Value of Automatically Derived Full Thrombus Characteristics: An Explorative Study of Their Associations with Outcomes in Ischemic Stroke Patients.

(1) Background: For acute ischemic strokes caused by large vessel occlusion, manually assessed thrombus volume and perviousness have been associated with treatment outcomes. However, the manual assessment of these characteristics is time-consuming and subject to inter-observer bias. Alternatively, a recently introduced fully automated deep learning-based algorithm can be used to consistently estimate full thrombus characteristics. Here, we exploratively assess the value of these novel biomarkers in terms of their association with stroke outcomes. (2) Methods: We studied two applications of automated full thrombus characterization as follows: one in a randomized trial, MR CLEAN-NO IV (n = 314), and another in a Dutch nationwide registry, MR CLEAN Registry (n = 1839). We used an automatic pipeline to determine the thrombus volume, perviousness, density, and heterogeneity. We assessed their relationship with the functional outcome defined as the modified Rankin Scale (mRS) at 90 days and two technical success measures as follows: successful final reperfusion, which is defined as an eTICI score of 2b-3, and successful first-pass reperfusion (FPS). (3) Results: Higher perviousness was significantly related to a better mRS in both MR CLEAN-NO IV and the MR CLEAN Registry. A lower thrombus volume and lower heterogeneity were only significantly related to better mRS scores in the MR CLEAN Registry. Only lower thrombus heterogeneity was significantly related to technical success; it was significantly related to a higher chance of FPS in the MR CLEAN-NO IV trial (OR = 0.55, 95% CI: 0.31-0.98) and successful reperfusion in the MR CLEAN Registry (OR = 0.88, 95% CI: 0.78-0.99). (4) Conclusions: Thrombus characteristics derived from automatic entire thrombus segmentations are significantly related to stroke outcomes.

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.

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.

Prognostic Value of Thrombus Volume and Interaction With First-Line Endovascular Treatment Device Choice.

BACKGROUND: A larger thrombus in patients with acute ischemic stroke might result in more complex endovascular treatment procedures, resulting in poorer patient outcomes. Current evidence on thrombus volume and length related to procedural and functional outcomes remains contradicting. This study aimed to assess the prognostic value of thrombus volume and thrombus length and whether this relationship differs between first-line stent retrievers and aspiration devices for endovascular treatment. METHODS: In this multicenter retrospective cohort study, 670 of 3279 patients from the MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) for endovascularly treated large vessel occlusions were included. Thrombus volume (0.1 mL) and length (0.1 mm) based on manual segmentations and measurements were related to reperfusion grade (expanded Treatment in Cerebral Infarction score) after endovascular treatment, the number of retrieval attempts, symptomatic intracranial hemorrhage, and a shift for functional outcome at 90 days measured with the reverted ordinal modified Rankin Scale (odds ratio >1 implies a favorable outcome). Univariable and multivariable linear and logistic regression were used to report common odds ratios (cORs)/adjusted cOR and regression coefficients (B/aB) with 95% CIs. Furthermore, a multiplicative interaction term was used to analyze the relationship between first-line device choice, stent retrievers versus aspiration device, thrombus volume, and outcomes. RESULTS: Thrombus volume was associated with functional outcome (adjusted cOR, 0.83 [95% CI, 0.71-0.97]) and number of retrieval attempts (aB, 0.16 [95% CI, 0.16-0.28]) but not with the other outcome measures. Thrombus length was only associated with functional independence (adjusted cOR, 0.45 [95% CI, 0.24-0.85]). Patients with more voluminous thrombi had worse functional outcomes if endovascular treatment was based on first-line stent retrievers (interaction cOR, 0.67 [95% CI, 0.50-0.89]; P=0.005; adjusted cOR, 0.74 [95% CI, 0.55-1.0]; P=0.04). CONCLUSIONS: In this study, patients with a more voluminous thrombus required more endovascular thrombus retrieval attempts and had a worse functional outcome. Patients with a lengthier thrombus were less likely to achieve functional independence at 90 days. For more voluminous thrombi, first-line stent retrieval compared with first-line aspiration might be associated with worse functional outcome.

