The future of laboratory medicine - A 2014 perspective.

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine

Telemedicine for improving access to health care in resource-constrained areas : from individual diagnosis to strengthening health systems

In many developing countries there is an acute shortage of trained medical specialists. This does not only hamper individual patients’ access to medical diagnostics but furthermore limits the development of health systems because a major role of the specialists is the provision of continuous medical education of health care personnel. The rapid development of information and communication technologies has enabled radically new forms of virtual collaboration at a distance. So-called telemedicine enables us today to transmit knowledge to the patient rather than to only transport patients to the centres where the knowledge is available; this has promising implications in particular for remote and under-served areas. Initiated by a request from a Swiss surgeon from Solomon Islands, a project for supporting the hospital in Honiara, capital of Solomon Islands, with pathology diagnoses was started between Honiara and the Department of Pathology in Basel in 2001. After a successful start this pilot project found broad interest, and the Internet platform that had been developed was soon utilised by projects from other countries and medical disciplines. Thus, questions arose about the diagnostic accuracy of such remote diagnoses as well as about their acceptance and impact on the local health care system. The work presented here was initiated on this background. It analyses the applicability of telemedicine in the context of resource-constrained areas and in particular the possibilities to extend its impact from improving individual diagnosis towards strengthening health care systems. A central part of this project was the development of iPath, an Internet- and email-based telemedicine platform, which facilitates medical consultations, knowledge exchange and continuous education on a global scale. A particular emphasis was put on the applicability and accessibility for users from developing countries with limited infrastructure and network connectivity. The complete software was released under an open-source licence in order to allow unrestricted reuse for other institutions. The diagnostic accuracy of this form of telemedicine was studied in two projects from the field of pathology. A retrospective review of over 200 glass slides from each project revealed complete diagnostic concordance between the telemedical diagnosis and review diagnosis in 69% and 85% respectively. Clinically relevant discrepancies were found in 8% and 3.3% of all examinations. Selection of images by the non-expert and communication were found to have the greatest impact on diagnostic accuracy. Both factors can be addressed by training and organisation of workflow. In comparison to submitting material for pathological examination by courier, the turn-around time could be reduced from weeks to days or hours. Besides the more rapid availability of diagnosis, telemedicine enabled a direct dialogue between the surgeon and the pathologist and thus facilitated an implicit permanent medical education. The educational aspects of telemedicine were studied within the scope of a tele-dermatology project in South Africa. Distance collaboration with a dermatologist empowered a general practitioner based in a rural area to diagnose and treat a majority of patients with dermatological problems. Besides the direct benefit of saving the patients the cost of transportation to visit the dermatologist, the general practitioner could strengthen his own diagnostic skills under direct guidance and quality control of a specialist. As a consequence he will be able to treat more patients locally, close to their homes and families. The whole project was implemented within the local health system in order to facilitate a future inclusion of other primary care facilities. Regional telemedicine networks play a major role to ensure relevance and acceptability of consultative and educational telemedicine. Within the scope of the Ukrainian Swiss Perinatal Health Program a telemedicine component was included, and it was found that the use of regional language as well as inclusion of the regional specialists are important for the acceptance of telemedicine and should not be neglected in a era of globalisation. The presented results demonstrate that save and reliable telemedicine can be implemented with limited resources. Telemedicine is suitable in particular to strengthen existing international collaborations and to support professionally isolated medical specialists. Regional collaboration and inclusion of regional specialists are desirable if telemedicine shall help to strengthen health care systems. The application of telemedicine should not only focus on providing care to individual patients, but should explicitly incorporate skills development and capacity building of primary care staff. Organisation of work flow and communication have been found to be the most challenging task for the implementation of telemedicine networks. Resources must be invested not only in technology but more importantly in training and organisation. Utilisation of existing technological infrastructure is advisable wherever possible and greatly reduces the complexity of providing support and maintenance. The presented telemedicine platform provides an efficient tool for the organisation of interdisciplinary, regional and international telemedicine networks. We hope that the unrestricted availability of the software developed during this project will enable other institutions to utilise it for their own purpose and that they will thus be able to allocate resources on the organisation of workflow rather than technology

The VPS ReplaySuite: development and evaluation of a novel, Internet based telepathology tool

