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Link to original content: https://doi.org/10.1007/s11517-017-1630-1
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Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships

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Abstract

In many computerized methods for cell detection, segmentation, and classification in digital histopathology that have recently emerged, the task of cell segmentation remains a chief problem for image processing in designing computer-aided diagnosis (CAD) systems. In research and diagnostic studies on cancer, pathologists can use CAD systems as second readers to analyze high-resolution histopathological images. Since cell detection and segmentation are critical for cancer grade assessments, cellular and extracellular structures should primarily be extracted from histopathological images. In response, we sought to identify a useful cell segmentation approach with histopathological images that uses not only prominent deep learning algorithms (i.e., convolutional neural networks, stacked autoencoders, and deep belief networks), but also spatial relationships, information of which is critical for achieving better cell segmentation results. To that end, we collected cellular and extracellular samples from histopathological images by windowing in small patches with various sizes. In experiments, the segmentation accuracies of the methods used improved as the window sizes increased due to the addition of local spatial and contextual information. Once we compared the effects of training sample size and influence of window size, results revealed that the deep learning algorithms, especially convolutional neural networks and partly stacked autoencoders, performed better than conventional methods in cell segmentation.

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References

  1. Bengio Y (2009) Learning deep architectures for AI. Found Trend Mach Learn 2(1):1–127

    Article  Google Scholar 

  2. Bilgin G (2013) Evaluation of spatial relations in the segmentation of histopathological images. In: IEEE 21st signal processing and communications applications conference, pp 1–4

  3. Bunyak F, Hafiane A, Palaniappan K (2011) Histopathology tissue segmentation by combining fuzzy clustering with multiphase vector level sets. In: Arabnia HR, Tran Q-N (eds) Software tools and algorithms for biological systems. Springer, Berlin, pp 413–424

  4. Chang CC, Lin CJ (2011) Libsvm: a library for support vector machines. ACM Trans Intell Syst Technol 2(3):27

    Article  Google Scholar 

  5. Chen Y, Lin Z, Zhao X, Wang G, Gu Y (2014) Deep learning-based classification of hyperspectral data. IEEE J Sel Top Appl 7(6):2094–2107

    Google Scholar 

  6. Cheng L, Ye N, Yu W, Cheah A (2012) A bag-of-words model for cellular image segmentation. In: Loménie N, Racoceanu D, Gouaillard A (eds) Advances in bio-imaging: from physics to signal understanding issues. Springer, Berlin, pp 209–222

  7. Chollet F (2015) Keras. http://github.com/fchollet/keras

  8. Ciresan DC, Meier U, Gambardella LM, Schmidhuber J (2011) Convolutional neural network committees for handwritten character classification. In: IEEE international conference on document analysis and recognition, ICDAR’11, pp 1135–1139

  9. Ciresan DC, Giusti A, Gambardella LM, Schmidhuber J (2013) Mitosis detection in breast cancer histology images with deep neural networks. In: 16th International conference of medical image computing and computer-assisted intervention (MICCAI’13). Springer, Berlin, pp 411–418

  10. Cruz-Roa A, Caicedo JC, Gonzalez FA (2011) Visual pattern mining in histology image collections using bag of features. Artif Intell Med 52(2):91–106

    Article  PubMed  Google Scholar 

  11. Cruz-Roa A, Xu J, Madabhushi A (2015) A note on the stability and discriminability of graph-based features for classification problems in digital pathology. In: Proceedings of the SPIE, vol 9287, pp 928703–928710

  12. Cun L, Boser B, Denker JS, Henderson D, Howard RE, Hubbard W, Jackel LD (1990) Handwritten digit recognition with a back-propagation network. In: Touretzky DS (ed) Advances in neural information processing systems. Morgan Kaufmann, Los Altos, pp 396–404

  13. Demir C, Yener B (2005) Automated cancer diagnosis based on histopathological images: a systematic survey. Rensselaer Polytechnic Institute, Technical Report

  14. Deng L, Yu D (2014) Deep learning: methods and applications. Found Trend Signal Process 7(3–4):197–387

    Article  Google Scholar 

  15. Dundar MM, Badve S, Bilgin G, Raykar V, Jain R, Sertel O, Gurcan MN (2011) Computerized classification of intraductal breast lesions using histopathological images. IEEE Trans Biomed Eng 58(7):1977–1984

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fukushima K (1980) Neocognitron: a self-organizing neural network model for a mechanism of pattern recognition unaffected by shift in position. Biol Cybern 36(4):193–202

    Article  CAS  PubMed  Google Scholar 

  17. Gelasca ED, Obara B, Fedorov D, Kvilekval K, Manjunath B (2009) A biosegmentation benchmark for evaluation of bioimage analysis methods. BMC Bioinform 10(1):1