Distal Embolization in Relation to Radiological Thrombus Characteristics, Treatment Details, and Functional Outcome.

BACKGROUND: Distal embolization (DE) is a common complication of endovascular treatment (EVT). We investigated the association of radiological thrombus characteristics and treatment details with DE. METHODS: Patients with thin-slice (≤2.5 mm) baseline noncontrast computed tomography and computed tomography angiography from the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) were included. Thrombus annotation was performed manually on coregistered scans by experienced readers. We assessed thrombus location, distance from internal carotid artery terminus, length, perviousness, absolute attenuation, and hyperdense artery sign. In addition, we evaluated balloon guide catheter use during EVT, first-line EVT approach, the number of thrombectomy passes, and prior intravenous thrombolysis administration. DE was defined as the occurrence of emboli distal to the target artery or in new territories during EVT. The association between thrombus characteristics, treatment details, and DE was evaluated using descriptive statistics and multivariable mixed-effects logistic regression, resulting in adjusted odds ratios (aOR) with 95% CI. Interaction between IVT and radiological thrombus characteristics was assessed by adding interaction terms in separate models. RESULTS: In total, 496 out of 1105 (44.9%) ESCAPE-NA1 patients were included. DE was detected in 251 out of 496 patients (50.6%). Patients with DE had longer thrombi (median, 28.5 [interquartile range, 20.8-42.3] mm versus 24.4 [interquartile range, 17.1-32.4] mm; P<0.01). There were no statistically significant differences in the other thrombus characteristics. Factors associated with DE were thrombus length (aOR, 1.02 [95% CI, 1.01-1.04]), balloon guide catheter use (aOR, 0.49 [95% CI, 0.29-0.85]), and number of passes (aOR, 1.24 [95% CI, 1.04-1.47]). In patients with hyperdense artery sign, IVT was associated with reduced odds of DE (aOR, 0.55 [95% CI, 0.31-0.97]), P for interaction=0.04. CONCLUSIONS: DE was associated with longer thrombi, no balloon guide catheter use, and more EVT passes. IVT was associated with a reduced risk of DE in patients with hyperdense artery sign. These findings may support treatment decisions on IVT and EVT approaches.

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.

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.

In silico thrombectomy trials for acute ischemic stroke.

BACKGROUND AND OBJECTIVE: In silico trials aim to speed up the introduction of new devices in clinical practice by testing device design and performance in different patient scenarios and improving patient stratification for optimizing clinical trials. In this paper, we demonstrate an in silico trial framework for thrombectomy treatment of acute ischemic stroke and apply this framework to compare treatment outcomes in different subpopulations and with different thrombectomy stent-retriever devices. We employ a novel surrogate thrombectomy model to evaluate the thrombectomy success in the in silico trial. METHODS: The surrogate thrombectomy model, built using data from a fine-grained finite-element model, is a device-specific binary classifier (logistic regression), to estimate the probability of successful recanalization, the outcome of interest. We incorporate this surrogate model within our previously developed in silico trial framework and demonstrate its use with three examples of in silico clinical trials. The first trial is a validation trial for the surrogate thrombectomy model. We then present two exploratory trials: one evaluating the performance of a commercially available device based on the fibrin composition in the occluding thrombus and one comparing the performance of two commercially available stent retrievers. RESULTS: The Validation Trial showed the surrogate thrombectomy model was able to reproduce a similar recanalization rate as the real-life MR CLEAN trial (p=0.6). Results from the first exploratory trial showed that the chance of successful thrombectomy increases with higher blood cell concentrations in the thrombi, which is in line with observations from clinical data. The second exploratory trial showed improved recanalization success with a newer stent retriever device; however, these results require further investigation as the surrogate model for the newer stent retriever device has not yet been validated. CONCLUSIONS: In this novel study, we have shown that in silico trials have the potential to help inform medical device developers on the performance of a new device and may also be used to select populations of interest for a clinical trial. This would reduce the time and costs involved in device development and traditional clinical trials.

