Validation of a digital pathology system including remote review during the COVID-19 pandemic.

Remote digital pathology allows healthcare systems to maintain pathology operations during public health emergencies. Existing Clinical Laboratory Improvement Amendments regulations require pathologists to electronically verify patient reports from a certified facility. During the 2019 pandemic of COVID-19 disease, caused by the SAR-CoV-2 virus, this requirement potentially exposes pathologists, their colleagues, and household members to the risk of becoming infected. Relaxation of government enforcement of this regulation allows pathologists to review and report pathology specimens from a remote, non-CLIA certified facility. The availability of digital pathology systems can facilitate remote microscopic diagnosis, although formal comprehensive (case-based) validation of remote digital diagnosis has not been reported. All glass slides representing routine clinical signout workload in surgical pathology subspecialties at Memorial Sloan Kettering Cancer Center were scanned on an Aperio GT450 at ×40 equivalent resolution (0.26 µm/pixel). Twelve pathologists from nine surgical pathology subspecialties remotely reviewed and reported complete pathology cases using a digital pathology system from a non-CLIA certified facility through a secure connection. Whole slide images were integrated to and launched within the laboratory information system to a custom vendor-agnostic, whole slide image viewer. Remote signouts utilized consumer-grade computers and monitors (monitor size, 13.3-42 in.; resolution, 1280 × 800-3840 × 2160 pixels) connecting to an institution clinical workstation via secure virtual private network. Pathologists subsequently reviewed all corresponding glass slides using a light microscope within the CLIA-certified department. Intraobserver concordance metrics included reporting elements of top-line diagnosis, margin status, lymphovascular and/or perineural invasion, pathology stage, and ancillary testing. The median whole slide image file size was 1.3 GB; scan time/slide averaged 90 s; and scanned tissue area averaged 612 mm2. Signout sessions included a total of 108 cases, comprised of 254 individual parts and 1196 slides. Major diagnostic equivalency was 100% between digital and glass slide diagnoses; and overall concordance was 98.8% (251/254). This study reports validation of primary diagnostic review and reporting of complete pathology cases from a remote site during a public health emergency. Our experience shows high (100%) intraobserver digital to glass slide major diagnostic concordance when reporting from a remote site. This randomized, prospective study successfully validated remote use of a digital pathology system including operational feasibility supporting remote review and reporting of pathology specimens, and evaluation of remote access performance and usability for remote signout.

Whole Slide Imaging: Technology and Applications.

Pathology has benefited from advanced innovation with novel technology to implement a digital solution. Whole slide imaging is a disruptive technology where glass slides are scanned to produce digital images. There have been significant advances in whole slide scanning hardware and software that have allowed for ready access of whole slide images. The digital images, or whole slide images, can be viewed comparable to glass slides in a microscope, as digital files. Whole slide imaging has increased in adoption among pathologists, pathology departments, and scientists for clinical, educational, and research initiatives. Worldwide usage of whole slide imaging has grown significantly. Pathology regulatory organizations (ie, College of American Pathologists) have put forth guidelines for clinical validation, and the US Food and Drug Administration have also approved whole slide imaging for primary diagnosis. This article will review the digital pathology ecosystem and discuss clinical and nonclinical applications of its use.

The Pathologist 2.0: An Update on Digital Pathology in Veterinary Medicine.

Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is changing dramatically. Digital pathology offers new forms of visualization, and delivery of images is facilitated in unprecedented ways. This new technology can untether us entirely from our light microscopes, with many pathologists already performing their jobs using virtual microscopy. Several veterinary colleges have integrated virtual microscopy in their curriculum, and some diagnostic histopathology labs are switching to virtual microscopy as their main tool for the assessment of histologic specimens. Considering recent technical advancements of slide scanner and viewing software, digital pathology should now be considered a serious alternative to traditional light microscopy. This review therefore intends to give an overview of the current digital pathology technologies and their potential in all fields of veterinary pathology (ie, research, diagnostic service, and education). A future integration of digital pathology in the veterinary pathologist's workflow seems to be inevitable, and therefore it is proposed that trainees should be taught in digital pathology to keep up with the unavoidable digitization of the profession.

Design and Validation of a Low-Cost Telepathology System.

