Skip to main content

Automated Analysis of Tissue Micro-Array Images on the Example of Renal Cell Carcinoma

  • Chapter
Similarity-Based Pattern Analysis and Recognition

Abstract

Automated tissue micro-array analysis forms a challenging problem in computational pathology. The detection of cell nuclei, the classification into malignant and benign as well as the evaluation of their protein expression pattern by immunohistochemical staining are crucial routine steps for human cancer research and oncology. Computational assistance in this field can extremely accelerate the high throughput of the upcoming patient data as well as facilitate the reproducibility and objectivity of qualitative and quantitative measures. In this chapter, we describe an automated pipeline for staining estimation of tissue micro-array images, which comprises nucleus detection, nucleus segmentation, nucleus classification and staining estimation among cancerous nuclei. This pipeline is a practical example for the importance of non-metric effects in this kind of image analysis, e.g., the use of shape information and non-Euclidean kernels improve the nucleus classification performance significantly. The pipeline is explained and validated on a renal clear cell carcinoma dataset with MIB-1 stained tissue micro-array images and survival data of 133 patients. Further, the pipeline is implemented for medical use and research purpose in the free program TMARKER.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Grignon, D.J., Eble, J.N., Bonsib, S.M., Moch, H.: Clear Cell Renal Cell Carcinoma. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press, Lyon (2004)

    Google Scholar 

  2. Bubendorf Juha Kononen, L., Bärlund Anne Kallionimeni, M., Leighton Peter Schraml, S., Mihatsch, M.J., Torhorst, J., Kallionimeni, O.-P., Sauter, G.: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4(7), 844–847 (1998)

    Article  Google Scholar 

  3. Takahashi, M., Rhodes, D.R., Furge, K.A., Kanayama, H.-o., Kagawa, S., Haab, B.B., Tean Teh, B.: Gene expression profiling of clear cell renal cell carcinoma: gene identification and prognostic classification. Proc. Natl. Acad. Sci. USA 98(17), 9754–9759 (2001)

    Article  Google Scholar 

  4. Schraml Holger Moch, P., Mirlacher Lukas Bubendorf, M., Gasser Juha Kononen, T., Kallioniemi, O.P., Mihatsch, M.J., Sauter, G.: High-throughput tissue microarray analysis to evaluate genes uncovered by CDNA microarray screening in renal cell carcinoma. Am. J. Pathol. 154(4), 981–986 (1999)

    Article  Google Scholar 

  5. Amin, M.B., Young, A.N., Lim, S.D., Moreno, C.S., Petros, J.A. Cohen, C., Neish, A.S., Marshall, F.F.: Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am. J. Pathol. 158(5), 1639–1651 (2001)

    Article  Google Scholar 

  6. Tannapfel, A., Hahn, H.A., Katalinic, A., Fietkau, R.J., Kühn, R., Wittekind, C.W.: Prognostic value of ploidy and proliferation markers in renal cell carcinoma. Cancer 77(1), 164–171 (1996)

    Article  Google Scholar 

  7. Nocito, A., Bubendorf, L., Maria Tinner, E., Süess, K., Wagner, U., Forster, T., Kononen, J., Fijan, A., Bruderer, J., Schmid, U., Ackermann, D., Maurer, R., Alund, G., Knönagel, H., Rist, M., Anabitarte, M., Hering, F., Hardmeier, T., Schoenenberger, A.J., Flury, R., Jäger, P., Luc Fehr, J., Schraml, P., Moch, H., Mihatsch, M.J., Gasser, T., Sauter, G.: Microarrays of bladder cancer tissue are highly representative of proliferation index and histological grade. J. Pathol. 194(3), 349–357 (2001)

    Article  Google Scholar 

  8. Yang, L., Meer, P., Foran, D.J.: Unsupervised segmentation based on robust estimation and color active contour models. IEEE Trans. Inf. Technol. Biomed. 9(3), 475–486 (2005)

