In Vivo Risk Analysis of Pancreatic Cancer Through Optical Characterization of Duodenal Mucosa

Abstract

ObjectivesTo reduce pancreatic cancer mortality, a paradigm shift in cancer screening is needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to predict the presence of pancreatic cancer by interrogating the duodenal mucosa. A previous ex vivo study (n = 203) demonstrated excellent diagnostic potential: sensitivity, 95%; specificity, 71%; and accuracy, 85%. The objective of the current case-control study was to evaluate this approach in vivo.MethodsWe developed a novel endoscope-compatible fiber-optic probe to measure LEBS in the periampullary duodenum of 41 patients undergoing upper endoscopy. This approach enables minimally invasive detection of the ultrastructural consequences of pancreatic field carcinogenesis.ResultsThe LEBS parameters and optical properties were significantly altered in patients harboring adenocarcinomas (including early-stage) throughout the pancreas relative to healthy controls. Test performance characteristics were excellent with sensitivity = 78%, specificity = 85%, and accuracy = 81%. Moreover, the LEBS prediction rule was not confounded by patients’ demographics.ConclusionWe demonstrate the feasibility of in vivo measurement of histologically normal duodenal mucosa to predict the presence of adenocarcinoma throughout the pancreas. This represents the next step in establishing duodenal LEBS analysis as a prescreening technique that identifies clinically asymptomatic patients who are at elevated risk of PC.

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

“…3c) collected with the spatial gating probe we utilize the fact that the contribution of backscattering to the total spatially resolved reflectance decreases with the increase in source-detector separation r , significantly faster than that of the multiple scattering signal 27 . Supplementary Figure 1 shows contribution of the single large angle backscattering component and the diffuse reflectance component in epithelial tissue with a reduced scattering coefficient 49 ${\mu }_s^{\prime }=3{\text{mm}}^{-1}$ for the closest ( r 1 = 120 μm ) and farthest ( r 2 = 240 μm ) fibers in the spatial gating probe. From here it is clear that while total reflectance should be calculated as a sum of the diffuse reflectance and single large angle backscattering for the closest fiber, it can be accurately approximated with the diffuse reflectance from the farthest one alone.…”

Fully automated fiber-based optical spectroscopy system for use in a clinical setting

“…Moreover, it is important to track the wavelength calibration Journal of Biomedical Optics 075003-3 July 2018 • Vol. 23 (7) with each calibration to monitor the changing state of the spectrometers in real-time and catch hardware failures before they have a negative impact on data. Due to its characterized spectrum in the ultraviolet, visible, and near-infrared range, we chose a Hg-Ar lamp (HG-1, Ocean Optics).…”

“…In the last three decades, there have been hundreds of in vivo studies using optical spectroscopy for a myriad of applications. [1][2][3][4][5][6][7][8][9] Many of the instruments in those studies have been fiber-optic-based probes, which can be extraordinarily robust, flexible, relatively cheap, and easy to assemble. While there have been many studies showing promising results in a number of different applications, currently there are few FDA-approved fiber-based optical spectroscopy techniques, which have been implemented in a clinical setting for diagnostic applications.…”

“…LEBS is an optical spectroscopy technique that our group invented and has developed for in vivo early detection of three separate cancers. 7,8,14 LEBS is capable of measuring subdiffuse (source-detector separations less than a transport mean free path) and diffuse (source-detector separations greater than a transport mean free path) spectrally resolved backscattered light. LEBS has been described in detail in numerous other publications.…”

The potential role of optical biopsy in the study and diagnosis of environmental enteric dysfunction

“…Another potential use of reflectance spectroscopy in EED could lie in determining some of the morphological changes relevant to the disease, such as the degree of cellular infiltration or the prevalence of breaks in the epithelial monolayer. Light scattering spectroscopy [84][85][86] and low-coherence enhanced backscattering spectroscopy 87 have both been used to assess aspects of cellular and tissue morphology (in vivo in the human oesophagus, colon and duodenum) and, as such, it might be pos sible to extend these techniques to EED. Fibre-optic fluorescence spectroscopy could also be used to monitor the leakage of intravenous fluorescent dye into the gut lumen in a similar manner to that described for fluorescence endomicroscopy.…”