Perivascular clearance of blood proteins after blood-brain barrier disruption in a rat model of microinfarcts.

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.

Effects of pulsed dye laser treatment in psoriasis: A nerve-wrecking process?

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.

Quantification of hypoxic regions distant from occlusions in cerebral penetrating arteriole trees.

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.

Non-Invasive Assessment of Damping of Blood Flow Velocity Pulsatility in Cerebral Arteries With MRI.

BACKGROUND: Damping of heartbeat-induced pressure pulsations occurs in large arteries such as the aorta and extends to the small arteries and microcirculation. Since recently, 7 T MRI enables investigation of damping in the small cerebral arteries. PURPOSE: To investigate flow pulsatility damping between the first segment of the middle cerebral artery (M1) and the small perforating arteries using magnetic resonance imaging. STUDY TYPE: Retrospective. SUBJECTS: Thirty-eight participants (45% female) aged above 50 without history of heart failure, carotid occlusive disease, or cognitive impairment. FIELD STRENGTH/SEQUENCE: 3 T gradient echo (GE) T1-weighted images, spin-echo fluid-attenuated inversion recovery images, GE two-dimensional (2D) phase-contrast, and GE cine steady-state free precession images were acquired. At 7 T, T1-weighted images, GE quantitative-flow, and GE 2D phase-contrast images were acquired. ASSESSMENT: Velocity pulsatilities of the M1 and perforating arteries in the basal ganglia (BG) and semi-oval center (CSO) were measured. We used the damping index between the M1 and perforating arteries as a damping indicator (velocity pulsatilityM1 /velocity pulsatilityCSO/BG ). Left ventricular stroke volume (LVSV), mean arterial pressure (MAP), pulse pressure (PP), and aortic pulse wave velocity (PWV) were correlated with velocity pulsatility in the M1 and in perforating arteries, and with the damping index of the CSO and BG. STATISTICAL TESTS: Correlations of LVSV, MAP, PP, and PWV with velocity pulsatility in the M1 and small perforating arteries, and correlations with the damping indices were evaluated with linear regression analyses. RESULTS: PP and PWV were significantly positively correlated to M1 velocity pulsatility. PWV was significantly negatively correlated to CSO velocity pulsatility, and PP was unrelated to CSO velocity pulsatility (P = 0.28). PP and PWV were uncorrelated to BG velocity pulsatility (P = 0.25; P = 0.68). PWV and PP were significantly positively correlated with the CSO damping index. DATA CONCLUSION: Our study demonstrated a dynamic damping of velocity pulsatility between the M1 and small cerebral perforating arteries in relation to proximal stress. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1.

Endothelial basement membrane laminin 511 is essential for shear stress response.

Shear detection and mechanotransduction by arterial endothelium requires junctional complexes containing PECAM-1 and VE-cadherin, as well as firm anchorage to the underlying basement membrane. While considerable information is available for junctional complexes in these processes, gained largely from in vitro studies, little is known about the contribution of the endothelial basement membrane. Using resistance artery explants, we show that the integral endothelial basement membrane component, laminin 511 (laminin α5), is central to shear detection and mechanotransduction and its elimination at this site results in ablation of dilation in response to increased shear stress. Loss of endothelial laminin 511 correlates with reduced cortical stiffness of arterial endothelium in vivo, smaller integrin ß1-positive/vinculin-positive focal adhesions, and reduced junctional association of actin-myosin II In vitro assays reveal that ß1 integrin-mediated interaction with laminin 511 results in high strengths of adhesion, which promotes p120 catenin association with VE-cadherin, stabilizing it at cell junctions and increasing cell-cell adhesion strength. This highlights the importance of endothelial laminin 511 in shear response in the physiologically relevant context of resistance arteries.

Value of Computed Tomographic Perfusion-Based Patient Selection for Intra-Arterial Acute Ischemic Stroke Treatment.

