Journal of Pathology Informatics Journal of Pathology Informatics
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Table of Contents    
ORIGINAL ARTICLE
J Pathol Inform 2013,  4:7

The history of pathology informatics: A global perspective


1 Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
2 Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
3 Department of Anatomical Pathology, and National Health Laboratory Service (NHLS), Walter Sisulu University, Mthatha, South Africa
4 Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
5 International Academy of Telepathology, Heidelberg, Germany
6 Department of Pathology and Laboratory Medicine, Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA
7 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
8 Hospital General de Ciudad Real, Ciudad Real, Spain
9 Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Faculty of Medicine, University of New South Wales, NSW, Australia
10 Institute of Pathology, University Freiburg, Freiburg, Germany
11 Institute of Pathology, Charite, Berlin, Germany
12 Centre for Health Informatics and e-Health Research, University of Wollongong, Wollongong, NSW, Australia
13 Department of Pathology and Laboratory Medicine, University of Calgary, and Calgary Laboratory Services, Calgary, Alberta, Canada
14 Department of Pathology, School of Medicine, Iwate Medical University, Iwate Prefecture, Japan
15 Weiner Consulting Services, Florence, OR, USA
16 Dennis Winsten and Associates, Inc., Healthcare Systems Consultants, Tucson, AZ, USA

Date of Submission02-Jan-2013
Date of Acceptance09-Mar-2013
Date of Web Publication30-May-2013

Correspondence Address:
Seung Park
Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2153-3539.112689

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   Abstract 

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold.

Keywords: History, pathology informatics, clinical informatics, electronic medical record, laboratory information systems, pathology education


How to cite this article:
Park S, Parwani AV, Aller RD, Banach L, Becich MJ, Borkenfeld S, Carter AB, Friedman BA, Rojo MG, Georgiou A, Kayser G, Kayser K, Legg M, Naugler C, Sawai T, Weiner H, Winsten D, Pantanowitz L. The history of pathology informatics: A global perspective. J Pathol Inform 2013;4:7

How to cite this URL:
Park S, Parwani AV, Aller RD, Banach L, Becich MJ, Borkenfeld S, Carter AB, Friedman BA, Rojo MG, Georgiou A, Kayser G, Kayser K, Legg M, Naugler C, Sawai T, Weiner H, Winsten D, Pantanowitz L. The history of pathology informatics: A global perspective. J Pathol Inform [serial online] 2013 [cited 2017 Mar 25];4:7. Available from: http://www.jpathinformatics.org/text.asp?2013/4/1/7/112689


   Introduction Top

"If I have seen further, it is by standing on the shoulders of giants."

- Sir Isaac Newton

The history of pathology informatics is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice of medicine. Under the surface, however, lie powerful forces - technical, regulatory, societal and beyond - that have all played their part in molding our discipline into what it is today. In this monograph, we take - perhaps for the first time in the history of our discipline - a truly global perspective of how the field of pathology informatics has evolved. In doing so, several large-scale trends are immediately obvious. For example, the advent of computers, the Internet and digital cameras were major disruptive events that advanced the practice of pathology in many countries. The prevalence of different technologies in different regions was related to both tangible factors (e.g., availability of trained staff and operational costs) and intangible factors (e.g., regulatory concerns). Though pathology informatics was born in the USA and Europe, it is now a truly global discipline; no single country or continent can lay claim to being the sole driver of our discipline's destiny. If we are to be wise stewards of our discipline, it is necessary for us to know where we have been, not only so that we may give our pioneers and discoverers their just recognition, but also so that we can learn from the successes and failures of past decades.

The aim of this collective effort was to record the history of pathology informatics around the world. Pathology informaticists with knowledge about the field, representing virtually all of the continents, were asked to share their experience, literature, publications, archived documents and images, as well as their insights. Their contributions have been collated and divided up in this monograph by continent and presented below in alphabetical order. While an attempt was made by the authors to comprehensively capture all available detail, we acknowledge that there may be voices and events that were missed.


   Africa Top


The history of pathology informatics in Africa is a story of struggle - and in many cases, triumph - against an almost overwhelming lack of infrastructure and resources. Particularly in sub-Saharan Africa, there was, and still remains, an extreme shortage of medical personnel, including pathologists. Even when medical personnel exist they are generally concentrated in the major cities. The tendency for doctors to emigrate - especially from war-torn areas in which they are arguably most needed - worsened this shortage. As a result, pathology services are often scarce and possibly below acceptable standards, especially with regard to the availability of certain laboratory tests (e.g., immunohistochemistry, molecular studies) and specimen processing. For example, in 2007 Uganda had 18 pathologists serving a population of 28 million, Tanzania had 15 pathologists serving a population of 38 million, and Sudan had 51 pathologists (40 of whom work mostly in the capital city of Khartoum) serving a population of 40 million. In Zambia, there is only one pathologist, at the University Teaching Hospital of Lusaka. [1]

It should therefore, come as no surprise that (a) Africa currently represents perhaps the greatest unmet need for pathology services in the world and (b) pathology informatics in Africa has historically focused most heavily on telepathology applications (primarily with European collaborators) to outsource their work and/or seek expert consultation. [2],[3] This is especially true in countries like Sudan and South Africa, which have more pathologists as well as relatively advanced telecommunications and Internet services, and as such were positioned to better leverage multiple telepathology efforts with collaborators from other countries. [1],[2],[3] A common theme in Africa, as was the case around the world, was the transformational change in medicine that was realized as a result of the introduction of computers, coupled to networking technologies like the Internet, into healthcare.

