A New Optical Density Granulometry-Based Descriptor for the Classification of Prostate Histological Images Using Shallow and Deep Gaussian Processes

[EN] Background and objective Prostate cancer is one of the most common male tumors. The increasing use of whole slide digital scanners has led to an enormous interest in the application of machine learning techniques to histopathological image classification. Here we introduce a novel family of morphological descriptors which, extracted in the appropriate image space and combined with shallow and deep Gaussian process based classifiers, improves early prostate cancer diagnosis. Method We decompose the acquired RGB image in its RGB and optical density hematoxylin and eosin components. Then, we define two novel granulometry-based descriptors which work in both, RGB and optical density, spaces but perform better when used on the latter. In this space they clearly encapsulate knowledge used by pathologists to identify cancer lesions. The obtained features become the inputs to shallow and deep Gaussian process classifiers which achieve an accurate prediction of cancer. Results We have used a real and unique dataset. The dataset is composed of 60 Whole Slide Images. For a five fold cross validation, shallow and deep Gaussian Processes obtain area under ROC curve values higher than 0.98. They outperform current state of the art patch based shallow classifiers and are very competitive to the best performing deep learning method. Models were also compared on 17 Whole Slide test Images using the FROC curve. With the cost of one false positive, the best performing method, the one layer Gaussian process, identifies 83.87% (sensitivity) of all annotated cancer in the Whole Slide Image. This result corroborates the quality of the extracted features, no more than a layer is needed to achieve excellent generalization results. Conclusion Two new descriptors to extract morphological features from histological images have been proposed. They collect very relevant information for cancer detection. From these descriptors, shallow and deep Gaussian Processes are capable of extracting the complex structure of prostate histological images. The new space/descriptor/classifier paradigm outperforms state-of-art shallow classifiers. Furthermore, despite being much simpler, it is competitive to state-of-art CNN architectures both on the proposed SICAPv1 database and on an external databaseThis work was supported by the Ministerio de Economia y Competitividad through project DPI2016-77869. The Titan V used for this research was donated by the NVIDIA CorporationEsteban, AE.; López-Pérez, M.; Colomer, A.; Sales, MA.; Molina, R.; Naranjo Ornedo, V. (2019). A New Optical Density Granulometry-Based Descriptor for the Classification of Prostate Histological Images Using Shallow and Deep Gaussian Processes. Computer Methods and Programs in Biomedicine. 178:303-317. https://doi.org/10.1016/j.cmpb.2019.07.003S30331717

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

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance.Comment: 26 pages, 5 figures, 8 tables + Supplementary material

Are you sure it's an artifact?:Artifact detection and uncertainty quantification in histological images

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions. This paper proposes an uncertainty-aware Deep Kernel Learning (DKL) model to detect blurry areas and folded tissues, two types of artifacts that can appear in WSIs. The proposed probabilistic model combines a CNN feature extractor and a sparse Gaussian Processes (GPs) classifier, which improves the performance of current state-of-the-art artifact detection DCNNs and provides uncertainty estimates. We achieved 0.996 and 0.938 F1 scores for blur and folded tissue detection on unseen data, respectively. In extensive experiments, we validated the DKL model on unseen data from external independent cohorts with different staining and tissue types, where it outperformed DCNNs. Interestingly, the DKL model is more confident in the correct predictions and less in the wrong ones. The proposed DKL model can be integrated into the preprocessing pipeline of CPATH systems to provide reliable predictions and possibly serve as a quality control tool.</p

Are you sure it's an artifact?:Artifact detection and uncertainty quantification in histological images

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions. This paper proposes an uncertainty-aware Deep Kernel Learning (DKL) model to detect blurry areas and folded tissues, two types of artifacts that can appear in WSIs. The proposed probabilistic model combines a CNN feature extractor and a sparse Gaussian Processes (GPs) classifier, which improves the performance of current state-of-the-art artifact detection DCNNs and provides uncertainty estimates. We achieved 0.996 and 0.938 F1 scores for blur and folded tissue detection on unseen data, respectively. In extensive experiments, we validated the DKL model on unseen data from external independent cohorts with different staining and tissue types, where it outperformed DCNNs. Interestingly, the DKL model is more confident in the correct predictions and less in the wrong ones. The proposed DKL model can be integrated into the preprocessing pipeline of CPATH systems to provide reliable predictions and possibly serve as a quality control tool.</p

Proportion constrained weakly supervised histopathology image classification

Multiple instance learning (MIL) deals with data grouped into bags of instances, of which only the global information is known. In recent years, this weakly supervised learning paradigm has become very popular in histological image analysis because it alleviates the burden of labeling all cancerous regions of large Whole Slide Images (WSIs) in detail. However, these methods require large datasets to perform properly, and many approaches only focus on simple binary classification. This often does not match the real-world problems where multi-label settings are frequent and possible constraints must be taken into account. In this work, we propose a novel multi-label MIL formulation based on inequality constraints that is able to incorporate prior knowledge about instance proportions. Our method has a theoretical foundation in optimization with logbarrier extensions, applied to bag-level class proportions. This encourages the model to respect the proportion ordering during training. Extensive experiments on a new public dataset of prostate cancer WSIs analysis, SICAP-MIL, demonstrate that using the prior proportion information we can achieve instance-level results similar to supervised methods on datasets of similar size. In comparison with prior MIL settings, our method allows for ∼ 13% improvements in instance-level accuracy, and ∼ 3% in the multi-label mean area under the ROC curve at the bag-level.Spanish Government PID2019-105142RB-C2European Commission 860627Generalitat Valenciana/European Union through the European Regional Development Fund (ERDF) of the Valencian Community IDIFEDER/2020/030Universitat Politecnica de Valenci

