A Containerized Software System for Generation, Management, and Exploration of Features from Whole Slide Tissue Images.
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ABSTRACT:
SUBMITTER: Saltz J
PROVIDER: S-EPMC5987533 | biostudies-literature | 2017 Nov
REPOSITORIES: biostudies-literature
Publications
A Containerized Software System for Generation, Management, and Exploration of Features from Whole Slide Tissue Images.
Saltz Joel J Sharma Ashish A Iyer Ganesh G Bremer Erich E Wang Feiqiao F Jasniewski Alina A DiPrima Tammy T Almeida Jonas S JS Gao Yi Y Zhao Tianhao T Saltz Mary M Kurc Tahsin T
Cancer research 20171101 21
Well-curated sets of pathology image features will be critical to clinical studies that aim to evaluate and predict treatment responses. Researchers require information synthesized across multiple biological scales, from the patient to the molecular scale, to more effectively study cancer. This article describes a suite of services and web applications that allow users to select regions of interest in whole slide tissue images, run a segmentation pipeline on the selected regions to extract nucle ...[more]
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Project description:The introduction of deep learning caused a significant breakthrough in digital pathology. Thanks to its capability of mining hidden data patterns in digitised histological slides to resolve diagnostic tasks and extract prognostic and predictive information. However, the high performance achieved in classification tasks depends on the availability of large datasets, whose collection and preprocessing are still time-consuming processes. Therefore, strategies to make these steps more efficient are worth investigation. This work introduces SlideTiler, an open-source software with a user-friendly graphical interface. SlideTiler can manage several image preprocessing phases through an intuitive workflow that does not require specific coding skills. The software was designed to provide direct access to virtual slides, allowing custom tiling of specific regions of interest drawn by the user, tile labelling, quality assessment, and direct export to dataset directories. To illustrate the functions and the scalability of SlideTiler, a deep learning-based classifier was implemented to classify 4 different tumour histotypes available in the TCGA repository. The results demonstrate the effectiveness of SlideTiler in facilitating data preprocessing and promoting accessibility to digitised pathology images for research purposes. Considering the increasing interest in deep learning applications of digital pathology, SlideTiler has a positive impact on this field. Moreover, SlideTiler has been conceived as a dynamic tool in constant evolution, and more updated and efficient versions will be released in the future.
| S-EPMC10787253 | biostudies-literature
Project description:BackgroundDeep learning has revolutionized digital pathology, allowing automatic analysis of hematoxylin and eosin (H&E) stained whole slide images (WSIs) for diverse tasks. WSIs are broken into smaller images called tiles, and a neural network encodes each tile. Many recent works use supervised attention-based models to aggregate tile-level features into a slide-level representation, which is then used for downstream analysis. Training supervised attention-based models is computationally intensive, architecture optimization of the attention module is non-trivial, and labeled data are not always available. Therefore, we developed an unsupervised and fast approach called SAMPLER to generate slide-level representations.MethodsSlide-level representations of SAMPLER are generated by encoding the cumulative distribution functions of multiscale tile-level features. To assess effectiveness of SAMPLER, slide-level representations of breast carcinoma (BRCA), non-small cell lung carcinoma (NSCLC), and renal cell carcinoma (RCC) WSIs of The Cancer Genome Atlas (TCGA) were used to train separate classifiers distinguishing tumor subtypes in FFPE and frozen WSIs. In addition, BRCA and NSCLC classifiers were externally validated on frozen WSIs. Moreover, SAMPLER's attention maps identify regions of interest, which were evaluated by a pathologist. To determine time efficiency of SAMPLER, we compared runtime of SAMPLER with two attention-based models. SAMPLER concepts were used to improve the design of a context-aware multi-head attention model (context-MHA).FindingsSAMPLER-based classifiers were comparable to state-of-the-art attention deep learning models to distinguish subtypes of BRCA (AUC = 0.911 ± 0.029), NSCLC (AUC = 0.940 ± 0.018), and RCC (AUC = 0.987 ± 0.006) on FFPE WSIs (internal test sets). However, training SAMLER-based classifiers was >100 times faster. SAMPLER models successfully distinguished tumor subtypes on both internal and external test sets of frozen WSIs. Histopathological review confirmed that SAMPLER-identified high attention tiles contained subtype-specific morphological features. The improved context-MHA distinguished subtypes of BRCA and RCC (BRCA-AUC = 0.921 ± 0.027, RCC-AUC = 0.988 ± 0.010) with increased accuracy on internal test FFPE WSIs.InterpretationOur unsupervised statistical approach is fast and effective for analyzing WSIs, with greatly improved scalability over attention-based deep learning methods. The high accuracy of SAMPLER-based classifiers and interpretable attention maps suggest that SAMPLER successfully encodes the distinct morphologies within WSIs and will be applicable to general histology image analysis problems.FundingThis study was supported by the National Cancer Institute (Grant No. R01CA230031 and P30CA034196).
