Digital pathology: current status and future perspectives

During the last decade pathology has benefited from the rapid progress of image digitizing technology. The improvement in this technology had led to the creation of slide scanners which are able to produce whole slide images (WSI) which can be explored by image viewers in a way comparable to the conventional microscope. The file size of the WSI ranges from a few megabytes to several gigabytes, leading to challenges in the area of image storage and management when they will be used routinely in daily clinical practice. Digital slides are used in pathology for education, diagnostic purposes (clinicopathological meetings, consultations, revisions, slide panels and, increasingly, for upfront clinical diagnostics) and archiving. As an alternative to conventional slides, WSI are generally well accepted, especially in education, where they are available to a large number of students with the full possibilities of annotations without the problem of variation between serial sections. Image processing techniques can also be applied to WSI, providing pathologists with tools assisting in the diagnosis-making process. This paper will highlight the current status of digital pathology applications and its impact on the field of pathology.     

Applications and implications of whole-slide imaging in breast pathology

Technological advances in whole slide imaging (WSI) technology and artificial intelligence (AI) applications in recent years have resulted in increasing adoption of this paradigm shift technology. This brings with it many advantages, new challenges, and potential adaptations to the microscopic assessment of specimens that pathologists need to be aware of. This article describes the applications and implications of WSI within the context of the reporting of breast pathology specimens. Challenging diagnostic entities in digital breast pathology are presented and the key areas in which AI could be useful in breast pathology are highlighted.     

Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies

By imaging large numbers of slides automatically at high resolution, modem automated whole slide imaging (WSI) systems have the potential to become useful tools in pathology practice. This article describes a pilot validation study for use of automated high-speed WSI systems for surgical pathology quality assurance (QA). This was a retrospective comparative study in which 24 full genitourinary cases (including 47 surgical parts and 391 slides) were independently reviewed with traditional microscopy and whole slide digital images. Approximately half the cases had neoplasia in the diagnostic line. At the end of the study, diagnostic discrepancies were evaluated by a pathology consensus committee. The study pathologists felt that the traditional and WSI methods were comparable for case review. They reported no difference in perceived case complexity or diagnostic confidence between the methods. There were 4 clinically insignificant discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI review. Of the 2 discrepancies reported by the WSI method, the committee agreed with the reviewer once and the original report once. At the end of the study, the participants agreed that automated WSI is a viable potential modality for surgical pathology QA, especially in multifacility health systems that would like to establish interfacility QA. The participants felt that major issues limiting the implementation of WSI-based QA did not involve image acquisition or quality but rather image management issues such as the pathologist's interface, the hospital's network, and integration with the laboratory information system.     

Whole-slide imaging in cytopathology: state of the art and future directions

Whole slide imaging (WSI) has been increasingly adopted for digital evaluation of surgical pathology specimens. Unlike histological slides, cytological preparations frequently display a heterogeneous distribution of cells throughout slides in different focal planes sometimes admixed with obscuring material, therefore requiring multiple scanning planes which significantly lengthens image acquisition and evaluation times. Although examination of digital images can be more advantageous than conventional glass slides, the challenges of focusing, scanning and screening cytological specimens and the associated increase in scan times and data storage needs have limited the routine application of WSI in cytopathology practice. Emerging digital systems designed to overcome image acquisition obstacles coupled with artificial intelligence algorithms augmenting screening of digital cytology slides offer innovative solutions to address these limitations. The aim of this review is to critically address the potential benefits and pitfalls of employing WSI in cytopathology practice and to introduce promising state-of-the-art solutions on the horizon.     

