Machine learning methods for histopathological image analysis

Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions.Comment: 23 pages, 4 figure

Blind color deconvolution, normalization, and classification of histological images using general super Gaussian priors and Bayesian inference

This work was sponsored in part by the Agencia Es-tatal de Investigacion under project PID2019-105142RB-C22/AEI/10.13039/50110 0 011033, Junta de Andalucia under project PY20_00286,and the work by Fernando Perez-Bueno was spon-sored by Ministerio de Economia, Industria y Competitividad un-der FPI contract BES-2017-081584. Funding for open access charge: Universidad de Granada/CBUA.Background and Objective: Color variations in digital histopathology severely impact the performance of computer-aided diagnosis systems. They are due to differences in the staining process and acquisition system, among other reasons. Blind color deconvolution techniques separate multi-stained images into single stained bands which, once normalized, can be used to eliminate these negative color variations and improve the performance of machine learning tasks. Methods: In this work, we decompose the observed RGB image in its hematoxylin and eosin components. We apply Bayesian modeling and inference based on the use of Super Gaussian sparse priors for each stain together with prior closeness to a given reference color-vector matrix. The hematoxylin and eosin components are then used for image normalization and classification of histological images. The proposed framework is tested on stain separation, image normalization, and cancer classification problems. The results are measured using the peak signal to noise ratio, normalized median intensity and the area under ROC curve on five different databases. Results: The obtained results show the superiority of our approach to current state-of-the-art blind color deconvolution techniques. In particular, the fidelity to the tissue improves 1,27 dB in mean PSNR. The normalized median intensity shows a good normalization quality of the proposed approach on the tested datasets. Finally, in cancer classification experiments the area under the ROC curve improves from 0.9491 to 0.9656 and from 0.9279 to 0.9541 on Camelyon-16 and Camelyon-17, respectively, when the original and processed images are used. Furthermore, these figures of merits are better than those obtained by the methods compared with. Conclusions: The proposed framework for blind color deconvolution, normalization and classification of images guarantees fidelity to the tissue structure and can be used both for normalization and classification. In addition, color deconvolution enables the use of the optical density space for classification, which improves the classification performance.Agencia Es-tatal de Investigacion PID2019-105142RB-C22/AEI/10.13039/50110 0 011033Junta de Andalucia PY20_00286Ministerio de Economia, Industria y Competitividad under FPI BES-2017-081584Universidad de Granada/CBU

Bayesian K-SVD for H and E blind color deconvolution. Applications to stain normalization, data augmentation and cancer classification

This work was supported by project PID2019-105142RB-C22 funded by MCIN / AEI / 10.13039 / 501100011033, Spain, and project P20_00286 funded by FEDER /Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Spain. The work by Fernando Pérez-Bueno was sponsored by Ministerio de Economía, Industria y Competitividad , Spain, under FPI contract BES-2017-081584 . Funding for open access charge: Universidad de Granada / CBUA, Spain.Stain variation between images is a main issue in the analysis of histological images. These color variations, produced by different staining protocols and scanners in each laboratory, hamper the performance of computer-aided diagnosis (CAD) systems that are usually unable to generalize to unseen color distributions. Blind color deconvolution techniques separate multi-stained images into single stained bands that can then be used to reduce the generalization error of CAD systems through stain color normalization and/or stain color augmentation. In this work, we present a Bayesian modeling and inference blind color deconvolution framework based on the K-Singular Value Decomposition algorithm. Two possible inference procedures, variational and empirical Bayes are presented. Both provide the automatic estimation of the stain color matrix, stain concentrations and all model parameters. The proposed framework is tested on stain separation, image normalization, stain color augmentation, and classification problems.CBUAJunta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y UniversidadesFamily Process Institute BES-2017-081584Universidad de GranadaEuropean Regional Development FundMinisterio de Economía, Industria y Competitividad, Gobierno de EspañaAgencia Estatal de Investigación P20_0028

Color and morphological features extraction and nuclei classification in tissue samples of colorectal cancer

Cancer is an important public health problem and the third most leading cause of death in North America. Among the highest impact types of cancer are colorectal, breast, lung, and prostate. This thesis addresses the features extraction by using different artificial intelligence algorithms that provide distinct solutions for the purpose of Computer-AidedDiagnosis (CAD). For example, classification algorithms are employed in identifying histological structures, such as lymphocytes, cancer-cells nuclei and glands, from features like existence, extension or shape. The morphological aspect of these structures indicates the degree of severity of the related disease. In this paper, we use a large dataset of 5000 images to classify eight different tissue types in the case of colorectal cancer. We compare results with another dataset. We perform image segmentation and extract statistical information about the area, perimeter, circularity, eccentricity and solidity of the interest points in the image. Finally, we use and compare four popular machine learning techniques, i.e., Naive Bayes, Random Forest, Support Vector Machine and Multilayer Perceptron to classify and to improve the precision of category assignation. The performance of each algorithm was measured using 3 types of metrics: Precision, recall and F1-Score representing a huge contribution to the existing literature complementing it in a quantitative way. The large number of images has helped us to circumvent the overfitting and reproducibility problems. The main contribution is the use of new characteristics different from those already studied, this work researches about the color and morphological characteristics in the images that may be useful for performing tissue classification in colorectal cancer histology