Thrombus radiomics in patients with anterior circulation acute ischemic stroke undergoing endovascular treatment.

BACKGROUND: Thrombus radiomics (TR) describe complex shape and textural thrombus imaging features. We aimed to study the relationship of TR extracted from non-contrast CT with procedural and functional outcome in endovascular-treated patients with acute ischemic stroke. METHODS: Thrombi were segmented on thin-slice non-contrast CT (≤1 mm) from 699 patients included in the MR CLEAN Registry. In a pilot study, we selected 51 TR with consistent values across two raters' segmentations (ICC >0.75). Random forest models using TR in addition or as a substitute to baseline clinical variables (CV) and manual thrombus measurements (MTM) were trained with 499 patients and evaluated on 200 patients for predicting successful reperfusion (extended Thrombolysis in Cerebral Ischemia (eTICI) ≥2B), first attempt reperfusion, reperfusion within three attempts, and functional independence (modified Rankin Scale (mRS) ≤2). Three texture and shape features were selected based on feature importance and related to eTICI ≥2B, number of attempts to eTICI ≥2B, and 90-day mRS with ordinal logistic regression. RESULTS: Random forest models using TR, CV or MTM had comparable predictive performance. Thrombus texture (inverse difference moment normalized) was independently associated with reperfusion (adjusted common OR (acOR) 0.85, 95% CI 0.72 to 0.99). Thrombus volume and texture were also independently associated with the number of attempts to successful reperfusion (acOR 1.36, 95% CI 1.03 to 1.88 and acOR 1.24, 95% CI 1.04 to 1.49). CONCLUSIONS: TR describing thrombus volume and texture were associated with more attempts to successful reperfusion. Compared with models using CV and MTM, TR had no added value for predicting procedural and functional outcome.

Modelling collateral flow and thrombus permeability during acute ischaemic stroke.

The presence of collaterals and high thrombus permeability are associated with good functional outcomes after an acute ischaemic stroke. We aim to understand the combined effect of the collaterals and thrombus permeability on cerebral blood flow during an acute ischaemic stroke. A cerebral blood flow model including the leptomeningeal collateral circulation is used to simulate cerebral blood flow during an acute ischaemic stroke. The collateral circulation is varied to capture the collateral scores: absent, poor, moderate and good. Measurements of the transit time, void fraction and thrombus length in acute ischaemic stroke patients are used to estimate thrombus permeability. Estimated thrombus permeability ranges between 10-7 and 10-4 mm2. Measured flow rates through the thrombus are small and the effect of a permeable thrombus on brain perfusion during stroke is small compared with the effect of collaterals. Our simulations suggest that the collaterals are a dominant factor in the resulting infarct volume after a stroke.

Quantitative thrombus characteristics on thin-slice computed tomography improve prediction of thrombus histopathology: results of the MR CLEAN Registry.

OBJECTIVES: Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. METHODS: Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R2. For patients with available thin-slice (≤ 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). RESULTS: In 332 included patients, the presence of HAS (aß 7.8 [95% CI 3.9-11.7]) and shift towards a more proximal occlusion location (aß 3.9 [95% CI 0.6-7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. CONCLUSIONS: Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. KEY POINTS: • With hyperdense artery sign and occlusion location, 12% of variability in thrombus RBC content can be explained. • With hyperdense artery sign, occlusion location, and quantitative thrombus characteristics on thin-slice (≤ 2.5 mm) non-contrast CT and CTA, 30% of variability in thrombus RBC content can be explained. • Absolute thrombus density and thrombus length were the strongest predictors for thrombus composition.

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.

Value of repeated imaging in patients with a stroke who are transferred for endovascular treatment.