    Article  Google Scholar 

  9. Mertz, K.D., Demichelis, F., Kim, R., Schraml, P., Storz, M., Diener, P.-A., Moch, H., Rubin, M.A.: Automated immunofluorescence analysis defines microvessel area as a prognostic parameter in clear cell renal cell cancer. Hum. Pathol. 38(10), 1454–1462 (2007)

    Article  Google Scholar 

  10. Fuchs, T.J., Wild, P.J., Schüffler, P.J.: Labeled IHC images of RCC (2012). doi:10.5881/LABELED-IHC-IMAGES-OF-RCC

  11. Fuchs, T.J., Haybaeck, J., Wild, P.J., Heikenwalder, M., Moch, H., Aguzzi, A., Buhmann, J.M.: Randomized tree ensembles for object detection in computational pathology. In: ISVC (1). Lecture Notes in Computer Science, vol. 5875, pp. 367–378. Springer, Berlin (2009)

    Google Scholar 

  12. Breiman, L.: Random forests. Mach. Learn. 45, 5–32 (2001)

    Article  MATH  Google Scholar 

  13. Strobl, C., Boulesteix, A.-L., Augustin, T.: Unbiased split selection for classification trees based on the Gini index. Comput. Stat. Data Anal. 52(1), 483–501 (2007)

    Article  MathSciNet  MATH  Google Scholar 

  14. Viola, P., Jones, M.: Rapid object detection using a boosted cascade of simple features. In: CVPR (2001)

    Google Scholar 

  15. Kuhn, H.W.: The Hungarian method for the assignment problem:. Nav. Res. Logist. Q. 2, 83–97 (1955)

    Article  Google Scholar 

  16. R Development Core Team: R: a Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna (2009). ISBN 3-900051-07-0

    Google Scholar 

  17. Glotsos, D., Spyridonos, P., Cavouras, D., Ravazoula, P., Arapantoni Dadioti, P., Nikiforidis, G.: An image-analysis system based on support vector machines for automatic grade diagnosis of brain-tumour astrocytomas in clinical routine. Med. Inform. Internet Med. 30(3), 179–193 (2005)

    Article  Google Scholar 

  18. Fuchs, T.J., Lange, T., Wild, P.J., Moch, H., Buhmann, J.M.: Weakly supervised cell nuclei detection and segmentation on tissue microarrays of renal cell carcinoma. In: Pattern Recognition. DAGM 2008. Lecture Notes in Computer Science, vol. 5096, pp. 173–182. Springer, Berlin (2008)

    Chapter  Google Scholar 

  19. Soille, P.: Morphological Image Analysis: Principles and Applications. Springer, New York (2003)

    Google Scholar 

  20. Boykov, Y., Kolmogorov, V.: An experimental comparison of min-cut/max-flow algorithms for energy minimization in vision. IEEE Trans. Pattern Anal. Mach. Intell. 26(9), 1124–1137 (2004)

    Article  Google Scholar 

  21. Boykov, Y., Veksler, O., Zabih, R.: Efficient approximate energy minimization via graph cuts. IEEE Trans. Pattern Anal. Mach. Intell. 20(12), 1222–1239 (2001)

    Article  Google Scholar 

  22. Kolmogorov, V., Zabih, R.: What energy functions can be minimized via graph cuts? IEEE Trans. Pattern Anal. Mach. Intell. 26(2), 147–159 (2004)

    Article  Google Scholar 

  23. Bagon, S.: Matlab wrapper for graph cut (2006)

    Google Scholar 

  24. Achanta, R., Shaji, A., Smith, K., Lucchi, A., Fua, P., Suesstrunk, S.: SLIC Superpixels. Technical report, EPFL, EPFL (2010)

    Google Scholar 

  25. Schüffler, P.J., Fuchs, T.J., Soon Ong, C., Roth, V., Buhmann, J.M.: Computational TMA analysis and cell nucleus classification of renal cell carcinoma. In: Proceedings of the 32nd DAGM Conference on Pattern Recognition, pp. 202–211. Springer, Berlin (2010)

