Abstract
BackgroundPancreatic cancer is a lethal disease with a 5-year survival rate of only 1–5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer.Methodology/Principal FindingsIn order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow.Conclusions/SignificanceIn this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an opportunity for the characterization of the progress of spontaneous pancreatic cancer and further application in a non-invasive manner.
Highlights
Pancreatic cancer is the fourth leading cause of cancer-related mortality in the worldwide, with an overall 5-year survival rate of 1–5% [1]
We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an opportunity for the characterization of the progress of spontaneous pancreatic cancer and further application in a non-invasive manner
In order to assess the potential of the label-free two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) techniques to characterize different stages during the growth of pancreatic cancer, the subcutaneous pancreatic tumor xenografts harvested at different time points after implantation were quantitatively analyzed based on their morphological characteristics
Summary
Pancreatic cancer is the fourth leading cause of cancer-related mortality in the worldwide, with an overall 5-year survival rate of 1–5% [1]. Conclusions/Significance: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. In an effort to evaluate the feasibility of NOM for the detailed morphological characterization of pancreatic tissues, we applied label-free TPEF and SHG techniques to normal rat pancreas and related with traditional histological staining images.
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