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ObjectivesTo integrate morphological, haemodynamic and mechanical analysis of carotid atheroma driving plaque disruption.Materials and methodsFirst, 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).ResultsIn 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.ConclusionsFibrous 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.

Background As access to patient emboli is limited, embolus analogs (EAs) have become critical to the research of large vessel occlusion (LVO) stroke and the development of thrombectomy technology. To date, techniques for fabricating standardized human blood-derived EAs are limited in the variety of compositions, and the mechanical properties relevant to thrombectomy are not quantified. Methods EAs were made by mixing human banked red blood cells (RBCs), plasma, and platelet concentrate in 10 different volumetric percentage combinations to mimic the broad range of patient emboli causing LVO strokes. The samples underwent histologic analysis and tensile testing to mimic the pulling action of thrombectomy devices, and were compared to patient emboli. Results EAs had histologic compositions of 0-96% RBCs, 0.78%-92% fibrin, and 2.1%-22% platelets, which can be correlated with the ingredients using a regression model. At fracture, EAs elongated from 81% to 136%, and the ultimate tensile stress ranged from 16 to 949 kPa. These EAs’ histologic compositions and tensile properties showed great similarity to those of emboli retrieved from LVO stroke patients, indicating the validity of such EA fabrication methods. EAs with lower RBC and higher fibrin contents are more extensible and can withstand higher tensile stress. Conclusions EAs fabricated and tested using the proposed new methods provide a platform for stroke research and pre-clinical development of thrombectomy devices.

Our understanding and management of carotid artery disease has largely relied on angiography, US and MR. However, existing modalities cannot accurately identify the spectrum of thrombogenic lesions on the vascular surface or reliably detect structural markers of instability. Thus, the natural history of the different histopathological hallmarks of advanced or complicated plaques is unknown, and many patients with culprit substenotic plaques are misdiagnosed with cryptogenic stroke. An intraluminal approach to directly inspect the endovascular surfaces at unprecedented resolutions would enable detailed structural analysis of carotid plaques and the identification of the root cause of carotid-related strokes. A scanning fiber angioscope (SFA), a high-definition 1.2-mm forward-viewing camera that generates videos by spirally scanning low-power laser beams, was developed for clinical use and employed to analyze the endovascular surfaces of ex vivo human carotid arteries (n=95) and endarterectomized plaques (n=20). Specimens were then imaged with US and micro-CT, and all vascular diagnostic tests obtained in the patients undergoing carotid revascularization were accessed. Imaging findings in the vascular surfaces were then validated by histomorphological analysis of >300 lesions, and an angioscopic classifier for atherosclerosis was generated. Full-color videos at 30Hz and at a resolution >200,000 pixels were generated from the entire endovascular circumference in all specimens with depth-of-focus larger than 5cm in saline solution. The ability to analyze the surface anatomy with unparalleled detail allowed the identification of early, intermediate, advanced and complex atherosclerotic lesions, including ulceration of fibrotic cap, excavation of the necrotic core leading to pseudolumens, intimal flaps, exposed necrotic core to the lumen, erosions, recent and remote intimal hemorrhages, luminal thrombus, eruptive calcified nodules and calcified intimal sheaths and plates. SFA offers a direct view of the endoluminal surfaces with unparalleled resolution and has the potential to revolutionize research, diagnosis, prognosis and image-guided therapy in carotid atherosclerosis.

Background Context Growing rod constructs are an important contribution for treating patients with early-onset scoliosis. These devices experience high failure rates, including rod fractures. Purpose The objective of this study was to identify the failure mechanism of retrieved growing rods, and to identify differences between patients with failed and intact constructs. Study Design/Setting Growing rod patients who had implant removal and were previously enrolled in a multicenter registry were eligible for this study. Patient Sample Forty dual-rod constructs were retrieved from 36 patients across four centers, and 34 of those constructs met the inclusion criteria. Eighteen constructs failed due to rod fracture. Sixteen intact constructs were removed due to final fusion (n=7), implant exchange (n=5), infection (n=2), or implant prominence (n=2). Outcome Measures Analyses of clinical registry data, radiographs, and retrievals were the outcome measures. Methods Retrievals were analyzed with microscopic imaging (optical and scanning electron microscopy) for areas of mechanical failure, damage, and corrosion. Failure analyses were conducted on the fracture surfaces to identify failure mechanism(s). Statistical analyses were performed to determine significant differences between the failed and intact groups. Results The failed rods fractured due to bending fatigue under flexion motion. Construct configuration and loading dictate high bending stresses at three distinct locations along the construct: (1) mid-construct, (2) adjacent to the tandem connector, or (3) adjacent to the distal anchor foundation. In addition, high torques used to insert set screws may create an initiation point for fatigue. Syndromic scoliosis, prior rod fractures, increase in patient weight, and rigid constructs consisting of tandem connectors and multiple crosslinks were associated with failure. Conclusion This is the first study to examine retrieved, failed growing rod implants across multiple centers. Our analysis found that rod fractures are due to bending fatigue, and that stress concentrations play an important role in rod fractures. Recommendations are made on surgical techniques, such as the use of torque-limiting wrenches or not exceeding the prescribed torques. Additional recommendations include frequent rod replacement in select patients during scheduled surgeries.