    Google Scholar 

  26. Gonzalez, R.C., Woods, R.E., Eddins, S.L.: Digital image processing using Matlab. 993475 (2003)

    Google Scholar 

  27. Bosch, A., Zisserman, A., Munoz, X.: Representing shape with a spatial pyramid kernel. In: CIVR’07: Proceedings of the 6th ACM International Conference on Image and Video Retrieval, pp. 401–408. ACM, New York (2007)

    Chapter  Google Scholar 

  28. Schüffler, P.J., Ulaş, A., Castellani, U., Murino, V.: A multiple kernel learning algorithm for cell nucleus classification of renal cell carcinoma. In: Proceedings of the International Conference on Image Analysis and Processing, ICIAP’11 (2011). Page accepted

    Google Scholar 

  29. Gönen, M., Ulaş, A., Schüffler, P.J., Castellani, U., Murino, V.: Combining data sources nonlinearly for cell nucleus classification of renal cell carcinoma. In: Pelillo, M., Hancock, E.R. (eds.) Proceedings of the International Workshop on Similarity-Based Pattern Analysis, SIMBAD’11. Lecture Notes in Computer Science, vol. 7005, pp. 250–260. Springer, Berlin (2011)

    Chapter  Google Scholar 

  30. Bach, F.R., Lanckriet, G.R.G., Jordan, M.I.: Multiple kernel learning, conic duality, and the SMO algorithm. In: Proceedings of the 21st International Conference on Machine Learning, pp. 41–48 (2004)

    Google Scholar 

  31. Cortes, C., Mohri, M., Rostamizadeh, A.: Learning non-linear combinations of kernels. In: Advances in Neural Information Processing Systems, vol. 22, pp. 396–404 (2010)

    Google Scholar 

  32. Ulaş, A., Schüffler, P.J., Bicego, M., Castellani, U., Murino, V.: Hybrid generative–discriminative nucleus classification of renal cell carcinoma. In: Pelillo, M., Hancock, E.R. (eds.) Proceedings of the International Workshop on Similarity-Based Pattern Analysis, SIMBAD’11. Lecture Notes in Computer Science, vol. 7005, pp. 77–88. Springer, Berlin (2011)

    Google Scholar 

  33. Bicego, M., Ulaş, A., Schüffler, P.J., Castellani, U., Mirtuono, P., Murino, V., Aguiar, P.M.Q., Martins, A., Figueiredo, M.A.T.: Renal cancer cell classification using generative embeddings and information theoretic kernels. In: Loog, M. (ed.) IAPR International Conference on Pattern Recognition in Bioinformatics, PRIB’11. Lecture Notes in Bioinformatics (accepted), vol. 7036. Springer, Berlin (2011)

    Google Scholar 

  34. Hall, M., Frank, E., Holmes, G., Pfahringer, B., Reutemann, P., Witten, I.H.: The WEKA data mining software: an update. ACM SIGKDD Explor. Newsl. 11, 10–18 (2009)

    Article  Google Scholar 

  35. Fuchs, T.J., Buhmann, J.M.: Computational pathology: challenges and promises for tissue analysis. Comput. Med. Imaging Graph. 35(7–8), 515–530 (2011)

    Article  Google Scholar 

Download references

Acknowledgement

We thank Aydın Ulaş, Umberto Castellani, Vittorio Murino, Mehmet Gönen, Manuele Bicego, Pasquale Mirtuono, André Martins, Pedro M.Q. Aguiar and Mário A.T. Figueiredo for successful collaborations and inspiring ideas. We want to thank all our co-workers and SIMBAD partners for fruitful discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter J. Schüffler .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Schüffler, P.J., Fuchs, T.J., Ong, C.S., Roth, V., Buhmann, J.M. (2013). Automated Analysis of Tissue Micro-Array Images on the Example of Renal Cell Carcinoma. In: Pelillo, M. (eds) Similarity-Based Pattern Analysis and Recognition. Advances in Computer Vision and Pattern Recognition. Springer, London. https://doi.org/10.1007/978-1-4471-5628-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-5628-4_9

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-5627-7

  • Online ISBN: 978-1-4471-5628-4

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics