Fiber-bundle microendoscopy with sub-diffuse reflectance spectroscopy and intensity mapping for multimodal optical biopsy of stratified epithelium

• Published in: Biomedical optics express Vol. 6; no. 12; pp. 4934 - 4950
• Main Authors: Greening, Gage J, James, Haley M, Powless, Amy J, Hutcheson, Joshua A, Dierks, Mary K, Rajaram, Narasimhan, Muldoon, Timothy J
• Format: Journal Article
• Language: English
• Published: United States Optical Society of America 01.12.2015
• Subjects: (170.6510) Spectroscopy, tissue diagnostics; (060.2310) Fiber optics; (110.2945) Illumination design; (170.2150) Endoscopic imaging; (120.4640) Optical instruments
• ISSN: 2156-7085; 2156-7085
• DOI: 10.1364/BOE.6.004934

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.