Histopathological image analysis : a review

Over the past decade, dramatic increases in computational power and improvement in image analysis algorithms have allowed the development of powerful computer-assisted analytical approaches to radiological data. With the recent advent of whole slide digital scanners, tissue histopathology slides can now be digitized and stored in digital image form. Consequently, digitized tissue histopathology has now become amenable to the application of computerized image analysis and machine learning techniques. Analogous to the role of computer-assisted diagnosis (CAD) algorithms in medical imaging to complement the opinion of a radiologist, CAD algorithms have begun to be developed for disease detection, diagnosis, and prognosis prediction to complement the opinion of the pathologist. In this paper, we review the recent state of the art CAD technology for digitized histopathology. This paper also briefly describes the development and application of novel image analysis technology for a few specific histopathology related problems being pursued in the United States and Europe

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field

The impact of pre- and post-image processing techniques on deep learning frameworks: A comprehensive review for digital pathology image analysis.

Recently, deep learning frameworks have rapidly become the main methodology for analyzing medical images. Due to their powerful learning ability and advantages in dealing with complex patterns, deep learning algorithms are ideal for image analysis challenges, particularly in the field of digital pathology. The variety of image analysis tasks in the context of deep learning includes classification (e.g., healthy vs. cancerous tissue), detection (e.g., lymphocytes and mitosis counting), and segmentation (e.g., nuclei and glands segmentation). The majority of recent machine learning methods in digital pathology have a pre- and/or post-processing stage which is integrated with a deep neural network. These stages, based on traditional image processing methods, are employed to make the subsequent classification, detection, or segmentation problem easier to solve. Several studies have shown how the integration of pre- and post-processing methods within a deep learning pipeline can further increase the model's performance when compared to the network by itself. The aim of this review is to provide an overview on the types of methods that are used within deep learning frameworks either to optimally prepare the input (pre-processing) or to improve the results of the network output (post-processing), focusing on digital pathology image analysis. Many of the techniques presented here, especially the post-processing methods, are not limited to digital pathology but can be extended to almost any image analysis field

Lensfree computational microscopy tools for cell and tissue imaging at the point-of-care and in low-resource settings.

The recent revolution in digital technologies and information processing methods present important opportunities to transform the way optical imaging is performed, particularly toward improving the throughput of microscopes while at the same time reducing their relative cost and complexity. Lensfree computational microscopy is rapidly emerging toward this end, and by discarding lenses and other bulky optical components of conventional imaging systems, and relying on digital computation instead, it can achieve both reflection and transmission mode microscopy over a large field-of-view within compact, cost-effective and mechanically robust architectures. Such high throughput and miniaturized imaging devices can provide a complementary toolset for telemedicine applications and point-of-care diagnostics by facilitating complex and critical tasks such as cytometry and microscopic analysis of e.g., blood smears, Pap tests and tissue samples. In this article, the basics of these lensfree microscopy modalities will be reviewed, and their clinically relevant applications will be discussed

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Tertiary lymphoid structures (TLS) identification and density assessment on H&E-stained digital slides of lung cancer

Tertiary lymphoid structures (TLS) are ectopic aggregates of lymphoid cells in inflamed, infected, or tumoral tissues that are easily recognized on an H&E histology slide as discrete entities, distinct from lymphocytes. TLS are associated with improved cancer prognosis but there is no standardised method available to quantify their presence. Previous studies have used immunohistochemistry to determine the presence of specific cells as a marker of the TLS. This has now been proven to be an underestimate of the true number of TLS. Thus, we propose a methodology for the automated identification and quantification of TLS, based on H&E slides. We subsequently determined the mathematical criteria defining a TLS. TLS regions were identified through a deep convolutional neural network and segmentation of lymphocytes was performed through an ellipsoidal model. This methodology had a 92.87% specificity at 95% sensitivity, 88.79% specificity at 98% sensitivity and 84.32% specificity at 99% sensitivity level based on 144 TLS annotated H&E slides implying that the automated approach was able to reproduce the histopathologists’ assessment with great accuracy. We showed that the minimum number of lymphocytes within TLS is 45 and the minimum TLS area is 6,245μm2. Furthermore, we have shown that the density of the lymphocytes is more than 3 times those outside of the TLS. The mean density and standard deviation of lymphocytes within a TLS area are 0.0128/μm2 and 0.0026/μm2 respectively compared to 0.004/μm2 and 0.001/μm2 in non-TLS regions. The proposed methodology shows great potential for automated identification and quantification of the TLS density on digital H&E slides