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A convolutional neural network model for semantic segmentation of mitotic events in microscopy images

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Abstract

Mitosis, which has important effects such as healing and growing for human body, has attracted considerable attention in recent years. Especially, cell division characteristics contain useful information for regenerative medicine. However, the analysis of this complex structure is very challenging process for experts, because many cells are scattered at random times and at different speeds. Therefore, we propose an automatic mitosis event detection method using convolutional neural network (CNN). In the proposed method, semantic segmentation has been applied with the help of CNN in order to make the complex mitosis images more easily understandable. The CNN structure consists of four convolution layers, four pooling layers, one rectified linear unit layer and softmax layer. Generally, the aim of CNN structure is to reduce the image size, but in this study, the image size is preserved for the semantic segmentation which provides high-level information. For this, the size of the images at each layer output is calculated and updated with the appropriate padding parameters. Thus, real-size images presented at the network output can be easily understood. BAEC and C2C12 phase-contrast microscopy image sequences are used for experiments. The precision, recall and F-score parameters are used for evaluating the success of the proposed method and compared with the other methods using the same datasets.

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References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66:7–30

    Article  Google Scholar 

  3. Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–212

    Article  Google Scholar 

  4. Yu K-H, Zhang C, Berry GJ, Altman RB, Ré C, Rubin DL et al (2016) Predicting non-small cell lung cancer prognosis by fully automated microscopic pathology image features. Nat Commun 7:12474

    Article  Google Scholar 

  5. Liu A, Lu Y, Nie W, Su Y, Yang Z (2016) HEp-2 cells classification via clustered multi-task learning. Neurocomputing 195:195–201

    Article  Google Scholar 

  6. Park SH, Gao Y, Shi Y, Shen D (2014) Interactive prostate segmentation using atlas-guided semi-supervised learning and adaptive feature selection. Med Phys 41:111715

    Article  Google Scholar 

  7. Hao T, Yu AL, Peng W, Wang B, Sun JS (2016) Cross domain mitotic cell recognition. Neurocomputing 195:6–12

    Article  Google Scholar 

  8. Motai Y, Siddique NA, Yoshida H (2017) Heterogeneous data analysis: online learning for medical-image-based diagnosis. Pattern Recogn 63:612–624

    Article  Google Scholar 

  9. Wang T, Xiao Z, Liu Z (2017) Performance evaluation of machine learning methods for leaf area index retrieval from time-series MODIS reflectance data. Sensors 17:81

    Article  Google Scholar 

  10. Iosifidis A, Tefas A, Pitas I (2017) Approximate kernel extreme learning machine for large scale data classification. Neurocomputing 219:210–220

    Article  Google Scholar 

  11. Diamant I, Klang E, Amitai M, Konen E, Goldberger J, Greenspan H (2017) Task driven dictionary learning based on mutual information for medical image classification. IEEE Trans Biomed Eng 6:1380–1392

    Article  Google Scholar 

  12. Prasad V, Rao TS, Babu MSP (2015) Thyroid disease diagnosis via hybrid architecture composing rough data sets theory and machine learning algorithms. Soft Comput 20:1179–1189

    Article  Google Scholar 

  13. Zheng X, Shi J, Li Y, Liu X, Zhang Q (2016) Multi-modality stacked deep polynomial network based feature learning for Alzheimer’s disease diagnosis. In: 2016 IEEE 13th international symposium on biomedical imaging (ISBI), pp 851–854

  14. Hergovich A (2016) Hippo signaling in mitosis: an updated view in light of the MEN pathway. Methods Mol Biol Mitotic Exit Netw 1505:265–277

    Article  Google Scholar 

  15. Balachandran RS, Kipreos ET (2017) Addressing a weakness of anticancer therapy with mitosis inhibitors: mitotic slippage. Mol Cell Oncol 4:e1277293

    Article  Google Scholar 

  16. Pilaz L-J, Mcmahon JJ, Miller EE, Lennox AL, Suzuki A, Salmon E et al (2016) Prolonged mitosis of neural progenitors alters cell fate in the developing brain. Neuron 89:83–99

    Article  Google Scholar 

  17. Leong FJW-M (2003) Correction of uneven illumination (vignetting) in digital microscopy images. J Clin Pathol 56:619–621