BACKGROUND: Patients with a stroke who are transferred to a comprehensive stroke center for endovascular treatment (EVT) often undergo repeated neuroimaging prior to EVT. OBJECTIVE: To evaluate the yield of repeating imaging and its effect on treatment times. METHODS: We included adult patients with a large vessel occlusion (LVO) stroke who were referred to our hospital for EVT by primary stroke centers (2016-2019). We excluded patients who underwent repeated imaging because primary imaging was unavailable, incomplete, or of insufficient quality. Outcomes included treatment times and repeated imaging findings. RESULTS: Of 677 transferred LVO stroke, 551 were included. Imaging was repeated in 165/551 patients (30%), mostly because of clinical improvement (86/165 (52%)) or deterioration (40/165 (24%)). Patients who underwent repeated imaging had higher door-to-groin-times than patients without repeated imaging (median 43 vs 27 min, adjusted time difference: 20 min, 95% CI 15 to 25). Among patients who underwent repeated imaging because of clinical improvement, the LVO had resolved in 50/86 (58%). In patients with clinical deterioration, repeated imaging led to refrainment from EVT in 3/40 (8%). No symptomatic intracranial hemorrhages (sICH) were identified. Ultimately, 75/165 (45%) of patients with repeated imaging underwent EVT compared with 326/386 (84%) of patients without repeated imaging (p<0.01). CONCLUSIONS: Neuroimaging was repeated in 30% of patients with an LVO stroke and resulted in a median treatment delay of 20 minutes. In patients with clinical deterioration, no sICH were detected and repeated imaging rarely changed the indication for EVT. However, in more than half of patients with clinical improvement, the LVO had resolved, resulting in refrainment from EVT.

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.

Associations of thrombus perviousness derived from entire thrombus segmentation with functional outcome in patients with acute ischemic stroke.

Thrombus perviousness is strongly associated with functional outcome and intravenous alteplase treatment success in patients with acute ischemic stroke. Accuracy of thrombus attenuation increase (TAI) assessment may be compromised by a heterogeneous thrombus composition and interobserver variations of currently used manual measurements. We hypothesized that TAI is more strongly associated with clinical outcomes when evaluated on the entire thrombus. In 195 patients, five TAI measures were performed: one manual by placing three regions of interest (TAImanual) and four automated ones assessing densities from the entire thrombus. The automated TAI measures were calculated by comparing quartiles; Q1, Q2, and Q3 of the non-contrast and contrast enhanced thrombus density distribution and using the lag of the maximum of the cross correlations (MCC). Associations with functional outcome (mRS at 90 days) were assessed with univariate and multivariable analyses. All entire TAI measures were significantly associated with functional outcome with odd ratios (OR) of 1.63(95 %CI:1.19-2.25, p = 0.003) for Q1, 1.56(95 %CI:1.16-2.10, p = 0.003) for Q2, 1.24(95 %CI:1.00-1.54, p = 0.045) for Q3, and 1.70(95 %CI:1.24-2.34, p = 0.001) for MCC per 10 HU increase in univariate models. TAImanual was not significantly associated with functional outcome (p = 0.055). In the multivariable logistic regression models including age, NIHSS, and recanalization, only TAI measures derived from the entire thrombus were independently associated with favorable outcome; OR of 1.64(95 %CI:1.01-2.66, p = 0.048) for Q2 and 1.82(1.13-2.95, p = 0.014) for MCC per 10 HU increase of thrombus attenuation. The novel perviousness measures of the entire thrombus are more strongly associated with functional outcome than the traditional manual perviousness assessments.

The first virtual patient-specific thrombectomy procedure.

Treatment of acute ischemic stroke has been recently improved with the introduction of endovascular mechanical thrombectomy, a minimally invasive procedure able to remove a clot using aspiration devices and/or stent-retrievers. Despite the promising and encouraging results, improvements to the procedure and to the stent design are the focus of the recent efforts. Computational studies can pave the road to these improvements, providing their ability to describe and accurately reproduce a real procedure. A patient with ischemic stroke due to intracranial large vessel occlusion was selected and after the creation of the cerebral vasculature from computed tomography images and a histologic analysis to determine the clot composition, the entire thrombectomy procedure was virtually replicated. As in the real situation, the computational replica showed that two attempts were necessary to remove the clot, as a result of the position of the stent retriever with respect to the clot. Furthermore, the results indicated that clot fragmentation did not occur as the deformations were mainly in a compressive state without the possibility for clot cracks to propagate. The accurate representation of the procedure can be used as an important step for operative optimization planning and future improvements of stent designs.

