Study of Cerebral Ischemia in Moyamoya Disease from the View of Development of the Anterior Choroidal Artery

ObjectivesThe anterior choroidal artery (AchA) is one of the collateral vessels in moyamoya disease (MMD). The incidence of cerebral ischemia in MMD was analyzed through the association between development of the AchA and advancement of MMD stage. Materials and MethodsTwelve patients of MMD with cerebral ischemia (infarction; 9 patients, transient ischemic attack; 3 patients) were enrolled. Advancement of MMD was evaluated using Suzuki's stage. The grades in Suzuki's stage were subclassified into a non-progressive stage for grades 1 and 2, and a progressive stage for grades 4 and 5. Dilatation of the AchA was judged as the presence of development of this artery. Development of the AchA was grouped into proximal type and proximal and distal type. ResultsMost frequent locations of infarcts were the anterior and parietal lobes in 6 patients each. Development of the AchA was confirmed on the ischemic side in all patients and on the non-ischemic side in 9 patients. Development of the AchA in the progressive stage was limited in the proximal and distal type on both sides. Development of the AchA in the non-progressive stage was the proximal type on the ischemic side. ConclusionsThe cause of cerebral ischemia was possibly associated with inadequate blood supply of the AchA in the non-progressive stage, and the lower blood flow from the internal carotid artery (ICA) in the progressive stage. Disparity between collateral blood flow from the AchA and the blood flow from the ICA was considered to relate to incidence of cerebral ischemia in MMD.

MCA-DN: Multi-path convolution leveraged attention deep network for salvageable tissue detection in ischemic stroke from multi-parametric MRI.

Accurate and timely treatment of ischemic stroke can restore the blood flow in the affected area and reduce the risk of disability and death. Identification and localisation of both direct and collateral blood flow restriction from MRI using computational intelligence play a crucial role in assisting manual diagnosis decisions in stroke treatment. A novel multi-path convolution leveraged attention based deep network (MCA-DN) is proposed to address this challenge. MCA-DN combines multi-path convolution derived attention making different weighted filters in each attention convolution sub-path, with interactions on the same level of abstraction. This facilitates the network to focus on voxels with enhanced weighted activations, directing to a plausible lesion. Such a proposition of acquiring attention by embedding multiple filter paths, also prioritizes the selective activation of multi-parametric MRI sequences. The multi-path convolution assisted attention block allows the network layers to gain more insights on the input tensor, enabling the expansion of hypothesis search space with a controlled parameter count. The algorithm is evaluated on 139 patients of 3 datasets with 4 sub-datasets, including 2 benchmarked challenge datasets of ISLES-2015, 2017. MCA-DN achieved parametric measures of Dice similarity coefficient: 77.3%, sensitivity: 82.8%, and specificity: 98.8%, for stroke segmentation, outperforming the five state-of-the-art methods in the field with encouraging success. Competitive performance of the MCA-DN demonstrates immense potential to assist patient-specific stroke treatment planning by estimating the benefit of reperfusion.

Abstract MP27: Endothelial Nogo-B Modulates Ischemia Induced Collateral Artery Remodeling

Nogo-B, a member of the reticulon 4 family of proteins, is the dominant isoform expressed in endothelial cells (EC). We have shown that Nogo-B is necessary for blood flow recovery in ischemia. Mice lacking Nogo-B exhibit reduced arteriogenesis and angiogenesis that are linked to a decrease in macrophage infiltration and inflammatory gene expression in vivo. However, whether endothelial Nogo-B regulates arteriogenesis and/or angiogenesis is unknown. We generated an inducible EC-specific mouse overexpressing Nogo-B (Ng ECtg ) and investigated the arteriogenesis and angiogenesis in limb ischemia. Ischemia increased endothelial and serum Nogo-B expression. Blood flow recovery was markedly diminished after femoral artery ligation (FAL) in Ng ECtg compared to WT mice, in association with lower collateral density accessed by micro-CT arteriography. There was no reduction in capillary density or decrease in smooth muscle/pericyte and macrophage recruitment in Ng ECtg mice, suggesting EC Nogo-B overexpression regulates arteriogenesis but not angiogenesis. While Ng ECtg mice have normal number of native collateral artery, the early remodeling of the collateral artery was impaired after ischemia. Furthermore, in line with impaired remodeling, Ng ECtg mice have decreased functional (exercise) hyperemia response in the non-ischemic limb in vivo, and resistant arteries from Ng ECtg have diminished flow induced vasodilatation ex vivo compared to WT mice. Moreover, endothelial reconstitution of Nogo-B in global Nogo knockout background (NogoKO ECrc ) restored blood flow recovery after ischemia in vivo, further suggesting the EC specific function of Nogo-B in arteriogenesis. Mechanistically, we have shown that EC isolated from Ng ECtg mice have decreased nitric oxide release. Nogo-B overexpression negatively regulates eNOS phosphorylation, expression and golgi localization in EC. Future parabiosis study is warranted to elucidate the contribution of paracrine or EC intrinsic Nogo-B in modulating arteriogenesis and angiogenesis. In conclusion, our data showed for the first time that endothelial Nogo-B plays important roles in regulating collateral artery remodeling and blood flow through, at least in part, regulating NO bioavailability.

