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.     

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.     

Utility of whole slide imaging and virtual microscopy in prostate pathology

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

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.     

Medicolegal and regulatory aspects of whole slide imaging-based telepathology

Telepathology is lauded for its potential to overcome geographic barriers and bring expert diagnostic opinions to underserved regions. However, the legal and regulatory aspects governing its use in the United States and abroad are disparate and incomplete. In addition, there is essentially no case law that specifically addressed telepathology. Important issues to consider for the implementation and practice of telepathology, including state and regional licensure requirements, credentialing and privileging, liability and medical malpractice coverage, privacy and security, medical device regulation, and reimbursement for services are reviewed here for several regions, including the United States, Canada, the European Union, and China.     

Virtual reality microscope versus conventional microscope regarding time to diagnosis: an experimental study

Aims: To create and evaluate a virtual reality (VR) microscope that is as efficient as the conventional microscope, seeking to support the introduction of digital slides into routine practice. Methods and results: A VR microscope was designed and implemented by combining ultra‐high‐resolution displays with VR technology, techniques for fast interaction, and high usability. It was evaluated using a mixed factorial experimental design with technology and task as within‐participant variables and grade of histopathologist as a between‐participant variable. Time to diagnosis was similar for the conventional and VR microscopes. However, there was a significant difference in the mean magnification used between the two technologies, with participants working at a higher level of magnification on the VR microscope. Conclusions: The results suggest that, with the right technology, efficient use of digital pathology for routine practice is a realistic possibility. Further work is required to explore what magnification is required on the VR microscope for histopathologists to identify diagnostic features, and the effect on this of the digital slide production process.     

Digital Pathology: A Tool for 21st Century Neuropathology

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

原发性脑淋巴瘤的MRI表现特点与诊断

目的：分析颅内原发性淋巴瘤的MRI表现特点，为临床诊断与治疗提供资料。方法：回顾分析28例经病理证实颅内原发性淋巴瘤的MRI资料，所有病例均行平扫及增强扫描。结果：病灶单发6例，多发22例，分布于幕上14例，幕下4例，幕上幕下同时存在10例，大多位于深部脑白质，病灶多呈圆形或不规则形，T1WI呈低信号，T2WI呈等或高信号，瘤周水肿较轻，增强扫描病灶均呈团块状显著强化。结论：颅内淋巴瘤的MRI表现缺乏特异性，需手术或活检才可作出定性诊断。     

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

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

High agreement between whole slide imaging and optical microscopy for assessment of HER2 expression in breast cancer: Whole slide imaging for the assessment of HER2 expression

Whole slide imaging (WSI) technology has been used for training, teaching, researching, and remote consultation. Few studies compared HER2 expression using optical microscopy (OM) and WSI evaluations in breast carcinomas. However, no consensus has been achieved comparing both assessments.Material and methodsSections from tissue microarray containing 200 preselected invasive breast carcinomas were submitted to immunohistochemistry applying three anti-HER2 antibodies (HercepTest™, CB11, SP3) and in situ hybridization (DDISH). Slides were evaluated using OM and WSI (Pannoramic MIDI and Viewer, 3DHISTECH). Sensitivity and specificity were calculated comparing the anti-HER2 antibodies and DDISH.ResultsWSI and OM HER2 evaluations agreement was considered good (SP3, k = 0.80) to very good (CB11 and HercepTest™, k = 0.81). WSI evaluation led to higher sensitivity (ranging from 100 of SP3 and HercepTest™ to 97 of CB11) and lower specificity (ranging from 86.4 of SP3 to 89.4 of HercepTest™) compared to OM evaluation (sensitivity ranged from 92.1 of CB11 to 98 of SP3 and specificity ranged from 95.2 of SP3 and HercepTest™ to 97.1 of CB11 and SP3).ConclusionHigh agreement was achieved between WSI and OM evaluations. All three antibodies were highly sensitive and specific using both evaluations. WSI can be considered a useful tool for HER2 immunohistochemical assessment.     

