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Background and Purpose: Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology.Methods: We determined the PRT for 113 aneurysms (61 unruptured, 53 ruptured) based on computational fluid dynamic models. Virtual particles were injected into the parent vessel and followed during multiple cardiac cycles. PRT was defined as the time needed for 99% of the particles that entered an aneurysm to leave the aneurysm. Subsequently, we evaluated the association between PRT, rupture, and morphology (aneurysm type, presence of blebs, or multiple lobulations).Results: PRT showed no significant difference between unruptured (1.1 seconds interquartile range [IQR .39-2.0 seconds]) and ruptured aneurysms (1.2 seconds [IQR .47-2.3 seconds]). PRT was influenced by aneurysm morphology. Longer PRTs were seen in bifurcation aneurysms (1.3 seconds [IQR .54-2.4 seconds], P = .01) and aneurysms with blebs or multiple lobulations (1.92 seconds [IQR .94-2.8 seconds], P < .001). Four of five partially thrombosed aneurysms had a long residence time (>1.9 seconds).Conclusions: Our study shows an influence of aneurysm morphology on PRT. Nevertheless, it suggests that PRT cannot be used to differentiate unruptured and ruptured aneurysms. [ABSTRACT FROM AUTHOR]

While matrix remodeling plays a key role in vascular physiology and pathology, the underlying mechanisms have remained incompletely understood. We studied the remodeling of collagen matrices by individual vascular smooth muscle cells (SMCs), clusters and monolayers. In addition, we focused on the contribution of transglutaminase 2 (TG2), which plays an important role in the remodeling of small arteries. Single SMCs displaced fibers in collagen matrices at distances up to at least 300 μm in the course of 8-12 h. This process involved both 'hauling up' of matrix by the cells and local matrix compaction at a distance from the cells, up to 200 μm. This exceeded the distance over which cellular protrusions were active, implicating the involvement of secreted enzymes such as TG2. SMC isolated from TG2 KO mice still showed compaction, with changed dynamics and relaxation. The TG active site inhibitor L682777 blocked local compaction by wild type cells, strongly reducing the displacement of matrix towards the cells. At increasing cell density, cells cooperated to establish compaction. In a ring-shaped collagen matrix, this resulted in preferential displacement in the radial direction, perpendicular to the cellular long axis. This process was unaffected by inhibition of TG2 cross-linking. These results show that SMCs are capable of matrix remodeling by prolonged, gradual compaction along their short axis. This process could add to the 3D organization and remodeling of blood vessels based on the orientation and contraction of SMCs. [ABSTRACT FROM AUTHOR]

In this study, the effect of polymer materials with different polarity, namely low density polyethylene (LDPE) and ethylene vinyl acetate (EVA), on the migration behaviour of α -tocopherol from active packaging was investigated. The antioxidant was also adsorbed onto silica materials, namely SBA-15 (Santa Barbara-15) and Syloblock, in order to protect the antioxidant during extrusion and to ensure a controlled and sufficient release during the shelf-life of the food product. Migration experiments were performed at 7.0 ± 0.5°C and 95% ethanol was used as fatty food simulant. All films contained a high concentration of α -tocopherol, ∼ 2000 mg kg -1 , to obtain an active packaging. Polymer matrix had a small influence on the migration profile. The migration of 80% of total migrated amount of antioxidant was retarded for 2.4 days by using LDPE instead of EVA. When α -tocopherol was adsorbed onto both silica materials, the migration of 80% of total migrated amount of antioxidant was retarded for 3.4 days in comparison to pure α -tocopherol. No difference was seen between the migration profiles of α -tocopherol adsorbed onto both silica materials. In the case of pure α-tocopherol, 82% of the initial amount of α -tocopherol in the film migrated into the food simulant at a rather fast migration rate. In the case of adsorption on silica materials, a total migration was observed. These antioxidative films can have positive food applications. [ABSTRACT FROM AUTHOR]

