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.

Impact of Intracranial Volume and Brain Volume on the Prognostic Value of Computed Tomography Perfusion Core Volume in Acute Ischemic Stroke.

BACKGROUND: Computed tomography perfusion (CTP)-estimated core volume is associated with functional outcomes in acute ischemic stroke. This relationship might differ among patients, depending on brain volume. MATERIALS AND METHODS: We retrospectively included patients from the MR CLEAN Registry. Cerebrospinal fluid (CSF) and intracranial volume (ICV) were automatically segmented on NCCT. We defined the proportion of the ICV and total brain volume (TBV) affected by the ischemic core as ICVcore and TBVcore. Associations between the core volume, ICVcore, TBVcore, and functional outcome are reported per interquartile range (IQR). We calculated the area under the curve (AUC) to assess diagnostic accuracy. RESULTS: In 200 patients, the median core volume was 13 (5-41) mL. Median ICV and TBV were 1377 (1283-1456) mL and 1108 (1020-1197) mL. Median ICVcore and TBVcore were 0.9 (0.4-2.8)% and 1.7 (0.5-3.6)%. Core volume (acOR per IQR 0.48 [95%CI 0.33-0.69]), ICVcore (acOR per IQR 0.50 [95%CI 0.35-0.69]), and TBVcore (acOR per IQR 0.41 95%CI 0.33-0.67]) showed a lower likelihood of achieving improved functional outcomes after 90 days. The AUC was 0.80 for the prediction of functional independence at 90 days for the CTP-estimated core volume, the ICVcore, and the TBVcore. CONCLUSION: Correcting the CTP-estimated core volume for the intracranial or total brain volume did not improve the association with functional outcomes in patients who underwent EVT.

Sex differences in clot, vessel and tissue characteristics in patients with a large vessel occlusion treated with endovascular thrombectomy.

INTRODUCTION: To improve our understanding of the relatively poor outcome after endovascular treatment (EVT) in women we assessed possible sex differences in baseline neuroimaging characteristics of acute ischemic stroke patients with large anterior vessel occlusion (LVO). PATIENTS AND METHODS: We included all consecutive patients from the MR CLEAN Registry who underwent EVT between 2014 and 2017. On baseline non-contrast CT and CT angiography, we assessed clot location and clot burden score (CBS), vessel characteristics (presence of atherosclerosis, tortuosity, size, and collateral status), and tissue characteristics with the Alberta Stroke Program Early Computed Tomography Score (ASPECTS). Radiological outcome was assessed with the extended thrombolysis in cerebral infarction score (eTICI) and functional outcome with the modified Rankin Scale score (mRS) at 90 days. Sex-differences were assessed with multivariable regression analyses with adjustments for possible confounders. RESULTS: 3180 patients were included (median age 72 years, 48% women). Clots in women were less often located in the intracranial internal carotid artery (ICA) (25%vs 28%, odds ratio (OR) 0.85;95% confidence interval: 0.73-1.00). CBS was similar between sexes (median 6, IQR 4-8). Intracranial (aOR 0.73;95% CI:0.62-0.87) and extracranial (aOR 0.64;95% CI:0.43-0.95) atherosclerosis was less prevalent in women. Vessel tortuosity was more frequent in women in the cervical ICA (aOR 1.89;95% CI:1.39-2.57) and women more often had severe elongation of the aortic arch (aOR 1.38;95% CI:1.00-1.91). ICA radius was smaller in women (2.3vs 2.5 mm, mean difference 0.22;95% CI:0.09-0.35) while M1 radius was essentially equal (1.6vs 1.7 mm, mean difference 0.09;95% CI:-0.02-0.21). Women had better collateral status (⩾50% filling in 62%vs 53% in men, aOR 1.48;95% CI:1.29-1.70). Finally, ASPECT scores were equal between women and men (median 9 in both sexes, IQR 8-10vs 9-10). Reperfusion rates were similar between women and men (acOR 0.94;95% CI:0.83-1.07). However, women less often reached functional independence than men (34%vs 46%, aOR 0.68;95% CI:0.53-0.86). DISCUSSION AND CONCLUSION: On baseline imaging of this Dutch Registry, men and women with LVO mainly differ in vessel characteristics such as atherosclerotic burden, extracranial vessel tortuosity, and collateral status. These sex differences do not result in different reperfusion rates and are, therefore, not likely to explain the worse functional outcome in women after EVT.

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.

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.

Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit.