An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study

This paper describes the design and fabrication of a novel array microscope for the first ultrarapid virtual slide processor (DMetrix DX-40 digital slide scanner). The array microscope optics consists of a stack of three 80-element 10 x 8-lenslet arrays, constituting a "lenslet array ensemble." The lenslet array ensemble is positioned over a glass slide. Uniquely shaped lenses in each of the lenslet arrays, arranged perpendicular to the glass slide constitute a single "miniaturized microscope." A high-pixel-density image sensor is attached to the top of the lenslet array ensemble. In operation, the lenslet array ensemble is transported by a motorized mechanism relative to the long axis of a glass slide. Each of the 80 miniaturized microscopes has a lateral field of view of 250 microns. The microscopes of each row of the array are offset from the microscopes in other rows. Scanning a glass slide with the array microscope produces seamless two-dimensional image data of the entire slide, that is, a virtual slide. The optical system has a numerical aperture of N.A.= 0.65, scans slides at a rate of 3 mm per second, and accrues up to 3,000 images per second from each of the 80 miniaturized microscopes. In the ultrarapid virtual slide processing cycle, the time for image acquisition takes 58 seconds for a 2.25 cm2 tissue section. An automatic slide loader enables the scanner to process up to 40 slides per hour without operator intervention. Slide scanning and image processing are done concurrently so that post-scan processing is eliminated. A virtual slide can be viewed over the Internet immediately after the scanning is complete. A validation study compared the diagnostic accuracy of pathologist case readers using array microscopy (with images viewed as virtual slides) and conventional light microscopy. Four senior pathologists diagnosed 30 breast surgical pathology cases each using both imaging modes, but on separate occasions. Of 120 case reads by array microscopy, there were 3 incorrect diagnoses, all of which were made on difficult cases with equivocal diagnoses by light microscopy. There was a strong correlation between array microscopy vs. "truth" diagnoses based on surgical pathology reports. The kappa statistic for the array microscopy vs. truth was 0.96, which is highly significant (z=10.33, p <0.001). There was no statistically significant difference between rates of agreement with truth between array microscopy and light microscopy (z=0.134, p >0.05). Array microscopy and light microscopy did not differ significantly with respect to the number/percent of correct decisions rendered (t=0.552, p=0.6376) or equivocal decisions rendered (t=2.449, p=0.0917). Pathologists rated 95.8% of array microscopy virtual slide images as good or excellent. None were rated as poor. The mean viewing time for a DMetrix virtual slide was 1.16 minutes. The DMetrix virtual slide processor has been found to reduce the virtual slide processing cycle more than 10 fold, as compared with other virtual slide systems reported to date. The virtual slide images are of high quality and suitable for diagnostic pathology, second opinions, expert opinions, clinical trials, education, and research.     

Toward whole tissue imaging of axolotl regeneration

The axolotl is a highly regenerative organism and has been studied in laboratories for over 150 years. Despite a long-standing fascination with regeneration in general and axolotl specifically, we are still scratching the surface trying to visualize and understand the complex cellular behavior that underlies axolotl regeneration. In this review, we will discuss the progress that has been made in visualizing these processes focusing on four major aspects: cell labeling approaches, the removal of pigmentation, reductionist approaches to perform live cell imaging, and finally recent developments applying tissue clearing strategies to visualize the processes that underly regeneration. We also provide several suggestions that the community could consider exploring, notably the generation of novel alleles that further reduce pigmentation as well as improvements in tissue clearing strategies.     

A Web-Based Solution for Viewing Large-Sized Microscopic Images

This paper demonstrates a pure web-based solution enabling the presentation of scanned pathologic microscopic images on the web. For each slide, an entire specimen is scanned, and a high-resolution digital image (in the order of giga-pixels) is reconstructed. These huge images are then tiled into many 256 × 256-pixel blocks with different resolutions, and information about the blocks of each scanned slide is included in an extensible markup language metafile. Based on the data, a virtual microscopy system is created for viewing the scanned pathologic slides on web. The functionalities (changing viewing resolution, location adjustment, and multimedia annotation presentation) of our virtual slide viewing system are accomplished using pure hypertext markup language (HTML) and JavaScript. We show that there is no need to add plug-in components to browsers in order to handle virtual slides on the web. In a heterogeneous healthcare environment, methods using pure HTML and JavaScript to deal with pathologic content are more appropriate than using proprietary technologies supported only by specific browsers.