Unifying theory of carotid plaque disruption based on structural phenotypes and forces expressed at the lumen/wall interface

Morphological analysis of plaque phenotypes contextualised to individualised haemodynamic conditions. Plaque ulcerations (A1) were identified as full thickness discontinuity of the fibrous cap of the atheroma per angioscopy (A2) and remained occult to CTA (arrowhead in (A3) points the approximate location of the ulcer identified per angioscopy in (A2)). CFD simulations revealed a region of local high dynamic pressure directed into the plaque in the same region of the ulcer ((A4) and arrowhead in insert). Blind-ended false luminal formation (FLF) (B1) was identified by SFE angioscopy as a crater excavating the atheroma from an ulcerative region generally associated with haematomas (arrowhead in (B2)). These excavations in the atheroma corresponded to deep surface irregularities in CTA (arrowhead in (B3)). CFD simulation in FLF demonstrated a region of local high dynamic pressure directed cranially ((B4) and arrowhead in insert). In shallow excavations, the jet of blood chisels the plaque core with high dynamic pressure (B5) and following a vigorous stream vortex (B6). In deeper excavations, the dynamic pressure of the blood significantly tapers off toward the apex of the crater (arrowhead in (B7)) and the jet of blood becomes slow and disorganised with stagnation towards the apex of the excavation (B8). Fenestrated FLF (C1) was identified per angioscopy as deep and broad excavations, usually parallel to the true lumen, with one or more opening communicating the false with the true lumen (arrowheads in (C2)). False lumens running through atheroma were also identified in CTA (inlet and outlet with arrowheads, point of maximal stenosis with asterisk in (C3)). In these cases, CFD simulation revealed localised regions of high dynamic pressure within the plaque’s FLF with maximal stress over the remaining fibrous cap from both the luminal and pseudoluminal surfaces (yellow and black arrowheads, respectively, in (C4)). Plaque haematomas (D1) were generally exposed at the lumen/wall interface and their geographic distribution and thrombus type readily identified by angioscopy (D2). Plaque haematomas frequently had an intraluminal extension with cranial propagation into the internal carotid artery (ICA) (arrowhead in a CTA in (D3)). In cases of critical stenosis, CFD simulation revealed a region of high dynamic pressure at the POMS with propagation to one side of the arterial wall circumference and minimal haemodynamic stress in the opposite side (arrowheads point high stress at the POMS and downstream in (D4)). As the flow passes through the narrowed luminal corridor, it is directed towards one side of the arterial lumen leaving the opposite side in relative stagnation, which favours clot formation (arrowheads in (D5)). Atheroma subcomponent in (A1–D1) are color coded: white for fibrous cap, light blue for calcified tissue, grey for necrotic core and red for thrombus. Refer to the online supplemental videos for the dynamic colour bars of the contour map of the CFD. ECA, external carotid artery.

Mechanical testing of atherosclerotic components of carotid plaques: needle penetration tests of atheroma was conducted in a custom-made platform (blue dots in (A) corresponds to insertion points in atheroma). The position of the needle and force data were recorded at a frequency of at 50 Hz and then datasets correlated with the corresponding atheroma cross section (dotted rectangle in (A) and cross section in (B)). Tissue correlation was refined by histological analysis of the atheroma section (note: blue trajectory of needle in (B) and corresponding histological cut in (C)). The number of cutting force datapoints, the mean cutting force and SD among the datapoints for each arterial and atherosclerotic component were calculated (D). The tissues analysed in the cohort (E–F) were: fibrous cap (FC), necrotic core (NC), thrombus (T), fibrotic intima (FI), calcification speckled (CS), calcification dense (CD) and tunica media (TM). Cutting force curves with histological correlation of representative advanced and complicated carotid atherosclerosis (complex atherothrombotic lesion in (G) and partially calcified in (H), thromboatheroma in (I) and calcified fibroatheroma in (J)) are presented (dotted yellow arrow in (C) and (G–J) indicates pathway of the needle).