OBJECTIVES: The beneficial effect of endovascular thrombectomy (EVT) on clinical outcome is assumed to be caused by reduced follow-up infarct volume (FIV), which could serve as an early imaging endpoint. However, the effect of EVT on the modified Rankin Scale (mRS) was poorly explained by FIV. NIHSS at 5-7 days could be a more specific measure of the effect of reperfusion therapy, as opposed to the mRS at 3 months. Therefore, we aimed to assess to what extent the effect of EVT on NIHSS is explained by FIV. MATERIALS AND METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n = 500) trial to evaluate the mediating role of FIV within 1 week in the relationship between EVT and baseline adjusted NIHSS at 5-7 days. RESULTS: Larger FIVs were associated with higher NIHSS after treatment (adjusted beta-coefficient (aß) 0.47;95%CI 0.39-0.55). EVT was associated with smaller FIVs (ß -0.35;95%CI-0.64 to -0.06) and lower NIHSS (ß -0.63;95%CI-0.90 to -0.35). After adjustment for FIV, the effect of EVT on NIHSS decreased (aß -0.47;95%CI-0.72 to -0.23), indicating that effect of EVT on neurologic deficit is partially mediated by FIV. Reduction of FIV explained 34% (95%CI;5%-93%) of the effect of EVT on the NIHSS at 5-7 days. CONCLUSIONS: Larger FIV was significantly associated with larger neurological deficits after treatment. Reduced infarct volume after EVT explains one third of treatment benefit in terms of neurological deficit. This suggests that FIV is of interest as an imaging biomarker of stroke treatment effect.

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.

Association of thrombus density and endovascular treatment outcomes in patients with acute ischemic stroke due to M1 occlusions.

PURPOSE: We aimed to study the association of non-contrast CT (NCCT) thrombus density with procedural and clinical outcomes in patients with acute ischemic stroke who underwent endovascular treatment (EVT). Since thrombus density is associated with thrombus location, we focused on M1 occlusions only. METHODS: Patients with available thin-slice (< 2.5 mm) NCCT were included from a nationwide registry. Regression models were used to assess the relation between thrombus density (per Hounsfield unit [HU]) and the following outcomes. For reperfusion grade, adjusted common odds ratios (acOR) indicated a 1-step shift towards improved outcome per HU increase in thrombus density. For the binary outcomes of first-pass reperfusion (first-pass extended thrombolysis in cerebral infarction [eTICI] 2C-3, FPR), functional independence [90-day modified Rankin Scale (mRS) score of 0-2] and mortality), aORs were reported. Adjusted ß coefficients (aß) were reported for 24-h NIHSS and procedure duration in minutes. Outcome differences between first-line treatment devices (stent retriever versus aspiration) were assessed with interaction terms. RESULTS: In 566 patients with M1 occlusions, thrombus density was not associated with reperfusion (acOR 1.01, 95% CI 0.99-1.02), FPR (aOR 1.01, 95% CI 0.99-1.03), mortality (aOR 0.98, 95% CI 0.95-1.00), 24-h NIHSS (aß - 0.7%, 95% CI - 1.4-0.2), or procedure duration (aß 0.27, 95% CI - 0.05-0.58). In multivariable analysis, thrombus density was associated with functional independence (aOR 1.02, 95% CI 1.00-1.05). No interaction was found between thrombus density and first-line treatment device for any outcome. CONCLUSION: In patients with M1 occlusions, thrombus density was not clearly associated with procedural and clinical outcomes after EVT.

Automated Final Lesion Segmentation in Posterior Circulation Acute Ischemic Stroke Using Deep Learning.

Final lesion volume (FLV) is a surrogate outcome measure in anterior circulation stroke (ACS). In posterior circulation stroke (PCS), this relation is plausibly understudied due to a lack of methods that automatically quantify FLV. The applicability of deep learning approaches to PCS is limited due to its lower incidence compared to ACS. We evaluated strategies to develop a convolutional neural network (CNN) for PCS lesion segmentation by using image data from both ACS and PCS patients. We included follow-up non-contrast computed tomography scans of 1018 patients with ACS and 107 patients with PCS. To assess whether an ACS lesion segmentation generalizes to PCS, a CNN was trained on ACS data (ACS-CNN). Second, to evaluate the performance of only including PCS patients, a CNN was trained on PCS data. Third, to evaluate the performance when combining the datasets, a CNN was trained on both datasets. Finally, to evaluate the performance of transfer learning, the ACS-CNN was fine-tuned using PCS patients. The transfer learning strategy outperformed the other strategies in volume agreement with an intra-class correlation of 0.88 (95% CI: 0.83-0.92) vs. 0.55 to 0.83 and a lesion detection rate of 87% vs. 41-77 for the other strategies. Hence, transfer learning improved the FLV quantification and detection rate of PCS lesions compared to the other strategies.

