C oronary heart disease is projected to remain the worldwide leading cause of death until 2030.1 Coronary heart disease is a major cause of morbidity and reduced quality of life with enormous economic consequences.2,3 Atherosclerosis, a multifocal lipid-driven inflammatory process, is the principal underlying pathology in patients with coronary heart disease, which commonly presents clinically with symptoms secondary to luminal narrowing of an epicardial coronary artery or Background-Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma. Methods and Results-D374Y-PCSK9 hypercholesterolemic minipigs (n=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately poststent, 19 weeks, and 34 weeks, and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially collected histological sections and coregistered to the distribution of each shear metric. The SMS caused a flow-limiting stenosis, and blood flow exiting the SMS caused regions of increased shear stress on the outer curvature and large regions of low and multidirectional shear stress on the inner curvature of the vessel. As a result, plaque burden was ≈3-fold higher downstream of the SMS than both upstream of the SMS and in the control artery (P<0.001). Advanced plaques were also primarily observed downstream of the SMS, in locations initially exposed to both low (P<0.002) and multidirectional (P<0.002) shear stress. Thin cap fibroatheroma regions demonstrated significantly lower shear stress that persisted over the duration of the study in comparison with other plaque types (P<0.005). Conclusions-These data support a causal role for lowered and multidirectional shear stress in the initiation of advanced coronary atherosclerotic plaques. Persistently lowered shear stress appears to be the principal flow disturbance needed for the formation of thin cap fibroatheroma. an acute coronary syndrome. The latter is a major cause of coronary heart disease death and most commonly results from rupture at the site of a thin cap fibroatheroma (TCFA) leading to coronary thrombosis. 4The precise environmental cues that lead plaques toward an advanced and high-risk phenotype are not yet fully elucidated, but disturbed blood flow is thought to play a central role in both lesion initiation and progression.5 Disturbed flow is most frequently quantified by metrics of shear stress, which is the frictional force imposed by blood flowing over the endothelial surface, and association between these metrics and coronary atherosclerotic lesion stage have been demonstrated in vivo in both animal models 6-9 and patients. 10,11 However, few studies have investigated the impact of prevalent shear co...

Functional optical coherence tomography (OCT) imaging based on the decorrelation of the intensity signal has been used extensively in angiography and is finding use in flowmetry and therapy monitoring. In this work, we present a rigorous analysis of the autocorrelation function, introduce the concepts of contrast bias, statistical bias and variability, and identify the optimal definition of the second-order autocorrelation function (ACF) g(2) to improve its estimation from limited data. We benchmark different averaging strategies in reducing statistical bias and variability. We also developed an analytical correction for the noise contributions to the decorrelation of the ACF in OCT that extends the signal-to-noise ratio range in which ACF analysis can be used. We demonstrate the use of all the tools developed in the experimental determination of the lateral speckle size depth dependence in a rotational endoscopic probe with low NA, and we show the ability to more accurately determine the rotational speed of an endoscopic probe to implement NURD detection. We finally present g(2)-based angiography of the finger nailbed, demonstrating the improved results from noise correction and the optimal bias mitigation strategies.

Hyperspectral imaging is a promising technique for resection margin assessment during cancer surgery. Thereby, only a specific amount of the tissue below the resection surface, the clinically defined margin width, should be