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.

Learning from crowds for automated histopathological image segmentation.

Automated semantic segmentation of histopathological images is an essential task in Computational Pathology (CPATH). The main limitation of Deep Learning (DL) to address this task is the scarcity of expert annotations. Crowdsourcing (CR) has emerged as a promising solution to reduce the individual (expert) annotation cost by distributing the labeling effort among a group of (non-expert) annotators. Extracting knowledge in this scenario is challenging, as it involves noisy annotations. Jointly learning the underlying (expert) segmentation and the annotators' expertise is currently a commonly used approach. Unfortunately, this approach is frequently carried out by learning a different neural network for each annotator, which scales poorly when the number of annotators grows. For this reason, this strategy cannot be easily applied to real-world CPATH segmentation. This paper proposes a new family of methods for CR segmentation of histopathological images. Our approach consists of two coupled networks: a segmentation network (for learning the expert segmentation) and an annotator network (for learning the annotators' expertise). We propose to estimate the annotators' behavior with only one network that receives the annotator ID as input, achieving scalability on the number of annotators. Our family is composed of three different models for the annotator network. Within this family, we propose a novel modeling of the annotator network in the CR segmentation literature, which considers the global features of the image. We validate our methods on a real-world dataset of Triple Negative Breast Cancer images labeled by several medical students. Our new CR modeling achieves a Dice coefficient of 0.7827, outperforming the well-known STAPLE (0.7039) and being competitive with the supervised method with expert labels (0.7723). The code is available at https://github.com/wizmik12/CRowd_Seg.

Annotation protocol and crowdsourcing multiple instance learning classification of skin histological images: The CR-AI4SkIN dataset.

Digital Pathology (DP) has experienced a significant growth in recent years and has become an essential tool for diagnosing and prognosis of tumors. The availability of Whole Slide Images (WSIs) and the implementation of Deep Learning (DL) algorithms have paved the way for the appearance of Artificial Intelligence (AI) systems that support the diagnosis process. These systems require extensive and varied data for their training to be successful. However, creating labeled datasets in histopathology is laborious and time-consuming. We have developed a crowdsourcing-multiple instance labeling/learning protocol that is applied to the creation and use of the CR-AI4SkIN dataset.2 CR-AI4SkIN contains 271 WSIs of 7 Cutaneous Spindle Cell (CSC) neoplasms with expert and non-expert labels at region and WSI levels. It is the first dataset of these types of neoplasms made available. The regions selected by the experts are used to learn an automatic extractor of Regions of Interest (ROIs) from WSIs. To produce the embedding of each WSI, the representations of patches within the ROIs are obtained using a contrastive learning method, and then combined. Finally, they are fed to a Gaussian process-based crowdsourcing classifier, which utilizes the noisy non-expert WSI labels. We validate our crowdsourcing-multiple instance learning method in the CR-AI4SkIN dataset, addressing a binary classification problem (malign vs. benign). The proposed method obtains an F1 score of 0.7911 on the test set, outperforming three widely used aggregation methods for crowdsourcing tasks. Furthermore, our crowdsourcing method also outperforms the supervised model with expert labels on the test set (F1-score = 0.6035). The promising results support the proposed crowdsourcing multiple instance learning annotation protocol. It also validates the automatic extraction of interest regions and the use of contrastive embedding and Gaussian process classification to perform crowdsourcing classification tasks.

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.

Learning from crowds in digital pathology using scalable variational Gaussian processes.

The volume of labeled data is often the primary determinant of success in developing machine learning algorithms. This has increased interest in methods for leveraging crowds to scale data labeling efforts, and methods to learn from noisy crowd-sourced labels. The need to scale labeling is acute but particularly challenging in medical applications like pathology, due to the expertise required to generate quality labels and the limited availability of qualified experts. In this paper we investigate the application of Scalable Variational Gaussian Processes for Crowdsourcing (SVGPCR) in digital pathology. We compare SVGPCR with other crowdsourcing methods using a large multi-rater dataset where pathologists, pathology residents, and medical students annotated tissue regions breast cancer. Our study shows that SVGPCR is competitive with equivalent methods trained using gold-standard pathologist generated labels, and that SVGPCR meets or exceeds the performance of other crowdsourcing methods based on deep learning. We also show how SVGPCR can effectively learn the class-conditional reliabilities of individual annotators and demonstrate that Gaussian-process classifiers have comparable performance to similar deep learning methods. These results suggest that SVGPCR can meaningfully engage non-experts in pathology labeling tasks, and that the class-conditional reliabilities estimated by SVGPCR may assist in matching annotators to tasks where they perform well.

A new optical density granulometry-based descriptor for the classification of prostate histological images using shallow and deep Gaussian processes.

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 database.

[Simón de Tovar (1528-1596): family networks, American nature and trade in curiosities in 16th century Seville]. / Simón de Tovar (1528-1596): redes familiares, naturaleza americana y comercio de maravillas en la Sevilla del XVI.

The central character of this work is Simón de Tovar, a citizen of late 16th century Seville, who was an outstanding collector of American plants. Beyond the traditional historiography of early modern Spanish botany, Tovar's activities have been set in the context of an expanding trade in marvels and curiosities.

[Some features of the relationship between Lullism and pseudo-Lullism in the early modern times]. / Algunos rasgos sobre la relación entre lulismo y pseudolulismo en la Edad Moderna.

In this work, the author presents, following a chronologic sequence, some aspects of Llull's image that became controversial during the 16th century, especially the discussion about the idea of Llull as alchemist, which developed around the 16th century. To this end, the author analyses the origin and development of the polemic since the 14th century, including the "official" positions. At the same time, the two positions (Llull the achemist and Llull the philosopher) are related to similar occurrences outside the Iberian Peninsular, especially in France and Italy.