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.
Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in ...selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues. Clot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&E staining. The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (>90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178-1624 kPa) than the stiffness of the RBC-rich clots (6-526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89-96%) compared to the RBC-rich clots (11-77%). CT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.
Background It has been suggested that selection of a first‐line endovascular thrombectomy device, that is, contact aspiration (CA) or stent retriever (SR) thrombectomy, could be based on thrombus ...type. Thrombus composition and mechanical behavior can partially be predicted with thrombus computed tomography (CT) characteristics. We aimed to assess the influence of thrombus CT characteristics on the association between first‐line device and outcomes of endovascular thrombectomy. Methods For patients enrolled in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) Registry between March 2014 and November 2017, we assessed thrombus density, thrombus length, and presence of hyperdense artery sign on thin‐slice (≤2.5 mm) admission CT. We used regression models to estimate the relationship between first‐line endovascular thrombectomy device (CA versus stent retriever) and first‐pass reperfusion (FPR, expanded Thrombolysis in Cerebral Infarction score 2C‐3 after first attempt), final reperfusion, procedure duration, 24‐hour National Institutes of Health Stroke Scale, and 90‐day modified Rankin scale score and tested for interaction of thrombus characteristics with first‐line device by adding interaction terms. Results Of 703 included patients, 520 (74%) received first‐line stent retriever and 183 (26%) first‐line CA. Overall, the first‐line device was not associated with FPR (adjusted odds ratio aOR, 1.32 95% CI, 0.88–1.98). In patients with thrombus density below the median (<50 Hounsfield units), FPR was more often achieved with CA than with a stent retriever (34% versus 24%, aOR, 1.95 95% CI, 1.09–3.50), whereas in patients with thrombus density above the median (≥50 Hounsfield units), first‐line device was not associated with FPR (aOR, 0.90 95% CI, 0.50–1.62). The interaction between thrombus density as a continuous variable and first‐line device on outcome was not significant ( P =0.38). There was also no interaction between first‐line device and the other thrombus characteristics for FPR or the other outcomes. Conclusion Our study does not provide evidence that the association between first‐line thrombectomy device and endovascular thrombectomy outcomes depends on thrombus CT characteristics. Based on our results, there are no arguments for thrombectomy device selection based on thrombus CT characteristics. A possible better performance of CA in low‐density, fibrin‐rich clots needs further study.
Background Contrary to anterior circulation stroke, studies on the association between thrombus imaging characteristics and outcomes are scarce in patients with posterior circulation stroke (PCS). We ...aimed to investigate the association of thrombus imaging characteristics with reperfusion and functional outcome in patients with PCS who underwent endovascular treatment. Methods In patients with PCS included in the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) Registry, thrombus imaging characteristics (thrombus density and perviousness in Hounsfield Units HU and thrombus length in mm) were assessed on thin‐slice imaging (<2.5 mm). Regression models were used to assess the relation between thrombus imaging characteristics, reperfusion, functional outcome (24‐hour National Institute of Health Stroke Scale NIHSS and 90‐day modified Rankin Scale score ), and safety outcomes. Results In 118 patients with PCS, median thrombus density and perviousness were 53 HU (interquartile range IQR, 47–61 HU) and 4 HU (IQR, −5 to 12 HU), respectively. Median thrombus length was 23 mm (IQR, 15–43 mm). IV alteplase treatment was administered to 57/118 patients with PCS (48%) before endovascular treatment. Thrombus length was associated with 24‐hour NIHSS (adjusted β coefficient 1.4%; 95% CI 0.5%–2.1% increase of NIHSS per mm increase in thrombus length; P =0.002) and reperfusion (adjusted common odds ratio 0.99; 95% CI 0.97–1.00; P =0.049). None of the other thrombus imaging characteristics were associated with 24‐hour NIHSS or reperfusion. No thrombus characteristic was associated with 90‐day modified Rankin Scale score. Conclusion In our population of patients with PCS who underwent endovascular treatment, only thrombus length was associated with 24‐hour NIHSS and reperfusion. None of the thrombus imaging characteristics were associated with 90‐day functional outcome. Our findings suggest that in patients with PCS, thrombus imaging characteristics are not useful predictors for functional outcome after endovascular treatment.
Thrombus composition and mechanical properties significantly impact the ease and outcomes of thrombectomy procedures in patients with acute ischemic stroke. A wide variation exists in the composition ...of thrombi between patients. If a relationship can be determined between the composition of a thrombus and its mechanical behaviour, as well as between the composition of a thrombus and its radiological imaging characteristics, then there is the potential to personalise thrombectomy treatment based on each individual thrombus. This review aims to give an overview of the current literature addressing this issue.