| S-EPMC10733087 | biostudies-literature
Project description:Modern pathology diagnostics is being driven toward large scale digitization of microscopic tissue sections. A prerequisite for its safe implementation is the guarantee that all tissue present on a glass slide can also be found back in the digital image. Whole-slide scanners perform a tissue segmentation in a low resolution overview image to prevent inefficient high-resolution scanning of empty background areas. However, currently applied algorithms can fail in detecting all tissue regions. In this study, we developed convolutional neural networks to distinguish tissue from background. We collected 100 whole-slide images of 10 tissue samples-staining categories from five medical centers for development and testing. Additionally, eight more images of eight unfamiliar categories were collected for testing only. We compared our fully-convolutional neural networks to three traditional methods on a range of resolution levels using Dice score and sensitivity. We also tested whether a single neural network can perform equivalently to multiple networks, each specialized in a single resolution. Overall, our solutions outperformed the traditional methods on all the tested resolutions. The resolution-agnostic network achieved average Dice scores between 0.97 and 0.98 across the tested resolution levels, only 0.0069 less than the resolution-specific networks. Finally, its excellent generalization performance was demonstrated by achieving averages of 0.98 Dice score and 0.97 sensitivity on the eight unfamiliar images. A future study should test this network prospectively.
| S-EPMC6924324 | biostudies-literature
Project description:ObjectiveDigital pathology is today a widely used technology, and the digitalization of microscopic slides into whole slide images (WSIs) allows the use of machine learning algorithms as a tool in the diagnostic process. In recent years, "deep learning" algorithms for image analysis have been applied to digital pathology with great success. The training of these algorithms requires a large volume of high-quality images and image annotations. These large image collections are a potent source of information, and to use and share the information, standardization of the content through a consistent terminology is essential. The aim of this project was to develop a pilot dataset of exhaustive annotated WSI of normal and abnormal human tissue and link the annotations to appropriate ontological information.Materials and methodsSeveral biomedical ontologies and controlled vocabularies were investigated with the aim of selecting the most suitable ontology for this project. The selection criteria required an ontology that covered anatomical locations, histological subcompartments, histopathologic diagnoses, histopathologic terms, and generic terms such as normal, abnormal, and artifact. WSIs of normal and abnormal tissue from 50 colon resections and 69 skin excisions, diagnosed 2015-2016 at the Department of Clinical Pathology in Linköping, were randomly collected. These images were manually and exhaustively annotated at the level of major subcompartments, including normal or abnormal findings and artifacts.ResultsSystemized nomenclature of medicine clinical terms (SNOMED CT) was chosen, and the annotations were linked to its codes and terms. Two hundred WSI were collected and annotated, resulting in 17,497 annotations, covering a total area of 302.19 cm2, equivalent to 107,7 gigapixels. Ninety-five unique SNOMED CT codes were used. The time taken to annotate a WSI varied from 45 s to over 360 min, a total time of approximately 360 h.ConclusionThis work resulted in a dataset of 200 exhaustive annotated WSIs of normal and abnormal tissue from the colon and skin, and it has informed plans to build a comprehensive library of annotated WSIs. SNOMED CT was found to be the best ontology for annotation labeling. This project also demonstrates the need for future development of annotation tools in order to make the annotation process more efficient.
| S-EPMC6669998 | biostudies-literature
Project description:High-throughput serial histology imaging provides a new avenue for the routine study of micro-anatomical structures in a 3D space. However, the emergence of serial whole slide imaging poses a new registration challenge, as the gigapixel image size precludes the direct application of conventional registration techniques. In this paper, we develop a three-stage registration with multi-resolution mapping and propagation method to dynamically produce registered subvolumes from serial whole slide images. We validate our algorithm with gigapixel images of serial brain tumor sections and synthetic image volumes. The qualitative and quantitative assessment results demonstrate the efficacy of our approach and suggest its promise for 3D histology reconstruction analysis.