The ReplaySuite is a web-based telepathology tool that replicates the doubleheaded microscope environment online, enabling a reviewing pathologist to ‘replay’ an archived virtual slide examination. Examination-tracking data obtained by the Virtual Pathology Slide (VPS) virtual slide viewer is exploited, allowing a remote pathologist to review an examination conducted at a different time and location. This removes temporal and spatial issues associated with double-headed microscopy. In order to conduct a preliminary evaluation of the technology, 9 pathologists used the ReplaySuite to review examination replays and diagnostic data from archived examinations of 10 needlecore breast biopsies. Diagnostically difficult cases were most frequently evaluated, either via diagnostic concordance graphs or examination replays, and all 3 participants who replayed more than 10 examinations stated the ReplaySuite to be of some or great benefit in pathology training and quality assurance. Of those who replayed an examination by another pathologist, 83% (5/6) agreed that replays provided an insight into the examining pathologists diagnosis, and 33% (2/6) reconsidered their own diagnosis for at least one case. Of those who reconsidered their original diagnosis, all reclassified either concordant with group consensus or original glass slide diagnosis. This study demonstrated that the ReplaySuite was of potential benefit in pathology education, however the technology required evaluation in a setting that would facilitate its impact on diagnostic performance. Accordingly, a redeveloped VPS and ReplaySuite were incorporated into the EQUALIS External Quality Assurance (EQA) study in chronic hepatitis staging and grading. During the study, 9 Swedish pathology departments examined and scored digital representations of liver needlecore biopsies during two sessions, with 10 cases per session and two digital slides per case. Between scoring sessions, participants were provided with access to two supplementary electronic resources: the ReplaySuite, and a library of pre-selected reference images. Comparison of concordance with gold standard (KVAST group) scoring before and after electronic resource use facilitated the elucidation of impact on diagnostic performance. Between scoring sessions, participant concordance with KVAST staging increased by 18% (49%-67%), while concordance with KVAST grading increased by 20% (34%-54%). Mean staging un-weighted kappa improved from 0.347 to 0.554 (+0.207), or from ‘fair’ to ‘moderate’ exact agreement with KVAST staging. Linear weighted staging kappa improved from 0.603 to 0.688 (+0.085), indicating close agreement in both sessions. Mean grading unweighted kappa increased from 0.132 to 0.412 (+0.280), or from a ‘poor’ to ‘moderate’ level o f exact agreement with KVAST, while linear weighted kappa improved from 0.328 to 0.624 (+0.295), or from ‘fair’ to ‘good’ level of approximate agreement with KVAST. Subsequent to the EQA scheme, an expert liver pathologist used the ReplaySuite to evaluate study examinations, assessing examination technique and identifying sources of error. Examinations scoring concordant with KVAST were observed to exhibit acceptable examination technique more frequently than discordantly scoring examinations. When grading, 28% (46% - 18%) more concordant than discordant examinations were considered to have viewed sufficient tissue, and at the appropriate magnification. A similar disparity of 24% (59% - 35%) was observed in staging, suggesting that examination technique was important both when determining the degree of necroinflammation within a biopsy, and when ascertaining the extent of fibrosis. In assessing sources of error, the expert pathologist identified a potential source in 50% of grading examinations, with misinterpretation of observed pathology cited in 19%, and missed pathology (oversight) cited in 31% of grading examinations. Of the 41% of staging examinations in which a source was identified, misinterpretation of observed pathology was cited in 20% of examinations, and missed pathology (oversight) in 21% of examinations. This study demonstrated that the use of supplementary electronic resources could result in improvements in diagnostic performance. It also illustrated the significant ‘add on’ value that could be provided by the ReplaySuite in EQA, by providing means to assess not only diagnostic concordance, but also diagnostic technique and identify sources of error. In order to assess Irish trainee pathologist’s perceptions of computer-assisted learning (CAL), a number of commercial systems were utilised to incorporate digital slides into a postgraduate seminar series, and provide subsequent access to seminar digital slides, diagnoses and expert annotations online. All surveyed trainees considered the use of digital slides and expert annotations of benefit in pathology training, and considered the potential implementation of expert examination replays, online self-assessment and the capability to search online for material by organ, diagnosis or pathological feature of benefit. The work described herein illustrates that both expert and trainee pathologists alike consider the use of supplementary electronic resources of benefit in pathology education, and demonstrates that their use can improve diagnostic performance. The ability to evaluate participation in EQA studies via the ReplaySuite provides significant additional value to education schemes, providing a depth of assessment not possible with conventional microscopy