Reconciliation of diverse telepathology system designs. Historic issues and implications for emerging markets and new applications

Telepathology, the distant service component of digital pathology, is a growth industry. The word "telepathology" was introduced into the English Language in 1986. Initially, two different, competing imaging modalities were used for telepathology. These were dynamic (real time) robotic telepathology and static image (store-and-forward) telepathology. In 1989, a hybrid dynamic robotic/static image telepathology system was developed in Norway. This hybrid imaging system bundled these two primary pathology imaging modalities into a single multi-modality pathology imaging system. Similar hybrid systems were subsequently developed and marketed in other countries as well. It is noteworthy that hybrid dynamic robotic/static image telepathology systems provided the infrastructure for the first truly sustainable telepathology services. Since then, impressive progress has been made in developing another telepathology technology, so-called "virtual microscopy" telepathology (also called "whole slide image" telepathology or "WSI" telepathology). Over the past decade, WSI has appeared to be emerging as the preferred digital telepathology digital imaging modality. However, recently, there has been a re-emergence of interest in dynamic-robotic telepathology driven, in part, by concerns over the lack of a means for up-and-down focusing (i.e., Z-axis focusing) using early WSI processors. In 2010, the initial two U.S. patents for robotic telepathology (issued in 1993 and 1994) expired enabling many digital pathology equipment companies to incorporate dynamic-robotic telepathology modules into their WSI products for the first time. The dynamic-robotic telepathology module provided a solution to the up-and-down focusing issue. WSI and dynamic robotic telepathology are now, rapidly, being bundled into a new class of telepathology/digital pathology imaging system, the "WSI-enhanced dynamic robotic telepathology system". To date, six major WSI processor equipment companies have embraced the approach and developed WSI-enhanced dynamic-robotic digital telepathology systems, marketed under a variety of labels. Successful commercialization of such systems could help overcome the current resistance of some pathologists to incorporate digital pathology, and telepathology, into their routine and esoteric laboratory services. Also, WSI-enhanced dynamic robotic telepathology could be useful for providing general pathology and subspecialty pathology services to many of the world's underserved populations in the decades ahead. This could become an important enabler for the delivery of patient-centered healthcare in the future.     

Whole-slide imaging: widening the scope of cytopathology

Whole slide imaging (WSI) is broadening the scope of cytopathology. Whole slide images are being used for telecytology, quality assurance activities (e.g. proficiency testing) and teaching (e.g. digital teaching sets and online virtual atlases). Progress in WSI technology that permits high resolution scanning, z-stacking, and hybrid robotic devices has encouraged the use of this imaging modality for cytology practice, education and research. However, widespread adoption in cytology still depends on overcoming barriers unrelated to cytology and challenges directly related to digitizing cytopathology slides. The aim of this article is to review WSI technology, applications and limitations specific to cytopathology.     

An efficient architecture to support digital pathology in standard medical imaging repositories

In the past decade, digital pathology and whole-slide imaging (WSI) have been gaining momentum with the proliferation of digital scanners from different manufacturers. The literature reports significant advantages associated with the adoption of digital images in pathology, namely, improvements in diagnostic accuracy and better support for telepathology. Moreover, it also offers new clinical and research applications. However, numerous barriers have been slowing the adoption of WSI, among which the most important are performance issues associated with storage and distribution of huge volumes of data, and lack of interoperability with other hospital information systems, most notably Picture Archive and Communications Systems (PACS) based on the DICOM standard.This article proposes an architecture of a Web Pathology PACS fully compliant with DICOM standard communications and data formats. The solution includes a PACS Archive responsible for storing whole-slide imaging data in DICOM WSI format and offers a communication interface based on the most recent DICOM Web services. The second component is a zero-footprint viewer that runs in any web-browser. It consumes data using the PACS archive standard web services. Moreover, it features a tiling engine especially suited to deal with the WSI image pyramids. These components were designed with special focus on efficiency and usability. The performance of our system was assessed through a comparative analysis of the state-of-the-art solutions. The results demonstrate that it is possible to have a very competitive solution based on standard workflows.     

Digital Pathology: A Tool for 21st Century Neuropathology

Digital pathology represents an electronic environment for performing pathologic analysis and managing the information associated with this activity. The technology to create and support digital pathology has largely developed over the last decade. The use of digital pathology tools is essential to adapt and lead in the rapidly changing environment of 21st century neuropathology. The utility of digital pathology has already been demonstrated by pathologists in several areas including consensus reviews, quality assurance (Q/A), tissue microarrays (TMAs), education and proficiency testing. These utilities notwithstanding, interface issues, storage and image formatting all present challenges to the integration of digital pathology into the neuropathology work environment. With continued technologic improvements, as well as the introduction of fluorescent side scanning and multispectral detection, future developments in digital pathology offer the promise of adding powerful analytic tools to the pathology work environment. The integration of digital pathology with biorepositories offers particular promise for neuropathologists engaged in tissue banking. The utilization of these tools will be essential for neuropathologists to continue as leaders in diagnostics, translational research and basic science in the 21st century.     