Tumor cell load and heterogeneity estimation from diffusion-weighted MRI calibrated with histological data: an example from lung cancer

Producción CientíficaDiffusion-weighted magnetic resonance imaging (DWI) is a key non-invasive imaging technique for cancer diagnosis and tumor treatment assessment, reflecting Brownian movement of water molecules in tissues. Since densely packed cells restrict molecule mobility, tumor tissues produce usually higher signal (a.k.a. less attenuated signal) on isotropic maps compared with normal tissues. However, no general quantitative relation between DWI data and the cell density has been established. In order to link low-resolution clinical cross-sectional data with high-resolution histological information, we developed an image processing and analysis chain, which was used to study the correlation between the diffusion coefficient (D value) estimated from DWI and tumor cellularity from serial histological slides of a resected non-small cell lung cancer tumor. Color deconvolution followed by cell nuclei segmentation was performed on digitized histological images to determine local and cell-type specific 2d (two-dimensional) densities. From these, the 3d cell density was inferred by a model-based sampling technique, which is necessary for the calculation of local and global 3d tumor cell count. Next, DWI sequence information was overlaid with high-resolution CT data and the resected histology using prominent anatomical hallmarks for co-registration of histology tissue blocks and non-invasive imaging modalities' data. The integration of cell numbers information and DWI data derived from different tumor areas revealed a clear negative correlation between cell density and D value. Importantly, spatial tumor cell density can be calculated based on DWI data. In summary, our results demonstrate that tumor cell count and heterogeneity can be predicted from DWI data, which may open new opportunities for personalized diagnosis and therapy optimization

Segmentation of Tumor Regions in Microscopic Images of Breast Cancer Tissue

Nowadays, advances in the domain of digital pathology gave the means to replace the old optical microscopes by the Whole Slide Imaging (WSI) scanners. These scanners enable pathologists viewing conventional tissue slides on a computer monitor. Currently, several applications that aim to analyze human tissue are evolving remarkably. Segmentation of tumor regions in microscopic images of breast cancer tissue in one of the application that researchers are investigating extensively. Indeed, researchers are interested in such application not only because breast cancer is one of the pervasive cancers for human beings, but also segmentation is one of the basic and frequent tasks that pathologists have to perform in order to perform tissue analysis. In this thesis, we addressed the task of segmentation of tumor regions in microscopic images of breast cancer tissue as a machine learning task. We developed different supervised and unsupervised learning frameworks. Our proposed frameworks encompass five steps: (1) pre-processing, (2) feature extraction, (3) feature reduction, (4) supervised and unsupervised learning, and (5) post-processing. We focused on the extraction of textural features, as well as utilization of supervised learning techniques. We investigated individually the MR8Fast, Gabor, and Phase Gradient features, as well as a combination of all these features. We investigated also different classifiers which are Naive Bayes, Artificial Neural Network, and Support Vector Machine, as well as a combination of the supervised learning results. We conducted different experiments in order to compare the different proposed frameworks. Therefore, we developed different conclusions. The MR8Fast features are the most discriminating features compared to the Gabor and Phase Gradient that come in the second and third place respectively. Furthermore, the Naive Bayes classifier and the combination of classification results, that have been overlooked for the segmentation of tumor regions in microscopic images of breast cancer tissue, achieved better results compared to the Support Vector Machine classifier which has been extensively employed for this task. These promising conclusions promote the need for further work to investigate other textural features as well as other classifiers

Appearance normalization of histology slides

This paper presents a method for automatic color and intensity normalization of digitized histology slides stained with two different agents. In comparison to previous approaches, prior information on the stain vectors is used in the plane estimation process, resulting in improved stability of the estimates. Due to the prevalence of hematoxylin and eosin staining for histology slides, the proposed method has significant practical utility. In particular, it can be used as a first step to standardize appearance across slides and is effective at countering effects due to differing stain amounts and protocols and counteracting slide fading. The approach is validated against non-prior plane-fitting using synthetic experiments and 13 real datasets. Results of application of the method to adjustment of faded slides are given, and the effectiveness of the method in aiding statistical classification is shown

An introduction to double stain normalization technique for brain tumour histopathological images

Stain normalization is an image pre-processing method extensively used to standardize multiple variances of staining intensity in histopathology image analysis. Staining variations may occur for several reasons, such as unstandardized protocols while preparing the specimens, using dyes from different manufacturers, and varying parameters set while capturing the digital images. In this study, a double stain normalization technique based on immunohistochemical staining is developed to improve the performance of the conventional Reinhard’s algorithm. The proposed approach began with preparing a target image by applying the contrast-limited adaptive histogram equalization (CLAHE) technique to the targeted cells. Later, the colour distribution of the input image will be matched to the colour distribution of the target image through the linear transformation process. In this study, the power-law transformation was applied to address the over-enhancement and contrast degradation issues in the conventional method. Five quality metrics comprised of entropy, tenengrad criterion (TEN), mean square error (MSE), structural similarity index (SSIM) and correlation coefficient were used to measure the performance of the proposed system. The experimental results demonstrate that the proposed method outperformed all conventional techniques. The proposed method achieved the highest average values of 5.59, 3854.11 and 94.65 for entropy, TEN, and MSE analyses