Abstract
At present, tumor-associated macrophages (TAMs) are receiving substantial attention owing to their potential as new therapeutic targets. However, the recognition and counting of TAMs remains an open problem. The results of existing algorithms and procedures are unsatisfactory and exhibit multiple defects such as blurred edges or a long inference time. In this work, we first propose an algorithm based on simple linear iterative clustering for the automatic selection of TAMs-dense hot spots in huge whole slide imaging. Subsequently, we present an end-to-end method based on U-Net for the segmentation and counting of pleomorphic TAMs. Edge detection is incorporated into the network architecture and nuclei information is used for verification. The experimental results demonstrate that our method achieved the highest F1-score and relatively good edge segmentation accuracy with an acceptable parameter size on a constructed dataset. The average counting results of our method also exhibited a comparatively small deviation, thereby demonstrating the possibility for clinical application.
The code and dataset are available at https://github.com/Meteorsc9/Decouple-U-Net.
Z. Chen and H. Yang—These authors have contributed equally to this work.
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References
Cheng, N., Bai, X., Shu, Y., Ahmad, O., Shen, P.: Targeting tumor-associated macrophages as an antitumor strategy. Biochem. Pharmacol. 183, 114354 (2021)
Petty, A.J., Owen, D.H., Yang, Y., Huang, X.: Targeting tumor-associated macrophages in cancer immunotherapy. Cancers 13, 5318 (2021)
Pan, Y., Yu, Y., Wang, X., Zhang, T.: Tumor-associated macrophages in tumor immunity. Front. Immunol., 3151 (2020)
Duraiyan, J., Govindarajan, R., Kaliyappan, K., Palanisamy, M.: Applications of immunohistochemistry. J. Pharm. Bioallied Sci. 4, S307 (2012)
Yoshida, C., et al.: Tumor-associated CD163+ macrophage as a predictor of tumor spread through air spaces and with CD25+ lymphocyte as a prognostic factor in resected stage I lung adenocarcinoma. Lung Cancer 167, 34–40 (2022)
Wagner, M., et al.: Automated macrophage counting in DLBCL tissue samples: a ROF filter based approach. Biol. Proced. Online 21, 1–18 (2019)
Cassetta, L., et al.: Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell 35, 588–602, e510 (2019)
Kumar, N., Gupta, R., Gupta, S.: Whole slide imaging (WSI) in pathology: current perspectives and future directions. J. Digit. Imaging 33, 1034–1040 (2020)
Baxi, V., Edwards, R., Montalto, M., Saha, S.: Digital pathology and artificial intelligence in translational medicine and clinical practice. Mod. Pathol., 1–10 (2021)
Achanta, R., Shaji, A., Smith, K., Lucchi, A., Fua, P., Süsstrunk, S.: SLIC superpixels compared to state-of-the-art superpixel methods. IEEE Trans. Pattern Anal. Mach. Intell. 34, 2274–2282 (2012)
Ronneberger, O., Fischer, P., Brox, T.: U-Net: convolutional networks for biomedical image segmentation. In: Navab, N., Hornegger, J., Wells, W., Frangi, A. (eds.) MICCAI 2015. LNCS, vol. 9351, pp. 234–241. Springer, Cham (2015). https://doi.org/10.1007/978-3-319-24574-4_28
Ren, S., He, K., Girshick, R., Sun, J.: Faster R-CNN: towards real-time object detection with region proposal networks. In: Advances in Neural Information Processing Systems 28 (2015)
Comaniciu, D., Meer, P.: Mean shift: a robust approach toward feature space analysis. IEEE Trans. Pattern Anal. Mach. Intell. 24, 603–619 (2002)
Shi, J., Malik, J.: Normalized cuts and image segmentation. IEEE Trans. Pattern Anal. Mach. Intell. 22, 888–905 (2000)
Otsu, N.: A threshold selection method from gray-level histograms. IEEE Trans. Syst. Man Cybern. 9, 62–66 (1979)
Canny, J.: A computational approach to edge detection. IEEE Trans. Pattern Anal. Mach. Intell. 6, 679–698 (1986)
Rother, C., Kolmogorov, V., Blake, A.: “GrabCut” interactive foreground extraction using iterated graph cuts. ACM Trans. Graph. (TOG) 23, 309–314 (2004)