Distinct intra‐arterial clot localization affects tissue‐level collaterals and venous outflow profiles

Arterial clot localization affects collateral flow to ischemic brain in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). We determined the association between vessel occlusion locations, tissue-level collaterals (TLC), and venous outflow (VO) profiles and their impact on good functional outcomes. We conducted a multicenter retrospective cohort study of consecutive AIS-LVO patients who underwent thrombectomy triage. Baseline computed tomographic angiography (CTA) was used to localize vessel occlusion, which was dichotomized into proximal vessel occlusion (PVO; internal carotid artery and proximal first segment of the middle cerebral artery [M1]) and distal vessel occlusion (DVO; distal M1 and M2), and to assess collateral scores. TLC were assessed on computed tomographic perfusion data using the hypoperfusion intensity ratio. VO was determined on baseline CTA by the cortical vein opacification score. Primary outcomes were favorable VO and TLC; secondary outcome was the modified Rankin Scale after 90days. A total of 649 patients met inclusion criteria. Of these, 376 patients (58%) had a PVO and 273 patients (42%) had a DVO. Multivariate ordinal logistic regression showed that DVO predicted favorable TLC (odds ratio [OR] = 1.77, 95% confidence interval [CI] = 1.24-2.52, p = 0.002) and favorable VO (OR = 7.2, 95% CI = 5.2-11.9, p < 0.001). DVO (OR = 3.4, 95% CI = 2.1-5.6, p < 0.001), favorable VO (OR = 6.4, 95% CI = 3.8-10.6, p < 0.001), and favorable TLC (OR = 3.2, 95% CI = 2-5.3, p < 0.001), but not CTA collaterals (OR = 1.07, 95% CI = 0.60-1.91, p = 0.813), were predictors of good functional outcome. DVO in AIS-LVO patients correlates with favorable TLC and VO profiles, which are associated with good functional outcome.

Pathomorphological manifestations of vascular remodeling in the perifocal areas of ischemic cerebral infarction

Abstract. Acute disorders of cerebral circulation remain one of the leading causes of death of patients throughout the world. Tissue recovery after a stroke is directly related to active revascularization, which is intensified in the peri-infarction area. Newly formed vessels contribute to the restoration of cellular metabolism in surviving neurons. The processes of vascular remodeling after stroke have been at the center of many clinical and morphological studies in recent years. The aim of the study. To study the processes of vascular remodeling and neoplasm of vessels in the perifocal areas of ischemic cerebral infarctions. Material and methods. The study researched the brain of 29 deceased patients with hemispheric infarctions with different periods of the disease: up to 3 days (n = 5), 6 days (n = 5), 9-12 (n = 10), 30 (n = 5), 45 days (n = 4). The object of the study was perifocal areas of cerebral infarction, as well as areas outside ischemic lesions. The studies were carried out using histological, morphometric and statistical techniques. Results. Studies have shown that in the perifocal areas of cerebral infarction within 3 days from the onset of the disease, the morpho-functional state of the microvasculature was characterized by circulatory and hemocoagulation disorders. Along with destructive changes in blood vessels, processes are directed to improve blood circulation in ischemic areas of the brain. Collateral blood flow increases, dilation of pial vessels is noted with a decrease in the Kernogan index. On the 6th day, the processes of angiogenesis and vasculogenesis are activated, which intensify in the subsequent stages of the disease. In the long term, the efficiency of collateral blood flow in the pial vessels decreases, reduction in the capillary network, and the lumen of large arteries is recalibrated. Conclusions. In the early stages of cerebral stroke (up to 3 days), increased blood circulation in the ischemic areas of the brain occurs due to increased collateral blood flow. From the 6th day, the processes of angiogenesis in the form of capillary budding and the processes of vasculogenesis intensify. In large arterioles, recalibration processes take place. After 30-45 days in the perifocal areas of cerebral infarction, a significant reduction of the capillary network is recorded, which is regarded as a reaction to a decrease in blood supply to the areas of organized infarction.

Immune Cells Invade the Collateral Circulation during Human Stroke: Prospective Replication and Extension.

