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.

Highlights

  • Lung cancer is the leading cause of cancer-related death in the United States

  • 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

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Summary

Introduction

Lung cancer is the leading cause of cancer-related death in the United States. In 2012, there were 226,160 projected new cases and 160,340 estimated lung cancer related deaths, accounting for 29% of cancer deaths in men and 26% of cancer deaths in women [1]. Early detection and accurate diagnosis are considered the key elements for improving long-term cancer survival rates, current routine diagnostic techniques such as computed tomography (CT) and chest radiograph are not able to distinguish malignant lung carcinoma from benign lesions such as organizing pneumonia and tuberculosis [5]. Invasive tissue biopsies are still required for pathological analysis and definitive cancer diagnosis. Because of the insufficient resolution of CT images, the respiratory motion of patients, and tumor heterogeneity, it is sometimes difficult to obtain samples precisely at the neoplastic site for pathological analysis [6]. Imaging the biopsy site prior to tissue aspiration can help reduce sampling errors and even eliminate the need for invasive tissue removal

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