    Article  Google Scholar 

  18. Liu A-A, Li K, Kanade T (2010) Mitosis sequence detection using hidden conditional random fields. In: 2010 IEEE international symposium on biomedical imaging: from nano to macro, pp 580–583

  19. Bise R, Li K, Eom S, Kanade T (2009) Reliably tracking partially overlapping neural stem cells in DIC microscopy image sequences. In: MICCAI Workshop on OPTIMHisE, vol 5

  20. Eom S, Huh SI, Ker DFE, Bise R, Kanade T (2007) Tracking of hematopoietic stem cells in microscopy images for lineage determination. J Latex Class Files 6(1):1–9

    Google Scholar 

  21. Li K, Miller ED, Chen M, Kanade T, Weiss LE, Campbell PG (2008) Cell population tracking and lineage construction with spatiotemporal context. Med Image Anal 12:546–566

    Article  Google Scholar 

  22. Liu A, Gao Z, Tong H, Su Y, Yang Z (2014) Sparse coding induced transfer learning for hep-2 cell classification. Bio-Med Mater Eng 24(1):237–243

    Google Scholar 

  23. Liu A, Li K, Kanade T (2010) Spatiotemporal mitosis event detection in time-lapse phase contrast microscopy image sequences. In: 2010 IEEE international conference on multimedia and expo, pp 161–166

  24. Liu A, Hao T, Yang Z, Gao Z, Su Y (2013) Sequential sparse representation for mitotic event recognition. Electron Lett 49:869–871

    Article  Google Scholar 

  25. Liu A-A, Li K, Kanade T (2012) A semi-Markov model for mitosis segmentation in time-lapse phase contrast microscopy image sequences of stem cell populations. IEEE Trans Med Imaging 31:359–369

    Article  Google Scholar 

  26. Herron J, Ranshaw R, Castle J, Wald N (1972) Automatic microscopy for mitotic cell location. Comput Biol Med 2:129–135

    Article  Google Scholar 

  27. Kaman EJ, Smeulders AWM, Verbeek PW, Young IT, Baak JPA (1984) Image processing for mitoses in sections of breast cancer: a feasibility study. Cytometry 5:244–249

    Article  Google Scholar 

  28. Kate TKT, Beliën JAM, Smeulders AWM, Baak JPA (1993) Method for counting mitoses by image processing in feulgen stained breast cancer sections. Cytometry 14:241–250

    Article  Google Scholar 

  29. Beliën J, Baak J, Diest PV, Ginkel AV (1997) Counting mitoses by image processing in Feulgen stained breast cancer sections: the influence of resolution. Cytometry 28:135–140

    Article  Google Scholar 

  30. Miroslaw L, Chorazyczewski A, Buchholz F, Kittler R (2005) Correlation-based method for automatic mitotic cell detection in phase contrast microscopy. In: Advances in soft computing computer recognition systems, pp 627–634

  31. Li K, Miller ED, Chen M, Kanade T, Weiss LE, Campbell PG (2008) Computer vision tracking of stemness. In: 2008 5th IEEE international symposium on biomedical imaging: from nano to macro, pp 847–850

  32. Huh S, Ker DFE, Bise R, Chen M, Kanade T (2011) Automated mitosis detection of stem cell populations in phase-contrast microscopy images. IEEE Trans Med Imaging 30:586–596

    Article  Google Scholar 

  33. Padfield D, Rittscher J, Roysam B (2011) Coupled minimum-cost flow cell tracking for high-throughput quantitative analysis. Med Image Anal 15:650–668

    Article  Google Scholar 

  34. Malon C, Brachtel E, Cosatto E, Graf HP, Kurata A, Kuroda M et al (2012) Mitotic figure recognition: agreement among pathologists and computerized detector. Anal Cell Pathol 35:97–100

    Article  Google Scholar 

  35. Irshad H (2013) Automated mitosis detection in histopathology using morphological and multi-channel statistics features. J Pathol Inform 4:10

    Article  Google Scholar 

  36. Cireşan DC, Giusti A, Gambardella LM, Schmidhuber J (2013) Mitosis detection in breast cancer histology images with deep neural networks. In: Medical image computing and computer-assisted intervention—MICCAI 2013 Lecture Notes in Computer Science, pp 411–418