OBJECTIVE: This work sought to evaluate the precision and repeatability of a telepathology prototype based on open software and hardware. MATERIALS AND METHODS: A prototype was designed with application in telepathology and telemicroscopy. Accuracy and prototype precision were evaluated by calculating the mean absolute error and the intraclass and repeatability correlation coefficients for a series of 190 displacements at 10, 25, 50, 75, and 100 µm. RESULTS AND CONCLUSIONS: This work developed a low-cost prototype that is accessible, easily reproducible, implementable, and scalable; based on the use of technology created under principles of open software and hardware. A pathologist reviewed the obtained images and found them to be of diagnostic quality. Its excellent repeatability, coupled with its good accuracy, allows for its application in telemicroscopy and static, dynamic, and whole-slide imaging pathology systems.

Design of New Procedures for Diagnosing Prevalent Diseases Using a Low-Cost Telemicroscopy System.

BACKGROUND: Currently, the diagnosis of prevalent diseases such as malaria, tuberculosis, or diarrheal diseases in rural areas of developing countries requires the displacement of the patient from their community health post to their reference health center or to ship a sample. This delays diagnosis and the treatment of disease. OBJECTIVE: Conduct research to develop a new method for rapid low-cost diagnosis of prevalent diseases in rural areas of developing countries (malaria, tuberculosis, parasitic infections, vaginal infections, and cervical cancer). METHODS: The study was divided into three phases. The first related to the drafting and validating of new protocols for the preparation of samples that should be adapted to be carried out in areas without power and with little trained personnel. The second phase consisted of developing a telemicroscopy system looking for low cost, software compatibility, and technical quality. Finally, the third phase evaluated the system as a diagnostic tool using direct observation with a conventional microscope as the gold standard. RESULTS: The validation of the new protocols showed that 100% of the vaginal swabs were processed correctly when using direct smear, while they were only 86.3% correct when using Gram stain; 68.3% of fecal samples were correctly processed using Kinyoun stain; 61.7% of blood samples when using thin film; and 83.8% when using thick film. Phase 2 permitted the development of a low-cost (<$250) and low-power (<15 W) telemicroscopy system that allows real-time consultation between health technicians and specialists. Finally, phase 3 proved that there was no difference between the diagnostics obtained by direct observation in a microscope and those ones obtained through the new telemicroscopy system. CONCLUSIONS: This study has verified the effectiveness of the telemicroscopy system as a diagnostic tool, given the complete agreement between the diagnoses made with it and those made with the gold standard.

Slide navigation patterns among pathologists with long experience of digital review.

AIMS: In order to develop efficient digital pathology workstations, we studied the navigation patterns of pathologists diagnosing whole-slide images. To gain a better understanding of these patterns, we built a conceptual model based on observations. We also determined whether or not new navigation patterns have emerged among pathologists with extensive digital experience. METHODS AND RESULTS: Five pathologists were asked to diagnose a set of four cases while thinking out loud. The navigation within the digital slides was recorded and divided into re-occurring navigation actions. The pathologists reused the same type of actions, but their occurrence differed. The most common action was a slow panning that followed an edge structure or covered an area systematically, which accounted for 30.2% of all actions and had a median duration of 7.2 s. Of all the actions, 49% were carried out within the navigation overview and 38% of the actions could not have been performed with a conventional microscope. CONCLUSIONS: The new navigation possibilities in the digital workstation were used to a large extent. The division of actions into different concepts can be used to find and prioritize between existing user interface designs as well as to understand the different navigation styles used by different pathologists.

Smartphone teledermoscopy referrals: a novel process for improved triage of skin cancer patients.

In this open, controlled, multicentre and prospective observational study, smartphone teledermoscopy referrals were sent from 20 primary healthcare centres to 2 dermatology departments for triage of skin lesions of concern using a smartphone application and a compatible digital dermoscope. The outcome for 816 patients referred via smartphone teledermoscopy was compared with 746 patients referred via the traditional paper-based system. When surgical treatment was required, the waiting time was significantly shorter using teledermoscopy for patients with melanoma, melanoma in situ, squamous cell carcinoma, squamous cell carcinoma in situ and basal cell carcinoma. Triage decisions were also more reliable with teledermoscopy and over 40% of the teledermoscopy patients could potentially have avoided face-to-face visits. Only 4 teledermoscopy referrals (0.4%) had to be excluded due to poor image quality. Smartphone teledermoscopy referrals allow for faster and more efficient management of patients with skin cancer as compared to traditional paper referrals.

Concordance and time estimation of store-and-forward mobile teledermatology compared to classical face-to-face consultation.

Smartphones have overcome the limitations of image quality seen in older devices and opened a new field of telemedicine called "mobile teledermatology". Technological advances and the need to reduce health service costs will strongly promote the development of telemedicine. For this reason, we evaluated the concordance between store-and-forward mobile teledermatology and the classical face-to-face dermatological visit. We also measured the time taken to submit a teleconsultation using a smartphone. Before conventional face-to-face visit, a final-year resident of the three-year course for general practitioners collected medical history, took digital images of skin diseases with a smartphone and, measuring the time required to complete this operation, transmitted them to an expert teledermatologist. In 391 patients we obtained a concordance between face-to-face and store-and-forward diagnosis of 91.05% (Cohen κ coefficient = 0.906). On average only few minutes needs to be added to a normal visit to transmit the cases to an expert teledermatologist.

Mobile teledermatology is a valid method to estimate prevalence of melanocytic naevi in children.

The prevalence of melanocytic naevi in children correlates with sun exposure and may serve as an objective population risk indicator of future melanoma incidence. The aim was to investigate if mobile teledermatology could offer a valid methodology compared with standard manual, face-to-face counting of naevi on the back of children. Ninety-seven children aged 7-16 years were enrolled. One dermatologist performed manual naevi counting and imaging of the child's back using an iPhone 4S comprising a safe-coded mobile application. Two other dermatologists independently counted naevi from the images. Cohen's weighted kappa (κw) coefficient demonstrated substantial agreement for both dermatologists: κw = 0.69 (0.57-0.81 [95% confidence intervals]) and κw = 0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability was also substantial (κw = 0.80 [0.73-0.87]). Use of mobile teledermatology proved valid for estimating naevi prevalence on the back and could provide a more feasible methodology following trends in sun exposure in children.

Telepathology in cytopathology: challenges and opportunities.

OBJECTIVE: Telepathology in cytopathology is becoming more commonly utilized, and newer technologic infrastructures afford the laboratory a variety of options. The options and design of a telepathology system are driven by the clinical needs. This is primarily focused on providing rapid on-site evaluation service for fine needle aspiration. STUDY DESIGN: The clinical requirements and needs of a system are described. Available tools to design and implement a telepathology system are covered, including methods of image capture, network connectivity and remote viewing options. RESULTS: The primary telepathology method currently used and described involves the delivery via a network connection of a live video image to a remote site which is passively viewed by an internet web-based browser. By utilizing live video information and a voice connection to the on-site location, the remote viewer can collect clinical information and direct their view of the slides. CONCLUSIONS: Telepathology systems for use in cytopathology can be designed and implemented with commercially available infrastructure. It is necessary for the laboratory to validate the designed system and adhere to the required regulatory requirements. Telepathology for cytopathology can be reliably utilized by adapting existing technology, and newer advances hold great promise for further applications in the cytopathology laboratory.

[A trial of integrated telepathology (iTP) in Nagano prefecture].

The shortage of pathologists is a major issue in Japan, and telepathology (TP) is considered one of the most innovative solutions to resolve this. About twenty years ago, robotic TP systems (RTS) were developed and are still used in Japan. Virtual slide (VS) systems appeared in the early 2000s and have being replacing RTS because of the ease of handling images, easy reference to previous images and synchronous discussion among pathologists. Both systems are currently used for intra-operative consultations, second opinions and consultations by specialists, and in education and research via the internet. With these systems, pathologists participating in consultations have to obtain a patient's clinical information by other methods, such as fax or e-mail, and they often make a diagnosis without this information and previous histological images. The author proposes an "integrated telepathology (iTP)" system in Nagano prefecture. This system is composed of an anatomic pathology information system (APIS) linking the VS system and is designed to connect all pathologists in community hospitals, including Shinshu University Hospital, using a virtual private network. Any registered pathologist can access APIS and view any pathological images of patients with the clinical information. Therefore, pathologists can make a diagnosis with substantial patient information at any time and from any location, and pathologists in different hospitals can consult one another in a secure network. Our iTP system will be able to streamline diagnosis duties in surgical pathology in Nagano prefecture, and may solve the shortage of pathologists by improving diagnosis efficiency.

TeleCyP (Telecytopathology): real-time fine-needle aspiration interpretation.