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.

Coupling one-dimensional arterial blood flow to three-dimensional tissue perfusion models for in silico trials of acute ischaemic stroke.

An acute ischaemic stroke is due to the sudden blockage of an intracranial blood vessel by an embolized thrombus. In the context of setting up in silico trials for the treatment of acute ischaemic stroke, the effect of a stroke on perfusion and metabolism of brain tissue should be modelled to predict final infarcted brain tissue. This requires coupling of blood flow and tissue perfusion models. A one-dimensional intracranial blood flow model and a method to couple this to a brain tissue perfusion model for patient-specific simulations is presented. Image-based patient-specific data on the anatomy of the circle of Willis are combined with literature data and models for vessel anatomy not visible in the images, to create an extended model for each patient from the larger vessels down to the pial surface. The coupling between arterial blood flow and tissue perfusion occurs at the pial surface through the estimation of perfusion territories. The coupling method is able to accurately estimate perfusion territories. Finally, we argue that blood flow can be approximated as steady-state flow at the interface between arterial blood flow and tissue perfusion to reduce the cost of organ-scale simulations.

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.

In-Silico Trials for Treatment of Acute Ischemic Stroke.

Despite improved treatment, a large portion of patients with acute ischemic stroke due to a large vessel occlusion have poor functional outcome. Further research exploring novel treatments and better patient selection has therefore been initiated. The feasibility of new treatments and optimized patient selection are commonly tested in extensive and expensive randomized clinical trials. in-silico trials, computer-based simulation of randomized clinical trials, have been proposed to aid clinical trials. In this white paper, we present our vision and approach to set up in-silico trials focusing on treatment and selection of patients with an acute ischemic stroke. The INSIST project (IN-Silico trials for treatment of acute Ischemic STroke, www.insist-h2020.eu) is a collaboration of multiple experts in computational science, cardiovascular biology, biophysics, biomedical engineering, epidemiology, radiology, and neurology. INSIST will generate virtual populations of acute ischemic stroke patients based on anonymized data from the recent stroke trials and registry, and build on the existing and emerging in-silico models for acute ischemic stroke, its treatment (thrombolysis and thrombectomy) and the resulting perfusion changes. These models will be used to design a platform for in-silico trials that will be validated with existing data and be used to provide a proof of concept of the potential efficacy of this emerging technology. The platform will be used for preliminary evaluation of the potential suitability and safety of medication, new thrombectomy device configurations and methods to select patient subpopulations for better treatment outcome. This could allow generating, exploring and refining relavant hypotheses on potential causal pathways (which may follow from the evidence obtained from clinical trials) and improving clinical trial design. Importantly, the findings of the in-silico trials will require validation under the controlled settings of randomized clinical trials.

Limitations of Quantitative Blush Evaluator (QuBE) as myocardial perfusion assessment method on digital coronary angiograms.

BACKGROUND AND AIM: Quantitative Blush Evaluator (QuBE) is a software application that allows quantifying myocardial perfusion in coronary angiograms after a percutaneous coronary intervention. QuBE has some limitations such as the application of a crude filter to remove large scale structures and the absence of correction for cardiac motion. This study investigates the extent of these limitations and we hypothesize that enhanced image analysis methods can provide improvements. METHODS: We calculated QuBE scores of 117 patients from the HEBE Trial and determined its association with the Myocardial Blush Grade (MBG) score. Accuracy of large-structure removal is qualitatively assessed for various sizes of a median filter. The influence of cardiac motion was evaluated by comparing the blush curve and QuBE score of the native QuBE with manually motion-corrected QuBE for 40 patients. The effect of different kernel sizes and motion correction to a potential improvement of the association between QuBE score and MBG was studied. RESULTS: In our population, there was no significant association between QuBE score and MBG (p = 0.14). Median filters of various kernel sizes were unable to remove large structure related noise. Variations in filters and cardiac movement correction did not result in an improvement in the association with MBG scores (observer 1: p = 0.66; observer 2: p = 0.72). CONCLUSIONS: There was no significant association of QuBE with MBG scores in our population, which suggests that QuBE is not suitable for a quantitative assessment of myocardial perfusion. Alternative kernel sizes for the large structure removal filter and cardiac motion correction did not improve QuBE performance. RELEVANCE FOR PATIENTS: Further improvements of QuBE to overcome its inherent limitations are necessary in order to establish QuBE as a reliable myocardial perfusion assessment method.