Whole-slide Imaging Scanners Research Articles

Abstract B061: Bridging the gap in inequality in timely cancer diagnosis: GLORIA network Colombia

Abstract Introduction: In Latin American countries, survival rates for highly malignant tumors show disparities in access to diagnosis and treatment between small and big cities. Colombia is an example where the rate of pathologists is 0.88 per 100,000 inhabitants. Oncopathologists are predominantly situated in major cities, being a minimal percentage of this specialty. Whole slide imaging (WSI) technology can be used to mitigate disparities by facilitating diagnostic support for less-experienced pathologists in distant locations from expert centers. Telepathology brings a solution in bridging these gaps, enabling connectivity and facilitating timely diagnoses and treatments. To achieve this goal, a Colombian research group developed the GLORIA Colombia Network, which will provide WSI scanners and a telepathology network in small cities connecting them to an expert central laboratory. This will facilitate decision-making for oncopathological diagnoses. We aim to show a preliminary phase of the project; knowledge, attitudes, and practices of general pathologists operating the scanners are explored to delve into fears and expectations so that an introduction of this technology can be made. Methods:Introductory phase consisted of a semi-structured survey piloted by the research group and conducted via Google Forms for general pathology laboratories in Colombia, through the network ASOCOLPAT (Colombian pathologist association). There were 23 close questions related to context recognition, and an open question to explore qualitative aspects related to telepathology. ResultsA total of 51 responses from general pathologists were obtained, 100% stated they had needed assistance of a subspecialist in high complexity cases; 47% noted soft tissue tumors were challenging diagnoses, 35.2% affirmed hematological tumors were also challenging. The 25.5% reported stress high levels in complex diagnoses. 64% reported 1-10 complex cases/month in capital cities. The most frequently requested type of tumor for consultation was lymph nodes (21.3%), followed by melanocytic tumors (23.5%). Furthermore, 27.4% stated the response time for interconsultation ranged from one week to one month. Additionally, 79.2% of pathologists attempt to diagnose the case themselves, but if unable to do so, they refer it to a specialist. The open question revealed doubts about general pathologists' roles, and their feeling of undervalue compared to subspecialists. This question highlighted the need for training, and telepathology emerged as an alternative to facilitate communication between general pathologists and subspecialists. Emphasizing the importance lies in improving diagnostic times, which affects patients’ quality of life. Conclusion GLORIA network, bridges healthcare gaps by connecting general pathologists with specialists, enabling faster and accurate diagnoses. This initiative reduces stress, offers training, and improves diagnostic reliability, benefiting patients in remote areas with complex malignant tumors. Citation Format: Gabriela Guerron-Gomez, Maria C. Restrepo-Guarnizo, Andres Mosquera-Zamudio, Oscar Mendoza, John J. Sprockel, Arley Gomez, Laura D. Olarte Suarez, Merideidy Plazas Vargas, Rafael Parra-Medina, Marcela Gomez-Suarez. Bridging the gap in inequality in timely cancer diagnosis: GLORIA network Colombia [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B061.

Viability of Whole-Slide Imaging for Intraoperative Touch Imprint Cytological Diagnosis of Axillary Sentinel Lymph Nodes in Breast Cancer Patients.

Whole-slide imaging (WSI) is a promising tool in pathology. However, the use of WSI in cytopathology has lagged behind that in histology. We aimed to evaluate the utility of WSI for the intraoperative touch imprint cytological diagnosis of axillary sentinel lymph nodes (SLNs) in breast cancer patients. Glass slides from touch imprint cytology of 480 axillary SLNs were scanned using two different WSI scanners. The intra- and interobserver concordance, accuracy, possible reasons for misdiagnosis, scanning time, and review time for three cytopathologists were compared between WSI and light microscopy (LM). A total of 4320 diagnoses were obtained. There was substantial to strong intraobserver concordance when comparing reads among paired LM slides and WSI digital slides (κ coefficient ranged from 0.63 to 0.88, and concordance rates ranged from 94.58% to 98.33%). Substantial to strong interobserver agreement was also observed among the three cytopathologists (κ coefficient ranged from 0.67 to 0.85, and concordance rates ranged from 95.42% to 97.92%). The accuracy of LM was slightly higher (average of 98.06%) than that of WSI (averages of 96.81% and 97.78%). The majority of misdiagnoses were false negative diagnoses due to the following top three causes: few cancer cells, confusing cancer cells with histiocytes, and confusing cancer cells with lymphocytes. This study is the first to address the feasibility of WSI in touch imprint cytology. The use of WSI for intraoperative touch imprint cytological diagnosis of SLNs is a practical option when experienced staff are not available on-site.