    Article  Google Scholar 

  18. Gençtav A, Aksoy S, Önder S (2012) Unsupervised segmentation and classification of cervical cell images. Pattern Recognit 45(12):4151–4168

    Article  Google Scholar 

  19. Goodfellow I, Lee H, Le QV, Saxe A, Ng AY (2009) Measuring invariances in deep networks. In: Advances in neural information processing systems, NIPS’09, pp 646–654

  20. Goodfellow I, Bengio Y, Courville A (2016) Deep learning. MIT Press, Cambridge (in preparation). http://www.deeplearningbook.org

  21. Gurcan MN, Boucheron LE, Can A, Madabhushi A, Rajpoot NM, Yener B (2009) Histopathological image analysis: a review. IEEE Rev Biomed Eng 2:147–171

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hatipoglu N, Bilgin G (2014) Classification of histopathological images using convolutional neural network. In: IEEE 4th international conference on image processing theory, tools and applications, IPTA’14, pp 1–6

  23. Hatipoglu N, Bilgin G (2015) Segmentation of histopathological images with convolutional neural networks using fourier features. In: IEEE 23th signal processing and communications applications conference, SIU’2015, pp 455–458

  24. He L, Long LR, Antani S, Thoma GR (2012) Histology image analysis for carcinoma detection and grading. Comput Meth Prog Biol 107(3):538–556

    Article  Google Scholar 

  25. Hinton GE, Salakhutdinov RR (2006) Reducing the dimensionality of data with neural networks. Science 313(5786):504–507

    Article  CAS  PubMed  Google Scholar 

  26. Irshad H, Montaser-Kouhsari L, Waltz G, Bucur O, Nowak J, Dong F, Knoblauch NW, Beck AH (2014) Crowdsourcing image annotation for nucleus detection and segmentation in computational pathology: evaluating experts, automated methods, and the crowd. In: Pacific symposium on biocomputing, PSB’15. NIH Public Access, pp 294–305

  27. Irshad H, Veillard A, Roux L, Racoceanu D (2014) Methods for nuclei detection, segmentation, and classification in digital histopathology: A review—current status and future potential. IEEE Rev Biomed Eng 7:97–114

    Article  PubMed  Google Scholar 

  28. Jaiantilal A (2009) Classification and regression by randomforest-matlab. http://code.google.com/p/randomforest-matlab

  29. Jothi JAA, Rajam VMA (2016) A survey on automated cancer diagnosis from histopathology images. Artif Intell Rev. doi:10.1007/s10462-016-9494-6

  30. Karakis R, Tez M, Guler I (2011) Classification the axillary lymph node status of breast cancer patients with the analysis of pattern recognition. In: IEEE 19th conference on signal processing and communications applications, SIU’2011, pp 988–991

  31. Ko B, Seo M, Nam JY (2009) Microscopic cell nuclei segmentation based on adaptive attention window. J Digit Imaging 22(3):259–274

    Article  PubMed  Google Scholar 

  32. Korkmaz SA, Korkmaz MF, Poyraz M (2016) Diagnosis of breast cancer in light microscopic and mammographic images textures using relative entropy via kernel estimation. Med Biol Eng Comput 54(4):561–573

    Article  PubMed  Google Scholar 

  33. Krizhevsky A, Sutskever I, Hinton GE (2012) Imagenet classification with deep convolutional neural networks. In: Advances in neural information processing systems, NIPS’12, pp 1097–1105

  34. Law YN, Lee HK, Ng MK, Yip AM (2012) A semisupervised segmentation model for collections of images. IEEE Trans Image Process 21(6):2955–2968

    Article  PubMed  Google Scholar 

  35. LeCun Y, Bottou L, Bengio Y, Haffner P (1998) Gradient-based learning applied to document recognition. Proc IEEE 86(11):2278–2324

    Article  Google Scholar 

  36. LeCun Y, Kavukcuoglu K, Farabet C, et al (2010) Convolutional networks and applications in vision. In: IEEE international symposium on circuits and systems, ISCAS’10, pp 253–256

  37. LeCun Y, Bengio Y, Hinton G (2015) Deep learning. Nature 521(7553):436–444

    Article  CAS  PubMed  Google Scholar 

  38. Lehmann TM, Gonner C, Spitzer K (1999) Survey: interpolation methods in medical image processing. IEEE Trans Med Imaging 18(11):1049–1075

    Article  CAS  PubMed  Google Scholar 

  39. Li G, Liu T, Nie J, Guo L, Chen J, Zhu J, Xia W, Mara A, Holley S, Wong S (2008) Segmentation of touching cell nuclei using gradient flow tracking. J Microsc 231(1):47–58

