Efficient automated detection of mitotic cells from breast histological images using deep convolution neutral network with wavelet decomposed patches
Introduction
Among the various criteria for histopathological assessment of cancer, mitotic cell counting is one of the most important diagnostic approaches. Mitotic cells are produced when mother cells divide into two genetically identical cells that can differ in their morphological appearance. As a result, there is a general morphological heterogeneity in mitotic cells. Detection of cell proliferation markers is important in patient risk assessment for cancer. An increase in mitotic cell count signifies a higher proliferative index, which might reflect high cell proliferation activity that is observed in cancer. In conventional practice, experts manually determine mitotic nuclei count in images of tissue samples. Specifically, mitotic cell counts are conducted using a 400× microscopic magnification and reported as number of mitotic cells in an area of 2 mm2 [1]. It is broadly accepted that manual counting of mitotic cells is very error-prone due to the morphological and textural variations in microscopic images [2]. Therefore, high inter-observer variability is noted in manual mitotic cell counts.
Various computational approaches have been developed to overcome the drawbacks of manual mitotic cell counting. These computational approaches are thought to be superior because algorithms lack observer bias [3]. Different probabilistic models, such as the hidden Markov model [4], Gamma-Gaussian mixture model [5], maximum likelihood (ML) estimation [6,7], and Bayesian modeling [8], have been implemented for detecting mitotic cells in breast cancer histological images. Furthermore, a method has been proposed for mitotic cell segmentation that uses a distance regularized level set approach [9]. Another approach by Irshad et al. adopts a hierarchical model that uses scale-invariant feature transform to detect mitotic cells from breast histological images [10]. Supervised classification approaches, such as support vector machine [6,7,9,[11], [12], [13], [14]], cascade adaboosts [15], deep residual learning [16], and random forest [17], have also been used for mitotic cell identification. Combination of support vector machine and random forest have been used for the same mitotic cells detection. Unsupervised classification approach like k-nearest neighbors has been utilized for mitotic cell detection [18].
Deep convolution neural networks (CNNs) have been implemented widely in the medical image analysis domain [[19], [20], [21], [22]]. A CNN is a type of deep neural network with multiple hidden layers, and it has been used for mitotic cell detection in breast cancer histological samples [23]. Others have combined a cascade model of CNN with handcrafted, domain adaptive descriptors for mitotic cell segmentation as well [2]. Deep CNN is an attractive computational approach for mitotic cell counting due to its ability to comprehend and perform nonlinear mapping of input and output variables [24]. It is able to do so because it has millions of training parameters, which are optimized during the training procedure. However, the immense amount of hyperparameters that is used for mitotic cell counting in deep CCN models makes it highly complex computationally [[25], [26], [27], [28]]. Of interest, its time complexity is computed based on four parameters, namely patch size of the input image, number of channels, convolution kernel size, and the number of filters. Among them, the size of input patches contributes greatly to the computation complexity of the network. With a larger patch size, the complexity of the deep CNN increases. To reduce computational complexity, we decomposed input image patches with Haar wavelet and subsequently introduced these patches to the CNN architecture. Other wavelets, such as Daubechies (db)1, db2, db3, and db4, were tested, but the Haar wavelet turned out to be the most effective in decomposing input patches [29,30]. This approach of using Harr wavelet decomposed patches (21 × 21 pixels) with CNN outperformed conventional CNN models with raw patches (81 × 81 pixels) in mitotic cell detection of breast cancer histological images in both computational efficiency and accuracy. Overall, we propose an efficient, accurate CNN-based approach for automated mitotic cell detection that uses Harr wavelet decomposed patches to reduce computational burden.
Section snippets
Proposed mitotic cell segmentation framework
The proposed mitotic cell segmentation framework is shown in Fig. 1. It consists of data acquisition; stain normalization; candidate cell segmentation; patch creation; Haar wavelet decomposition of image patches; construction of a deep CNN architecture that learns the patterns of the decomposed data; mitotic cell detection in test datasets using our proposed CNN-based model and the conventional CNN model; and performance analysis of both CNN models.
Experimental results
In this study, we focused on identifying mitotic cells from breast histological images in an automated manner. We initially determined the most suitable input image patch size and convolution kernel or filter size for the conventional 18-layer CNN architecture (Fig. 7) to identify mitotic cells from raw images based on performance. Specifically, we tested the conventional CNN architecture with raw input patches of 61 × 61, 81 × 81, and 101 × 101 pixels and convolution kernels of 3 × 3 and 5 × 5
Discussion
The proposed method focused on improving the performance of deep CNN model-based automated mitotic cell detection systems by introducing a wavelet downsampling process on candidate mitotic cell image patches before subjecting them to a CNN architecture. Our method was applied on breast histological images. We demonstrated that our proposed CNN approach performed better than the conventional practice of using raw images patches for deep CNN. In particular, the patch image decomposition process
Conclusions
This study describes a new approach for mitotic cell detection in breast histological images. Specifically, a new CNN architecture that uses wavelet decomposed image patches is introduced here to reduce the computational complexity of conventional CNN models that use raw image patches. The proposed segmentation approach consists of candidate cell detection; patch extraction and their Haar wavelet decomposition; and mitotic cell detection using a CNN architecture that is design for decomposed
Conflicts of interest
Authors have no conflicts of interest to disclose.
Acknowledgements
The authors would like to thank Dr. Ludovic Roux of the IPAL Laboratory, A*STAR/I2R, Institute for Infocomm Research, CNRS UMI 2955, Singapore. Dr. Roux was an organizer of the MITOS-ATYPIA-14 grand challenge contest, and he independently evaluated the performance of our Harr-wavelet decomposed patch-based CNN approach on the test dataset of MITOS-ATYPIA-14. First author would like to acknowledge IIT Kharagpur for providing institute research fellowship grant to carry out this research.
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