Telepathology

In 1991, Heinz Hoenecke of the USA founded the volunteer organization called Pathologists Overseas with the express purpose of setting up and running pathology laboratories for resource-restricted nations in Africa. Emphasis was initially placed on providing pathology services where the need was greatest and on training local medical professionals to become pathologists. [4] Thereafter, when resources become available and technical limitations were overcome, this organization embraced telepathology in several African countries. [5]

In France, a private company named Réseau Internationale de Télémédecine (RESINTEL) was founded in 1992 at the University of Dijon to provide telemedicine services - with a special emphasis on telepathology - to geographically isolated areas of France. The telepathology system and international telecommunications network that it created - collectively known as TRANSPATH - together provided a platform for static telemicroscopy that was originally telephone-based, but quickly moved to Integrated Services Digital Network (ISDN) and satellite communication methods. By 1994, RESINTEL had signed contracts with - and was providing telepathology services for - hospitals in India, the Middle East, Morocco, and several countries in Africa. Unfortunately, circa 1998 the TRANSPATH network was shut down due to the fact that RESINTEL could not secure funding for continued operation. [6]

In 1997, the Fundamentals of Modern Telemedicine in Africa (FOMTA) project developed regional networks between research centers and universities of many African countries, using up to 256 kbps ISDN connections for the store-and-forward of medical images (including static telemicroscopy) and the remote control of medical instruments. These initial efforts were limited by the lack of high-quality network infrastructure in many of the target nations and by the nascent state of network-capable collaborative editing and publication software stacks at the time, but were nevertheless successful in providing static telepathology services where none had previously existed. [7] By the mid-2000's, FOMTA - and other regional telepathology projects like it - largely migrated to open-architecture telepathology platforms written atop Linux, Apache, MySQL, PHP (LAMP) stacks, of which iPath has been the most successful in Africa (see section: Data Management Platforms). [8]

The first reports of telepathology and teleradiology services in Tunisia date from 1999. These services - primarily between hospitals in Tunis (Institut Pasteur, Hτpital de l'Enfance) and Nice (Hτpital Antoine) and Marseilles (Hτpital de la Timore) in France - focused primarily on cancer diagnoses utilizing static images. Other similar telepathology projects were developed (e.g., between the Farhat Hached Hospital in Sousse, Tunisia and several French cancer centers), which utilized videoconferencing stations for real-time presentation of cases. This was the first appearance of non-static telepathology methods in Africa. [9],[10]

The year 2000 was momentous for telepathology in Africa. In Madagascar, the Pathologists Overseas laboratory adapted a commodity digital camera for use with a microscope, pairing it via Universal Serial Bus to a computer for rapid transmission of static photomicrographs over the Internet. [4] In August of that year, Dr. Agostino Faravelli of Associazione Patologi Oltre Frontiera (APOF) travelled with a microscope and a digital camera to Mwanza, Tanzania, where he enabled static telemicroscopy by E-mailing digital photographs as E-mail attachments to colleagues in various institutions in Italy. APOF subsequently established a local presence in Mwanza, which continued experimentation with telepathology methods over a 7-year period before it closed in 2007. [11] The use of static and live telemicroscopy by these pathologists was discussed with a multinational group of participants in a live online videoconference hosted by the Regional Dermatology Training Centre in Moshi, Northern Tanzania. [12]

2001 marked the startup of the Generic Advanced Low-cost trans-European Network Over Satellite (GALENOS) network, a satellite-based telecommunication infrastructure that offered 2 Mbps interfaces to participating clinics. GALENOS eventually covered a total of 14 clinics in Bulgaria, France, Germany, Greece, Italy, and Tunisia; it enabled intraoperative telepathology using a robotic microscope with a video camera and remote control capability. [2] The iPath platform for telepathology gained significant traction during this year, being extensively used by the Eastern Cape Province Department of Health in South Africa [13],[14] and the Réseau Afrique Francophone de Télémédecine (RAFT) project (organized by the Geneva University Hospitals) in developing countries in Western Africa. Both of these pathology education projects delivered interactive courses and the ability for tele-consultation utilizing a single common infrastructure. The RAFT project was particularly successful, extending to 17 African countries (Mali 2001, Mauritania 2002, Morocco 2003, Burkina Faso 2004, Sengal 2004, Tunisia 2004, Cameroon 2005, Ivory Coast 2005, Madagascar 2005, Niger 2006, Benin 2006, Burundi 2007, Congo 2007, Algeria 2007, Chad 2008, Guinea 2008, and Rwanda 2008) as of the time of the writing of this monograph. [2],[15],[16]

