Cockrum, Joshua

Objectives To integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption. Materials and methods First, we analysed the phenotypes of carotid endarterectomy specimens in a photographic dataset A, and matched them with the likelihood of preoperative stroke. Second, laser angioscopy was used to further define the phenotypes in intact specimens (dataset B) and benchmark with histology. Third, representative vascular geometries for each structural phenotype were analysed with Computational Fluid Dynamics (CFD), and the mechanical strength of the complicated atheroma to resist penetrating forces was quantified (n=14). Results In dataset A (n=345), ulceration (fibrous cap disruption) was observed in 82% of all plaques, intraplaque haemorrhage in 68% (93% subjacent to an ulcer) and false luminal formation in 48%. At least one of these ‘rupture’ phenotypes was found in 97% of symptomatic patients (n=69) compared with 61% in asymptomatic patients. In dataset B (n=30), laser angioscopy redemonstrated the structural phenotypes with near-perfect agreement with histology. In CFD, haemodynamic stress showed a large pulse magnitude, highest upstream to the point of maximal stenosis and on ulceration the inflow stream excavates the necrotic core cranially and then recirculates into the true lumen. Based on mechanical testing (n=14), the necrotic core is mechanically weak and penetrated by the blood on fibrous cap disruption. Conclusions Fibrous cap ulceration, plaque haemorrhage and excavation are sequential phenotypes of plaque disruption resulting from the chiselling effect of haemodynamic forces over unmatched mechanical tissue strength. This chain of events may result in thromboembolic events independently of the degree of stenosis.

OBJECTIVE The development of new endovascular technologies and techniques for mechanical thrombectomy in stroke has greatly relied on benchtop simulators. This paper presents an affordable, versatile, and realistic benchtop simulation model for stroke. METHODS A test bed for embolic occlusion of cerebrovascular arteries and mechanical thrombectomy was developed with 3D-printed and commercially available cerebrovascular phantoms, a customized hydraulic system to generate physiological flow rate and pressure, and 2 types of embolus analogs (elastic and fragment-prone) capable of causing embolic occlusions under physiological flow. RESULTS The test bed was highly versatile and allowed realistic, radiation-free mechanical thrombectomy for stroke due to large-vessel occlusion with rapid exchange of geometries and phantom types. Of the transparent cerebrovascular phantoms tested, the 3D-printed phantom was the easiest to manufacture, the glass model offered the best visibility of the interaction between embolus and thrombectomy device, and the flexible model most accurately mimicked the endovascular system during device navigation. None of the phantoms modeled branches smaller than 1 mm or perforating arteries, and none underwent realistic deformation or luminal collapse from device manipulation or vacuum. The hydraulic system created physiological flow rate and pressure leading to iatrogenic embolization during thrombectomy in all phantoms. Embolus analogs with known fabrication technique, structure, and tensile strength were introduced and consistently occluded the middle cerebral artery bifurcation under physiological flow, and their interaction with the device was accurately visualized. CONCLUSIONS The test bed presented in this study is a low-cost, comprehensive, realistic, and versatile platform that enabled high-quality analysis of embolus–device interaction in multiple cerebrovascular phantoms and embolus analogs.

OBJECTIVE This study’s purpose was to improve understanding of the forces driving the complex mechanical interaction between embolic material and current stroke thrombectomy devices by analyzing the histological composition and strength of emboli retrieved from patients and by evaluating the mechanical forces necessary for retrieval of such emboli in a middle cerebral artery (MCA) bifurcation model. METHODS Embolus analogs (EAs) were generated and embolized under physiological pressure and flow conditions in a glass tube model of the MCA. The forces involved in EA removal using conventional endovascular techniques were described, analyzed, and categorized. Then, 16 embolic specimens were retrieved from 11 stroke patients with large-vessel occlusions, and the tensile strength and response to stress were measured with a quasi-static uniaxial tensile test using a custom-made platform. Embolus compositions were analyzed and quantified by histology. RESULTS Uniaxial tension on the EAs led to deformation, elongation, thinning, fracture, and embolization. Uniaxial tensile testing of patients’ emboli revealed similar soft-material behavior, including elongation under tension and differential fracture patterns. At the final fracture of the embolus (or dissociation), the amount of elongation, quantified as strain, ranged from 1.05 to 4.89 (2.41 ± 1.04 [mean ± SD]) and the embolus-generated force, quantified as stress, ranged from 63 to 2396 kPa (569 ± 695 kPa). The ultimate tensile strain of the emboli increased with a higher platelet percentage, and the ultimate tensile stress increased with a higher fibrin percentage and decreased with a higher red blood cell percentage. CONCLUSIONS Current thrombectomy devices remove emboli mostly by applying linear tensile forces, under which emboli elongate until dissociation. Embolus resistance to dissociation is determined by embolus strength, which significantly correlates with composition and varies within and among patients and within the same thrombus. The dynamic intravascular weakening of emboli during removal may lead to iatrogenic embolization.