Virtual Versus Light Microscopy Usage among Students: A Systematic Review and Meta-Analytic Evidence in Medical Education.

BACKGROUND: The usage of whole-slide images has recently been gaining a foothold in medical education, training, and diagnosis. OBJECTIVES: The first objective of the current study was to compare academic performance on virtual microscopy (VM) and light microscopy (LM) for learning pathology, anatomy, and histology in medical and dental students during the COVID-19 period. The second objective was to gather insight into various applications and usage of such technology for medical education. MATERIALS AND METHODS: Using the keywords "virtual microscopy" or "light microscopy" or "digital microscopy" and "medical" and "dental" students, databases (PubMed, Embase, Scopus, Cochrane, CINAHL, and Google Scholar) were searched. Hand searching and snowballing were also employed for article searching. After extracting the relevant data based on inclusion and execution criteria, the qualitative data were used for the systematic review and quantitative data were used for meta-analysis. The Newcastle Ottawa Scale (NOS) scale was used to assess the quality of the included studies. Additionally, we registered our systematic review protocol in the prospective register of systematic reviews (PROSPERO) with registration number CRD42020205583. RESULTS: A total of 39 studies met the criteria to be included in the systematic review. Overall, results indicated a preference for this technology and better academic scores. Qualitative analyses reported improved academic scores, ease of use, and enhanced collaboration amongst students as the top advantages, whereas technical issues were a disadvantage. The performance comparison of virtual versus light microscopy meta-analysis included 19 studies. Most (10/39) studies were from medical universities in the USA. VM was mainly used for teaching pathology courses (25/39) at medical schools (30/39). Dental schools (10/39) have also reported using VM for teaching microscopy. The COVID-19 pandemic was responsible for the transition to VM use in 17/39 studies. The pooled effect size of 19 studies significantly demonstrated higher exam performance (SMD: 1.36 [95% CI: 0.75, 1.96], p < 0.001) among the students who used VM for their learning. Students in the VM group demonstrated significantly higher exam performance than LM in pathology (SMD: 0.85 [95% CI: 0.26, 1.44], p < 0.01) and histopathology (SMD: 1.25 [95% CI: 0.71, 1.78], p < 0.001). For histology (SMD: 1.67 [95% CI: -0.05, 3.40], p = 0.06), the result was insignificant. The overall analysis of 15 studies assessing exam performance showed significantly higher performance for both medical (SMD: 1.42 [95% CI: 0.59, 2.25], p < 0.001) and dental students (SMD: 0.58 [95% CI: 0.58, 0.79], p < 0.001). CONCLUSIONS: The results of qualitative and quantitative analyses show that VM technology and digitization of glass slides enhance the teaching and learning of microscopic aspects of disease. Additionally, the COVID-19 global health crisis has produced many challenges to overcome from a macroscopic to microscopic scale, for which modern virtual technology is the solution. Therefore, medical educators worldwide should incorporate newer teaching technologies in the curriculum for the success of the coming generation of health-care professionals.

The Nomadic Digital Pathologist. Validation of a simple, dual slide scanner with remote reporting for a regional upper gastrointestinal specialist multidisciplinary meeting.

Background: This article describes how a simple slide scanner with remote viewing software enabled a remote "nomadic" pathologist to continue his role as specialist lead for a regional gastrointestinal multidisciplinary team meeting (MDTM) after relocating to another site in the 5 hospital Southwest UK Peninsula cancer network just prior to the COVID-19 pandemic. Materials and methods: The author used digital pathology (DP) to supplement a conventional workflow as a way of minimising delay in reporting and reviewing slides for a regional specialist Oesophagogastric MDTM (the OGSMDT). The specialist centre at University Hospital Plymouth (UHP) is 58 miles from the author's new workplace at Royal Cornwall Hospital (RCHT). Slides from the 44 cases (10% of this specialist annual workload) in this validation study were reported or reviewed digitally using the slide scanner. All were listed for the OGSMDT due to being clinically suspicious for upper gastrointestinal malignancy, having been processed at UHP, or one of the other hospitals in the cancer network. Results: The scanner allowed the author who was only on site at UHP 1 day per week to prevent delays in reporting/reviewing glass slides, using remote DP. Confidence in digital diagnosis was assessed using the Royal College of Pathologists recommendations. The author was the primary pathologist signing out 31, and second opinion for the remaining 13 cases. These comprised a mixture of biopsies as well as endoscopic and surgical excision specimens. The DP system enabled the author to report the cases digitally with an equivalent degree of confidence to glass slides and no significant discrepancies were identified between the author's digital and final glass slide diagnosis. Conclusions: The scanner was found to be safe and effective for remote reporting and review for OGSMDT cases. It was recognised that DP was advantageous to enable this role to continue remotely but that a fully integrated digital reporting system capable of high-capacity scanning would be preferable to the simple system used.