Primary histologic diagnosis using automated whole slide imaging: a validation study

Background  

Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution.     

The future of telepathology for the developing world

Physician shortages are acute in developing countries, where disease burden is the greatest and resources for health care are very limited. A lack of pathologists in these countries has lead to delays in diagnosis and misdiagnoses that adversely affect patient care and survival. The introduction of telepathology into countries with limited resources for health care is but one of multiple approaches that can be used to alleviate the problem. Telepathology is the electronic transmission of digital images that can be used for education and diagnostic consultation. A basic system consists of a microscope with a mounted digital camera linked to a computer. The ability to produce histologic slides, to repair and maintain equipment, and to provide training are also needed for the successful use of this technology. iPath is a Web-based, open platform, software application which was developed at the University of Basel, Switzerland, for telepathology and which brings together pathologists from around the world to provide telepathology support for diagnostic consultation and provides education to centers with limited resources. The use of virtual-slide technology to provide a digital image of an entire glass slide is another technology for diagnostic consultation and pathology education. This technology requires more costly resources to support it, which may limit its utility in many areas. Telepathology can generate collections of digital images and virtual slides needed for training indigenous pathologists in their countries to become self-sufficient. Thus, the long-term goal of this technology is to improve patient care and survival.     

Modern imaging technologies in toxicologic pathology: An overview

Modern imaging technology, now utilized in most biomedical research areas (bioimaging), enables the detection and visualization of biological processes at various levels of the molecule, organelle, cell, tissue, organ and/or whole body. In toxicologic pathology, the impact of modern imaging technology is becoming apparent from digital histopathology to novel molecular imaging for in vivo studies. This overview summarizes recent progresses in digital microscopy imaging and newly developed digital slide techniques. Applications of virtual microscopy imaging are discussed and compared to traditional optical microscopy reading. New generation digital pathology approaches, including automatic slide inspection, digital slide databases and image management are briefly introduced. Commonly used in vivo preclinical imaging technologies are also summarized. While most of these new imaging techniques are still undergoing rapid development, it is important that toxicologic pathologists embrace and utilize these technologies as advances occur.     

Utility of whole slide imaging and virtual microscopy in prostate pathology

Whole slide imaging (WSI) has been used in conjunction with virtual microscopy (VM) for training or proficiency testing purposes, multicentre research, remote frozen section diagnosis and to seek specialist second opinion in a number of organ systems. The feasibility of using WSI/VM for routine surgical pathology reporting has also been explored. In this review, we discuss the utility and limitations of WSI/VM technology in the histological assessment of specimens from the prostate. Features of WSI/VM that are particularly well suited to assessment of prostate pathology include the ability to examine images at different magnifications as well as to view histology and immunohistochemistry side-by-side on the screen. Use of WSI/VM would also solve the difficulty in obtaining multiple identical copies of small lesions in prostate biopsies for teaching and proficiency testing. It would also permit annotation of the virtual slides, and has been used in a study of inter-observer variation of Gleason grading to facilitate precise identification of the foci on which grading decisions had been based. However, the large number of sections examined from each set of prostate biopsies would greatly increase time required for scanning as well as the size of the digital file, and would also be an issue if digital archiving of prostate biopsies is contemplated. Z-scanning of glass slides, a process that increases scanning time and file size would be required to permit focusing a virtual slide up and down to assess subtle nuclear features such as nucleolar prominence. The common use of large blocks to process prostatectomy specimens would also be an issue, as few currently available scanners can scan such blocks. A major component of proficiency testing of prostate biopsy assessment involves screening of the cores to detect small atypical foci. However, screening virtual slides of wavy fragmented prostate cores using a computer mouse aided by an overview image is very different from screening glass slides using a microscope stage. Hence, it may be more appropriate in this setting to mark the lesional area and focus only on the interpretation component of competency testing. Other issues limiting the use of digital pathology in prostate pathology include the cost of high quality slide scanners for WSI and high resolution monitors for VM as well as the requirement for fast Internet connection as even a subtle delay in presentation of images on the screen may be very disturbing for a pathologist used to the rapid viewing of glass slides under a microscope. However, these problems are likely to be overcome by technological advances in the future.     

