title: Fiber-bundle microendoscopy with sub-diffuse reflectance spectroscopy and intensity mapping for multimodal optical biopsy of stratified epithelium.
abstract: Early detection of structural or functional changes in dysplastic epithelia may be crucial for improving long-term patient care. Recent work has explored myriad non-invasive or minimally invasive "optical biopsy" techniques for diagnosing early dysplasia, such as high-resolution microendoscopy, a method to resolve sub-cellular features of apical epithelia, as well as broadband sub-diffuse reflectance spectroscopy, a method that evaluates bulk health of a small volume of tissue. We present a multimodal fiber-based microendoscopy technique that combines high-resolution microendoscopy, broadband (450-750 nm) sub-diffuse reflectance spectroscopy (sDRS) at two discrete source-detector separations (374 and 730 μm), and sub-diffuse reflectance intensity mapping (sDRIM) using a 635 nm laser. Spatial resolution, magnification, field-of-view, and sampling frequency were determined. Additionally, the ability of the sDRS modality to extract optical properties over a range of depths is reported. Following this, proof-of-concept experiments were performed on tissue-simulating phantoms made with poly(dimethysiloxane) as a substrate material with cultured MDA-MB-468 cells. Then, all modalities were demonstrated on a human melanocytic nevus from a healthy volunteer and on resected colonic tissue from a murine model. Qualitative in vivo image data is correlated with reduced scattering and absorption coefficients.
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Gage J
authors.initials: GJ
authors.lastname: Greening
authors.affiliation: Department of Chemistry and Biochemistry, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Haley M
authors.initials: HM
authors.lastname: James
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Powless
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hutcheson
authors.affiliation: Department of Biological Sciences, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Dierks
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Narasimhan
authors.initials: N
authors.lastname: Rajaram
authors.affiliation: Department of Biomedical Engineering, University of Arkansas, 1 University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Muldoon
keywords: (060.2310) Fiber optics; (110.2945) Illumination design; (120.4640) Optical instruments; (170.2150) Endoscopic imaging; (170.6510) Spectroscopy, tissue diagnostics