
1.Electrical and Computer Engineering Department, University of California, Los Angeles, CA 90095, USA
2.Bioengineering Department, University of California, Los Angeles, CA 90095, USA
3.California NanoSystems Institute (CNSI), University of California, Los Angeles, CA 90095, USA
4.Department of Computer Science, University of California, Los Angeles, CA 90095, USA
5.Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
Yair Rivenson (rivensonyair@ucla.edu)
Aydogan Ozcan (ozcan@ucla.edu)
Published:2020,
Published Online:06 May 2020,
Received:26 March 2020,
Revised:14 April 2020,
Accepted:15 April 2020
Scan QR Code
Zhang, Y. J. et al. Digital synthesis of histological stains using micro-structured and multiplexed virtual staining of label-free tissue. Light: Science & Applications, 9, 751-763 (2020).
Zhang, Y. J. et al. Digital synthesis of histological stains using micro-structured and multiplexed virtual staining of label-free tissue. Light: Science & Applications, 9, 751-763 (2020). DOI: 10.1038/s41377-020-0315-y.
Histological staining is a vital step in diagnosing various diseases and has been used for more than a century to provide contrast in tissue sections
rendering the tissue constituents visible for microscopic analysis by medical experts. However
this process is time consuming
labour intensive
expensive and destructive to the specimen. Recently
the ability to virtually stain unlabelled tissue sections
entirely avoiding the histochemical staining step
has been demonstrated using tissue-stain-specific deep neural networks. Here
we present a new deep-learning-based framework that generates virtually stained images using label-free tissue images
in which different stains are merged following a micro-structure map defined by the user. This approach uses a single deep neural network that receives two different sources of information as its input: (1) autofluorescence images of the label-free tissue sample and (2) a "digital staining matrix"
which represents the desired microscopic map of the different stains to be virtually generated in the same tissue section. This digital staining matrix is also used to virtually blend existing stains
digitally synthesizing new histological stains. We trained and blindly tested this virtual-staining network using unlabelled kidney tissue sections to generate micro-structured combinations of haematoxylin and eosin (H & E)
Jones' silver stain
and Masson's trichrome stain. Using a single network
this approach multiplexes the virtual staining of label-free tissue images with multiple types of stains and paves the way for synthesizing new digital histological stains that can be created in the same tissue cross section
which is currently not feasible with standard histochemical staining methods.
Titford, M. The long history of hematoxylin.Biotech. Histochem.80, 73–78 (2005)..
Alturkistani, H. A., Tashkandi, F. M.&Mohammedsaleh, Z. M. Histological stains: a literature review and case study.Glob. J. Health Sci.8, 72–79 (2016)..
Yamabayashi, S. Periodic acid-Schiff-Alcian Blue: a method for the differential staining of glycoproteins.Histochem. J.19, 565–571 (1987)..
Tao, Y. K. et al. Assessment of breast pathologies using nonlinear microscopy.Proc. Natl Acad. Sci. USA111, 15304–15309 (2014)..
Orringer, D. A. et al. Rapid intraoperative histology of unprocessed surgical specimens via fibre-laser-based stimulated Raman scattering microscopy.Nat. Biomed. Eng.1, 0027 (2017)..
Tu, H. H. et al. Stain-free histopathology by programmable supercontinuum pulses.Nat. Photonics10, 534–540 (2016)..
González, S.&Gilaberte‐Calzada, Y.In vivoreflectance-mode confocal microscopy in clinical dermatology and cosmetology.Int. J. Cosmet. Sci.30, 1–17 (2008)..
Mayerich, D. et al. Stain-less staining for computed histopathology.Technology3, 27–31 (2015)..
Yoshitake, T. et al. Rapid histopathological imaging of skin and breast cancer surgical specimens using immersion microscopy with ultraviolet surface excitation.Sci. Rep.8, 4476 (2018)..
Rivenson, Y. et al. Deep learning enhanced mobile-phone microscopy.ACS Photonics5, 2354–2364 (2018)..
Rivenson, Y. et al. Deep learning microscopy.Optica4, 1437–1443 (2017)..
Christiansen, E. M. et al. In silico labeling: predicting fluorescent labels in unlabeled images.Cell173, 792–803.e19 (2018)..
Wu, Y. C. et al. Bright-field holography: cross-modality deep learning enables snapshot 3D imaging with bright-field contrast using a single hologram.Light.: Sci. Appl.8, 25 (2019)..
de Haan, K. et al. Deep-learning-based image reconstruction and enhancement in optical microscopy.Proc. IEEE108, 30–50 (2020)..
Rivenson, Y. et al. Virtual histological staining of unlabelled tissue-autofluorescence images via deep learning.Nat. Biomed. Eng.3, 466–477 (2019)..
Rivenson, Y. et al. PhaseStain: the digital staining of label-free quantitative phase microscopy images using deep learning.Light.: Sci. Appl.8, 23 (2019)..
Borhani, N. et al. Digital staining through the application of deep neural networks to multi-modal multi-photon microscopy.Biomed. Opt. Express10, 1339–1350 (2019)..
Bulten, W.&Litjens, G. Unsupervised prostate cancer detection on H&E using convolutional adversarial autoencoders.Medical Imaging with Deep Learning(2018).
Bentaieb, A.&Hamarneh, G. Adversarial stain transfer for histopathology image analysis.IEEE Trans. Med. Imaging37, 792–802 (2018)..
Zhou, W. et al. Image quality assessment: from error visibility to structural similarity.IEEE Trans. Image Process.13, 600–612 (2004)..
Fischer, A. H. et al. Hematoxylin and eosin staining of tissue and cell sections.Cold Spring Harbor Protocols.https://doi.org/10.1101/pdb.prot4986https://doi.org/10.1101/pdb.prot4986(2008)..
Herrera, G. A.&Lott, R. L. Silver stains in diagnostic renal pathology.J. Histotechnol.19, 219–223 (1996)..
Register Multimodal MRI Images. athttps://www.mathworks.com/help/images/registering-multimodal-mri-images.htmlhttps://www.mathworks.com/help/images/registering-multimodal-mri-images.html(MathWorks, 2020).
Ronneberger, O., Fischer, P.&Brox, T. U-Net: convolutional networks for biomedical image segmentation.Proc. 18th International Conference on Medical Image Computing and Computer-Assisted Intervention(Springer, Munich, Germany, 2015).
Wada, K. labelme: Image Polygonal Annotation with Python.https://github.com/wkentaro/labelmehttps://github.com/wkentaro/labelme(2016).
0
Views
0
Downloads
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621