摘要
Histopathology relies upon the staining and sectioning of biological tissues,which can be laborious and may cause artifacts and distort tissues.We develop label-free volumetric imaging of thick-tissue slides,exploiting refractive index distributions as intrinsic imaging contrast.The present method systematically exploits label-free quantitative phase imaging techniques,volumetric reconstruction of intrinsic refractive index distributions in tissues,and numerical algorithms for the seamless stitching of multiple three-dimensional tomograms and for reducing scattering-induced image distortion.We demonstrated label-free volumetric imaging of thick tissues with the field of view of 2 mm×1.75 mm×0.2 mm with a spatial resolution of 170 nm×170 nm×1400 nm.The number of optical modes,calculated as the reconstructed volume divided by the size of the point spread function,was∼20 giga voxels.We have also demonstrated that different tumor types and a variety of precursor lesions and pathologies can be visualized with the present method.
基金
H.H.,R.H.H.,S.-M.H.,and Y.P.conceived the initial idea.H.H.developed the optical system and analysis methods.H.H.and Y.W.K.performed the experiments and analyzed the data.M.L.and S.S.provided the analysis methods and analyzed the data.All authors wrote and revised the manuscript.This work was supported by KAIST,Up Program,BK21+program,Tomocube,and National Research Foundation of Korea(2017M3C1A3013923,2015R1A3A2066550,and 2018K000396).Professor Park and Mr.Moosung Lee have financial interests in Tomocube Inc.,a company that commercializes optical diffraction tomography and quantitative phase imaging instruments and is one of the sponsors of the work.
