Detection and treatment of dysplasia in Barrett’s esophagus: a pivotal challenge in translating biophotonics from bench to bedside

Abstract

Barrett's esophagus (BE) is a condition that poses high risk of developing dysplasia leading to cancer. Detection of dysplasia is a critical element in determining therapy but is extremely challenging, so that standard white-light endoscopy is used only as a means to guide biopsy. Many novel optical techniques have been aimed at this problem, including various forms of improved wide-field white-light (chromoendscopy/magnification and narrow-band) and fluorescence imaging, and "optical biopsy" techniques (diffuse reflectance, elastic light scattering, fluorescence and Raman spectroscopies, confocal microendoscopy, and optical coherence tomography). While promising, either as stand-alone modalities or in combination, to date none has solved this pivotal challenge to the point of clinical adoption. Likewise, minimally invasive treatment of BE patients with dysplasia remains suboptimal, despite recent approval of photodynamic therapy for this indication. This work presents a critique and summary of each of these biophotonic technologies, and discusses the fundamental advantages and limitations of each. The future directions for this field are considered, particularly from the perspective of relying on intrinsic (endogenous) optical signatures compared with the use of exogenous contrast agents.

Design and validation of an angle-resolved low-coherence interferometry fiber probe for in vivo clinical measurements of depth-resolved nuclear morphology

“…A number of advanced techniques have demonstrated potential as promising clinical tools in assisting physicians with timely and accurate diagnosis. [6][7][8] Light-scattering spectroscopy (LSS), 9 for instance, obtains quantitative information of nuclear morphology by extracting the singly backscattered light from epithelial layers of tissue using modeling. LSS has been shown effective for in vivo identification of precancerous cells in a variety of epithelial tissues using the population density and percentage of enlarged cell nuclei as biomarkers; [10][11][12] although, certain aspects of the approach have recently been called into question.…”

Plum pudding random medium model of biological tissue toward remote microscopy from spectroscopic light scattering

“…Given the background squared scattering amplitude (6) and (8) specified, respectively, in the fractal and Whittle-Matern models, the scattering properties originating from the background refractive fluctuation is simply determined by Eqs. (2)(3)(4). Figure 1 shows the trends of various scattering properties: the scattering coefficient μ s , the reduced scattering coefficient μ s , the anisotropy factor g ≡ 1 − μ s /μ s , and the scattering power b (μ s ∝ λ −b ) predicted by the two models.…”

“…(3,4). For most tissues, the size parameter of their core within visible and near-infrared spectral range is less than 1.245 |m c − 1| −1.725 and resides in the neighborhood of 2 |m c − 1| −1 .…”

“…Scattered light carries important information about the morphology and optical properties of the individual scatterers and can be used to identify structural alterations or heterogeneities in tissue due to disease or physiological variations [2][3][4]. The scattering and absorption properties of tissue determine light transport (such as penetration, reflection, and transmission) and energy deposition in tissue, key to both diagnostic and therapeutic applications of light.…”

Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging

“…[1][2][3][4][5][6] Numerous endoscopic applications for tracking exogenous targeted fluorescence are under investigation, such as detection and diagnosis of early cancerous lesions in Barrett's esophagus, 7 navigation and demarcation of tumor margins during brain surgery, 8,9 and detection of early neoplasia in oral tissue, 10 lung, 11 bladder, 12 and smaller gastrointestinal (GI) ducts. 13 Moreover, translational studies for first-in-human application of fluorescence molecular targets have been demonstrated in colonic dysplasia detection as well as surgical guidance for ovarian cancer.…”