Here, we present a scoping review detailing associations between thrombus composition, mechanical behaviour and radiological imaging characteristics. We conducted two searches 1) on the association between thrombus composition and the mechanical behaviour of the tissue and 2) on the association between radiological imaging characteristics and thrombus composition in the acute stroke setting.
The review suggests that higher fibrin and lower red blood cell (RBC) content contribute to stiffer thrombi independent of the loading mode. Further, platelet-contracted thrombi are stiffer than non-contracted compositional counterparts. Fibrin content contributes to the elastic portion of viscoelastic behaviour while RBC content contributes to the viscous portion. It is possible to identify fibrin-rich or RBC-rich thrombi with computed tomography and magnetic resonance imaging vessel signs. Standardisation is required to quantify the association between thrombus density on non-contrast computed tomography and the RBC content. The characterisation of the thrombus fibrin network has not been addressed so far in radiological imaging but may be essential for the prediction of device-tissue interactions and distal thrombus embolization. The association between platelet-driven clot contraction and radiological imaging characteristics has not been explicitly investigated. However, evidence suggests that perviousness may be a marker of clot contraction.
Mechanical properties of thromboemboli play an important role in the efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke. However, very limited data on mechanical properties of ...human stroke thrombi are available. We aimed to mechanically characterize thrombi retrieved with EVT, and to assess the relationship between thrombus composition and thrombus stiffness.
Forty-one thrombi from 19 patients with acute stroke who underwent EVT between July and October 2019 were mechanically analyzed, directly after EVT. We performed unconfined compression experiments and determined tangent modulus at 75% strain (Et75) as a measure for thrombus stiffness. Thrombi were histologically analyzed for fibrin/platelets, erythrocytes, leukocytes, and platelets, and we assessed the relationship between histological components and Et75 with univariable and multivariable linear mixed regression.
Median Et75 was 560 (interquartile range, 393–1161) kPa. In the multivariable analysis, fibrin/platelets were associated with increased Et75 (aβ, 9 95% CI, 5 to 13) kPa, erythrocytes were associated with decreased Et75% (aβ, −9 95% CI, −5 to −13) kPa. We found no association between leukocytes and Et75. High platelet values were strongly associated with increased Et75 (aβ, 56 95% CI, 38–73).
Fibrin/platelet content of thrombi retrieved with EVT for acute ischemic stroke is strongly associated with increased thrombus stiffness. For thrombi with high platelet values, there was a very strong relationship with thrombus stiffness. Our data provide a basis for future research on the development of next-generation EVT devices tailored to thrombus composition.
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.
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).
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.
CTP seems useful for predicting functional outcome, but cannot reliably identify patients who will not benefit from intra-arterial therapy.
Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may ...increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome.
Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Δ) and thrombus void fraction (ε). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume.
Patients with Δ≥10.9 HU (n=81 44%) and ε≥6.5% (n=77 42%) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Δ based classification, and similarly for ε. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Δ and -0.40 for ε).
This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate.
The benefit of endovascular treatment (EVT) for posterior circulation stroke (PCS) remains uncertain, and little is known on treatment outcomes in clinical practice. This study evaluates outcomes of ...a large PCS cohort treated with EVT in clinical practice. Simultaneous to this observational study, several intervention centers participated in the BASICS trial (Basilar Artery International Cooperation Study), which tested the efficacy of EVT for basilar artery occlusion in a randomized setting. We additionally compared characteristics and outcomes of patients treated outside BASICS in trial centers to those from nontrial centers.
We included patients with PCS from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry: a prospective, multicenter, observational study of patients who underwent EVT in the Netherlands between 2014 and 2018. Primary outcome was a score of 0 to 3 on the modified Rankin Scale at 90 days. Secondary outcomes included reperfusion status and symptomatic intracranial hemorrhage. For outcome comparison between patients treated in trial versus nontrial centers, we used ordinal logistic regression analysis.
We included 264 patients of whom 135 (51%) had received intravenous thrombolysis. The basilar artery was most often involved (77%). Favorable outcome (modified Rankin Scale score 0-3) was observed in 115/252 (46%) patients, and 109/252 (43%) patients died. Successful reperfusion was achieved in 178/238 (75%), and symptomatic intracranial hemorrhage occurred in 9/264 (3%). The 154 nontrial patients receiving EVT in BASICS trial centers had similar characteristics and outcomes as the 110 patients treated in nontrial centers (modified Rankin Scale adjusted cOR: 0.77 95% CI, 0.5-1.2).
Our study shows that high rates of favorable clinical outcome and successful reperfusion can be achieved with EVT for PCS, despite high mortality. Characteristics and outcomes of patients treated in trial versus nontrial centers were similar indicating that our cohort is representative of clinical practice in the Netherlands. Randomized studies using modern treatment approaches are needed for further insight in the benefit of EVT for PCS.
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