Microelectrode impalement of human macrophages evokes a transient hyperpolarizing response (HR) of the membrane potential. This HR was found to be dependent on the extracellular concentration of K+ but not on that of Na+ or Cl-. It was not influenced by low temperature (12 degrees C) or by 0.2 mM ouabain, but was blocked by 0.2 mM quinine or 0.2 mM Mg2+-EGTA. These findings indicate that the HR in human macrophages is caused by the activation of a K+ (Ca2+) conductance. Two types of ionic channels were identified in intact cells by use of the patch-clamp technique in the cell-attached-patch configuration, low and high-conductance voltage-dependent K+ channels. The low-conductance channels had a mean conductance of 38 pS with Na+-saline and 32 pS with K+-saline in the pipette. The high-conductance channels had a conductance of 101 and 114 pS with Na+- and K+-saline in the pipette, respectively. Cell-attached patch measurements made during evocation of an HR by microelectrode penetration showed enhanced channel activity associated with the development of the HR. These channels were also high-conductance channels (171 pS with Na+- and 165 pS K+-saline in the pipette) and were voltage dependent. They were, however, active at less positive potentials than the high-conductance K+ channels seen prior to the microelectrode-evoked HR. It is concluded that the high-conductance voltage-dependent ionic channels active during the HR in human macrophages contribute to the development of the HR. [ABSTRACT FROM AUTHOR]

Endothelial blood-brain barrier (BBB) dysfunction is critical in the pathophysiology of brain injury. Rho-associated protein kinase (ROCK) activation disrupts BBB integrity in the injured brain. We aimed to test the efficacy of a novel ROCK2 inhibitor in preserving the BBB after acute brain injury. We characterized the molecular structure and pharmacodynamic and pharmacokinetic properties of a novel selective ROCK2 inhibitor, NRL-1049, and its first metabolite, 1-hydroxy-NRL-1049 (referred to as NRL-2017 hereon) and tested the efficacy of NRL-1049 on the BBB integrity in rodent models of acute brain injury. Our data show that NRL-1049 and NRL-2017 both inhibit ROCK activity and are 44-fold and 17-fold more selective towards ROCK2 than ROCK1, respectively. When tested in a mouse model of cortical cryoinjury, NRL-1049 significantly attenuated the increase in water content. Interestingly, 60% of the mice in the vehicle arm developed seizures within 2 hours after cryoinjury versus none in the NRL-1049 arm. In spontaneously hypertensive rats, NRL-1049 attenuated the dramatic surge in Evans Blue extravasation compared with the vehicle arm after transient middle cerebral artery occlusion. Hemorrhagic transformation was also reduced. We show that NRL-1049, a selective ROCK2 inhibitor, is a promising drug candidate to preserve the BBB after brain injury., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. McKerracher is CEO of BioAxone BioSciences, Inc. and hold an ownership interest in the company and has a significant competing interest. The data for this article were collected while Drs. Abbinanti, Woller, Ruschel and Rosen were employed at BioAxone BioSciences, and they have a modest conflict of interest. The opinions expressed in this article are the author’s own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. Neurelis, Inc. acquired the rights to BA-1049 (now referred to as NRL-1049) from BioAxone in June 2021. Ayata is on the scientific advisory board of Neurelis, Inc. and declares sponsored research agreements with Praxis and Takeda Pharmaceutical Company. Mulder declares a past sponsored research agreement with BioAxone BioSciences, Inc. (concerning work not included in this manuscript). The other authors declare no conflict of interest. No writing assistance was utilized in the production of this manuscript.

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment., (© 2024. The Author(s).)