    Article  CAS  PubMed  Google Scholar 

  40. Li X, Plataniotis KN (2015) Color model comparative analysis for breast cancer diagnosis using H&E stained images. In: SPIE medical imaging, international society for optics and photonics, p 94200L

  41. Naik S, Doyle S, Agner S, Madabhushi A, Feldman M, Tomaszewski J (2008) Automated gland and nuclei segmentation for grading of prostate and breast cancer histopathology. In: IEEE 5th international symposium on biomedical imaging: from nano to macro, ISBI’2008, pp 284–287

  42. Ng A, Ngiam J, Foo CY, Mai Y, Suen C (2012) Unsupervised feature learning and deep learning tutorial (online). Accessed 2016-01-07

  43. Ojansivu V, Linder N, Rahtu E, Pietikäinen M, Lundin M, Joensuu H, Lundin J (2013) Automated classification of breast cancer morphology in histopathological images. Diagn Pathol 8(1):1–4

    Google Scholar 

  44. Onder D, Sarioglu S, Karacali B (2013) Automated labelling of cancer textures in colorectal histopathology slides using quasi-supervised learning. Micron 47:33–42

    Article  PubMed  Google Scholar 

  45. Oquab M, Bottou L, Laptev I, Sivic J (2015) Is object localization for free?-weakly-supervised learning with convolutional neural networks. In: Proceedings of the IEEE conference on computer vision and pattern recognition, CVPR’15, pp 685–694

  46. Palm RB (2012) Prediction as a candidate for learning deep hierarchical models of data. Master’s thesis, Technical University of Denmark, Palm

  47. Pan X, Li L, Yang H, Liu Z, Yang J, Zhao L, Fan Y (2017) Accurate segmentation of nuclei in pathological images via sparse reconstruction and deep convolutional networks. Neurocomputing 229:88–99. doi:10.1016/j.neucom.2016.08.103

    Article  Google Scholar 

  48. Petersen K, Nielsen M, Diao P, Karssemeijer N, Lillholm M (2014) Breast tissue segmentation and mammographic risk scoring using deep learning. In: Breast imaging: proceedings of 12th international workshop on digital mammography, IWDM’14. Springer, Berlin, pp 88–94

  49. Phung SL, Bouzerdoum A (2009) Matlab library for convolutional neural networks. Tech. rep., ICT Research Institute, Visual and Audio Signal Processing Laboratory, University of Wollongong

  50. Poultney C, Chopra S, Cun YL, et al (2006) Efficient learning of sparse representations with an energy-based model. In: Advances in neural information processing systems, NIPS’06, pp 1137–1144

  51. Ross NE, Pritchard CJ, Rubin DM, Dusé AG (2006) Automated image processing method for the diagnosis and classification of malaria on thin blood smears. Med Biol Eng Comput 44(5):427–436

    Article  PubMed  Google Scholar 

  52. Saraswat M, Arya KV (2014) Feature selection and classification of leukocytes using random forest. Med Biol Eng Comput 52(12):1041–1052

    Article  PubMed  Google Scholar 

  53. Veta M, van Diest PJ, Kornegoor R, Huisman A, Viergever MA, Pluim JP (2013) Automatic nuclei segmentation in H&E stained breast cancer histopathology images. PloS ONE 8(7):e70,221

    Article  CAS  Google Scholar 

  54. Veta M, Pluim JP, van Diest PJ, Viergever MA (2014) Breast cancer histopathology image analysis: a review. IEEE Trans Biomed Eng 61(5):1400–1411

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  56. Wittenberg T, Grobe M, Munzenmayer C, Kuziela H, Spinnler K (2004) A semantic approach to segmentation of overlapping objects. Method Inform Med 43(4):343–353

    CAS  Google Scholar 

  57. Xu J, Luo X, Wang G, Gilmore H, Madabhushi A (2016) A deep convolutional neural network for segmenting and classifying epithelial and stromal regions in histopathological images. Neurocomputing 191:214–223

    Article  PubMed  PubMed Central  Google Scholar 

  58. Xu Y, Zhu JY, Eric I, Chang C, Lai M, Tu Z (2014) Weakly supervised histopathology cancer image segmentation and classification. Med Image Anal 18(3):591–604

    Article  PubMed  Google Scholar 

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Acknowledgements

This research has been supported by Yildiz Technical University, Scientific Research Projects Coordination Department, Project Number: 2014-04-01-KAP01.

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Correspondence to Gokhan Bilgin.

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Hatipoglu, N., Bilgin, G. Cell segmentation in histopathological images with deep learning algorithms by utilizing spatial relationships. Med Biol Eng Comput 55, 1829–1848 (2017). https://doi.org/10.1007/s11517-017-1630-1

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