title: Multimodal non-linear optical imaging for label-free differentiation of lung cancerous lesions from normal and desmoplastic tissues.
abstract: Lung carcinoma is the leading cause of cancer-related death in the United States, and non-small cell carcinoma accounts for 85% of all lung cancer cases. One major characteristic of non-small cell carcinoma is the appearance of desmoplasia and deposition of dense extracellular collagen around the tumor. The desmoplastic response provides a radiologic target but may impair sampling during traditional image-guided needle biopsy and is difficult to differentiate from normal tissues using single label free imaging modality; for translational purposes, label-free techniques provide a more promising route to clinics. We thus investigated the potential of using multimodal, label free optical microscopy that incorporates Coherent Anti-Stokes Raman Scattering (CARS), Two-Photon Excited AutoFluorescence (TPEAF), and Second Harmonic Generation (SHG) techniques for differentiating lung cancer from normal and desmoplastic tissues. Lung tissue samples from patients were imaged using CARS, TPEAF, and SHG for comparison and showed that the combination of the three non-linear optics techniques is essential for attaining reliable differentiation. These images also illustrated good pathological correlation with hematoxylin and eosin (H&E) stained sections from the same tissue samples. Automated image analysis algorithms were developed for quantitative segmentation and feature extraction to enable lung tissue differentiation. Our results indicate that coupled with automated morphology analysis, the proposed tri-modal nonlinear optical imaging technique potentially offers a powerful translational strategy to differentiate cancer lesions reliably from surrounding non-tumor and desmoplastic tissues.
authors.affiliation: Systems Medicine and Bioengineering Department, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas 77030 USA ; Authors contributed equally to this work.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Xu
authors.affiliation: Systems Medicine and Bioengineering Department, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas 77030 USA ; Authors contributed equally to this work.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas 77030 USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thrall
authors.affiliation: Systems Medicine and Bioengineering Department, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas 77030 USA ; School of Optoelectronics, Beijing Institute of Technology, Beijing, China.
authors.forename: Zhengfan
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Systems Medicine and Bioengineering Department, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas 77030 USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Systems Medicine and Bioengineering Department, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, Texas 77030 USA ; Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas 77030 USA ; Department of Radiology, Houston Methodist Hospital, Weill Cornell Medical College, Houston, Texas 77030 USA.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
keywords: (170.2520) Fluorescence microscopy; (170.3880) Medical and biological imaging; (170.4580) Optical diagnostics for medicine; (190.1900) Diagnostic applications of nonlinear optics; (270.4180) Multiphoton processes; (300.6230) Spectroscopy, coherent anti-Stokes Raman scattering