The early management of transferred patients with a large vessel occlusion (LVO) stroke could be improved by identifying patients who are likely to recanalize early. We aim to predict early recanalization based on patient clinical and thrombus imaging characteristics. We included 81 transferred anterior-circulation LVO patients with an early recanalization, defined as the resolution of the LVO or the migration to a distal location not reachable with endovascular treatment upon repeated radiological imaging. We compared their clinical and imaging characteristics with all (322) transferred patients with a persistent LVO in the MR CLEAN Registry. We measured distance from carotid terminus to thrombus (DT), thrombus length, density, and perviousness on baseline CT images. We built logistic regression models to predict early recanalization. We validated the predictive ability by computing the median area-under-the-curve (AUC) of the receiver operating characteristics curve for 100 5-fold cross-validations. The administration of intravenous thrombolysis (IVT), longer transfer times, more distal occlusions, and shorter, pervious, less dense thrombi were characteristic of early recanalization. After backward elimination, IVT administration, DT and thrombus density remained in the multivariable model, with an AUC of 0.77 (IQR 0.72-0.83). Baseline thrombus imaging characteristics are valuable in predicting early recanalization and can potentially be used to optimize repeated imaging workflow., Competing Interests: N. Arrarte Terreros is co-founder of inSteps, a start-up that focuses on in-silico stroke models. D.W.J. Dippel reports unrestricted grants from Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, LLC, Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and Thrombolytic Science, LLC for research, paid to institution. H.A. Marquering is co-founder of inSteps and Nico.lab, a company that focuses on the use of artificial intelligence for medical image analysis. C.B.L.M. Majoie reports grants from the European Commission during the conducting of the study; grants from CVON/Dutch Heart Foundation, TWIN Foundation, Healthcare Evaluation Netherlands and Stryker, outside the submitted work; and is a shareholder of Nico.lab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Drug development for neurological diseases is greatly impeded by the presence of the blood-brain barrier (BBB). We and others previously reported on extravasation of micrometer-sized particles from the cerebral microcirculation - across the BBB - into the brain tissue over the course of several weeks. This mechanism could potentially be used for sustained parenchymal drug delivery after extravasation of biodegradable microspheres. As a first step toward this goal, we set out to evaluate the extravasation potential in the rat brain of three classes of biodegradable microspheres with drug-carrying potential, having a median diameter of 13 µm (80% within 8-18 µm) and polyethylene glycol concentrations of 0%, 24% and 36%. Extravasation, capillary recanalization and tissue damage were determined in a rat cerebral microembolization model at day 14 after microsphere injection. Microspheres of all three classes had the potential to extravasate from the vessel into the brain parenchyma, with microspheres without polyethylene glycol extravasating the fastest. Microembolization with biodegradable microspheres led to impaired local capillary perfusion, which was substantially restored after bead extravasation. We did not observe overt tissue damage after microembolization with any microsphere: we found very limited BBB disruption (IgG extravasation), no microgliosis (Iba1 staining) and no large neuronal infarctions (NeuN staining). In conclusion, biodegradable microspheres with different polymer compositions can extravasate into the brain parenchyma while causing minimal tissue damage.

Background: The effects of thrombus imaging characteristics on procedural and clinical outcomes after ischemic stroke are increasingly being studied. These thrombus characteristics - for eg, size, location, and density - are commonly analyzed as separate entities. However, it is known that some of these thrombus characteristics are strongly related. Multicollinearity can lead to unreliable prediction models. We aimed to determine the distribution, correlation and clustering of thrombus imaging characteristics based on a large dataset of anterior-circulation acute ischemic stroke patients., Methods: We measured thrombus imaging characteristics in the MR CLEAN Registry dataset, which included occlusion location, distance from the intracranial carotid artery to the thrombus (DT), thrombus length, density, perviousness, and clot burden score (CBS). We assessed intercorrelations with Spearman's coefficient (ρ) and grouped thrombi based on 1) occlusion location and 2) thrombus length, density and perviousness using unsupervised