392 A Morphological Study of Non-Stenotic Carotid Atheromas Causing Recurrent Strokes: Chronicle of Disruption and Stabilization

Abstract

INTRODUCTION: Symptomatic non-stenotic carotid (SyNC) artery disease is a recognized etiology of ischemic strokes with a putative thromboembolic mechanism. To date, the structural phenotypes expressed at the lumen/wall interface of these lesions are not completely understood resulting in misdiagnosis and hindering the development of targeted therapies. METHODS: After IRB approval, en block endarterectomy specimen were obtained from patients with recurrent strokes from SyNC (n=9). Additionally, segments of superficial temporal artery (STA) of patients undergoing cerebral artery bypass surgeries were obtained as controls (n=3). The endovascular surfaces of the samples were imaged with laser microangioscopy and scanning electron microscopy (SEM). Images were benchmarked with histological sections and immunohistochemistry (IHC). RESULTS: Normal endothelial surfaces in STA were light pink, smooth and homogenous by angioscopy with typical cobblestone endothelial pattern. Features recognized as those associated with plaque disruption and thrombosis were de-endothelialization, inflammatory infiltrates within and under the endothelium, delamination (flaps oriented to the flow) with superficial intimal hemorrhages, plaque erosion and disruption of the fibrous cap with fissuring, ulceration, excavation and plaque hemorrhage. Additionally, cellular and acellular structures actively involved in plaque stabilization, seen on SEM and confirmed with histology and IHC, were also identified including activated platelets, fibrin band, bridges and webs, neutrophil extracellular traps and endothelial progenitor cells. CONCLUSIONS: This ultrastructural study of the vascular surface of SyNC specimens reveals concurrent phenotypes of flow-dependent disruption and stabilization that could become new imaging biomarkers and enable the development of targeted therapies.