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Project description:Many physiological processes and pathological phenomena in the liver tissue are spatially heterogeneous. At a local scale, biomarkers can be quantified along the axis of the blood flow, from portal fields (PFs) to central veins (CVs), i.e., in zonated form. This requires detecting PFs and CVs. However, manually annotating these structures in multiple whole-slide images is a tedious task. We describe and evaluate a fully automated method, based on a convolutional neural network, for simultaneously detecting PFs and CVs in a single stained section. Trained on scans of hematoxylin and eosin-stained liver tissue, the detector performed well with an F1 score of 0.81 compared to annotation by a human expert. It does, however, not generalize well to previously unseen scans of steatotic liver tissue with an F1 score of 0.59. Automated PF and CV detection eliminates the bottleneck of manual annotation for subsequent automated analyses, as illustrated by two proof-of-concept applications: We computed lobulus sizes based on the detected PF and CV positions, where results agreed with published lobulus sizes. Moreover, we demonstrate the feasibility of zonated quantification of biomarkers detected in different stainings based on lobuli and zones obtained from the detected PF and CV positions. A negative control (hematoxylin and eosin) showed the expected homogeneity, a positive control (glutamine synthetase) was quantified to be strictly pericentral, and a plausible zonation for a heterogeneous F4/80 staining was obtained. Automated detection of PFs and CVs is one building block for automatically quantifying physiologically relevant heterogeneity of liver tissue biomarkers. Perspectively, a more robust and automated assessment of zonation from whole-slide images will be valuable for parameterizing spatially resolved models of liver metabolism and to provide diagnostic information.
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Project description:Tumor grading is an essential factor for cancer staging and survival prognostication. The widely used the WHO grading system defines the histological grade of CRC adenocarcinoma based on the density of glandular formation on whole-slide images (WSIs). We developed a fully automated approach for stratifying colorectal cancer (CRC) patients' risk of mortality directly from histology WSI relating to gland formation. A tissue classifier was trained to categorize regions on WSI as glands, stroma, immune cells, background, and other tissues. A gland formation classifier was trained on expert annotations to categorize regions as different degrees of tumor gland formation versus normal tissues. The glandular formation density can thus be estimated using the aforementioned tissue categorization and gland formation information. This estimation was called a semi-quantitative gland formation ratio (SGFR), which was used as a prognostic factor in survival analysis. We evaluated gland formation percentage and validated it by comparing it against the WHO cutoff point. Survival data and gland formation maps were then used to train a spatial pyramid pooling survival network (SPPSN) as a deep survival model. We compared the survival prediction performance of estimated gland formation percentage and the SPPSN deep survival grade and found that the deep survival grade had improved discrimination. A univariable Cox model for survival yielded moderate discrimination with SGFR (c-index 0.62) and deep survival grade (c-index 0.64) in an independent institutional test set. Deep survival grade also showed better discrimination performance in multivariable Cox regression. The deep survival grade significantly increased the c-index of the baseline Cox model in both validation set and external test set, but the inclusion of SGFR can only improve the Cox model less in external test and is unable to improve the Cox model in the validation set.
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Project description:Computational image analysis is one means for evaluating digitized histopathology specimens that can increase the reproducibility and reliability with which cancer diagnoses are rendered while simultaneously providing insight as to the underlying mechanisms of disease onset and progression. A major challenge that is confronted when analyzing samples that have been prepared at disparate laboratories and institutions is that the algorithms used to assess the digitized specimens often exhibit heterogeneous staining characteristics because of slight differences in incubation times and the protocols used to prepare the samples. Unfortunately, such variations can render a prediction model learned from one batch of specimens ineffective for characterizing an ensemble originating from another site. In this work, we propose to adopt unsupervised domain adaptation to effectively transfer the discriminative knowledge obtained from any given source domain to the target domain without requiring any additional labeling or annotation of images at the target site. In this paper, our team investigates the use of two approaches for performing the adaptation: (1) color normalization and (2) adversarial training. The adversarial training strategy is implemented through the use of convolutional neural networks to find an invariant feature space and Siamese architecture within the target domain to add a regularization that is appropriate for the entire set of whole-slide images. The adversarial adaptation results in significant classification improvement compared with the baseline models under a wide range of experimental settings.
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Project description:OBJECTIVES:With the objective of bringing clinical decision support systems to reality, this article reviews histopathological whole-slide imaging informatics methods, associated challenges, and future research opportunities. TARGET AUDIENCE:This review targets pathologists and informaticians who have a limited understanding of the key aspects of whole-slide image (WSI) analysis and/or a limited knowledge of state-of-the-art technologies and analysis methods. SCOPE:First, we discuss the importance of imaging informatics in pathology and highlight the challenges posed by histopathological WSI. Next, we provide a thorough review of current methods for: quality control of histopathological images; feature extraction that captures image properties at the pixel, object, and semantic levels; predictive modeling that utilizes image features for diagnostic or prognostic applications; and data and information visualization that explores WSI for de novo discovery. In addition, we highlight future research directions and discuss the impact of large public repositories of histopathological data, such as the Cancer Genome Atlas, on the field of pathology informatics. Following the review, we present a case study to illustrate a clinical decision support system that begins with quality control and ends with predictive modeling for several cancer endpoints. Currently, state-of-the-art software tools only provide limited image processing capabilities instead of complete data analysis for clinical decision-making. We aim to inspire researchers to conduct more research in pathology imaging informatics so that clinical decision support can become a reality.
| S-EPMC3822114 | biostudies-literature