The need for measurement science in digital pathology.

Background: Pathology services experienced a surge in demand during the COVID-19 pandemic. Digitalisation of pathology workflows can help to increase throughput, yet many existing digitalisation solutions use non-standardised workflows captured in proprietary data formats and processed by black-box software, yielding data of varying quality. This study presents the views of a UK-led expert group on the barriers to adoption and the required input of measurement science to improve current practices in digital pathology. Methods: With an aim to support the UK's efforts in digitalisation of pathology services, this study comprised: (1) a review of existing evidence, (2) an online survey of domain experts, and (3) a workshop with 42 representatives from healthcare, regulatory bodies, pharmaceutical industry, academia, equipment, and software manufacturers. The discussion topics included sample processing, data interoperability, image analysis, equipment calibration, and use of novel imaging modalities. Findings: The lack of data interoperability within the digital pathology workflows hinders data lookup and navigation, according to 80% of attendees. All participants stressed the importance of integrating imaging and non-imaging data for diagnosis, while 80% saw data integration as a priority challenge. 90% identified the benefits of artificial intelligence and machine learning, but identified the need for training and sound performance metrics.Methods for calibration and providing traceability were seen as essential to establish harmonised, reproducible sample processing, and image acquisition pipelines. Vendor-neutral data standards were seen as a "must-have" for providing meaningful data for downstream analysis. Users and vendors need good practice guidance on evaluation of uncertainty, fitness-for-purpose, and reproducibility of artificial intelligence/machine learning tools. All of the above needs to be accompanied by an upskilling of the pathology workforce. Conclusions: Digital pathology requires interoperable data formats, reproducible and comparable laboratory workflows, and trustworthy computer analysis software. Despite high interest in the use of novel imaging techniques and artificial intelligence tools, their adoption is slowed down by the lack of guidance and evaluation tools to assess the suitability of these techniques for specific clinical question. Measurement science expertise in uncertainty estimation, standardisation, reference materials, and calibration can help establishing reproducibility and comparability between laboratory procedures, yielding high quality data and providing higher confidence in diagnosis.

Impact of COVID-19 on the adoption of digital pathology

Digital pathology was developed decades ago to allow pathologists to remotely collaborate on cases and improve the accuracy of diagnostic techniques by sharing digital images across laboratories. Before the COVID-19 pandemic, the United States lagged behind most other developed countries in terms of digital pathology adoption due to strict federal regulations of the US Food and Drug Administration (FDA) and the Clinical Laboratory Improvement Amendments (CLIA) from the Centers for Medicare & Medicaid Services (CMS). The FDA relaxed some of its requirements to approve and validate digital pathology-related technology to meet the pandemic response's needs. Similarly, the CMS waived restrictive CLIA rules that now allowed pathologists to use digital pathology platforms from home. Thereby, the COVID-19 pandemic accelerated the broad adoption of digital pathology for remotely rendering pathology diagnoses. This imaging technology has provided pathologists and pathologists-in-training with a variety of resources to help them continue to remotely care for patients, collaborate, and support virtual education. This paradigm shift will impact not only how we routinely work in the postpandemic era but also how we will virtually teach pathology in the future and possibly even modify regulations that govern how digital pathology systems can be used and get approved for diagnostic use. The focus of this chapter is on digital pathology concerning the COVID-19 pandemic. © 2022 Elsevier Inc. All rights reserved.

Cultivating Clinical Clarity through Computer Vision: A Current Perspective on Whole Slide Imaging and Artificial Intelligence.

Diagnostic devices, methodological approaches, and traditional constructs of clinical pathology practice, cultivated throughout centuries, have transformed radically in the wake of explosive technological growth and other, e.g., environmental, catalysts of change. Ushered into the fray of modern laboratory medicine are digital imaging devices and machine-learning (ML) software fashioned to mitigate challenges, e.g., practitioner shortage while preparing clinicians for emerging interconnectivity of environments and diagnostic information in the era of big data. As computer vision shapes new constructs for the modern world and intertwines with clinical medicine, cultivating clarity of our new terrain through examining the trajectory and current scope of computational pathology and its pertinence to clinical practice is vital. Through review of numerous studies, we find developmental efforts for ML migrating from research to standardized clinical frameworks while overcoming obstacles that have formerly curtailed adoption of these tools, e.g., generalizability, data availability, and user-friendly accessibility. Groundbreaking validatory efforts have facilitated the clinical deployment of ML tools demonstrating the capacity to effectively aid in distinguishing tumor subtype and grade, classify early vs. advanced cancer stages, and assist in quality control and primary diagnosis applications. Case studies have demonstrated the benefits of streamlined, digitized workflows for practitioners alleviated by decreased burdens.

Types and frequency of whole slide imaging scan failures in a clinical high throughput digital pathology scanning laboratory.

Digital workflow transformation continues to sweep throughout a diversity of pathology departments spanning the globe following catalyzation of whole slide imaging (WSI) adoption by the SARS-CoV-2 (COVID-19) pandemic. The utility of WSI for a litany of use cases including primary diagnosis has been emphasized during this period, with WSI scanning devices gaining the approval of healthcare regulatory bodies and practitioners alike for clinical applications following extensive validatory efforts. As successful validation for WSI is predicated upon pathologist diagnostic interpretability of digital images with high glass slide concordance, departmental adoption of WSI is tantamount to the reliability of such images often predicated upon quality assessment notwithstanding image interpretability but extending to quality of practice following WSI adoption. Metrics of importance within this context include failure rates inclusive of different scanning errors that result in poor image quality and the potential such errors may incur upon departmental turnaround time (TAT). We sought to evaluate the impact of WSI implementation through retrospective evaluation of scan failure frequency in archival versus newly prepared slides, types of scanning error, and impact upon TAT following commencement of live WSI operation in May 2017 until the present period within a fully digitized high-volume academic institution. A 1.19% scan failure incidence rate was recorded during this period, with re-scanning requested and successfully executed for 1.19% of cases during the reported period of January 2019 until present. No significant impact upon TAT was deduced, suggesting an outcome which may be encouraging for departments considering digital workflow adoption.

Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP).

The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe.

Diagnostic Pitfalls of Digital Microscopy Versus Light Microscopy in Gastrointestinal Pathology: A Systematic Review.

Digital microscopy (DM) is one of the cutting-edge advances in pathology, which entails improved efficiency, diagnostic advantages, and potential application in virtual diagnosis, particularly in the current era of the coronavirus disease (COVID-19) pandemic. However, the diagnostic challenges are the remaining concerns for its wider adoption by pathologists, and these concerns should be addressed in a specific subspecialty. We aim to identify the common diagnostic pitfalls of whole slide imaging (WSI), one modality of DM, in gastrointestinal (GI) pathology. From validating studies of primary diagnosis performance, we included 16 records with features on GI cases involved, at least two weeks wash-out periods, and more than 60 case study designs. A tailored quality appraisal assessment was utilized to evaluate the risks of bias for these diagnostic accuracy studies. Furthermore, due to the highly heterogeneous studies and unstandardized definition of discordance, we extract the discordant cases in GI pathology and calculate the discrepant rate, resulting from 0.5% to 64.28%. Targeting discrepancy cases between digital microscopy and light microscopy, we demonstrate five main diagnostic pitfalls regarding WSI as follows: additional time to review slides in WSI, hard to identify dysplasia nucleus, missed organisms like Helicobacter pylori (H. pylori), specific cell recognitions, and technical issues. After detailed reviews and analysis, we generate two essential suggestions for further GI cases signing out by DM. One is to use systematized 20x scans for diagnostic workouts and requesting 40x or even 60x scans for challenging cases; another is that a high-volume slides training should be set before the real clinical application of WSI for primary diagnosis, particularly in GI pathology.

The utility of digital pathology in improving the diagnostic skills of pathology trainees in commonly encountered pigmented cutaneous lesions during the COVID-19 pandemic: A single academic institution experience.

Digital pathology has become an integral part of pathology education in recent years, particularly during the COVID-19 pandemic, for its potential utility as a teaching tool that augments the traditional 1-to-1 sign-out experience. Herein, we evaluate the utility of whole slide imaging (WSI) in reducing diagnostic errors in pigmented cutaneous lesions by pathology fellows without subspecialty training in dermatopathology. Ten cases of 4 pigmented cutaneous lesions commonly encountered by general pathologists were selected. Corresponding whole slide images were distributed to our fellows, along with two sets of online surveys, each composed of 10 multiple-choice questions with 4 answers. Identical cases were used for both surveys to minimize variability in trainees' scores depending on the perceived level of difficulty, with the second set being distributed after random shuffling. Brief image-based teaching slides as self-assessment tool were provided to trainees between each survey. Pre- and post-self-assessment scores were analyzed. 61% (17/28) and 39% (11/28) of fellows completed the first and second surveys, respectively. The mean score in the first survey was 5.2/10. The mean score in the second survey following self-assessment increased to 7.2/10. 64% (7/11) of trainees showed an improvement in their scores, with 1 trainee improving his/her score by 8 points. No fellow scored less post-self-assessment than on the initial assessment. The difference in individual scores between two surveys was statistically significant (p = 0.003). Our study demonstrates the utility of WSI-based self-assessment learning as a source of improving diagnostic skills of pathology trainees in a short period of time.

Integrated digital pathology at scale: A solution for clinical diagnostics and cancer research at a large academic medical center.

OBJECTIVE: Broad adoption of digital pathology (DP) is still lacking, and examples for DP connecting diagnostic, research, and educational use cases are missing. We blueprint a holistic DP solution at a large academic medical center ubiquitously integrated into clinical workflows; researchapplications including molecular, genetic, and tissue databases; and educational processes. MATERIALS AND METHODS: We built a vendor-agnostic, integrated viewer for reviewing, annotating, sharing, and quality assurance of digital slides in a clinical or research context. It is the first homegrown viewer cleared by New York State provisional approval in 2020 for primary diagnosis and remote sign-out during the COVID-19 (coronavirus disease 2019) pandemic. We further introduce an interconnected Honest Broker for BioInformatics Technology (HoBBIT) to systematically compile and share large-scale DP research datasets including anonymized images, redacted pathology reports, and clinical data of patients with consent. RESULTS: The solution has been operationally used over 3 years by 926 pathologists and researchers evaluating 288 903 digital slides. A total of 51% of these were reviewed within 1 month after scanning. Seamless integration of the viewer into 4 hospital systems clearly increases the adoption of DP. HoBBIT directly impacts the translation of knowledge in pathology into effective new health measures, including artificial intelligence-driven detection models for prostate cancer, basal cell carcinoma, and breast cancer metastases, developed and validated on thousands of cases. CONCLUSIONS: We highlight major challenges and lessons learned when going digital to provide orientation for other pathologists. Building interconnected solutions will not only increase adoption of DP, but also facilitate next-generation computational pathology at scale for enhanced cancer research.

Pathology Informatics Education during the COVID-19 Pandemic at Memorial Sloan Kettering Cancer Center (MSKCC).

This review details the development and structure of a four-week rotation in pathology informatics for a resident trainee at Memorial Sloan Kettering Cancer Center (MSKCC) in New York City so that other programs interested in such a rotation can refer to. The role of pathology informatics is exponentially increasing in research and clinical practice. With an ever-expanding role, training in pathology informatics is paramount as pathology training programs and training accreditation bodies recognize the need for pathology informatics in training future pathologists. However, due to its novelty, many training programs are unfamiliar with implementing pathology informatics training. The rotation incorporates educational resources for pathology informatics, guidance in the development, and general topics relevant to pathology informatics training. Informatics topics include anatomic pathology related aspects such as whole slide imaging, laboratory information systems, image analysis, and molecular pathology associated issues such as the bioinformatics pipeline and data processing. Additionally, we highlight how the rotation pivoted to meet the department's informatics needs while still providing an educational experience during the onset of the COVID-19 pandemic. CONCLUSION: As pathology informatics continues to grow and integrate itself into practice, informatics education must also grow to meet the future needs of pathology. As informatics programs develop across institutions, such as the one detailed in this paper, these programs will better equip future pathologists with informatics to approach disease and pathology.

Rapid Validation of Whole-Slide Imaging for Primary Histopathology Diagnosis.

OBJECTIVES: The ongoing global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitates adaptations in the practice of surgical pathology at scale. Primary diagnosis by whole-slide imaging (WSI) is a key component that would aid departments in providing uninterrupted histopathology diagnosis and maintaining revenue streams from disruption. We sought to perform rapid validation of the use of WSI in primary diagnosis meeting recommendations of the College of American Pathologists guidelines. METHODS: Glass slides from clinically reported cases from 5 participating pathologists with a preset washout period were digitally scanned and reviewed in settings identical to typical reporting. Cases were classified as concordant or with minor or major disagreement with the original diagnosis. Randomized subsampling was performed, and mean concordance rates were calculated. RESULTS: In total, 171 cases were included and distributed equally among participants. For the group as a whole, the mean concordance rate in sampled cases (n = 90) was 83.6% counting all discrepancies and 94.6% counting only major disagreements. The mean pathologist concordance rate in sampled cases (n = 18) ranged from 90.49% to 97%. CONCLUSIONS: We describe a novel double-blinded method for rapid validation of WSI for primary diagnosis. Our findings highlight the occurrence of a range of diagnostic reproducibility when deploying digital methods.

Remote Reporting from Home for Primary Diagnosis in Surgical Pathology: A Tertiary Oncology Center Experience during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic accelerated the widespread adoption of digital pathology (DP) for primary diagnosis in surgical pathology. This paradigm shift is likely to influence how we function routinely in the postpandemic era. We present learnings from early adoption of DP for a live digital sign-out from home in a risk-mitigated environment. MATERIALS AND METHODS: We aimed to validate DP for remote reporting from home in a real-time environment and evaluate the parameters influencing the efficiency of a digital workflow. Eighteen pathologists prospectively validated DP for remote use on 567 biopsy cases including 616 individual parts from 7 subspecialties over a duration from March 21, 2020, to June 30, 2020. The slides were digitized using Roche Ventana DP200 whole-slide scanner and reported from respective homes in a risk-mitigated environment. RESULTS: Following re-review of glass slides, there was no major discordance and 1.2% (n = 7/567) minor discordance. The deferral rate was 4.5%. All pathologists reported from their respective homes from laptops with an average network speed of 20 megabits per second. CONCLUSION: We successfully validated and adopted a digital workflow for remote reporting with available resources and were able to provide our patients, an undisrupted access to subspecialty expertise during these unprecedented times.

Whole-Slide Imaging Allows Pathologists to Work Remotely in Regions with Severe Logistical Constraints Due to Covid-19 Pandemic.

INTRODUCTION: In this study, we report on our experience using digital pathology to overcome the severe limitations imposed on health care by the Covid-19 outbreak in Northern Italy. Social distancing had a major impact on public transportation, causing it to run with reduced timetables. This resulted in a major challenge for hospital commuters. To limit the presence in our hospital of no more than two pathologists at a time out of four, a web-based digital pathology system (DPS) was employed to work remotely. SUBJECTS AND METHODS: We used a DPS in which a scanner, a laboratory information system, a storage device, and a web server were interfaced so that tissue slides could be viewed over the Internet by whole-slide imaging (WSI). After a brief internal verification test, the activity on the DPS was recorded, taking track of a set of performance and efficiency indicators. At the end of the study, 405 cases were signed out remotely. RESULTS: Of 693 cases, 58.4% were signed out remotely by WSI, while 8.4% needed to be kept on hold to return to the original microscope slide. In three cases, at least one slide had to be rescanned. In eight cases, one slide was recut. Panel discussion by WSI was necessary in 34 cases, a condition in which all pathologists were asked for their opinion. A consultation with a more experienced colleague was necessary in 17 cases. CONCLUSIONS: We show that WSI easily allows pathologists to overcome the problems caused by the severe social distancing measures imposed by the Covid-19 pandemic. Our experience shows that soon there will not be alternatives to digital pathology, given that there is no assurance that other similar outbreaks will not occur.

Use of whole slide imaging (WSI) for distance teaching.

BACKGROUND: Time, travel and financial constraints have meant that traditional visiting teaching engagements are more difficult to accomplish. This has been exacerbated with the advent of the COVID-19 pandemic. The use of digital pathology and whole slide imaging (WSI) as an educational tool for distance teaching is underutilised and not fully exploited. This paper highlights the utility and feedback on the use of WSI for distance education/teaching. MATERIALS AND METHODS: Building on an existing relationship with the University of the West Indies (UWI), pathologists at University Health Network, Toronto, provided distance education using WSI, a digitised slide image hosting repository and videoconferencing facilities to provide case-based teaching to 15 UWI pathology trainees. Feedback was obtained from residents via a questionnaire and from teachers via a discussion. RESULTS: There was uniform support from teachers who felt that teaching was not hampered by the 'virtual' engagement. Comfort levels grew with each engagement and technical issues with sound diminished with the use of a portable speaker. The residents were very supportive and enthusiastic in embracing this mode of teaching. While technical glitches marred initial sessions, the process evened out especially when the slide hosting facility, teleconferencing and sound issues were changed. CONCLUSIONS: There was unanimous endorsement that use of WSI was the future, especially for distance teaching. However, it was not meant to supplant the use of glass slides in their current routine, daily practice.