Multi-contrast digital histopathology of mouse organs using quantitative phase imaging and virtual staining.

Quantitative phase imaging (QPI) has emerged as a new digital histopathologic tool as it provides structural information of conventional slide without staining process. It is also capable of imaging biological tissue sections with sub-nanometer sensitivity and classifying them using light scattering properties. Here we extend its capability further by using optical scattering properties as imaging contrast in a wide-field QPI. In our first step towards validation, QPI images of 10 major organs of a wild-type mouse have been obtained followed by H&E-stained images of the corresponding tissue sections. Furthermore, we utilized deep learning model based on generative adversarial network (GAN) architecture for virtual staining of phase delay images to a H&E-equivalent brightfield (BF) image analogues. Using the structural similarity index, we demonstrate similarities between virtually stained and H&E histology images. Whereas the scattering-based maps look rather similar to QPI phase maps in the kidney, the brain images show significant improvement over QPI with clear demarcation of features across all regions. Since our technology provides not only structural information but also unique optical property maps, it could potentially become a fast and contrast-enriched histopathology technique.

[1]  Ian Goodfellow,et al.  Generative adversarial networks , 2020, Commun. ACM.

[2]  Aydogan Ozcan,et al.  Deep learning-based transformation of H&E stained tissues into special stains , 2020, Nature Communications.

[3]  Jie Tian,et al.  Deep Learning for Virtual Histological Staining of Bright-Field Microscopic Images of Unlabeled Carotid Artery Tissue , 2020, Molecular Imaging and Biology.

[4]  Kevin de Haan,et al.  Digital synthesis of histological stains using micro-structured and multiplexed virtual staining of label-free tissue , 2020, Light: Science & Applications.

[5]  A. Ozcan,et al.  Virtual histological staining of unlabelled tissue-autofluorescence images via deep learning , 2019, Nature Biomedical Engineering.

[6]  David Mayerich,et al.  Digital Staining of High-Definition Fourier Transform Infrared (FT-IR) Images Using Deep Learning , 2019, Applied spectroscopy.

[7]  C. Depeursinge,et al.  Quantitative phase imaging in biomedicine , 2018, Nature Photonics.

[8]  A. Ozcan,et al.  PhaseStain: the digital staining of label-free quantitative phase microscopy images using deep learning , 2018, Light, science & applications.

[9]  Tan H. Nguyen,et al.  Label-free quantitative evaluation of breast tissue using Spatial Light Interference Microscopy (SLIM) , 2018, Scientific Reports.

[10]  Ellen Kuhl,et al.  The mechanical importance of myelination in the central nervous system. , 2017, Journal of the mechanical behavior of biomedical materials.

[11]  Gabriel Popescu,et al.  Label-free, multi-scale imaging of ex-vivo mouse brain using spatial light interference microscopy , 2016, Scientific Reports.

[12]  Pasquale Memmolo,et al.  Tomographic flow cytometry by digital holography , 2016, Light: Science & Applications.

[13]  Kyoohyun Kim,et al.  Label-free optical quantification of structural alterations in Alzheimer’s disease , 2016, Scientific Reports.

[14]  G. Popescu,et al.  Prediction of Prostate Cancer Recurrence Using Quantitative Phase Imaging , 2015, Scientific Reports.

[15]  Gabriel Popescu,et al.  Label-Free Characterization of Emerging Human Neuronal Networks , 2014, Scientific Reports.

[16]  Zhuo Wang,et al.  Optical measurement of cycle-dependent cell growth , 2011, Proceedings of the National Academy of Sciences.

[17]  Yongkeun Park,et al.  Refractive index maps and membrane dynamics of human red blood cells parasitized by Plasmodium falciparum , 2008, Proceedings of the National Academy of Sciences.

[18]  Gabriel Popescu,et al.  Observation of dynamic subdomains in red blood cells. , 2006, Journal of biomedical optics.

[19]  Gabriel Popescu,et al.  Erythrocyte structure and dynamics quantified by Hilbert phase microscopy. , 2005, Journal of biomedical optics.