Virtual health care center in Georgia

Application of telemedicine systems to cover distant geographical areas has increased recently. However, the potential usefulness of similar systems for creation of national networks does not seem to be widely appreciated. The article describes the "Virtual Health Care Knowledge Center in Georgia" project. Its aim was the set up of an online integrated web-based platform to provide remote medical consultations and eLearning cycles. The project "Virtual Health Care Knowledge Center in Georgia" was the NATO Networking Infrastructure Grant dedicated for development of telemedicine in non-NATO countries. The project implemented a pilot to organize the creation of national eHealth network in Georgia and to promote the use of innovative telemedicine and eLearning services in the Georgian healthcare system. In June 2007 it was continued under the NATO Networking Infrastructure Grant "ePathology – Virtual Pathology Center in Georgia as the Continuation of Virtual Health Care Center"

Development and evaluation of the virtual pathology slide: a new tool for understanding inter-observer variability in diagnostic microscopy

The VPS (Virtual Pathology Slide) is a microscope emulator enabling the examination of pathology slides via the Internet or CD-Rom. A novel feature of the VPS is the ability to record the migratory traces (image viewed and magnification) of pathologists examinations on a remote relational database located in Dublin City University. In order to evaluate the VPS, Ten breast needle core biopsies were randomly selected and presented to 17 pathologists or trainee pathologists with at least 2 years experience in pathology practice. Participants were required to examine each case online and provide a diagnostic classification using online feedback forms, based on the Core Biopsy Reporting Guidelines for Non-operative Diagnostic Procedures and Reporting in Breast Cancer screening as used by the British National Co-ordinating Committee for Breast Screening Pathology. The recorded data permitted examination of interobserver variability and user satisfaction. The study demonstrated that Pathologists can make a correct diagnosis using the VPS. Consensus glass diagnosis agreed with consensus VPS diagnosis in 9 out of 10 cases. Consensus diagnosis for Slide 8 differed from glass slide diagnosis by one classification grade. Several Participants using the VPS achieved strong individual performance, with 10 of the 17 participants displaying “good” to “exce//e«i” (>0.6) agreement with VPS consensus, based on a weighted Kappa rating. Modification of diagnostic classification based on a review of text diagnosis resulted in VPS consensus diagnosis for Slide 8 concurring with glass slide diagnosis and demonstrated a lack o f familiarity and understanding amongst participants in the application of the applied diagnostic guidelines, particularly in the diagnosis of Intraductal Pappilloma. Modification of diagnostic classification based on text diagnosis increased average overall slide consensus from 66.5% to 69.4% but decreased individual Kappa performance by 0.76 to 0.72. Participants diagnostic performance was found to be unrelated to their confidence in making a diagnostic decision using the VPS. Perception of image quality was demonstrated to be clearly dependent on participants screen resolution and colour depth, but was shown not to influence diagnostic performance. Perception of download speed was found to be unrelated to individual diagnostic performance. However, it was demonstrated that there is an increase in the number of fields of view examined by participants as their perception of download speed improves. The number of fields of view examined per slide was found to be representative of the histological difficulty in interpreting a case. In general, as slide consensus decreases, the number of fields view examined for that slide increases. The number of fields of view examined at a particular magnification was found to be unique for each slide and dependent on the histological complexity of each slide. To elucidate reasons for diagnostic inconsistency, a software application called ‘Bitmapper’ was developed. This generates a graphical representation of a diagnostic trace using data stored on the VPS database. This takes the form of 128x128 pixel bitmap image, where each pixel is representative of an individual field of view on a VPS slide at the highest magnification available. The colour value of each pixel is determined by whether the field of view it represents has been viewed, and if so, at what magnification. This diagnostic trace was used to locate hotspot regions of potential diagnostic importance within a slide. For each of the slides a pathologist, specialist in breast disorders, examined images from these hotspots and successfully deduced a reason for diagnostic inconsistencies. This demonstrated that Bitmapper is an extremely useful tool for determining reasons for observer variation. The development of the VPS and ancillary software tools was successful in that pathologists were willing to use the system. Pathologists could make a correct diagnostic decision using the system. The degree of observer variation could be quantified and using Bitmapper, reasons for observer variation could be determined. This technology has applications in determining the cause of observer variability and will prove a useful tool in external quality assurance studies (EQA) in pathology