It remains unclear if principal components of the local cerebral stroke immune response can be reliably and reproducibly observed in patients with acute large-vessel-occlusion (LVO) stroke. We prospectively studied a large independent cohort of n = 318 consecutive LVO stroke patients undergoing mechanical thrombectomy during which cerebral blood samples from within the occluded anterior circulation and systemic control samples from the ipsilateral cervical internal carotid artery were obtained. An extensive protocol was applied to homogenize the patient cohort and to standardize the procedural steps of endovascular sample collection, sample processing, and laboratory analyses. N = 58 patients met all inclusion criteria. (1) Mean total leukocyte counts were significantly higher within the occluded ischemic cerebral vasculature (I) vs. intraindividual systemic controls (S): +9.6%, I: 8114/µL ± 529 vs. S: 7406/µL ± 468, p = 0.0125. (2) This increase was driven by neutrophils: +12.1%, I: 7197/µL ± 510 vs. S: 6420/µL ± 438, p = 0.0022. Leukocyte influx was associated with (3) reduced retrograde collateral flow (R2 = 0.09696, p = 0.0373) and (4) greater infarct extent (R2 = 0.08382, p = 0.032). Despite LVO, leukocytes invade the occluded territory via retrograde collateral pathways early during ischemia, likely compromising cerebral hemodynamics and tissue integrity. This inflammatory response can be reliably observed in human stroke by harvesting immune cells from the occluded cerebral vascular compartment.

A rare case of sigmoid colon cancer in which the lower limbs received collateral blood flow from the inferior mesenteric artery owing to peripheral artery disease

BackgroundColorectal cancer and peripheral artery disease are common conditions in older adults and may coexist in this population. Lymph node dissection along the inferior mesenteric artery is a vital procedure in cases of left-sided colorectal cancer. However, the inferior mesenteric artery may show a collateral blood pathway in rare cases of peripheral artery disease. We report a case of advanced sigmoid colon cancer in which the lower limbs received inferior mesenteric artery flow owing to asymptomatic peripheral artery disease. The possibility of catastrophic lower-limb ischemia because of complete mesenteric excision with ligation of the inferior mesenteric artery was a matter of concern in this case.Case presentationA 73-year-old man with asymptomatic peripheral artery disease was diagnosed with stage IIIB advanced sigmoid colon cancer. Angiography using a balloon-occlusion catheter revealed that his lower limbs received prominent inferior mesenteric artery blood flow through a collateral pathway. Therefore, interventional radiologists and cardiovascular surgeons evaluated the indications for endovascular stents or bypass grafts. The patient also had dilated cardiomyopathy, so the cardiovascular physicians evaluated his tolerance in the worst-case scenario of a colorectal anastomotic leak. The patient underwent axillofemoral artery bypass and two-stage laparoscopic sigmoid colectomy without anastomosis. The postoperative course was uneventful, and he resumed his job within a month after the resection.ConclusionsAlthough collateral flow from the inferior mesenteric artery is rare in patients with peripheral artery disease, a few case reports have described fatal lower-limb ischemia following anterior resection. The perioperative multidisciplinary evaluation enabled us to understand the patient’s condition and risks, and allowed successful cancer treatment without ischemia of the lower limbs.

Optimizing Emergency Stroke Transport Strategies Using Physiological Models.

The criteria for choosing between drip and ship and mothership transport strategies in emergency stroke care is widely debated. Although existing data-driven probability models can inform transport decision-making at an epidemiological level, we propose a novel mathematical, physiologically derived framework that provides insight into how patient characteristics underlying infarct core growth influence these decisions. We represent the physiology of time-dependent infarct core growth within an ischemic penumbra as an exponential function with consideration to rate-determining collateral blood flow. Monte Carlo methods generate distributions of infarct core volumes, which are translated to distributions of 90-day modified Rankin Scale scores. We apply the model to a stroke network that serves rural Bastrop County and urban Travis County by simulating transport strategies from thousands of potential patient pickup locations. In every pickup location, the simulation yields a distribution of outcomes corresponding to each transport strategy. A 2-sample Kolmogorov-Smirnov test and Student t test determine which transport strategy provides a significantly better probability of a good outcome for a given pickup location in each respective county (P<0.01). In Travis County, drip and ship provides significantly better probabilities of a good outcome in 24.0% of the pickup locations, while 59.8% favor mothership. In Bastrop County, 11.3% of the pickup locations favor drip and ship, while only 7.1% favor mothership. The remaining pickup locations in each county are not statistically significant in either direction. We also reveal how differing rates of infarct core growth, the application of bypass policies, and the use of large vessel occlusion field tests impact these results. Modeling stroke physiology enables the use of clinically relevant metrics for determining comparative significance between drip and ship and mothership in a given geography. This formalism can help understand and inform emergency medical service transport decision-making, as well as regional bypass policies.