Colour reproduction evaluation of whole-slide imaging scanners for digital pathology

ABSTRACT Digital pathology using whole-slide imaging (WSI) scanners aids pathologists challenged by diagnostic volume and novel diagnostic methods. Colour reproducibility of WSI scanners is crucial for accurate digital diagnoses. We propose an objective and quantitative method for evaluating colour reproduction in digital images of pathological specimens from two perspectives: true colour value reproduction and colour discrimination. We define 57 critical features for evaluation, extract tissue structures, and establish diagnostic criteria. Our method is unique and useful for clinical use. We tested a prototype scanner, and it satisfied all criteria for true colour value reproduction (all the colour samples corresponding to the selected tissue evaluation points were experimentally within the acceptable range) and colour discrimination (the colour difference ΔE2000 calculated from the corresponding colour sample combinations exceeded the lower permissible limit for the selected discrimination points). This evaluation method and WSI scanner can contribute to accurate colour reproduction in digital pathology.

Diagnostic validation of a portable whole slide imaging scanner for lymphoma diagnosis in resource-constrained setting: A cross-sectional study

BackgroundTelepathology utilizing high-throughput static whole slide image scanners is proposed to address the challenge of limited pathology services in resource-restricted settings. However, the prohibitive equipment costs and sophisticated technologies coupled with large amounts of space to set up the devices make it impractical for use in resource-limited settings. Herein, we aimed to address this challenge by validating a portable whole slide imaging (WSI) device against glass slide microscopy (GSM) using lymph node biopsies from suspected lymphoma cases from Sub-Saharan Africa. Material and methodsThis was part of a multicenter prospective case–control head-to-head comparison study of liquid biopsy against conventional pathology. For the portable WSI scanner validation, the study pathologists evaluated 105 surgical lymph node specimens initially confirmed by gold-standard pathology between February and December 2021. The tissues were processed according to standard protocols for Hematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) staining by well-trained histotechnicians, then digitalized the H& E and IHC slides at each center. The digital images were anonymized and uploaded to a HIPAA-compliant server by the histotechnicians. Three study pathologists independently accessed and reviewed the images after a 6-week washout. The agreement between diagnoses established on GSM and WSI across the pathologists was described and measured using Cohens’ kappa coefficient (κ). ResultsOn GSM, 65.5% (n=84) of specimens were lymphoma; 25% were classified as benign, while 9.5% were metastatic. Morphological quality assessment on GSM and WSI established that 79.8% and 53.6% of cases were of high quality, respectively. When diagnoses by GSM were compared to WSI, the overall concordance for various diagnostic categories was 93%, 100%, and 86% for lymphoma, metastases, and benign conditions respectively. The sensitivity and specificity of WSI for the detection of lymphoma were 95.2% and 85.7%, respectively, with an overall inter-observer agreement (κ) of 0.86; 95% CI (0.70–0.95). ConclusionsWe demonstrate that mobile whole slide imaging (WSI) is non-inferior to conventional glass slide microscopy (GSM) for the primary diagnosis of malignant infiltration of lymph node specimens. Our results further provide proof of concept that mobile WSI can be adapted to resource-restricted settings for primary surgical pathology and would significantly improve patient outcomes.

A Survival Guide for the Rapid Transition to a Fully Digital Workflow: The "Caltagirone Example".

Digital pathology for the routine assessment of cases for primary diagnosis has been implemented by few laboratories worldwide. The Gravina Hospital in Caltagirone (Sicily, Italy), which collects cases from 7 different hospitals distributed in the Catania area, converted the entire workflow to digital starting from 2019. Before the transition, the Caltagirone pathology laboratory was characterized by a non-tracked workflow, based on paper requests, hand-written blocks and slides, as well as manual assembling and delivering of the cases and glass slides to the pathologists. Moreover, the arrangement of the spaces and offices in the department was illogical and under-productive for the linearity of the workflow. For these reasons, an adequate 2D barcode system for tracking purposes, the redistribution of the spaces inside the laboratory and the implementation of the whole-slide imaging (WSI) technology based on a laboratory information system (LIS)-centric approach were adopted as a needed prerequisite to switch to a digital workflow. The adoption of a dedicated connection for transfer of clinical and administrative data between different software and interfaces using an internationally recognised standard (Health Level 7, HL7) in the pathology department further facilitated the transition, helping in the integration of the LIS with WSI scanners. As per previous reports, the components and devices chosen for the pathologists’ workstations did not significantly impact on the WSI-based reporting phase in primary histological diagnosis. An analysis of all the steps of this transition has been made retrospectively to provide a useful “handy” guide to lead the digital transition of “analog”, non-tracked pathology laboratories following the experience of the Caltagirone pathology department. Following the step-by-step instructions, the implementation of a paperless routine with more standardized and safe processes, the possibility to manage the priority of the cases and to implement artificial intelligence (AI) tools are no more an utopia for every “analog” pathology department.

Colorimetrical uncertainty estimation for the performance assessment of whole slide imaging scanners.

Purpose: Whole slide imaging (WSI) scanners produce tissue slide images with a large field of view and a high resolution for pathologists to use in diagnoses. Color performance tests of these color imaging devices are necessary and can use stained tissue slides if the color truth is established using a hyperspectral imaging microscopy system (HIMS). The purpose of this study was to estimate the reproducibility uncertainty of CIELAB coordinates for a reference tissue slide measured by both the HIMS and a WSI scanner. Approach: We compared the color performances of the WSI scanner to those of the reference established by the HIMS using the International Commission on Illumination (Commission Internationale de l'Éclairage, or CIE) 1976 color difference with the just noticeable color difference (JNCD, ), and the results from the overlap of the CIELAB coordinates' uncertainty within the error bar, with a coverage factor . The reported uncertainty results from measurements and image registration uncertainties. Results: For the blank area common to the HIMS and the WSI average images, the color agreement was higher using the JNCD condition versus the CIELAB uncertainty overlap criterion (82% and 20% of the pixels in the images, respectively). This difference is explained by the fact that numerous pixels have CIELAB coordinates near one another but corresponding to CIELAB uncertainty values small enough not to overlap. In the colored area of the images, the JNCD condition was met for 0.19% of the pixels in the images, compared with 4.3% for the CIELAB uncertainty overlap criterion. Conclusions: The distribution of uncertainties on the CIELAB coordinates was broader for the HIMS compared with the WSI scanner. The WSI scanner had a systemic error in the color reproduction, which pointed to a potential inadequate color calibration of this device.

Automated 3D scoring of fluorescence in situ hybridization (FISH) using a confocal whole slide imaging scanner

Fluorescence in situ hybridization (FISH) is a technique to visualize specific DNA/RNA sequences within the cell nuclei and provide the presence, location and structural integrity of genes on chromosomes. A confocal Whole Slide Imaging (WSI) scanner technology has superior depth resolution compared to wide-field fluorescence imaging. Confocal WSI has the ability to perform serial optical sections with specimen imaging, which is critical for 3D tissue reconstruction for volumetric spatial analysis. The standard clinical manual scoring for FISH is labor-intensive, time-consuming and subjective. Application of multi-gene FISH analysis alongside 3D imaging, significantly increase the level of complexity required for an accurate 3D analysis. Therefore, the purpose of this study is to establish automated 3D FISH scoring for z-stack images from confocal WSI scanner. The algorithm and the application we developed, SHIMARIS PAFQ, successfully employs 3D calculations for clear individual cell nuclei segmentation, gene signals detection and distribution of break-apart probes signal patterns, including standard break-apart, and variant patterns due to truncation, and deletion, etc. The analysis was accurate and precise when compared with ground truth clinical manual counting and scoring reported in ten lymphoma and solid tumors cases. The algorithm and the application we developed, SHIMARIS PAFQ, is objective and more efficient than the conventional procedure. It enables the automated counting of more nuclei, precisely detecting additional abnormal signal variations in nuclei patterns and analyzes gigabyte multi-layer stacking imaging data of tissue samples from patients. Currently, we are developing a deep learning algorithm for automated tumor area detection to be integrated with SHIMARIS PAFQ.

Evaluation of Renal Biopsy for Transplant: The Significance of Whole Slide Imaging (WSI) in Telepathology

Abstract Introduction/Objective Percutaneous Renal biopsy remains a gold standard technique to provide diagnostic and prognostic information post kidney transplantation. Recently Whole slide imaging (WSI) telepathology systems have been widely used for clinical, education and research purposes. Our aim was to examine reliability and accuracy of WSI telepathology service in the pathology diagnosis of biopsy specimens from transplanted kidney. Methods At our institution we have two renal pathologists. They utilize WSI telepathology service with Aperio scanner for rapid initial assessment of the transplant renal biopsy specimens. We retrospectively reviewed reports of all transplant renal biopsies which were examined remotely utilizing WSI telepathology service and compared the results for initial versus final diagnoses. Results In period from Jan 2019 to April 2020 total 160 renal transplant biopsies were evaluated remotely utilizing the WSI scanner. The diagnosis was divided in 4 subcategories as reperfusion injury, rejection (Antibody mediated or T cell mediated), mixed inflammation-favor infection and Polyoma virus infection. There were 48 cases of reperfusion injury; 5 cases of polyoma virus infection, 37 cases of rejection and 28 cases with mixed inflammation and 42 cases with no significant histopathologic findings. There was no discrepancy between the preliminary and final diagnosis for all 160 cases. The ancillary studies including special stains and electron microscopy added to the final diagnosis or confirmed the preliminary diagnosis. Conclusion WSI telepathology is a reliable and simple method to rapidly review transplant kidney biopsies. The ability to transmit images from hospitals to pathologists with WSI scanner has the potential for not only an accurate assessment of the rejection but also for additional histopathological findings. Digital pathology enhances the clinical usefulness of immediate assessments of transplant biopsy samples and also provides a platform to share the scanned images with clinicians which also can be utilized for education of trainees.

ImageBox 2 – Efficient and Rapid Access of Image Tiles from Whole-Slide Images Using Serverless HTTP Range Requests

Background: Whole-slide images (WSI) are produced by a high-resolution scanning of pathology glass slides. There are a large number of whole-slide imaging scanners, and the resulting images are frequently larger than 100,000 × 100,000 pixels which typically image 100,000 to one million cells, ranging from several hundred megabytes to many gigabytes in size. Aims and Objectives: Provide HTTP access over the web to Whole Slide Image tiles that do not have localized tiling servers but only basic HTTP access. Move all image decode and tiling functions to calling agent (ImageBox). Methods: Current software systems require tiling image servers to be installed on systems providing local disk access to these images. ImageBox2 breaks this requirement by accessing tiles from remote HTTP source via byte-level HTTP range requests. This method does not require changing the client software as the operation is relegated to the ImageBox2 server which is local (or remote) to the client and can access tiles from remote images that have no server of their own such as Amazon S3 hosted images. That is, it provides a data service [on a server that does not need to be managed], the definition of serverless execution model increasingly favored by cloud computing infrastructure. Conclusions: The specific methodology described and assessed in this report preserves normal client connection semantics by enabling cloud-friendly tiling, promoting a web of http connected whole-slide images from a wide-ranging number of sources, and providing tiling where local tiling servers would have been otherwise unavailable.

Whole-Slide Imaging of Esophageal Squamous Cell Carcinoma.

Whole-slide imaging (WSI) contributes to medical education, collaboration, quality assurance, examination, and consultation in pathology. The images obtained from WSI are of high quality and could be stored indefinitely. In research involving esophageal squamous cell carcinoma, the combination of WSI and image processing program allows effective interpretations of expressions of various immunomarkers related to pathogenesis, prognosis, and response to therapy in tissue microarray sections. The operation and basic principles of whole-slide imaging of esophageal squamous cell carcinoma are also presented. Common use of WSI will occur with modifications of the whole-slide imaging scanners to adapt to the workflows in diagnostic and research laboratories.

Reproducible Color Gamut of Hematoxylin and Eosin Stained Images in Standard Color Spaces

A whole-slide imaging (WSI) system is a digital color imaging system used in digital pathology with the potential to substitute the conventional light microscope. A WSI system digitalizes a glass slide by converting the optical image to digital data with a scanner and then converting the digital data back to the optical image with a display. During the digital-to-optical or optical-to-digital conversion, a color space is required to define the mapping between the digital domain and the optical domain so that the numerical data of each color pixel can be interpreted meaningfully. Unfortunately, many current WSI products do not specify the designated color space clearly, which leaves the user using the universally default color space, sRGB. sRGB is a legacy color space that has a limited color gamut, which is known to be unable to reproduce all color shades present in histology slides. In this work, experiments were conducted to quantitatively investigate the limitation of the sRGB color space used in WSI systems. Eight hematoxylin and eosin (H and E)-stained tissue samples, including human bladder, brain, breast, colon, kidney, liver, lung, and uterus, were measured with a multispectral imaging system to obtain the true colors at the pixel level. The measured color truth of each pixel was converted into the standard CIELAB color space to test whether it was within the color gamut of the sRGB color space. Experiment results show that all the eight images have a portion of pixels outside the sRGB color gamut. In the worst-case scenario, the bladder sample, about 35% of the image exceeded the sRGB color gamut. The results suggest that the sRGB color space is inadequate for WSI scanners to encode H and E-stained whole-slide images, and an sRGB display may have insufficient color gamut for displaying H and E-stained histology images.

Validation of mitotic cell quantification via microscopy and multiple whole-slide scanners

BackgroundThe establishment of whole-slide imaging (WSI) as a medical diagnostic device allows that pathologists may evaluate mitotic activity with this new technology. Furthermore, the image digitalization provides an opportunity to develop algorithms for automatic quantifications, ideally leading to improved reproducibility as compared to the naked eye examination by pathologists. In order to implement them effectively, accuracy of mitotic figure detection using WSI should be investigated. In this study, we aimed to measure pathologist performance in detecting mitotic figures (MFs) using multiple platforms (multiple scanners) and compare the results with those obtained using a brightfield microscope.MethodsFour slides of canine oral melanoma were prepared and digitized using 4 WSI scanners. In these slides, 40 regions of interest (ROIs) were demarcated, and five observers identified the MFs using different viewing modes: microscopy and WSI. We evaluated the inter- and intra-observer agreements between modes with Cohen’s Kappa and determined “true” MFs with a consensus panel. We then assessed the accuracy (agreement with truth) using the average of sensitivity and specificity.ResultsIn the 40 ROIs, 155 candidate MFs were detected by five pathologists; 74 of them were determined to be true MFs. Inter- and intra-observer agreement was mostly “substantial” or greater (Kappa = 0.594–0.939). Accuracy was between 0.632 and 0.843 across all readers and modes. After averaging over readers for each modality, we found that mitosis detection accuracy for 3 of the 4 WSI scanners was significantly less than that of the microscope (p = 0.002, 0.012, and 0.001).ConclusionsThis study is the first to compare WSIs and microscopy in detecting MFs at the level of individual cells. Our results suggest that WSI can be used for mitotic cell detection and offers similar reproducibility to the microscope, with slightly less accuracy.

Toxicologic Pathology Forum*: Opinion on Considerations for the Use of Whole Slide Images in GLP Pathology Peer Review.

Whole slide imaging (WSI) technology has advanced to a point where it has replaced the glass slide as the primary means of pathology evaluation within many areas of medical pathology. The deployment of WSI in the field of toxicologic pathology has been delayed by a lack of clarity around the degree of validation required for its use on Good Laboratory Practice (GLP) studies. The current opinion piece attempts to provide a high-level overview of WSI technology to include basic methodology, advantages and disadvantages over a conventional microscope, validation status of WSI scanners, and perceived concerns over regulatory acceptance for the use of WSI for (GLP) peer review in the field of toxicologic pathology. Observations are based on the extensive use by AstraZeneca of WSI for the peer review of non-GLP studies conducted at Charles River facilities and represent the experiences of the authors. Note: This is an opinion article submitted to the Toxicologic Pathology Forum. It represents the views of the author(s). It does not constitute an official position of the Society of Toxicologic Pathology, British Society of Toxicological Pathology, or European Society of Toxicologic Pathology, and the views expressed might not reflect the best practices recommended by these Societies. This article should not be construed to represent the policies, positions, or opinions of their respective organizations, employers, or regulatory agencies.

Evaluation of an Automated Tissue Sectioning Machine for Digital Pathology

Background: Automation and digital pathology are the trends for future anatomic pathology with the increasing workload in histology laboratories. While tissue process, embedding, staining and coverslipping, and digitizing have been available for automated use, tissue sectioning appears to be the biggest roadblock to a fully automated histology process. In this study we were aimed to investigate a tissue automated sectioning machine for both clinical and research use.Methods: Totally 77 surgical resection blocks of various organs embedded with clinical standard paraffin were sectioned automatically using AS-410 (Dainippon Seiki Co. LTD., Japan) at 5 μm thickness with the default setting (Setting A). 10 slides per block were sectioned and the last 5 slides were stained with H&E. All stained slides were digitized with whole-slide imaging scanner, and then evaluated by the image scientist and the pathologist. The image scientist scored the images base on the extent of imperfection (Evaluation I), while the pathologist scored the images based on the clinical diagnosis purpose (Evaluation II). Both scoring systems were scored from 1 to 5, with 1 the worst quality and 5 the highest quality. Tissues with unsatisfied score were sectioned with modified setting (Setting B), and evaluated again by the same image scientist and pathologist using the same scoring systems. And the scores from the two different settings were compared. Auto-trimming and barcode reading and printing of AS-410 were also evaluated.Results: The AS-410 provided auto-trimming function to detect exposed tissue for cutting, accomplished by the installed camera and calculation software. It read sample information and printed barcode as well as input text and automatically generated slide order information. It produced good quality of sections for most cases with median score more than 4 in both Evaluation I and Evaluation II using setting A. The scores of the unsatisfied blocks sectioned with setting A improved significantly when those blocks were sectioned with setting B.Conclusion: The AS-410 tissue sectioning machine produces high-quality sections with clinical standard paraffin tissue blocks of a variety of organs with proper settings. It promises high automation with sound sectioning quality in the era of digital pathology for both clinical and research use. Lung Breast Prostate

Cytomorphological description and intra-observer agreement in whole slide imaging for canine lymphoma

Whole slide imaging (WSI) uses robotic microscopes for computerising entire slides into digital images. The aim of this study was to assess the agreement between WSI and optical microscopy for evaluating canine lymphoma cytological samples. Forty-four slides were computerised using a WSI scanner and the digital and glass slides were examined by three observers with different levels of expertise. Morphology and grade of lymphoma were scored on the basis of the updated Kiel classification and intra-observer agreement was assessed. The accuracy of determining the grade of lymphoma with digital and glass slides based on the results of flow cytometry (FC) was established. The overall intra-observer agreement for cytomorphological features was fair to moderate (κ=0.34–0.52) for the three observers and moderate (κ=0.44–0.53) for the evaluation of grade of malignancy. The diagnostic agreement between FC and digital slides was slight (κ=0.16) for the inexperienced observer, fair (κ=0.32) for the mildly experienced observer and moderate (κ=0.50) for the very experienced observer. The diagnostic agreement between FC and glass slides was fair (κ=0.37) for the inexperienced observer, substantial (κ=0.63) for the mildly experienced observer and moderate (κ=0.50) for the very experienced observer. These findings underline the importance of observer experience in determining the grade of malignancy, especially if digital slides are used. The study also identifies some technical limitations of the WSI scanner used in this study, mainly linked to image quality, which might affect the morphological evaluation of neoplastic cells.

Whole-slide imaging at primary pathological diagnosis: Validation of whole-slide imaging-based primary pathological diagnosis at twelve Japanese academic institutes.

Several reports have demonstrated the use of whole-slide imaging (WSI) for primary pathological diagnosis, but no such studies have been published from Asia. We retrospectively collected 1070 WSI specimens from 900 biopsies and small surgeries conducted in nine hospitals. Nine pathologists, who participated in this study, trained for the College of American Pathologists guidelines, reviewed the specimens and made diagnoses based on digitized, 20× or 40× optically magnified images with a WSI scanner. After a washout interval of over 2 weeks, the same observers reviewed conventional glass slides and diagnosed them by light microscopy. Discrepancies between microscopy- and WSI-based diagnoses were evaluated at the individual institutes, and discrepant cases were further reviewed by all pathologists. Nine diagnoses (0.9%) showed major discrepancies with significant clinical differences between the WSI- and microscopy-based diagnoses, and 37 (3.5%) minor discrepancies occurred without a clinical difference. Eight out of nine diagnoses with a major discrepancy were considered concordant with the microscopy-based diagnoses. No association was observed between the level of discrepancy and the organ type, collection method, or digitized optical magnification. Our results indicate the availability of WSI-based primary diagnosis of biopsies and small surgeries in routine daily practice.

Why is digital pathology in cytopathology lagging behind surgical pathology?

Why is digital pathology in cytopathology lagging behind surgical pathology?

Development of a database system and image viewer to assist in the correlation of histopathologic features and digital image analysis with clinical and molecular genetic information.

Pathologists are required to integrate data from multiple sources when making a diagnosis. Furthermore, whole slide imaging (WSI) and next generation sequencing will escalate data size and complexity. Development of well-designed databases that can allow efficient navigation between multiple data types is necessary for both clinical and research purposes. We developed and evaluated an interactive, web-based database that integrates clinical, histologic, immunohistochemical and genetic information to aid in pathologic diagnosis and interpretation with nine lung adenocarcinoma cases. To minimize sectioning artifacts, representative blocks were serially sectioned using automated tissue sectioning (Kurabo Industries, Osaka Japan) and selected slides were stained by multiple techniques, (hematoxylin and eosin [H&E], immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH]). Slides were digitized by WSI scanners. An interactive relational database was designed based on a list of proposed fields covering a variety of clinical, pathologic and molecular parameters. By focusing on the three main tasks of 1.) efficient management of textual information, 2.) effective viewing of all varieties of stained whole slide images (WSI), and 3.) assistance in evaluating WSI with computer-aided diagnosis, this database prototype shows great promise for multi-modality research and diagnosis.

A quantitative approach to evaluate image quality of whole slide imaging scanners

Context: The quality of images produced by whole slide imaging (WSI) scanners has a direct influence on the readers’ performance and reliability of the clinical diagnosis. Therefore, WSI scanners should produce not only high quality but also consistent quality images. Aim: We aim to evaluate reproducibility of WSI scanners based on the quality of images produced over time and among multiple scanners. The evaluation is independent of content or context oftest specimen. Methods: The ultimate judge of image quality is a pathologist, however, subjective evaluations are heavily influenced by the complexity of a case and subtle variations introduced by a scanner can be easily overlooked. Therefore, we employed a quantitative image quality assessment method based on clinically relevant parameters, such as sharpness and brightness, acquired in a survey of pathologists. The acceptable level of quality per parameter was determined in a subjective study. The evaluation of scanner reproducibility was conducted with Philips Ultra-Fast Scanners. A set of 36 HercepTest™ slides were used in three sub-studies addressing variations due to systems and time, producing 8640 test images for evaluation. Results: The results showed that the majority of images in all the sub-studies are within the acceptable quality level; however, some scanners produce higher quality images more often than others. The results are independent of case types, and they match our perception of quality. Conclusion: The quantitative image quality assessment method was successfully applied in the HercepTest™ slides to evaluate WSI scanner reproducibility. The proposed method is generic and applicable to any other types of slide stains and scanners.

Exploring virtual reality technology and the Oculus Rift for the examination of digital pathology slides

Background: Digital slides obtained from whole slide imaging (WSI) platforms are typically viewed in two dimensions using desktop personal computer monitors or more recently on mobile devices. To the best of our knowledge, we are not aware of any studies viewing digital pathology slides in a virtual reality (VR) environment. VR technology enables users to be artificially immersed in and interact with a computer-simulated world. Oculus Rift is among the world’s first consumer-targeted VR headsets, intended primarily for enhanced gaming. Our aim was to explore the use of the Oculus Rift for examining digital pathology slides in a VR environment. Methods: An Oculus Rift Development Kit 2 (DK2) was connected to a 64-bit computer running Virtual Desktop software. Glass slides from twenty randomly selected lymph node cases (ten with benign and ten malignant diagnoses) were digitized using a WSI scanner. Three pathologists reviewed these digital slides on a 27-inch 5K display and with the Oculus Rift after a 2-week washout period. Recorded endpoints included concordance of final diagnoses and time required to examine slides. The pathologists also rated their ease of navigation, image quality, and diagnostic confidence for both modalities. Results: There was 90% diagnostic concordance when reviewing WSI using a 5K display and Oculus Rift. The time required to examine digital pathology slides on the 5K display averaged 39 s (range 10–120 s), compared to 62 s with the Oculus Rift (range 15–270 s). All pathologists confirmed that digital pathology slides were easily viewable in a VR environment. The ratings for image quality and diagnostic confidence were higher when using the 5K display. Conclusion: Using the Oculus Rift DK2 to view and navigate pathology whole slide images in a virtual environment is feasible for diagnostic purposes. However, image resolution using the Oculus Rift device was limited. Interactive VR technologies such as the Oculus Rift are novel tools that may be of use in digital pathology.