Kass, M., Witkin, A., Terzopoulos, D.: Snakes: active contour models. Int. J. Comput. Vis. 1, 321–331 (1988)
Long, J., Shelhamer, E., Darrell, T.: Fully convolutional networks for semantic segmentation. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 3431–3440 (2015)
He, K., Zhang, X., Ren, S., Sun, J.: Deep residual learning for image recognition. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 770–778 (2016)
Chen, L.-C., Papandreou, G., Kokkinos, I., Murphy, K., Yuille, A.L.: DEEPLAB: semantic image segmentation with deep convolutional nets, atrous convolution, and fully connected CRFs. IEEE Trans. Pattern Anal. Mach. Intell. 40, 834–848 (2017)
Zhou, Z., Rahman Siddiquee, M.M., Tajbakhsh, N., Liang, J.: UNet++: a nested U-Net architecture for medical image segmentation. In: Stoyanov, D., et al. (eds.) DLMIA ML-CDS 2018 2018. LNCS, vol. 11045, pp. 3–11. Springer, Cham (2018). https://doi.org/10.1007/978-3-030-00889-5_1
Oktay, O., et al.: Attention U-Net: learning where to look for the pancreas. arXiv preprint arXiv:1804.03999 (2018)
Chen, L.-C., Zhu, Y., Papandreou, G., Schroff, F., Adam, H.: Encoder-decoder with atrous separable convolution for semantic image segmentation. In: Ferrari, V., Hebert, M., Sminchisescu, C., Weiss, Y. (eds.) ECCV 2018. LNCS, vol. 11211, pp. 833–851. Springer, Cham (2018). https://doi.org/10.1007/978-3-030-01234-2_49
Takikawa, T., Acuna, D., Jampani, V., Fidler, S.: Gated-SCNN: gated shape CNNs for semantic segmentation. In: Proceedings of the IEEE/CVF International Conference on Computer Vision, pp. 5229–5238 (2019)
Zhen, M., et al.: Joint semantic segmentation and boundary detection using iterative pyramid contexts. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 13666–13675 (2020)
Li, X., et al.: Improving semantic segmentation via decoupled body and edge supervision. In: Vedaldi, A., Bischof, H., Brox, T., Frahm, JM. (eds.) ECCV 2020. LNCS, vol. 12362, pp. 435–452. Springer, Cham (2020). https://doi.org/10.1007/978-3-030-58520-4_26
Zhan, G., Wang, W., Sun, H., Hou, Y., Feng, L.: Auto-CSC: a transfer learning based automatic cell segmentation and count framework. Cyborg Bionic Syst. 2022 (2022)
Vahadane, A., et al.: Structure-preserving color normalization and sparse stain separation for histological images. IEEE Trans. Med. Imaging 35, 1962–1971 (2016)
Hu, J., Shen, L., Sun, G.: Squeeze-and-excitation networks. In: Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition, pp. 7132–7141 (2018)
Lin, T.-Y., Goyal, P., Girshick, R., He, K., Dollár, P.: Focal loss for dense object detection. In: Proceedings of the IEEE International Conference on Computer Vision, pp. 2980–2988 (2017)
Zhu, Y., et al.: Improving semantic segmentation via video propagation and label relaxation. In: Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition, pp. 8856–8865 (2019)
Crum, W.R., Camara, O., Hill, D.L.: Generalized overlap measures for evaluation and validation in medical image analysis. IEEE Trans. Med. Imaging 25, 1451–1461 (2006)
Kingma, D.P., Ba, J.: Adam: A method for stochastic optimization. arXiv preprint arXiv:1412.6980 (2014)
Acknowledgements
This work is supported by Clinical Medicine Plus X - Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities PKU2022LCXQ19 and Innovative Experiment Project for Undergraduates of Peking University Health Science Center 2021-SSDC-14. We would like to thank Yan Gao and Jianyun Zhang for their work on annotating images.
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Chen, Z., Yang, H., Gao, M., Hu, X., Li, Y., Wang, L. (2022). Decouple U-Net: A Method for the Segmentation and Counting of Macrophages in Whole Slide Imaging. In: Yu, S., et al. Pattern Recognition and Computer Vision. PRCV 2022. Lecture Notes in Computer Science, vol 13535. Springer, Cham. https://doi.org/10.1007/978-3-031-18910-4_9
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