In Vitro Analysis of the Efficacy of Endovascular Thrombectomy Techniques according to the Vascular Tortuosity Using 3D Printed Models

DISCUSSION

The current in vitro study shows that the tortuosity of the cerebral vessels may impact the outcome of EVT techniques. The efficacy of EVT was inferior in the tortuous anatomy compared with the nontortuous anatomy irrespective of the techniques used. We found that both CA and SR techniques with proximal flow arrest showed acceptable FPE and DE results in the nontortuous anatomy. On the other hand, in the tortuous anatomy model showing severe angulations, the application of the CA technique was more effective in achieving better FPE and DE results than other techniques. The combined technique failed to show its effectiveness in terms of the FPE and DE in both the nontortuous and tortuous anatomy models.

In our experiment, CA showed the best FPE achievement with no DE in the nontortuous anatomy. It also showed relatively favorable FPE and DE results (FPE, 80%; DE, 20%) in the tortuous model. Many studies have reported that the CA technique shows angiographic and clinical outcomes comparable with those of conventional SR.^2,14 However, in a real-world patient, whether to pursue CA in the face of a tortuous anatomy or switch early to another technique may be a dilemma. Our in vitro study suggests that CA may be preferred in terms of improving the FPE and preventing DE in the tortuous anatomy scenario. Our analysis showed that complete ingestion of the thrombus was the main reason for the better results of CA in the tortuous anatomy. When the thrombus was completely ingested into the catheter lumen, DE did not occur. Arslanian et al¹⁵ also reported the positive effects of CA on FPE and DE when the clot was completely ingested into the catheter lumen. On the other hand, Madjidyar et al¹⁶ showed, with a flow model study, that the likelihood of DE increased when the thrombus was clogged without being completely ingested into the catheter tip.

Our results also showed that the thrombus fragmentation could occur when the catheter tip was clogged with a long segment of the thrombus outside the catheter tip. The catheter-clogged thrombus remaining outside the catheter failed to remain intact due to the friction with the vessel wall, especially when deflection and straightening of the catheter tip occurred while passing through the angled curvature. According to Alverne et al,¹⁷ the retraction force of the thrombectomy devices can be physically reduced as it disperses through the different vectors in the tortuous vessels. Bernava et al¹⁸ showed that the angle of interaction between the aspiration catheter tip and the thrombus also influences the thrombectomy efficacy at MCA branches in an in vitro study. In this regard, larger inner-diameter aspiration catheters capable of complete ingestion of the clot may be the best solution for patients with severely tortuous vascular anatomy.¹⁹ However, despite the in vitro advantages of CA clot retrieval in the tortuous anatomy shown in this experiment, the tortuous anatomy may preclude fast and safe navigation of the aspiration catheter to the occlusion site in real-world patients. Development of more flexible and soft-tipped aspiration catheters with larger inner diameters is warranted.

The FPE and DE rates were 80.0% and 20.0%, respectively, in the nontortuous anatomy model when the SR technique was used with a BGC. In the tortuous anatomy model, the FPE rate decreased (40.0%) and DE was observed with a higher incidence (60.0%). The mechanisms of thrombectomy failure with the SR has been reported in several studies.^20,21 Insufficient thrombus integration into the stent strut and thrombus rolling between the vessel wall and the strut are known to be common mechanisms and were observed in our analysis as well.²⁰ Elongation and collapse of the device was observed in several cases of our tortuous anatomy model. The integrated thrombus was dislodged from the stent lumen at these collapsed segments. It has been reported that the elongation and collapse of the SR mesh may occur in curved and angulated segments.^21,22 Also, the longer retrieval length of the SR due to the tortuous anatomy is thought to be associated with failure of thrombus retrieval. The physical elongation and collapse of the stent together with the increased length of the retrieval from the M1 to the cervical ICA in the severely angulated vessel may be the cause of the poor performance of SR in these cases. Considering these mechanisms of thrombectomy failure shown in this study, SR may be a suboptimal technique, especially in patients with a tortuous vascular anatomy. A longer length of the SR may be an alternative option. Recent introduction of many new SRs with modified structures such as segmented/hybrid design, dual-layer, and closed-end structures of the device may show improvement in the outcome.^23-26

