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Graph-regularized 3D shape reconstruction from highly anisotropic and noisy images

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Abstract

Analysis of microscopy images can provide insight into many biological processes. One particularly challenging problem is cellular nuclear segmentation in highly anisotropic and noisy 3D image data. Manually localizing and segmenting each and every cellular nucleus is very time-consuming, which remains a bottleneck in large-scale biological experiments. In this work, we present a tool for automated segmentation of cellular nuclei from 3D fluorescent microscopic data. Our tool is based on state-of-the-art image processing and machine learning techniques and provides a user-friendly graphical user interface. We show that our tool is as accurate as manual annotation and greatly reduces the time for the registration.

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References

  1. Santella, A., Du, Z., Nowotschin, S., Hadjantonakis, A., Bao, Z.: A hybrid blob-slice model for accurate and efficient detection of fluorescence labeled nuclei in 3D. BMC Bioinformatics 11(1), 580–2010 (2010)

    Article  Google Scholar 

  2. Li, G., Liu, T., Tarokh, A., Nie, J., Guo, L., Mara, A., Holley, S., Wong, S.: 3D cell nuclei segmentation based on gradient flow tracking. BMC Cell Biol. 8(1), 40 (2007)

    Article  Google Scholar 

  3. Coelho, L.P., Shariff, A., Murphy, R.F.: Nuclear segmentation in microscope cell images: a hand-segmented dataset and comparison of algorithms. In IEEE International Symposium on Biomedical Imaging: From Nano to Macro, (2009)

  4. Cremers, D., Rousson, M., Deriche, R.: A review of statistical approaches to level set segmentation: integrating color, texture, motion and shape. Int. J. Comput. Vis. 72(2), 195–215 (2007)

    Article  Google Scholar 

  5. Dufour, A., Shinin, V., Tajbakhsh, S., et al.: Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces. IEEE Trans. Image Process. 14(9), 13961410 (2005)

    Article  Google Scholar 

  6. Srinivasa, G., Fickus, M.C., Guo, Y., et al.: Segmenting and tracking fluorescent cells in dynamic 3-D microscopy with coupled active surfaces. IEEE Trans. Image Process. 18(8), 1817–1829 (2009)

    Article  MathSciNet  Google Scholar 

  7. Boykov, Y., Funka-Lea, G.: Graph cuts and efficient ND image segmentation. Int. J. Comput. Vis. 70(2), 109–131 (2006)

    Article  Google Scholar 

  8. Al-Kofahi, Y., Lassoued, W., Lee, W., et al.: Improved automatic detection and segmentation of cell nuclei in histopathology images. IEEE Trans. Biomed. Eng. 57(4), 841–852 (2010)

    Article  Google Scholar 

  9. Heinrich, S., Geissen, E., Kamenz, J., Trautmann, S., Widmer, C., Drewe, P., Knop, M., Radde, N., Hasenauer, J., Hauf, S.: Determinants of robustness in spindle assembly checkpoint signalling. Nat. Cell Biol. 15(11), 1328–1339 (2013)

    Article  Google Scholar 

  10. Pécot, T., Singh, S., Caserta, E., Huang, K., Machiraju, R., Leone, G.: Non parametric cell nuclei segmentation based on a tracking over depth from 3D fluorescence confocal images. In 9th IEEE International Symposium on Biomedical Imaging (ISBI), 170–173, (2012)

  11. Uzunbas, M.G., Soldea, O., Unay, D., Cetin, M., Unal, G., Ercil, A., Ekin, A.: Coupled nonparametric shape and moment-based intershape pose priors for multiple basal ganglia structure segmentation. IEEE Trans. Med. Imaging 29(12), 1959–1978 (2010)

    Article  Google Scholar 

  12. Stegmaier, J., Otte, J.C., Kobitski, A., Bartschat, A., Garcia, A., Nienhaus, G.U., Strähle, U., Mikut, R.: Fast segmentation of stained nuclei in terabyte-scale, time resolved 3D microscopy image stacks. PloS One 9(2), e90036 (2014)

    Article  Google Scholar 

  13. Svoboda, D., Kozubek, M., Stejskal, S.: Generation of digital phantoms of cell nuclei and simulation of image formation in 3D image cytometry. Cytometry A 75(6), 494–5099 (2009)

    Article  Google Scholar 

  14. Lou, X., Kang, M., Xenopoulos, P., Muñoz-Descalzo, S., Hadjantonakis, A.K.: A rapid and efficient 2D/3D nuclear segmentation method for analysis of early mouse embryo and stem cell image data. Stem Cell Reports 2(3), 382–397 (2014)