OBJECTIVE: To assess the application of TeleCyP for real-time fine-needle aspiration interpretation (RFI) necessary for case management and specimen triage. STUDY DESIGN: Twenty-two endobronchial ultrasound (EBUS)-guided mediastinal and pulmonary cases were included in the learning phase to determine the time and efficiency of TeleCyP. Slides were scanned by a cytopathology fellow in real time, and high-speed transmitted images over a secure network were interpreted by a cytopathologist while maintaining audio communication. In the validation phase, an additional 38 pancreas cases from endoscopic ultrasound (EUS) were evaluated recapitulating the RFI scenario from the learning phase. The cytopathologist was blinded to the results of the diagnosis in both phases. RESULTS: The time to provide assessment of specimen adequacy and a preliminary diagnosis was 53 s in the learning phase and 49 s in the validation phase. There was 100% correlation between RFI and TeleCyP assessment for specimen adequacy. TeleCyP particularly posed challenges in providing definitive interpretation on EUS-fine-needle aspiration of some of the pancreatic solid masses (11%, 4/36). CONCLUSION: TeleCyP can serve as a powerful alternative, time-efficient strategy to provide RFI, and for specimen triaging which is critical for personalized medicine and patient management.

Implementation of telecytology for immediate assessment of endoscopic ultrasound-guided fine-needle aspirations compared to conventional on-site evaluation: analysis of 240 consecutive cases.

OBJECTIVE: To evaluate the implementation of telecytology in an academic cytology service for immediate assessment of endoscopic ultrasound (EUS) and endobronchoscopic ultrasound (EBUS) fine-needle aspiration (FNA). STUDY DESIGN: Telecytology was evaluated over a 10-month period. Using an Olympus BX41(®) microscope and an Olympus DP72(®) camera with Olympus cellSens(®) software, real-time dynamic images of air-dried Diff-Quik(®)-stained smears were transmitted by a cytopathology fellow or cytotechnologist using a secure internet connection. The cytopathologists remotely accessed the real-time images on a computer in their office and rendered immediate assessments. Mean procedure times, and preliminary and final diagnoses were compared between telecytology and conventional on-site evaluation. RESULTS: Two hundred and forty consecutive EUS-FNA and EBUS-FNA procedures with immediate assessments were performed during the evaluation period, of which 158 (66%) utilized telecytology and 82 (34%) did not utilize telecytology. The mean procedure time required for cytotechnologists and cytology fellows was 1.1 h for both conventional on-site and telecytology evaluations. The mean procedure time for cytopathologists was 0.74 h for conventional on-site evaluations and 0.2 h for telecytology. CONCLUSIONS: Incorporation of telecytology for immediate assessment of EUS-FNA increased cytopathologist efficiency.

[The Eastern Quebec telepathology network: a real collective project]. / Le réseau de télépathologie de l'Est du Québec - Un véritable projet collectif.

The aim of the Eastern Québec telepathology network is to provide uniform diagnostic telepathology services across a huge geographic region with a low population density. This project is intended to provide surgeons and pathologists with frozen section and second opinion services anywhere and at any time across the entire region, in order to avoid unnecessary patient transfer. The project has been implemented in 21 sites, each equipped with a whole slide scanner, a macroscopy station, a videoconferencing device and a viewer/case management and collaboration solution. Of the 21 sites, 6 are devoid of a pathology laboratory, two have no pathologist and 5 have only one pathologist on site. Signs of improvement of medical care in this region are already apparent since the Eastern Québec telepathology network has been implemented. However, it is important not to underestimate the challenges related to change management in the course of implementation of such a new technology.

[Whole slide imaging technology: from digitization to online applications]. / Technologie des lames virtuelles - De la numérisation à la mise en ligne.

As e-health becomes essential to modern care, whole slide images (virtual slides) are now an important clinical, teaching and research tool in pathology. Virtual microscopy consists of digitizing a glass slide by acquiring hundreds of tiles of regions of interest at different zoom levels and assembling them into a structured file. This gigapixel image can then be remotely viewed over a terminal, exactly the way pathologists use a microscope. In this article, we will first describe the key elements of this technology, from the acquisition, using a scanner or a motorized microscope, to the broadcasting of virtual slides through a local or distant viewer over an intranet or Internet connection. As virtual slides are now commonly used in virtual classrooms, clinical data and research databases, we will highlight the main issues regarding its uses in modern pathology. Emphasis will be made on quality assurance policies, standardization and scaling.

An ultra-high speed Whole Slide Image viewing system.