clustering., Results: We included 934 patients, of which 22% had an internal carotid artery (ICA) occlusion, 61% M1, 16% M2, and 1% another occlusion location. All thrombus characteristics were significantly correlated. Higher CBS was strongly correlated with longer DT (ρ=0.67, p<0.01), and moderately correlated with shorter thrombus length (ρ=-0.41, p<0.01). In more proximal occlusion locations, thrombi were significantly longer, denser, and less pervious. Unsupervised clustering analysis resulted in four thrombus groups; however, the cohesion within and distinction between the groups were weak., Conclusions: Thrombus imaging characteristics are significantly intercorrelated - strong correlations should be considered in future predictive modeling studies. Clustering analysis showed there are no distinct thrombus archetypes - novel treatments should consider this thrombus variability., Competing Interests: Competing interests: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 777072 (INSIST project), and the AMC medical Research BV, Amsterdam UMC, location AMC, under project No 21937. The MR CLEAN registry is partially funded by unrestricted grants from the Applied Scientific Institute for Neuromodulation (Toegepast Wetenschappelijk Instituut voor Neuromodulatie), Erasmus Medical Center, Amsterdam University Medical Center and Maastricht University Medical Center. HAM reports being a co-founder and shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. CBLMM reports grants from European Commission during the conduct of the study; grants from CVON/Dutch Heart Foundation, TWIN Foundation, Health Evaluation Netherlands, and Stryker, outside the submitted work; and shareholder of Nicolab. DWJD reports unrestricted grants from Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, LLC, Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and Thrombolytic Science, LLC for research, paid to institution. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Microinfarcts result in a transient loss of the blood-brain barrier (BBB) in the ischemic territory. This leads to the extravasation of blood proteins into the brain parenchyma. It is not clear how these proteins are removed. Here we studied the role of perivascular spaces in brain clearance from extravasated blood proteins. Male and female Wistar rats were infused with microspheres of either 15, 25, or 50 μm in diameter (n = 6 rats per group) via the left carotid artery. We infused either 25,000 microspheres of 15 μm, 5500 of 25 μm, or 1000 of 50 μm. One day later, rats were infused with lectin and hypoxyprobe to label perfused blood vessels and hypoxic areas, respectively. Rats were then euthanized and perfusion-fixed. Brains were excised, sectioned, and analyzed using immunostaining and confocal imaging. Microspheres induced a size-dependent increase in ischemic volume per territory, but the cumulative ischemic volume was similar in all groups. The total volumes of ischemia, hypoxia and infarction affected 1-2 % of the left hemisphere. Immunoglobulins (IgG) were present in ischemic brain tissue surrounding lodged microspheres in all groups. In addition, staining for IgG was found in perivascular spaces of blood vessels nearby areas of BBB disruption. About 2/3 of these vessels were arteries, while the remaining 1/3 of these vessels were veins. The subarachnoid space (SAS) of the affected hemisphere stained stronger for IgG than the contralateral hemisphere in all groups: +27 %, +44 % and +27 % respectively. Microspheres of various sizes induce a local loss of BBB integrity, evidenced by parenchymal IgG staining. The presence of IgG in perivascular spaces of both arteries and veins distinct from the ischemic territories suggests that both contribute to the removal of blood proteins. The strong staining for IgG in the SAS of the affected hemisphere suggests that this perivascular route egresses via the CSF. Perivascular spaces therefore play a previously unrecognized role in tissue clearance of fluid and extravasated proteins after BBB disruption induced by microinfarcts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulsed dye laser (PDL) therapy can be effective in treating psoriasis, with a long duration of remission. Although PDL therapy, albeit on a modest scale, is being used for decades now, the underlying mechanisms responsible for the long-term remission of psoriasis remain poorly understood. The selective and rapid absorption of energy by the blood causes heating of the vascular wall and surrounding structures, like perivascular nerves. Several studies indicate the importance of nerves in psoriatic inflammation. Interestingly, denervation leads to a spontaneous remission of the psoriatic lesion. Among all dermal nerves, the perivascular nerves are the most likely to be affected during PDL treatment, possibly impairing the neuro-inflammatory processes that promote T-cell activation, expression