Optical diagnosis for lung cancer using multiphoton imaging.

Currently, hematoxylin-eosin (H-E) stained histopathology is the golden standard for diagnosing lung cancer. This time-consuming procedure needs tissue biopsy, sample fixation, slicing, and labeling. Therefore, the availability of a noninvasive optical diagnosis that can obtain real-time analysis comparable to golden standard H-E stained histopathology will be of extraordinary benefit to the medical community. In this study, we investigated whether multiphoton imaging can make real-time optical diagnosis for normal and cancerous lung tissue, compared with H-E stained histopathology. In the normal lung tissue, we found that multiphoton imaging could display normal lung parenchyma composed of alveolar spaces separated by thin septa. In the cancerous lung tissue, multiphoton imaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. These cancer cells were characterized by irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic ratio. All of these histopathological features of tissue architecture and cell morphology identified by multiphoton images were readily correlated with H-E staining images. All together, multiphoton imaging can make real-time optical diagnosis for lung cancer. This study provides the groundwork for further using multiphoton imaging to perform real-time noninvasive "optical biopsy" for lung cancer in the near future.