  37. Lu C, Mandal M (2014) Toward automatic mitotic cell detection and segmentation in multispectral histopathological images. IEEE J Biomed Health Inform 18:594–605

    Article  Google Scholar 

  38. Tashk A, Helfroush MS, Danyali H, Akbarzadeh M (2013) An automatic mitosis detection method for breast cancer histopathology slide images based on objective and pixel-wise textural features classification. In: The 5th conference on information and knowledge technology, vol 4(2), p 139

  39. Gilad T, Bray M-A, Carpenter AE, Raviv TR (2015) Symmetry-based mitosis detection in time-lapse microscopy. In: 2015 IEEE 12th international symposium on biomedical imaging (ISBI), pp 164–167

  40. Tashk A, Helfroush MS, Danyali H, Akbarzadeh-Jahromi M (2015) Automatic detection of breast cancer mitotic cells based on the combination of textural, statistical and innovative mathematical features. Appl Math Model 39:6165–6182

    Article  MathSciNet  Google Scholar 

  41. Beevi KS, Nair MS, Bindu GR (2016) Detection of mitotic nuclei in breast histopathology images using localized ACM and Random Kitchen Sink based classifier. In: 2016 38th annual international conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp 2435–2439

  42. Xing F, Xie Y, Yang L (2016) An automatic learning-based framework for robust nucleus segmentation. IEEE Trans Med Imaging 35:550–566

    Article  Google Scholar 

  43. Ferrari A, Lombardi S, Signoroni A (2017) Bacterial colony counting with convolutional neural networks in digital microbiology imaging. Pattern Recogn 61:629–640

    Article  Google Scholar 

  44. Krizhevsky A, Sutskever I, Hinton GE (2012) Imagenet classification with deep convolutional neural networks. In: NIPS'12 proceedings of the 25th international conference on neural information processing systems, Lake Tahoe, Nevada, 3–6 Dec 2012, vol 1. Curran Associates Inc, USA, pp 1097–1105

  45. Girshick R (2015) Fast R-CNN. In: 2015 IEEE international conference on computer vision (ICCV), pp 1440–1448

  46. Sun Y, Liang D, Wang X, Tang X (2015) Deepid3: face recognition with very deep neural networks. arXiv preprint arXiv:1502.00873

  47. Targ S, Almeida D, Lyman K (2016) Resnet in Resnet: generalizing residual architectures. arXiv preprint arXiv:1603.08029

  48. Hubel DH, Wiesel TN (1968) Receptive fields and functional architecture of monkey striate cortex. J Physiol 195:215–243

    Article  Google Scholar 

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

    Article  MATH  Google Scholar 

  50. Lecun Y, Boser B, Denker JS, Henderson D, Howard RE, Hubbard W et al (1989) Backpropagation applied to handwritten zip code recognition. Neural Comput 1:541–551

    Article  Google Scholar 

  51. Lecun Y, Bengio Y, Hinton G (2015) Deep learning. Nature 521:436–444

    Article  Google Scholar 

  52. Amaral T, Silva LM, Alexandre LA, Kandaswamy C, Santos JM, Sa JMD (2016) Using different cost functions to train stacked auto-encoders. In: 2013 12th Mexican international conference on artificial intelligence, pp 114–120

  53. Huh S, Chen M (2011) Detection of mitosis within a stem cell population of high cell confluence in phase-contrast microscopy images. In: Cvpr 2011, pp 1033–1040

  54. Liu A, Hao T, Gao Z, Su Y, Yang Z (2013) Nonnegative mixed-norm convex optimization for mitotic cell detection in phase contrast microscopy. Comput Math Methods Med 2013:1–10

    MathSciNet  MATH  Google Scholar 

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Correspondence to Şaban Öztürk.

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Öztürk, Ş., Akdemir, B. A convolutional neural network model for semantic segmentation of mitotic events in microscopy images. Neural Comput & Applic 31, 3719–3728 (2019). https://doi.org/10.1007/s00521-017-3333-9

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  • DOI: https://doi.org/10.1007/s00521-017-3333-9

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