Deep Gaussian processes for multiple instance learning: Application to CT intracranial hemorrhage detection

Background and objective: Intracranial hemorrhage (ICH) is a life-threatening emergency that can lead to brain damage or death, with high rates of mortality and morbidity. The fast and accurate detection of ICH is important for the patient to get an early and efficient treatment. To improve this diagnostic process, the application of Deep Learning (DL) models on head CT scans is an active area of research. Although promising results have been obtained, many of the proposed models require slice-level annotations by radiologists, which are costly and time-consuming. Methods: We formulate the ICH detection as a problem of Multiple Instance Learning (MIL) that allows training with only scan-level annotations. We develop a new probabilistic method based on Deep Gaussian Processes (DGP) that is able to train with this MIL setting and accurately predict ICH at both slice- and scan-level. The proposed DGPMIL model is able to capture complex feature relations by using multiple Gaussian Process (GP) layers, as we show experimentally. Results: To highlight the advantages of DGPMIL in a general MIL setting, we first conduct several controlled experiments on the MNIST dataset. We show that multiple GP layers outperform one-layer GP models, especially for complex feature distributions. For ICH detection experiments, we use two public brain CT datasets (RSNA and CQ500). We first train a Convolutional Neural Network (CNN) with an attention mechanism to extract the image features, which are fed into our DGPMIL model to perform the final predictions. The results show that DGPMIL model outperforms VGPMIL as well as the attention-based CNN for MIL and other state-of-the-art methods for this problem. The best performing DGPMIL model reaches an AUC-ROC of 0.957 (resp. 0.909) and an AUC-PR of 0.961 (resp. 0.889) on the RSNA (resp. CQ500) dataset. Conclusion: The competitive performance at slice- and scan-level shows that DGPMIL model provides an accurate diagnosis on slices without the need for slice-level annotations by radiologists during training. As MIL is a common problem setting, our model can be applied to a broader range of other tasks, especially in medical image classification, where it can help the diagnostic process.Project P20_00286 funded by FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidadesthe European Union’s Horizon 2020 research and innovation programme under the Marie Skodowska Curie grant agreement No 860627 (CLARIFY Project).Funding for open access charge: Universidad de Granada / CBUA

The Devil is in the Details: Whole Slide Image Acquisition and Processing for Artifacts Detection, Color Variation, and Data Augmentation: A Review

Whole Slide Images (WSI) are widely used in histopathology for research and the diagnosis of different types of cancer. The preparation and digitization of histological tissues leads to the introduction of artifacts and variations that need to be addressed before the tissues are analyzed. WSI preprocessing can significantly improve the performance of computational pathology systems and is often used to facilitate human or machine analysis. Color preprocessing techniques are frequently mentioned in the literature, while other areas are usually ignored. In this paper, we present a detailed study of the state-of-the-art in three different areas of WSI preprocessing: Artifacts detection, color variation, and the emerging field of pathology-specific data augmentation. We include a summary of evaluation techniques along with a discussion of possible limitations and future research directions for new methods.European Commission 860627Ministerio de Ciencia e Innovacion (MCIN)/Agencia Estatal de Investigacion (AEI) PID2019-105142RB-C22Fondo Europeo de Desarrollo Regional (FEDER)/Junta de Andalucia-Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades B-TIC-324-UGR20Instituto de Salud Carlos III Spanish Government European Commission BES-2017-08158

Artificial intelligence in digital pathology: a diagnostic test accuracy systematic review and meta-analysis

Ensuring diagnostic performance of AI models before clinical use is key to the safe and successful adoption of these technologies. Studies reporting AI applied to digital pathology images for diagnostic purposes have rapidly increased in number in recent years. The aim of this work is to provide an overview of the diagnostic accuracy of AI in digital pathology images from all areas of pathology. This systematic review and meta-analysis included diagnostic accuracy studies using any type of artificial intelligence applied to whole slide images (WSIs) in any disease type. The reference standard was diagnosis through histopathological assessment and / or immunohistochemistry. Searches were conducted in PubMed, EMBASE and CENTRAL in June 2022. We identified 2976 studies, of which 100 were included in the review and 48 in the full meta-analysis. Risk of bias and concerns of applicability were assessed using the QUADAS-2 tool. Data extraction was conducted by two investigators and meta-analysis was performed using a bivariate random effects model. 100 studies were identified for inclusion, equating to over 152,000 whole slide images (WSIs) and representing many disease types. Of these, 48 studies were included in the meta-analysis. These studies reported a mean sensitivity of 96.3% (CI 94.1-97.7) and mean specificity of 93.3% (CI 90.5-95.4) for AI. There was substantial heterogeneity in study design and all 100 studies identified for inclusion had at least one area at high or unclear risk of bias. This review provides a broad overview of AI performance across applications in whole slide imaging. However, there is huge variability in study design and available performance data, with details around the conduct of the study and make up of the datasets frequently missing. Overall, AI offers good accuracy when applied to WSIs but requires more rigorous evaluation of its performance

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