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

Single fiber reflectance (SFR) spectroscopy is a technique that is sensitive to small-scale changes in tissue. An additional benefit is that SFR measurements can be performed through endoscopes or biopsy needles. In SFR spectroscopy, a single fiber emits and collects light. Tissue optical properties can be extracted from SFR spectra and related to the disease state of tissue. However, the model currently used to extract optical properties was derived for tissues with modified Henyey-Greenstein phase functions only and is inadequate for other tissue phase functions. Here, we will present a model for SFR spectroscopy that provides accurate results for a large range of tissue phase functions, reduced scattering coefficients, and absorption coefficients. Our model predicts the reflectance with a median error of 5.6% compared to 19.3% for the currently used model. For two simulated tissue spectra, our model fit provides accurate results.

Cancer progression leads to changing scattering properties of affected tissues. Single fiber reflectance (SFR) spectroscopy detects these changes at small spatial scales, making it a promising tool for early in situ detection. Despite its simplicity and versatility, SFR signal modeling is hugely complicated so that, presently, only approximate models exist. We use a classic approach from geometrical probability to derive accurate analytical expressions for diffuse reflectance in SFR that shows a strong improvement over existing models. We consider the case of limited collection efficiency and the presence of absorption. A Monte Carlo light transport study demonstrates that we adequately describe the contribution of diffuse reflectance to the SFR signal. Additional steps are required to include semi-ballistic, non-diffuse reflectance also present in the SFR measurement.

Abstract. To detect small-scale changes in tissue with optical techniques, small sampling volumes and, therefore, short source-detector separations are required. In this case, reflectance measurements are not adequately described by the diffusion approximation. Previous studies related subdiffusive reflectance to γ or σ, which parameterize the phase function. Recently, it was demonstrated that σ predicts subdiffusive reflectance better than γ, and that σ becomes less predictive for lower numerical apertures (NAs). We derive and evaluate the parameter R pNA , which incorporates the NA of the detector and the integral of the phase function over the NA in the backward and forward directions. Monte Carlo simulations are performed for overlapping source/detector geometries for a range of phase functions, reduced scattering coefficients, NAs, and source/detector diameters. R pNA improves prediction of the measured reflectance compared to γ and σ. It is, therefore, expected that R pNA will improve derivation of optical properties from subdiffusive measurements. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Abstract. To accurately determine sample optical properties using single fiber reflectance spectroscopy (SFR), an absolute calibration of the reflectance is required. We investigated two SFR calibration methods, using a calibrated mirror and using the Fresnel reflection at the fiber tip as a reference. We compared these to commonly used calibration methods, using either Intralipid-20% in combination with Monte Carlo simulations or Spectralon as a reference. The Fresnel reflection method demonstrated the best reproducibility and yielded the most reliable result. We therefore recommend the Fresnel reflection method for the measured absolute reflectance calibration of SFR. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Patients with Barrett's esophagus are at an increased risk to develop esophageal cancer and, therefore, undergo regular endoscopic surveillance. Early detection of neoplasia enables endoscopic treatment, which improves outcomes. However, early Barrett's neoplasia is easily missed during endoscopic surveillance. This study investigates multidiameter single fiber reflectance spectroscopy (MDSFR) to improve Barrett's surveillance. Based on the concept of field cancerization, it may be possible to identify the presence of a neoplastic lesion from measurements elsewhere in the esophagus or even the oral cavity. In this study, MDSFR measurements are performed on non‐dysplastic Barrett's mucosa, squamous mucosa, oral mucosa, and the neoplastic lesion (if present). Based on logistic regression analysis on the scattering parameters measured by MDSFR, a classifier is developed that can predict the presence of neoplasia elsewhere in the Barrett's segment from measurements on the non‐dysplastic Barrett's mucosa (sensitivity 91%, specificity 71%, AUC = 0.77). Classifiers obtained from logistic regression analysis for the squamous and oral mucosa do not result in an AUC significantly different from 0.5.