Although a synergistic effect of the combined method may have been expected, our results show that there was no obvious advantage in achieving FPE and reducing DE compared with other techniques (Table 1). Rather, the FPE rate was quite low, especially in the tortuous anatomy (20%). Several SR-aspiration catheter combination thrombectomy techniques have been studied.^7,27 Prior reports have reported that these combination techniques may be effective in improving the recanalization rate and reducing the distal embolization compared with single-device techniques.²⁸ However, Yoo et al²⁹ reported that when the SR was retrieved inside the aspiration catheter, there could be a risk of shearing off the thrombus between the aspiration catheter tip and thrombus-engaged SR. McTaggart et al³⁰ emphasized the importance of appropriate tension adjustments to prevent shearing of the clot from the length mismatch of the SR and the aspiration catheter during retrieval. This shearing-off phenomenon may be difficult to visualize during the real-world patient treatment. However, the analysis of our study revealed that as the SR is retrieved into the tip of aspiration catheter, shearing off or squeezing out of the noningested thrombus occurs followed by fragmentation. This phenomenon was more pronounced in cases of tortuous curves where control of the length and tension mismatch between the stent and the aspiration catheter may be more difficult during retrieval.

Also, the stent struts may actually pin the clot to the vessel wall and interfere in the ingestion process of the thrombus by the CA catheter. Recently, Koge et al³¹ reported that the combined method showed more superior FPE results than in the SR and CA groups in the nontortuous ICA curve group, but the superiority was lost in the tortuous curve group. This finding seems to partly contradict our experimental results, which showed no superiority of the combined method in both the nontortuous and the tortuous models. Our analysis suggests that the shearing-off phenomenon is associated with not only vascular tortuosity but also multiple other factors. Our experiment included only M1 occlusions, but Okuda et al³² showed that the efficacy of the combined method may be influenced by the location of the occlusion, ie, it is more effective in ICA and M2 occlusions. Another concern of the combined method in the tortuous anatomy may be the safety of the procedure. Although the tensile force for retrieval of the devices was not analyzed in our study, more force was often necessary to retrieve the aspiration catheter and stent retriever together, probably due to the higher friction related to the combined use of the devices.

This study has some limitations inherently related to the in vitro nature of the experiment. Although the main arterial flow and its arrest with the BGC were simulated, the effects of the collateral flow on the thrombus could not be completed replicated. Other limitations include the endothelium and the coagulation factors and their effects on the friction and tension of the actual vessel wall. Also, only 1 type of red blood cell–rich thrombus analog and single models of the nontortuous and tortuous vascular anatomy were used. Another limitation is that although video recordings were used, the thrombectomy failure mechanisms could not be identified in some of the experiments; thus, quantitative analysis was not performed. The angle of the video recording was not optimal to visualize and identify the exact mechanism in some of the cases.

On the other hand, the major strength of this study is the anatomic simulation of the real human vasculature. Various model studies have attempted to simulate the real human cerebrovascular anatomy. Animal experiments may simulate relatively angulated vascular anatomy, but the anatomy and blood vessel size are different from those of actual human arteries. Fabrications of silicone or glass tubes may allow angulated and tortuous curvature models. However, this procedure also has limitations in simulating the actual curvature of human blood vessels. Flow-model production using 3D printing has the advantage of being able to accurately depict the cerebrovascular structure of a real patient. Furthermore, with a transparent material, the mechanisms of the device-thrombus-anatomic interaction can be directly observed. More diverse experiments such as the impact of the different histologic clot components and the efficacy of various devices/techniques in various models should be the subject of future studies.