Validation of whole slide imaging for frozen section diagnosis of lymph node metastasis: A retrospective study from a tertiary care hospital in Thailand

BackgroundThe use of whole slide imaging (WSI) for frozen section (FS) diagnosis is helpful, particularly in the context of pathologist shortages. However, there is minimal data on such usage in resource-limited settings. This study aims to validate the use of WSI for FS diagnosis of lymph node metastasis using a low-cost virtual microscope scanner with consumer-grade laptops at a tertiary care hospital in Thailand.MethodsFS slides were retrieved for which the clinical query was to evaluate lymph node metastasis. They were digitized by a virtual microscope scanner (MoticEasyScan, Hong Kong) using up to 40× optical magnification. Three observers with different pathology experience levels diagnosed each slide, reviewing glass slides (GS) followed by digital slides (DS) after two weeks of a wash out period. WSI and GS diagnoses were compared. The time used for scanning and diagnosis of each slide was recorded.Results295 FS slides were retrieved and digitized. The first-time successful scanning rate was 93.6 %. The mean scanning time was 2 min per slide. Both intraobserver agreement and interobserver agreement of WSI and GS diagnoses were high (Cohen's K; kappa value >0.84). The time used for DS diagnosis decreased as the observer's experience with WSI increased.ConclusionsDespite varying pathological experiences, observers using WSI provided accurate FS diagnoses of lymph node metastasis. The time required for DS diagnoses decreased with additional observer's experience with WSI. Therefore, a WSI system containing low-cost scanners and consumer-grade laptops could be used for FS services in hospital laboratories lacking pathologists.     

Software-assisted decision support in digital histopathology

Tissue diagnostics is the world of pathologists, and it is increasingly becoming digitalised to leverage the enormous potential of personalised medicine and of stratifying patients, enabling the administration of modern therapies. Therefore, the daily task for pathologists is changing drastically and will become increasingly demanding in order to take advantage of the development of modern computer technologies. The role of pathologist has rapidly evolved from exclusively describing the morphology and phenomenology of a disease, to becoming a gatekeeper for novel and most effective treatment options. This is possible based on the retrieval and management of a wide range of complex information from tissue or a group of cells and associated meta-data. Intelligent and self-learning software solutions can support and guide pathologists to score clinically relevant decisions based on the accurate and robust quantification of multiple target molecules or surrogate biomarker as companion or complimentary diagnostics along with relevant spatial relationships and contextual information from digital H&E and multiplexed images. With the availability of multiplex staining techniques on a single slide, high-resolution image analysis tools, and high-end computer hardware, machine and deep learning solutions now offer diagnostic rulesets and algorithms that still require clinical validation in well-designed studies. Before entering the clinical practice, the ‘human factor’ pathologist needs to develop trust in the output coming from the ‘digital black box of computational pathology’, including image analysis solutions and artificial intelligence algorithms to support critical clinical decisions which otherwise would not be available. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Evaluation of whole slide image immunohistochemistry interpretation in challenging prostate needle biopsies