Endovascular treatment for calcified cerebral emboli in patients with acute ischemic stroke.

OBJECTIVE: Calcified cerebral emboli (CCE) are a rare cause of acute ischemic stroke. The authors aimed to assess the association of CCE with functional outcome, successful reperfusion, and mortality. Furthermore, they aimed to assess the effectiveness of intravenous alteplase treatment and endovascular treatment (EVT), as well as the best first-line EVT approach in patients with CCE. METHODS: The Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry is a prospective, observational multicenter registry of patients treated with EVT for acute ischemic stroke in 16 intervention hospitals in the Netherlands. The association of CCE with functional outcome, reperfusion, and mortality was evaluated using logistic regression models. Univariable comparisons were made to determine the effectiveness of intravenous alteplase treatment and the best first-line EVT approach in CCE patients. RESULTS: The study included 3077 patients from the MR CLEAN Registry. Fifty-five patients (1.8%) had CCE. CCE were not significantly associated with worse functional outcome (adjusted common OR 0.71, 95% CI 0.44-1.15), and 29% of CCE patients achieved functional independence. An extended Thrombolysis in Cerebral Infarction score ≥ 2B was significantly less often achieved in CCE patients compared to non-CCE patients (adjusted OR [aOR] 0.52, 95% CI 0.28-0.97). Symptomatic intracranial hemorrhage occurred in 8 CCE patients (15%) vs 171 of 3022 non-CCE patients (6%; p = 0.01). The median improvement on the National Institutes of Health Stroke Scale (NIHSS) was 2 in CCE patients versus 4 in non-CCE patients (p = 0.008). CCE were not significantly associated with mortality (aOR 1.16, 95% CI 0.64-2.12). Intravenous alteplase use in CCE patients was not associated with functional outcome or reperfusion. In CCE patients with successful reperfusion, stent retrievers were more often used as the primary treatment device (p = 0.04). CONCLUSIONS: While patients with CCE had significantly lower reperfusion rates and less improvement on the NIHSS after EVT, CCE were not significantly associated with worse functional outcome or higher mortality rates. Therefore, EVT should still be considered in this specific group of patients.

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.

From perviousness to permeability, modelling and measuring intra-thrombus flow in acute ischemic stroke.

Thrombus permeability determines blood flow through the occluding thrombus in acute ischemic stroke (AIS) patients. The quantification of thrombus permeability is challenging since it cannot be directly measured nor derived from radiological imaging data. As a proxy of thrombus permeability, thrombus perviousness has been introduced, which assesses the amount of contrast agent that has penetrated the thrombus on single-phase computed tomography angiography (CTA). We present a method to assess thrombus permeability rather than perviousness. We follow a three-step approach: (1) we propose a theoretical channel-like structure model describing the thrombus morphology. Using Darcy's law, we provide an analytical description of the permeability for this model. According to the channel-like model, permeability depends on the number of channels in the thrombus, the radius of the occluded artery, and the void fraction representing the volume available for the blood to flow; (2) we measure intra-thrombus blood flow and velocity on dynamic CTA; and (3) we combine the analytical model with the dynamic CTA measurements to estimate thrombus permeability. Analysis of dynamic CTA data from 49 AIS patients showed that the median blood velocity in the thrombus was 0.58 (IQR 0.26-1.35) cm/s. The median flow within the thrombus was 3.48 · 10-3 (IQR 1.71 · 10-3-9.21 · 10-3) ml/s. Thrombus permeability was of the order of 10-3-10-5 mm2, depending on the number of channels in the thrombus. The channel-like thrombus model offers an intuitive way of modelling thrombus permeability, which can be of interest when studying the effect of thrombolytic drugs.