of adhesion molecules, leukocyte infiltration and cytokine production. Repeated PDL therapy could cause a prolonged loss of innervation through nerve damage, or result in a 'reset' of neurogenic inflammation after temporary denervation. The current hypothesis provides strong arguments that PDL treatment affects nerve fibres in the skin and thereby abrogates the persistent and exaggerated inflammatory process underlying psoriasis, causing a long-term remission of psoriasis., (© 2023 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background and Objective: Mechanical thrombectomy is a minimally invasive procedure that aims at removing the occluding thrombus from the vasculature of acute ischemic stroke patients. Thrombectomy success and failure can be studied using in-silico thrombectomy models. Such models require realistic modeling steps to be effective. We here present a new approach to model microcatheter tracking during thrombectomy., Methods: For 3 patient-specific vessel geometries, we performed finite-element simulations of the microcatheter tracking (1) following the vessel centerline (centerline method) and (2) as a one-step insertion simulation, where the microcatheter tip was advanced along the vessel centerline while its body was free to interact with the vessel wall (tip-dragging method). Qualitative validation of the two tracking methods was performed with the patient's digital subtraction angiography (DSA) images. In addition, we compared simulated thrombectomy outcomes (successful vs unsuccessful thrombus retrieval) and maximum principal stresses on the thrombus between the centerline and tip-dragging method., Results: Qualitative comparison with the DSA images showed that the tip-dragging method more realistically resembles the patient-specific microcatheter-tracking scenario, where the microcatheter approaches the vessel walls. Although the simulated thrombectomy outcomes were similar in terms of thrombus retrieval, the thrombus stress fields (and the associated fragmentation of the thrombus) were strongly different between the two methods, with local differences in the maximum principal stress curves up to 84%., Conclusions: Microcatheter positioning with respect to the vessel affects the stress fields of the thrombus during retrieval, and therefore, may influence thrombus fragmentation and retrieval in-silico thrombectomy., Competing Interests: Declaration of Competing Interest HAM reports co-founder and shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. CBLMM reports grants from the European Commission during the conduct of the study; grants from CVON/ Dutch Heart Foundation, TWIN Foundation, Healthcare Evaluation Netherlands, and Stryker, outside the submitted work; and shareholder of Nicolab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A thrombus in the M1 segment of the middle cerebral artery (MCA) can occlude this main stem only or extend into the M1-M2 bifurcation. The occlusion pattern may affect endovascular treatment (EVT) success, as a bifurcated thrombus may be more prone to fragmentation during retrieval., Objective: To investigate whether bifurcated thrombus patterns are associated with EVT procedural and clinical outcomes., Methods: Occlusion patterns of MCA thrombi on CT angiography from MR CLEAN Registry patients were classified into three groups: main stem occlusion, bifurcation occlusion extending into one M2 branch, and bifurcation occlusion extending into both M2 branches. Procedural parameters, procedural outcomes (reperfusion grade and embolization to new territory), and clinical outcomes (24-48 hour National Institutes of Health Stroke Scale [NIHSS FU ] score, change in NIHSS scores between 24 and 48 hours and baseline ∆ [NIHSS], and 90-day modified Rankin Scale [mRS] scores) were compared between occlusion patterns., Results: We identified 1023 patients with an MCA occlusion of whom 370 (36%) had a main stem occlusion, 151 (15%) a single branch, and 502 (49%) a double branch bifurcation occlusion. There were no statistically significant differences in retrieval method, procedure time, number of retrieval attempts, reperfusion grade, and embolization to new territory between occlusion patterns. Patients with main stem occlusions had lower NIHSS FU scores than patients with single (7 vs 11, p=0.01) or double branch occlusions (7 vs 9, p=0.04). However, there were no statistically significant differences in ∆ NIHSS or in 90-day mRS scores., Conclusions: In our population, EVT procedural and long-term clinical outcomes were similar for MCA bifurcation occlusions and MCA main stem occlusions., Competing Interests: Competing interests: This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 777072 (INSIST project), and the AMC medical Research BV, Amsterdam UMC, location AMC, under project No 21937. The MR CLEAN registry is partially funded by unrestricted grants from the Applied Scientific Institute