Quantitative optical biomarkers of lung cancer based intrinsic two-photon excited fluorescence signal

Alterations in the elastic fibers have been implicated in lung cancer. However, the label-free, microscopic imaging of elastic fibers in situ remains a major challenge. Here, we present the use of intrinsic two-photon excited fluorescence (TPEF) signal as a novel means for quantification of the elastic fibers in intact fresh human lung tissues. We obtained the TPEF images of elastic fibers from ex vivo the human lung tissues. We found that three features, including the elastic fibers area, the elastic fibers orientation, the elastic fibers structure, provide the quantitative identification of lung cancer and the direct visual cues for cancer versus non-cancer areas. These results suggest that the TPEF signal can be used as the label-free optical biomarkers for rapid clinical lung diagnosis and instant image-guided surgery.

[1]  Masao Nakata,et al.  Surgical treatments for multiple primary adenocarcinoma of the lung. , 2004, The Annals of thoracic surgery.

[2]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[3]  Raghu Kalluri,et al.  Fibroblasts in cancer , 2006, Nature Reviews Cancer.

[4]  W. Webb,et al.  Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  B R Masters,et al.  Two-photon excitation fluorescence microscopy. , 2000, Annual review of biomedical engineering.

[6]  Rong Chen,et al.  The layered–resolved microstructure and spectroscopy of mouse oral mucosa using multiphoton microscopy , 2007, Physics in medicine and biology.

[7]  Shuangmu Zhuo,et al.  Quantitatively linking collagen alteration and epithelial tumor progression by second harmonic generation microscopy , 2010 .

[8]  L. Coussens,et al.  Tumor stroma and regulation of cancer development. , 2006, Annual review of pathology.

[9]  M. Sporn,et al.  Recent advances in chemoprevention of cancer. , 1997, Science.

[10]  Shuangmu Zhuo,et al.  Extracting diagnostic stromal organization features based on intrinsic two-photon excited fluorescence and second-harmonic generation signals. , 2009, Journal of biomedical optics.

[11]  Jun Nagata,et al.  Multiphoton imaging can be used for microscopic examination of intact human gastrointestinal mucosa ex vivo. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[12]  Shuangmu Zhuo,et al.  Label-free and real-time imaging of dehydration-induced DNA conformational changes in cellular nucleus using second harmonic microscopy , 2014, Scientific Reports.

[13]  Shuangmu Zhuo,et al.  Depth-cumulated epithelial redox ratio and stromal collagen quantity as quantitative intrinsic indicators for differentiating normal, inflammatory, and dysplastic epithelial tissues , 2010 .

[14]  Shuangmu Zhuo,et al.  Multimode nonlinear optical imaging of the dermis in ex vivo human skin based on the combination of multichannel mode and Lambda mode. , 2006, Optics express.

[15]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[16]  Francesco S Pavone,et al.  Time- and Spectral-resolved two-photon imaging of healthy bladder mucosa and carcinoma in situ. , 2010, Optics express.