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.     

Fibrocartilaginous mesenchymoma of bone: a single‐institution experience with molecular investigations and a review of the literature

Whole slide imaging is being used increasingly in research applications and in frozen section, consultation and external quality assurance practice. Digital pathology, when integrated with other digital tools such as barcoding, specimen tracking and digital dictation, can be integrated into the histopathology workflow, from specimen accession to report sign‐out. These elements can bring about improvements in the safety, quality and efficiency of a histopathology department. The present paper reviews the evidence for these benefits. We then discuss the challenges of implementing a fully digital pathology workflow, including the regulatory environment, validation of whole slide imaging and the evidence for the design of a digital pathology workstation.     

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.     

Integration of digital pathology in multidisciplinary breast site group rounds

Whole slide scanning and digitizing an entire glass slide technology opens multiple opportunities for integration in clinical practice. Clinical applications other than primary diagnosis include the use of digitized slides in multidisciplinary rounds. Integration of this emerging technology requires not only adaptation by pathologists but also investment in infrastructure for hardware and software components, electronic storage solutions, support from clinicians and hospital administration as well as training personal. The process of replacing conventional glass with digitized slides in pathology case presentation in multidisciplinary rounds is discussed highlighting the strengths and weaknesses of this transition. Successful implementation relies heavily on careful preliminary workflow process design and support from leaders within Anatomic Pathology and the cancer center.     

Digital pathology and artificial intelligence as the next chapter in diagnostic hematopathology

Digital pathology has a crucial role in diagnostic pathology and is increasingly a technological requirement in the field. Integration of digital slides into the pathology workflow, advanced algorithms, and computer-aided diagnostic techniques extend the frontiers of the pathologist's view beyond the microscopic slide and enable true integration of knowledge and expertise. There is clear potential for artificial intelligence (AI) breakthroughs in pathology and hematopathology.In this review article, we discuss the approach of using machine learning in the diagnosis, classification, and treatment guidelines of hematolymphoid disease, as well as recent progress of artificial intelligence in flow cytometric analysis of hematolymphoid diseases. We review these topics specifically through the potential clinical applications of CellaVision, an automated digital image analyzer of peripheral blood, and Morphogo, a novel artificial intelligence-based bone marrow analyzing system. Adoption of these new technologies will allow pathologists to streamline workflow and achieve faster turnaround time in diagnosing hematological disease.     

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.     

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.     

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.     

Whole-slide imaging: routine pathologic diagnosis

Digital pathology systems offer pathologists an alternate, emerging mechanism to manage and interpret information. They offer increasingly fast and scalable hardware platforms for slide scanning and software that facilitates remote viewing, slide conferencing, archiving, and image analysis. Deployed initially and validated largely within the research and biopharmaceutical industries, WSI is increasingly being implemented for direct patient care. Improvements in image quality, scan times, and imageviewing browsers will hopefully allow pathologists to more seamlessly convert to digital pathology, much like our radiology colleagues have done before us. However, WSI creates both opportunities and challenges. Although niche applications of WSI technology for clinical, educational, and research purposes are clearly successful, it is evident that several areas still require attention and careful consideration before more widespread clinical adoption of WSI takes place. These include regulatory issues, development of standards of practice and validation guidelines, workflow modifications, as well as defining situations where WSI technology will really improve practice in a cost-effective way. Current progress on these and other issues, along with improving technology, will no doubt pave the way for increased adoption over the next decade, allowing the pathology community as a whole to harness the true potential of WSI for patient care. The digital decade will likely redefine how pathology is practiced and the role of the pathologist.     

Eye-movement study and human performance using telepathology virtual slides: implications for medical education and differences with experience