for Neuromodulation (Toegepast Wetenschappelijk Instituut voor Neuromodulatie), Erasmus Medical Center, Amsterdam University Medical Center and Maastricht University Medical Center. HAM reports co-founder and shareholder of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. CBLMM reports grants from European Commission during the conduct of the study; grants from CVON/Dutch Heart Foundation, TWIN Foundation, and Stryker, outside the submitted work; and shareholder of Nicolab. IGHJ reports shareholder of Nicolab. DWJD and AvdL report unrestricted grants from Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, LLC, Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences and Health, and Thrombolytic Science, LLC for research, paid to institution. BvdW received funds from Bayer and LivaNova for consultancy, paid to his institution, and grants from the Dutch Heart Foundation, the Horizon 2020 programme, and Stryker, paid to his institution, all outside the work submitted. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The microvasculature plays a key role in oxygen transport in the mammalian brain. Despite the close coupling between cerebral vascular geometry and local oxygen demand, recent experiments have reported that microvascular occlusions can lead to unexpected distant tissue hypoxia and infarction. To better understand the spatial correlation between the hypoxic regions and the occlusion sites, we used both in vivo experiments and in silico simulations to investigate the effects of occlusions in cerebral penetrating arteriole trees on tissue hypoxia. In a rat model of microembolisation, 25 μm microspheres were injected through the carotid artery to occlude penetrating arterioles. In representative models of human cortical columns, the penetrating arterioles were occluded by simulating the transport of microspheres of the same size and the oxygen transport was simulated using a Green's function method. The locations of microspheres and hypoxic regions were segmented, and two novel distance analyses were implemented to study their spatial correlation. The distant hypoxic regions were found to be present in both experiments and simulations, and mainly due to the hypoperfusion in the region downstream of the occlusion site. Furthermore, a reasonable agreement for the spatial correlation between hypoxic regions and occlusion sites is shown between experiments and simulations, which indicates the good applicability of in silico models in understanding the response of cerebral blood flow and oxygen transport to microemboli., Competing Interests: The authors have declared that no competing interests exist.

Background: We performed an exploratory analysis to identify patient and thrombus characteristics associated with early recanalization in large-vessel occlusion (LVO) stroke patients transferred for endovascular treatment (EVT) from a primary (PSC) to a comprehensive stroke center (CSC)., Methods: We included patients with an LVO stroke of the anterior circulation who were transferred to our hospital for EVT and underwent repeated imaging between January 2016 and June 2019. We compared patient characteristics, workflow time metrics, functional outcome (modified Rankin Scale at 90 days), and baseline thrombus imaging characteristics, which included: occlusion location, thrombus length, attenuation, perviousness, distance from terminus of intracranial carotid artery to the thrombus (DT), and clot burden score (CBS), between early-recanalized LVO (ER-LVO), and non-early-recanalized LVO (NER-LVO) patients., Results: One hundred and forty-nine patients were included in the analysis. Early recanalization occurred in 32% of patients. ER-LVO patients less often had a medical history of hypertension (31% vs 49%, P=0.04), and more often had clinical improvement between PSC and CSC (ΔNIHSS -5 vs 3, P<0.01), compared with NER-LVO patients. Thrombolysis administration was similar in both groups (88% vs 78%, P=0.18). ER-LVO patients had no ICA occlusions (0% vs 27%, P<0.01), more often an M2 occlusion (35% vs 17%, P=0.01), longer DT (27 mm vs 12 mm, P<0.01), shorter thrombi (17 mm vs 27 mm, P<0.01), and higher CBS (8 vs 6, P<0.01) at baseline imaging. ER-LVO patients had lower mRS scores (1 vs 3, P=0.02)., Conclusions: Early recanalization is associated with clinical improvement between PSC and CSC admission, more distal occlusions and shorter thrombi at baseline imaging, and better functional outcome., Competing Interests: Competing interests: H.A. Marquering is co-founder and shareholder of Nico.lab, a company that focuses on the use of artificial intelligence for medical image analysis. C.B.L.M. Majoie reports grants from the European Commission during the conduct of the study; grants from CVON/Dutch Heart Foundation, TWIN Foundation, and Stryker, outside the submitted work; and is shareholder of Nico.lab. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)