The Process of Digital Pathology and its Application in a Study

Digital pathology saw its advent in the 60’s with the introduction of telepathology and was brought into a brighter spotlight in the late 90’s through the technological breakthrough in histopathological imaging, called whole slide imaging (WSI). With steady growth in interest among experts, the latest breakthrough in WSI happened in 2017, when both the US Food and Drug Administration and the European Union approved the use of WSI systems in primary diagnostics. So far, the adoption of digital pathology has been slower than many expected, but many laboratories around the world are looking to switch into a digital workflow. In this text, I aim to describe the history and the technical basics of digital pathology and WSI, as well as discuss some of its most widely used and promising applications in education, research, telepathology, clinical work, and image analysis. To better illuminate the digital workflow, I describe the use of digital pathology in a study by Anttinen M et al., in which the author of this text participated in the form of digitizing the whole slide images used in the study. With the advancements in digital pathology in the past two decades and with the regulation catching up, wider adoption WSI systems is to be expected. Many advantages can be associated with digital pathology e.g., better results in learning for students, cost reductions in clinical work, and the reduction in pathologists’ workload due to automated image analysis methods

On Edge Computing for Remote Pathology Consultations and Computations

Telepathology aims to replace the pathology operations performed on-site, but current systems are limited by their prohibitive cost, or by the adopted underlying technologies. In this work, we contribute to overcoming these limitations by bringing the recent advances of edge computing to reduce latency and increase local computation abilities to the pathology ecosystem. In particular, this paper presents LiveMicro, a system whose benefit is twofold: on one hand, it enables edge computing driven digital pathology computations, such as data-driven image processing on a live capture of the microscope. On the other hand, our system allows remote pathologists to diagnosis in collaboration in a single virtual microscope session, facilitating continuous medical education and remote consultation, crucial for under-served and remote hospital or private practice. Our results show the benefits and the principles underpinning our solution, with particular emphasis on how the pathologists interact with our application. Additionally, we developed simple yet effective diagnosis-aided algorithms to demonstrate the practicality of our approach

Development and preliminary evaluation of the VPS ReplaySuite: a virtual double-headed microscope for pathology

BACKGROUND: Advances in computing and telecommunications have resulted in the availability of a range of online tools for use in pathology training and quality assurance. The majority focus on either enabling pathologists to examine and diagnose cases, or providing image archives that serve as reference material. Limited emphasis has been placed on analysing the diagnostic process used by pathologists to reach a diagnosis and using this as a resource for improving diagnostic performance. METHODS: The ReplaySuite is an online pathology software tool that presents archived virtual slide examinations to pathologists in an accessible video-like format, similar to observing examinations with a double-headed microscope. Delivered through a customised web browser, it utilises PHP (Hypertext PreProcessor) to interact with a remote database and retrieve data describing virtual slide examinations, performed using the Virtual Pathology Slide (VPS). To demonstrate the technology and conduct a preliminary evaluation of pathologists opinions on its potential application in pathology training and quality assurance, 70 pathologists were invited to use the application to review their own and other pathologists examinations of 10 needle-core breast biopsies and complete an electronic survey. 9 pathologists participated, and all subsequently completed an exit survey. RESULTS: Of those who replayed an examination by another pathologist, 83.3% (5/6) agreed that replays provided an insight into the examining pathologists diagnosis and 33.3% (2/6) reconsidered their own diagnosis for at least one case. Of those who reconsidered their original diagnosis, all re-classified either concordant with group consensus or original glass slide diagnosis. 77.7% (7/9) of all participants, and all 3 participants who replayed more than 10 examinations stated the ReplaySuite to be of some or great benefit in pathology training and quality assurance. CONCLUSION: Participants conclude the ReplaySuite to be of some or of great potential benefit to pathology training and quality assurance and consider the ReplaySuite to be beneficial in evaluating the diagnostic trace of an examination. The ReplaySuite removes temporal and spatial issues that surround the use of double-headed microscopes by allowing examinations to be reviewed at different times and in different locations to the original examination. While the evaluation set was limited and potentially subject to bias, the response of participants was favourable. Further work is planned to determine whether use of the ReplaySuite can result in improved diagnostic ability

Future perspectives of digital pathology

Technological advances have enabled innovative solutions to be achieved in pathology based on digital imaging, now superseding those of conventional microscopy. Digital pathology has been defined as ‘virtual microscopy’ and depends on computer-generated digital imaging of microscope slides (WSI — whole slide imaging) which are in turn created, reviewed, managed, shared, analysed and interpreted. Such WSI systems and digital consulting platforms are now used for teaching, scientific research, telepathology / teleconsultation and diagnostics. They also permit easy and interactive sharing of WSI that can be integrated into other medical information systems. The software for automated image analysis and computer aided diagnosis can thereby make highly accurate diagnoses and help standardise study findings. Despite the technique’s many advantages, its noted drawbacks include high equipment and software costs, image quality issues of standardisation and most importantly, that pathologists are reluctant to use it routinely for making diagnoses