A core skill in diagnostic pathology is light microscopy. Remarkably little is known about human factors that affect the proficiency of pathologists as light microscopists. The cognitive skills of pathologists have received relatively little attention in comparison with the large literature on human performance studies in radiology. One reason for this lack of formal visual search studies in pathology has been the physical restrictions imposed by the close positioning of a microscope operator's head to the microscope's eyepieces. This blocks access to the operator's eyes and precludes assessment of the microscopist's eye movements. Virtual slide microscopy now removes this barrier and opens the door for studies on human factors and visual search strategies in light microscopy. The aim of this study was to assess eye movements of medical students, pathology residents, and practicing pathologists examining virtual slides on a digital display monitor. Whole histopathology glass slide digital images, so-called virtual slides, of 20 consecutive breast core biopsy cases were used in a retrospective study. These high-quality virtual slides were produced with an array-microscope equipped DMetrix DX-40 ultrarapid virtual slide processor (DMetrix, Tucson, Ariz). Using an eye-tracking device, we demonstrated for the first time that when a virtual slide reader initially looks at a virtual slide his or her eyes are very quickly attracted to regions of interest (ROIs) within the slide and that these ROIs are likely to contain diagnostic information. In a matter of seconds, critical decisions are made on the selection of ROIs for further examination at higher magnification. We recorded: (1) the time virtual slide readers spent fixating on self-selected locations on the video monitor; (2) the characteristics of the ways the eyes jumped between fixation locations; and (3) x and y coordinates for each virtual slide marking the sites the virtual slide readers manually selected for zooming to higher ROI magnifications. We correlated the locations of the visually selected fixation locations and the manually selected ROIs. Viewing profiles were identified for each group. Fully trained pathologists spent significantly less time (mean, 4.471 seconds) scanning virtual slides when compared to pathology residents (mean, 7.148 seconds) or medical students (mean, 11.861 seconds), but had relatively prolonged saccadic eye movements (P < .0001). Saccadic eye movements are defined as eye movements between fixation locations. On the other hand, the pathologists spent significantly more time than trainees dwelling on the 3 locations they subsequently chose for zooming. Unlike either the medical students or the residents, the pathologists frequently choose areas for viewing at higher magnification outside of areas of foveal (central) vision. Eye movement studies of scanning pathways (scan paths) may be useful for developing eye movement profiles for individuals and for understanding the difference in performances between novices and experts. They may also be useful for developing new visual search strategies for rendering diagnoses on telepathology virtual slides.     

Digital breast pathology: validation and training for primary digital practice

Digital pathology is a technology which is transforming the way in which breast histopathology specimens are assessed, reported and reviewed. Large scale clinical laboratory deployments of whole slide imaging systems are occurring in diagnostic pathology departments across the world, requiring laboratory and diagnostic staff to navigate new skills and workflows. Transferring from conventional light microscopy assessment of breast specimens to the use of whole slide images (WSI) can be a challenging experience. This article describes an approach to training and validation for breast consultant histopathologists, which has been used and adapted at a number of sites. Examples of types of case that are suitable for training, and some of the potential “pitfalls” of digital reporting for the novice are described, and practical advice regarding clinical digital breast workflow is shared.     

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.     

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.     

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.     

The use of digital images in pathology

Digital images are routinely used by the publishing industry, but most diagnostic pathologists are unfamiliar with the technology and its possibilities. This review aims to explain the basic principles of digital image acquisition, storage, manipulation and use, and the possibilities provided not only in research, but also in teaching and in routine diagnostic pathology. Images of natural objects are usually expressed digitally as ‘bitmaps’—rectilinear arrays of small dots. The size of each dot can vary, but so can its information content in terms, for example, of colour, greyscale or opacity. Various file formats and compression algorithms are available. Video cameras connected to microscopes are familiar to most pathologists; video images can be converted directly to a digital form by a suitably equipped computer. Digital cameras and scanners are alternative acquisition tools of relevance to pathologists. Once acquired, a digital image can easily be subjected to the digital equivalent of any conventional darkroom manipulation and modern software allows much more flexibility, to such an extent that a new tool for scientific fraud has been created. For research, image enhancement and analysis is an increasingly powerful and affordable tool. Morphometric measurements are, after many predictions, at last beginning to be part of the toolkit of the diagnostic pathologist. In teaching, the potential to create dramatic yet informative presentations is demonstrated daily by the publishing industry; such methods are readily applicable to the classroom. The combination of digital images and the Internet raises many possibilities; for example, instead of seeking one expert diagnostic opinion, one could simultaneously seek the opinion of many, all around the globe. It is inevitable that in the coming years the use of digital images will spread from the laboratory to the medical curriculum and to the whole of diagnostic pathology. © 1997 John Wiley & Sons, Ltd.     

Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study

Whole slide digital imaging technology enables researchers to study pathologists’ interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists’ actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors.     