BACKGROUND AND PURPOSE: The utility of computed tomographic perfusion (CTP)-based patient selection for intra-arterial treatment of acute ischemic stroke has not been proven in randomized trials and requires further study in a cohort that was not selected based on CTP. Our objective was to study the relationship between CTP-derived parameters and outcome and treatment effect in patients with acute ischemic stroke because of a proximal intracranial arterial occlusion. METHODS: We included 175 patients who underwent CTP in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands (MR CLEAN). Association of CTP-derived parameters (ischemic-core volume, penumbra volume, and percentage ischemic core) with outcome was estimated with multivariable ordinal logistic regression as an adjusted odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale. Interaction between CTP-derived parameters and treatment effect was determined using multivariable ordinal logistic regression. Interaction with treatment effect was also tested for mismatch (core <70 mL; penumbra core >1.2; penumbra core >10 mL). RESULTS: The adjusted odds ratio for improved functional outcome for ischemic core, percentage ischemic core, and penumbra were 0.79 per 10 mL (95% confidence interval: 0.71-0.89; P<0.001), 0.82 per 10% (95% confidence interval: 0.66-0.90; P=0.002), and 0.97 per 10 mL (96% confidence interval: 0.92-1.01; P=0.15), respectively. No significant interaction between any of the CTP-derived parameters and treatment effect was observed. We observed no significant interaction between mismatch and treatment effect. CONCLUSIONS: CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy.

The novel ROCK2 selective inhibitor NRL-1049 preserves the blood-brain barrier after acute injury.

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.

Thrombus Imaging Characteristics to Predict Early Recanalization in Anterior Circulation Large Vessel Occlusion Stroke.

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.

Testosterone and ß-oestradiol prevent inward remodelling of rat small mesenteric arteries: role of NO and transglutaminase.

Increasing evidence shows that sex hormones exert a protective effect on the vasculature, especially in the regulation of the active vasomotor responses. However, whether sex hormones affect vascular remodelling is currently unclear. In the present study, we tested the hypothesis that testosterone in males and ß-oestradiol in females prevent inward remodelling, possibly through inhibition of cross-linking activity induced by enzymes of the TG (transglutaminase) family. Small mesenteric arteries were isolated from male and female Wistar rats. Dose-dependent relaxation to testosterone and ß-oestradiol was inhibited by the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester), confirming that these hormones induce NO release. When arteries were cannulated, pressurized and kept in organ culture with ET-1 (endothelin-1) for 3 days we observed strong vasoconstriction and inward remodelling. Remodelling was significantly inhibited by testosterone in males, and by ß-oestradiol in females. This preventive effect of sex hormones was not observed in the presence of L-NAME. Inward remodelling was also reduced by the inhibitor of TG L682.777, both in males and females. In arteries from female rats, ET-1 increased TG activity, and this effect was prevented by ß-oestradiol. L-NAME induced a significant increase in TG activity in the presence of sex hormones in arteries from both genders. We conclude that testosterone and ß-oestradiol prevent constriction-induced inward remodelling. Inward remodelling, both in males and females, depends on NO and TG activity. In females, inhibition of inward remodelling could be mediated by NO-mediated inhibition of TG activity.

k-t BLAST and SENSE accelerated time-resolved three-dimensional phase contrast MRI in an intracranial aneurysm.

OBJECTIVE: The objective of this study was to investigate the performance of k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) accelerated time-resolved 3D PC-MRI compared to SENSE (SENSitivity Encoding) acceleration in an in vitro and in vivo intracranial aneurysm. MATERIALS AND METHODS: Non-accelerated, SENSE and k-t BLAST accelerated time-resolved 3D PC-MRI measurements were performed in vivo and in vitro. We analysed the consequences of various temporal resolutions in vitro. RESULTS: Both in vitro and in vivo measurements showed that the main effect of k-t BLAST was underestimation of velocity during systole. In the phantom, temporal blurring decreased with increasing temporal resolution. Quantification of the differences between the non-accelerated and accelerated measurements confirmed that in systole SENSE performed better than k-t BLAST in terms of mean velocity magnitude. In both in vitro and in vivo measurements, k-t BLAST had higher SNR compared to SENSE. Qualitative comparison between measurements showed good similarity. CONCLUSION: Comparison with SENSE revealed temporal blurring effects in k-t BLAST accelerated measurements.

Extravasation of biodegradable microspheres in the rat brain.

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.

Microcatheter tracking in thrombectomy procedures: A finite-element simulation study.

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.

Thrombus imaging characteristics within acute ischemic stroke: similarities and interdependence.

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.

Bifurcation occlusions and endovascular treatment outcome in acute ischemic stroke.

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 [NIHSSFU] 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 NIHSSFU 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.