Whole slide images (WSIs), also known as virtual slides, can support electronic distribution of immunohistochemistry (IHC) stains to pathologists that rely on remote sites for these services. This may lead to improvement in turnaround times, reduction of courier costs, fewer errors in slide distribution, and automated image analyses. Although this approach is practiced de facto today in some large laboratories, there are no clinical validation studies on this approach. Our retrospective study evaluated the interpretation of IHC stains performed in difficult prostate biopsies using WSIs. The study included 30 foci with IHC stains identified by the original pathologist as both difficult and pivotal to the final diagnosis. WSIs were created from the glass slides using a scanning robot (T2, Aperio Technologies, Vista, CA). An evaluation form was designed to capture data in 2 phases: (1) interpretation of WSIs and (2) interpretation of glass slides. Data included stain interpretations, diagnoses, and other parameters such as time required to diagnose and image/slide quality. Data were also collected from an expert prostate pathologist, consensus meetings, and a poststudy focus group. WSI diagnostic validity (intraobserver pairwise kappa statistics) was "almost perfect" for 1 pathologist, "substantial" for 3 pathologists, and "moderate" for 1 pathologist. Diagnostic agreement between the final/consensus diagnoses of the group and those of the domain expert was "almost perfect" (kappa = 0.817). Except for one instance, WSI technology was not felt to be the cause of disagreements. These results are encouraging and compare favorably with other efforts to quantify diagnostic variability in surgical pathology. With thorough training, careful validation of specific applications, and regular postsignout review of glass IHC slides (eg, quality assurance review), WSI technology can be used for IHC stain interpretation.     

Whole slide images for primary diagnostics of gastrointestinal tract pathology: a feasibility study

During the last decade, whole slide images have been used in many areas of pathology such as teaching, research, digital archiving, teleconsultation, and quality assurance testing. However, whole slide images have as yet not much been used for up-front diagnostics because of the lack of validation studies. The aim of this study was, therefore, to test the feasibility of whole slide images for diagnosis of gastrointestinal tract specimens, one of the largest areas of diagnostic pathology. One hundred gastrointestinal tract biopsies and resections that had been diagnosed using light microscopy 1 year before were rediagnosed on whole slide images scanned at ×20 magnification by 5 pathologists (all reassessing their own cases), having the original clinical information available but blinded to their original light microscopy diagnoses. The original light microscopy and whole slide image-based diagnoses were compared and classified as concordant, slightly discordant (without clinical consequences), and discordant. The diagnoses based on light microscopy and the whole slide image-based rediagnoses were concordant in 95% of the cases. Light microscopy and whole slide image diagnosis in the remaining 5% of cases were slightly discordant, none of these were with clinical or prognostic implications. Up-front histopathologic diagnosis of gastrointestinal biopsies and resections can be done on whole slide images.     

A review and a framework of handheld computer adoption in healthcare

Wide adoption of mobile computing technology can potentially improve information access, enhance workflow, and promote evidence-based practice to make informed and effective decisions at the point of care. Handheld computers or personal digital assistants (PDAs) offer portable and unobtrusive access to clinical data and relevant information at the point of care. This article reviews the literature on issues related to adoption of PDAs in health care and barriers to PDA adoption. Studies showed that PDAs were used widely in health care providers' practice, and the level of use is expected to rise rapidly. Most care providers found PDAs to be functional and useful in areas of documentation, medical reference, and access to patient data. Major barriers to adoption were identified as usability, security concerns, and lack of technical and organizational support. PDAs offer health care practitioners advantages to enhance their clinical practice. However, better designed PDA hardware and software applications, more institutional support, seamless integration of PDA technology with hospital information systems, and satisfactory security measures are necessary to increase acceptance and wide use of PDAs in healthcare.     

A whole-slide imaging based workflow reduces the reading time of pathologists

Even though entirely digitized microscopic tissue sections (whole slide images, WSIs) are increasingly being used in histopathology diagnostics, little data is still available on the effect of this technique on pathologists' reading time. This study aimed to compare the time required to perform the microscopic assessment by pathologists between a conventional workflow (an optical microscope) and digitized WSIs. WSI was used in primary diagnostics at the Laboratory for Pathology Eastern Netherlands for several years (LabPON, Hengelo, The Netherlands). Cases were read either in a traditional workflow, with the pathologist recording the time required for diagnostics and reporting, or entirely digitally. Reading times were extracted from image management system log files, and the digitized workflow was fully integrated into the laboratory information system. The digital workflow saved time in the majority of case categories, with prostate biopsies saving the most (68% time gain). Taking into account case distribution, the digital workflow produced an average gain of 12.3%. Using WSI instead of conventional microscopy significantly reduces pathologists' reading times. Pathologists must work in a fully integrated environment to fully reap the benefits of a digital workflow.