Interobserver and intraobserver reproducibility in digital and routine microscopic assessment of prostate needle biopsies

Advances in whole slide digital imaging in the past decade necessitate validation of these tools in each organ system in advance of clinical adoption. We assessed reproducibility in reporting prostate needle biopsy parameters among urologic pathologists using routine and digital microscopy in a consultation/second opinion-like setting. Four urologic pathologists evaluated a single core level from 50 diagnostically challenging needle biopsy specimens by routine microscopy and whole slide digital imaging. Interobserver and intraobserver agreement were calculated for primary and secondary Gleason grades, Gleason score, tumor quantitation (percentage and size in millimeters), and perineural invasion. Interobserver agreement for routine microscopy was excellent for primary Gleason grade (κ = 0.72) and good for all other parameters (κ ranging from 0.36 to 0.55). Whole slide digital imaging assessment yielded similar agreement for all parameters. Intraobserver agreement for primary Gleason grade and Gleason score was very good to excellent for all pathologists (all κ ≥ 0.65 and ≥ 0.73, respectively). Size of tumor in millimeters consistently displayed higher levels of agreement than percentage of tumor across media and pathologists. Digital assessment of routinely reported cancer parameters on prostatic needle biopsy for a given scanned core level is comparable to that of routine microscopy. These findings imply that histologic interpretation using dynamic whole slide images may accurately simulate routine microscopic evaluation in the consultation setting. Implementation of whole slide digital imaging in these scenarios may significantly reduce the workload of large referral centers in the near future and impact the manner in which pathologists seek second opinion consultation on challenging cases.     

Accuracy is in the eyes of the pathologist: The visual interpretive process and diagnostic accuracy with digital whole slide images

Digital whole slide imaging is an increasingly common medium in pathology, with application to education, telemedicine, and rendering second opinions. It has also made it possible to use eye tracking devices to explore the dynamic visual inspection and interpretation of histopathological features of tissue while pathologists review cases. Using whole slide images, the present study examined how a pathologist’s diagnosis is influenced by fixed case-level factors, their prior clinical experience, and their patterns of visual inspection. Participating pathologists interpreted one of two test sets, each containing 12 digital whole slide images of breast biopsy specimens. Cases represented four diagnostic categories as determined via expert consensus: benign without atypia, atypia, ductal carcinoma in situ (DCIS), and invasive cancer. Each case included one or more regions of interest (ROIs) previously determined as of critical diagnostic importance. During pathologist interpretation we tracked eye movements, viewer tool behavior (zooming, panning), and interpretation time. Models were built using logistic and linear regression with generalized estimating equations, testing whether variables at the level of the pathologists, cases, and visual interpretive behavior would independently and/or interactively predict diagnostic accuracy and efficiency. Diagnostic accuracy varied as a function of case consensus diagnosis, replicating earlier research. As would be expected, benign cases tended to elicit false positives, and atypia, DCIS, and invasive cases tended to elicit false negatives. Pathologist experience levels, case consensus diagnosis, case difficulty, eye fixation durations, and the extent to which pathologists’ eyes fixated within versus outside of diagnostic ROIs, all independently or interactively predicted diagnostic accuracy. Higher zooming behavior predicted a tendency to over-interpret benign and atypia cases, but not DCIS cases. Efficiency was not predicted by pathologist- or visual search-level variables. Results provide new insights into the medical interpretive process and demonstrate the complex interactions between pathologists and cases that guide diagnostic decision-making. Implications for training, clinical practice, and computer-aided decision aids are considered.     

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.     

Digital Pathology Consultations—a New Era in Digital Imaging, Challenges and Practical Applications

Digital pathology has grown dramatically in the last 10 years and has created opportunities to not only support the triaging of difficult cases among specialists within an organization, but also enable remote pathology consultations with external organizations across the world. This study investigated one organization's need for a vendor agnostic Digital Pathology Consultation workflow solution that overcomes the challenges associated with the transfer of large studies across a local area network or across the Internet. The organization investigated is a large multifacility healthcare organization that consists of 20 hospitals spread across a wide geographical area. The organization has one of the largest academic pathology departments in the USA, with more than 100 diagnostic anatomic pathologists. This organization developed a set of web-based tools to support the workflow of digital pathology consultations and allow the viewing of whole slide images. The challenges and practical implementations of two different use cases are addressed: the occasional end user (professional or patient) requesting a second opinion and the external laboratory or hospital looking for an established consultative relationship with a large volume of cases. The solution presented in this study addresses the challenges associated with the distribution of large images and the lack of established imaging standards, while providing for a convenient and secure portal for pathologist report entry and distribution.