Quantitative Fluorescence Imaging of Perfusion-An Algorithm to Predict Anastomotic Leakage.

This study tests fluorescence imaging-derived quantitative parameters for perfusion evaluation of the gastric tube during surgery and correlates these parameters with patient outcomes in terms of anastomotic leakage. Poor fundus perfusion is seen as a major factor for the development of anastomotic leakage and strictures. Fluorescence perfusion imaging may reduce the incidence of complications. Parameters for the quantification of the fluorescence signal are still lacking. Quantitative parameters in terms of maximal intensity, mean slope and influx timepoint were tested for significant differences between four perfusion areas of the gastric tube in 22 patients with a repeated ANOVA test. These parameters were compared with patient outcomes. Maximal intensity, mean slope and influx timepoint were significantly different between the base of the gastric tube and the fundus (p < 0.0001). Patients who developed anastomotic leakage showed a mean slope of almost 0 in Location 4. The distance of the demarcation of ICG to the fundus was significantly higher in the three patients who developed anastomotic leakage (p < 0.0001). This study presents quantitative intra-operative perfusion imaging with fluorescence. Quantification of the fluorescence signal allows for early risk stratification of necrosis.

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.

Early recanalization in large-vessel occlusion stroke patients transferred for endovascular treatment.

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.

Value of CT Perfusion for Collateral Status Assessment in Patients with Acute Ischemic Stroke.

Good collateral status in acute ischemic stroke patients is an important indicator for good outcomes. Perfusion imaging potentially allows for the simultaneous assessment of local perfusion and collateral status. We combined multiple CTP parameters to evaluate a CTP-based collateral score. We included 85 patients with a baseline CTP and single-phase CTA images from the MR CLEAN Registry. We evaluated patients' CTP parameters, including relative CBVs and tissue volumes with several time-to-maximum ranges, to be candidates for a CTP-based collateral score. The score candidate with the strongest association with CTA-based collateral score and a 90-day mRS was included for further analyses. We assessed the association of the CTP-based collateral score with the functional outcome (mRS 0-2) by analyzing three regression models: baseline prognostic factors (model 1), model 1 including the CTA-based collateral score (model 2), and model 1 including the CTP-based collateral score (model 3). The model performance was evaluated using C-statistic. Among the CTP-based collateral score candidates, relative CBVs with a time-to-maximum of 6-10 s showed a significant association with CTA-based collateral scores (p = 0.02) and mRS (p = 0.05) and was therefore selected for further analysis. Model 3 most accurately predicted favorable outcomes (C-statistic = 0.86, 95% CI: 0.77-0.94) although differences between regression models were not statistically significant. We introduced a CTP-based collateral score, which is significantly associated with functional outcome and may serve as an alternative collateral measure in settings where MR imaging is not feasible.

Impact of the Internal Carotid Artery Morphology on in silico Stent-Retriever Thrombectomy Outcome.

The aim of this work is to propose a methodology for identifying relationships between morphological features of the cerebral vasculature and the outcome of in silico simulations of thrombectomy, the mechanical treatment for acute ischemic stroke. Fourteen patient-specific cerebral vasculature segmentations were collected and used for geometric characterization of the intracranial arteries mostly affected by large vessel occlusions, i.e., internal carotid artery (ICA), middle cerebral artery (MCA) and anterior cerebral artery (ACA). First, a set of global parameters was created, including the geometrical information commonly provided in the clinical context, namely the total length, the average diameter and the tortuosity (length over head-tail distance) of the intracranial ICA. Then, a more exhaustive geometrical analysis was performed to collect a set of local parameters. A total of 27 parameters was measured from each patient-specific vascular configuration. Fourteen virtual thrombectomy simulations were performed with a blood clot with the same length and composition placed in the middle of the MCA. The model of TREVO ProVue stent-retriever was used for all the simulations. Results from simulations produced five unsuccessful outcomes, i.e., the clot was not removed from the vessels. The geometric parameters of the successful and unsuccessful simulations were compared to find relations between the vascular geometry and the outcome. None of the global parameters alone or combined proved able to discriminate between positive and negative outcome, while a combination of local parameters allowed to correctly identify the successful from the unsuccessful simulations. Although these results are limited by the number of patients considered, this study indicates a promising methodology to relate patient-specific geometry to virtual thrombectomy outcome, which might eventually guide decision making in the treatment of acute ischemic stroke.