Rodrigues, Gabriel Martins

Background Intra-procedural characterization of stroke thromboemboli might guide mechanical thrombectomy (MT) device choice to improve recanalization rates. Electrochemical impedance spectroscopy (EIS) has been used to characterize various biological tissues in real time but has not been used in thrombus. Objective To perform a feasibility study of EIS analysis of thrombi retrieved by MT to evaluate: (1) the ability of EIS and machine learning to predict red blood cell (RBC) percentage content of thrombi and (2) to classify the thrombi as “RBC-rich” or “RBC-poor” based on a range of cutoff values of RBC. Methods ClotbasePilot was a multicentric, international, prospective feasibility study. Retrieved thrombi underwent histological analysis to identify proportions of RBC and other components. EIS results were analyzed with machine learning. Linear regression was used to evaluate the correlation between the histology and EIS. Sensitivity and specificity of the model to classify the thrombus as RBC-rich or RBC-poor were also evaluated. Results Among 514 MT,179 thrombi were included for EIS and histological analysis. The mean composition in RBC of the thrombi was 36% ± 24. Good correlation between the impedance-based prediction and histology was achieved (slope of 0.9, R 2 = 0.53, Pearson coefficient = 0.72). Depending on the chosen cutoff, ranging from 20 to 60% of RBC, the calculated sensitivity for classification of thrombi ranged from 77 to 85% and the specificity from 72 to 88%. Conclusion Combination of EIS and machine learning can reliably predict the RBC composition of retrieved ex vivo AIS thrombi and then classify them into groups according to their RBC composition with good sensitivity and specificity.

Background Several animal studies have demonstrated that mechanical thrombectomy (MT) for acute ischemic stroke (AIS) may cause vessel wall injury (VWI). However, the histological changes in human cerebral arteries following MT are difficult to determine. Objective To investigate the occurrence of VWI during MT by histological and immunohistochemical evaluation of AIS clots. Methods As part of the multicenter STRIP registry, 277 clots from 237 patients were analyzed using Martius Scarlett Blue stain and immunohistochemistry for CD34 (endothelial cells) and smooth muscle actin (smooth muscle cells). Results MT devices used were aspiration catheters (100 cases), stentriever (101 cases), and both (36 cases). VWI was found in 33/277 clots (12%). There was no significant correlation between VWI and MT device. The degree of damage varied from grade I (mild intimal damage, 24 clots), to grade II (relevant intimal and subintimal damage, 3 clots), and III (severe injury, 6 clots). VWI clots contained significantly more erythrocytes (p=0.006*) and less platelets/other (p=0.005*) than non-VWI clots suggesting soft thrombus material. Thrombolysis correlated with a lower rate of VWI (p=0.04*). VWI cases showed a significantly higher number of passes (2 [1–4] vs 1 [1–3], p=0.028*) and poorer recanalization outcome (p=0.01*) than cases without VWI. Conclusions Histological markers of VWI were present in 12% of AIS thrombi, suggesting that VWI might be related to MT. VWI was associated with soft thrombus consistency, higher number of passes and poorer revascularization outcome. There was no significant correlation between VWI and MT device.

Background and aim Mechanical thrombectomy (MT) for large vessel occlusion often requires multiple passes to retrieve the entire thrombus load. In this multi-institutional study we sought to examine the composition of thrombus fragments retrieved with each pass during MT. Methods Patients who required multiple passes during thrombectomy were included. Histopathological evaluation of thrombus fragments retrieved from each pass was performed using Martius Scarlet Blue staining and the composition of each thrombus component including RBC, fibrin and platelet was determined using image analysis software. Results 154 patients underwent MT and 868 passes was performed which resulted in 263 thrombus fragments retrieval. The analysis of thrombus components per pass showed higher RBC, lower fibrin and platelet composition in the pass 1 and 2 when compared to pass 3 and passes 4 or more combined (P values <0.05). There were no significant differences between thrombus fragments retrieved in pass 1 and pass 2 in terms of RBC, WBC, fibrin, and platelet composition (P values >0.05). Similarly, when each composition of thrombus fragments retrieved in pass 3 and passes 4 or more combined were compared with each other, no significant difference was noted (P values >0.05). Conclusion Our findings confirm that thrombus fragments retrieved with each pass differed significantly in histological content. Fragments in the first passes were associated with lower fibrin and platelet composition compared to fragments retrieved in passes three and four or higher. Also, thrombus fragments retrieved after failed pass were associated with higher fibrin and platelet components.

Background and Purpose: The hypoperfusion intensity ratio (HIR) is a perfusion-weighted imaging parameter defined as the ratio of Tmax>10 seconds : Tmax>6 seconds volume and is believed to be reflective of collateral strength and consequently influence infarct growth. We sought to assess the utility of the HIR in predicting infarct growth in patients undergoing thrombectomy at a comprehensive stroke center (CSC). Methods: Consecutive acute ischemic stroke patients transferred to our CSC from 09/2010-11/2018 were identified and included if the following criteria were met: 1)computed tomography perfusion (CTP) imaging enabling assessment of baseline ischemic core volume and HIR 2) follow-up neuroimaging for assessment of final infarct volumes and 3)modified Thrombolysis In Cerebral Infarction scale (mTICI) 2c status or greater post-thrombectomy. Infarct growth rate (IGR) was calculated as the difference between infarct volume on follow-up imaging and the acute DWI lesion volume, divided by time from CTP to reperfusion in hours. Results: 461 patients (median age, 64 [55-75] years, median baseline NIHSS, 16 [12-21]) were eligible for this analysis. HIR poorly correlated with IGR (Spearman’s rho=0.001, p=0.89). An HIR cut-off of 0.5 was not able to discriminate ‘fast progressors’ (IGR>5 mL/hr) (AUC 0.42, sensitivity 40%, specificity 51%), or IGR at thresholds of either 2.5 or 10 mL/hr (AUC 0.44 and 0.49 respectively, with 95% confidence intervals [0.35-0.52] and [0.41-0.57], respectively). Similarly, an HIR of 0.5 only weakly distinguished ‘fast progression’ in patients reperfused beyond 120 min from imaging and patients with early CTP (last known well to CTP<6 hrs) (AUC 0.59, sensitivity 43%, specificity 68% and AUC 0.50, sensitivity 45%, specificity 55%). On multiple regression analysis, HIR was not predictive of infarct growth (regression equation=18.09+8.48x, F=2.46, p=0.11, R 2 =0.13) but was predictive of ‘fast progression’ (OR 0.22, 95% CI [0.09-0.60], p=0.003, pseudo-R 2 =0.16). Conclusions: Though predictive of fast progression, the HIR is a poor discriminator of infarct growth in successfully reperfused thrombectomy patients who undergo perfusion imaging at a CSC, and thus should not be factored into treatment decision-making.