BACKGROUND: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed. METHOD: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course. RESULTS: Pathologists were being able to use the system comfortably after 0-15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out. CONCLUSIONS: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.

Telecytopathology for rapid preliminary diagnosis of ultrasound-guided fine-needle aspiration of thyroid nodules.

BACKGROUND: Onsite evaluation of ultrasound-guided fine-needle aspiration (USGFNA) of thyroid nodules is essential to procure adequate samples and provide initial assessment. We present our experience with onsite evaluation of USGFNA of thyroid nodules using telecytopathology. METHODS: Real-time images of Diff-Quik-stained cytology smears were obtained with an Olympus Digital camera attached to an Olympus CX41 microscope and transmitted via ethernet by a cytotechnologist to a pathologist who rendered a preliminary diagnosis while communicating with an onsite cytotechnologist over the phone. Accuracy of preliminary diagnosis was compared with final diagnosis, retrospectively. RESULTS: A total of 79 patients (mean age 48.9 year) underwent USGFNA of 100 thyroid nodules. Preliminary diagnoses of benign, suspicious/malignant, and unsatisfactory were 72%, 7%, and 21%, respectively. Of the 72 cases initially reported as benign all remained benign on the final cytology. Of the seven suspicious/malignant cases on initial cytology, five were suspicious/malignant and two were benign on final cytology. Of the 21 cases that were initially interpreted as unsatisfactory only four were reclassified as benign on final diagnosis. The accuracy rate between the final cytology and preliminary telecytopathology diagnosis was 94%. Presence of additional material on Papanicolaou-stained slides and cellblock sections was the main reason for discrepancy that accounted for six discrepant cases. CONCLUSIONS: On-site telecytopathology for thyroid USGFNAs is highly accurate compared with final cytologic evaluation. It allows pathologists to use their time more efficiently and makes onsite evaluation at a remote site possible.

Digital Pathology Initiatives and Experience of a Large Academic Institution During the Coronavirus Disease 2019 (COVID-19) Pandemic.

CONTEXT.­: Pathology practices have begun integrating digital pathology tools into their routine workflow. During 2020, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a pandemic, causing a global health crisis that significantly affected the world population in several areas, including medical practice, and pathology was no exception. OBJECTIVE.­: To summarize our experience in implementing digital pathology for remote primary diagnosis, education, and research during this pandemic. DESIGN.­: We surveyed our pathologists (all subspecialized) and trainees to gather information about their use of digital pathology tools before and during the pandemic. Quality assurance and slide distribution data were also examined. RESULTS.­: During the pandemic, the widespread use of digital tools in our institution allowed a smooth transition of most clinical and academic activities into remote with no major disruptions. The number of pathologists using whole slide imaging (WSI) for primary diagnosis increased from 20 (62.5%) to 29 (90.6%) of a total of 32 pathologists, excluding renal pathology and hematopathology, during the pandemic. Furthermore, the number of pathologists exclusively using whole slide imaging for primary diagnosis also increased from 2 (6.3%) to 5 (15.6%) during the pandemic. In 35 (100%) survey responses from attending pathologists, 21 (60%) reported using whole slide imaging for remote primary diagnosis following the Centers for Medicare and Medicaid Services waiver. Of these 21 pathologists, 18 (86%) responded that if allowed, they will continue using whole slide imaging for remote primary diagnosis after the pandemic. CONCLUSIONS.­: The pandemic served as a catalyst to pathologists adopting a digital workflow into their daily practice and realizing the logistic and technical advantages of such tools.

Telepathology for patient care: what am I getting myself into?

The vast advancements in telecommunications and converting medical information to a digital format have increased the number of applications within telemedicine. Telepathology, in simplest terms, is the practice of formally rendering a pathologic diagnosis based upon examination of an image rather than of a glass slide through traditional microscopy. The use of telepathology for clinical patient care has so far been limited to relatively few large academic institutions. Although a number of challenges remain, there is increasing demand for the use of information technology in pathology as a whole owing to the expansion of health care networks and the opportunity to enhance the quality of service delivered to patients. The software used to acquire, display, and manage digital images for clinical patient care may be subject to national and federal regulations just as is any other electronic information system. Despite the barriers, telepathology systems possess the capability to help manage pathology cases on a global scale, improve laboratory workload distribution, increase standardization of practice and enable new classes of ancillary studies to facilitate diagnosis and education even in the most remote parts of the earth.