    Article  Google Scholar 

  15. Mitchell I.M.: A toolbox of level set methods. In UBC Department of Computer Science Technical Report, TR-2007-11, (2007)

  16. Wienert, S., Heim, D., Saeger, K., Stenzinger, A., Beil, M., Hufnagl, P., Dietel, M., Denkert, C., Klauschen, F.: Detection and segmentation of cell nuclei in virtual microscopy images: a minimum-model approach. Sci. Rep. 2, 503 (2012)

    Article  Google Scholar 

  17. Evgeniou, T., Micchelli, C.A., Pontil, M.: Learning multiple tasks with kernel methods. J. Mach. Learn. Res. 6(1), 615–637 (2005)

    MATH  MathSciNet  Google Scholar 

  18. Lou, X., Koethe, U., Wittbrodt, J., Hamprecht, F. A.: Learning to segment dense cell nuclei with shape prior. In CVPR (2012)

  19. Gonzalez, R.C., Woods, R.E.: Digital Image Processing. Prentice Hall, Upper Saddle River (2008)

    Google Scholar 

  20. Lou, X., Koethe, U., Wittbrodt, J., Hamprecht, F.A.: Improved automatic detection and segmentation of cell nuclei in histopathology images. In IEEE on Computer Vision and Pattern Recognition (CVPR)(2012)

  21. Weisstein, E. W.: “Ellipse”. From MathWorld—A Wolfram Web Resource. http://mathworld.wolfram.com/Ellipse.html

  22. Rosin, P.L.: Assessing error of fit functions for ellipses. Graph. Models Image Process. 58(5), 494–502 (1996)

    Article  Google Scholar 

  23. Fitzgibbon, A., Pilu, M., Fisher, R.B.: Direct least square fitting of ellipses. IEEE Trans. Pattern Anal. Mach. Intell. 21(5), 476–480 (1999)

    Article  Google Scholar 

  24. Newcomb, S.: A generalized theory of the combination of observations so as to obtain the best result. Am. J. Math. 8, 343–366 (1886)

    Article  MATH  MathSciNet  Google Scholar 

  25. Huber, P.J.: The 1972 wald lecture robust statistics: a review. Ann. Math. Stat. 43(4), 1041–1067 (1972)

    Article  MATH  Google Scholar 

  26. Vapnik, V.: The Nature of Statistical Learning Theory. Volume 8 of Statistics for Engineering and Information Science. Springer, Berlin (1995)

  27. Smola, A. J., Schölkopf, B.: Learning with Kernels: Support Vector Machines, Regularization, Optimization, and Beyond. Volume 64 of Adaptive Computation and Machine Learning. MIT Press, Cambridge (2001)

  28. Smola, A.J., Schölkopf, B.: A tutorial on support vector regression. Stat. Comput. 14(3), 199–222 (2004)

    Article  MathSciNet  Google Scholar 

  29. Boyd, S., Vandenberghe, L.: Convex Optimization. Cambridge University Press, Cambridge (2004)

    Book  MATH  Google Scholar 

  30. Widmer, C., Kloft, M., Görnitz, N., Rätsch, G.: Efficient training of graph-regularized multitask SVMs. In ECML2012, pp. 633–647, Springer, Berlin (2012)

  31. Fischler, M.A., Bolles, R.C.: Random sample consensus: a paradigm for model fitting with applications to image analysis and automated cartography. Commun. ACM 24.6, 381–395 (1981)

    Article  MathSciNet  Google Scholar 

  32. Elsasser, W.M.: Outline of a theory of cellular heterogeneity. In Proceedings of the National Academy of Sciences, 5126–5129, (1984)

  33. Li, G., Liu, T., Tarokh, A., et al.: 3D cell nuclei segmentation. BMC Cell Biol. 8(1), 40 (2007)

    Article  Google Scholar 

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Acknowledgments

We gratefully acknowledge core funding from the Sloan Kettering Institute (to G.R.), from the Ernst Schering foundation (to S.H.) and from the Max Planck Society (to G.R. and S.H.). Part of this work was done while C.W., S.H., P.D. and G.R. were at the Friedrich Miescher Laboratory of the Max Planck Society and while C.W. was at the Machine Learning Group at TU-Berlin.

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Correspondence to Christian Widmer.

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Widmer, C., Heinrich, S., Drewe, P. et al. Graph-regularized 3D shape reconstruction from highly anisotropic and noisy images. SIViP 8 (Suppl 1), 41–48 (2014). https://doi.org/10.1007/s11760-014-0694-8

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  • DOI: https://doi.org/10.1007/s11760-014-0694-8

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