Association between Rectal Optical Signatures and Colonic Neoplasia: Potential Applications for Screening

Abstract

Field carcinogenesis detection represents a promising means for colorectal cancer (CRC) screening, although current techniques (e.g., flexible sigmoidoscopy) lack the requisite sensitivity. The novel optical technology low-coherence enhanced backscattering (LEBS) spectroscopy, allows identification of microscale architectural consequences of the field carcinogenesis in preclinical CRC models with unprecedented accuracy. To investigate the potential clinical translatability of this approach, we obtained biopsies from the normalappearing rectal mucosa from patients undergoing colonoscopy (n = 219). LEBS signals were recorded through a bench-top instrument. Four parameters characterizing LEBS signal were linearly combined into a single marker. We found that LEBS signal parameters generally mirrored neoplasia progression from patients with no neoplasia, to 5 to 9 mm adenoma and to advanced adenomas. The composite LEBS marker calculated from the LEBS signal paralleled this risk status (ANOVA P < 0.001). Moreover, this was independent of CRC risk factors, benign colonic findings, or clinically unimportant lesions (diminutive adenomas, hyperplastic polyps). For advanced adenomas, the LEBS marker had a sensitivity of 100%, specificity of 80%, and area under the receiver operator characteristic curve of 0.895. Leave-oneout cross-validation and an independent data set (n = 51) supported the robustness of these findings. In conclusion, we provide the first demonstration that LEBS-detectable alterations in the endoscopically normal rectum were associated with the presence of neoplasia located elsewhere in the colon. This study provides the proof of concept that rectal LEBS analysis may potentially provide a minimally intrusive CRC screening technique. Further studies with an endoscopically compatible fiber optic probe are under way for multicenter clinical validation. [Cancer Res 2009;69(10):4476-83]

Measurement of optical scattering properties with low-coherence enhanced backscattering spectroscopy

“…These parameters have been found to have diagnostic value for the detection of colon, pancreatic, and skin cancer. 20,[47][48][49] In this section, we will discuss the dependence of these parameters on the optical properties l * s , g, and m. Several inverse models for the calculation of these optical properties are presented in Sec. 5.…”

“…LEBS spectroscopy has previously been shown to have promise for the detection of several types of epithelial cancers. 14,19,20 These studies have shown that LEBS parameters such as the peak width, enhancement factor, and spectral dependence have diagnostic potential for cancer detection. The aim of this work is to relate the measured LEBS parameters (width, enhancement factor, and spectral dependence) to the optical properties of the scattering media.…”

Network signatures of nuclear and cytoplasmic density alterations in a model of pre and postmetastatic colorectal cancer

“…These strategies include light scattering spectroscopy, 4,5 angle-resolved low coherence interferometry, 6,7 Raman spectroscopy, 8,9 diffuse optical spectroscopy, 10 partial wave spectroscopic (PWS) microscopy, 11,12 low-coherence enhanced backscattering, 12,13 quantitative phase microscopy, [14][15][16] and noninterferometric quantitative phase microscopy (NIQPM). 17 Cellular level observations of cancerous cells enabled by these technologies include an increase in subcellular constituent size, 4,5,7,13,14,17,18 changes in density, 7,14,17,18 alterations of the organization of this density to a more inhomogeneous state, 12,14,18 alterations in cellular metabolism, 10 and changes in biochemical composition 8 including higher concentrations of nuclear acids. 9 To date, label-free optical studies undertaking a detailed analysis of cellular physical properties in the context of cancer have been focused on measuring single parameters to establish one-dimensional biophysical signatures of cellular and/or tissue alterations due to cancer.…”

Open source software for electric field Monte Carlo simulation of coherent backscattering in biological media containing birefringence

“…17,18 Combining these sensitivities with the ability to selectively interrogate different layers of tissue through implementation of a partial spatial coherence source, CBS has become a promising technique for the characterization and detection of colorectal and pancreatic cancers. 19,20 In order to accurately characterize a tissue sample using CBS, it is necessary to understand the dependencies of the peak shape on tissue structural composition. While various analytical formalisms have been developed to describe the CBS peak shape for different sample properties, each of these calculations rely on simplifying assumptions (e.g., scalar approximation 21 or double scattering 22 ) which cannot fully describe the complex sensitivities of the CBS peak.…”