In 2002, apart from reports about the success of the long-running live telemicroscopy projects of Farhat Hached Hospital in Tunisia, other hospitals in this region such as the Aziza Othmana Hospital in Tunis also reported on their telecytology and telehematopathology projects. [10] Also in 2002, the Nkosi Albert Luthuli Central Hospital in Durban, KwaZulu-Natal (South Africa) - the first hospital in Africa designed for truly paperless operation - opened its doors, and has since been a regional champion of enabling telemedicine through the use of radiology and pathology picture archiving and communication system (PACS) systems. [17]

Another two telepathology systems - both of which have experienced enthusiastic growth to the present day - were born in 2003. The first - a pilot project between the Italian Hospital in Cairo, Egypt and the Civico Hospital in Palermo, Italy - utilized both static and video telepathology. This project has expanded to neighboring countries in recent years and is expected to continue operating into at least the near future. [18] The second telepathology system was located in a more bandwidth-limited milieu: The Kijabe Hospital in Kenya. This latter system - which currently provides telepathology services for over 50 mission hospitals throughout Africa - utilizes a microscope camera attached to a computer, permitting static photomicrographs to be E-mailed to international colleagues for consultation and diagnosis confirmation. [19]

2004 saw the advent of robotic microscopes integrating rudimentary whole slide imaging (WSI) technology in Africa. At the Allada Hospital in Benin, a Nikon Coolscope was utilized in conjunction with a broadband Internet connection to send both digitized (scanned) slides and digital static photomicrographs of selected regions of interest on glass slides to collaborators in Milan, Italy. [20] Later that year, another Nikon Coolscope was installed aboard a non-governmental hospital ship initially based in Cotonou, Benin, also for static and live telepathology applications. An onboard satellite communication system provided Internet connectivity for this system, which is still in operation in its original configuration today. [21],[22] In that same year in Casablanca, Morocco, a telemedicine unit equipped with a satellite connection and four ISDN lines was deployed, utilizing a microscope with an attached digital camera for telepathology. [23] Ethiopia also made large strides in telepathology in 2004, launching a project that connected 10 regional hospitals in the country with the Tikur Anbessa Hospital and the Faculty of Medicine of Addis Ababa University. In the same timeframe, the "Ethiopia Pathology" group in iPath was organized for the purpose of providing second opinion consultations with pathologists from Switzerland and Germany. Moreover, this work has improved access to continuing education and training, raised the level of access to care and drastically reduced the waiting time and cost associated with long-distance travel by patients for diagnosis in that country. [2],[24]

In 2005, APOF installed a Nikon Coolscope at the Mtendere Mission Hospital in Chirundu, Zambia, leveraging pre-existing satellite Internet connectivity and Skype (a commercial voice-over-IP videoconferencing application) to allow APOF pathologists (living in Italy) to easily provide telepathology services. This system remains popular in the present day, and has made the Mtendere Mission Hospital the definitive regional hub for pathology services within a 100 km radius. [11] Also in 2005, the Euro-Mediterranean Internet-Satellite Platform for Health, Medical Education and Research (EMISPHER) went live, providing real-time online telemedicine services with high emphasis on network quality of service to most of the countries in the Mediterranean region, including Morocco, Algeria, Tunisia, Egypt, Cyprus, Turkey, Greece, Italy, France, and Germany. EMISPHER integrates satellite Internet connectivity known as MEDSKY (up to 2 Mbps) and a custom real-time telemedicine and telepathology application known as WinVicos. It still remains considerably popular, especially in geographically isolated regions where traditional wired Internet connections may not be possible. [2]

The year 2006 marked the first appearance of modern WSI scanners in Africa. During 2006, the Euro-Mediterranean Network for Genetic Services (MedGeNet) - a European Union funded project - installed an Aperio ScanScope GL at the Hospital Charles Nicolle in Tunisia, and then used that WSI scanner to successfully validate the first ever WSI-based telepathology service in the Mediterranean region. [25] One year later, in 2007, APOF built on their already-successful efforts at the Mtendere Mission Hospital in Chirundu, Zambia, with the installation of an Aperio ScanScope CS. Digitized whole slides were stored on a local File transfer protocol server that was made accessible to Italian collaborators via the pre-existing satellite Internet connection, which had been substantially upgraded to provide sufficient bandwidth to support the upload and download of large WSI files. [11] Two pathologists, located in Italy, independently examined the scanned WSIs remotely. [26]

Of note, 2007 proved to be a landmark year for telepathology throughout the rest of Africa as well. The Africa Teledermatology Project (http://africa.telederm.org/) - which provides dermatology support to local providers throughout Africa (Uganda, Botswana, Malawi, Swaziland, Burkina Faso, and Lesotho) - began operations during this year, utilizing a platform (telederm.org) that was initially only capable of static digital gross photographs and photomicrographs. The main limitations at this time were the number and quality of images available to the remote consultant and their reliance on the referring provider, who usually lacked dermatopathology training, to provide representative photomicrographs. [17] In May 2007, a histology laboratory was created at St. Joseph's Mission Hospital Peramiho in Tanzania, but without a local practicing pathologist. iPath was therefore, used to enable telepathology at this site, utilizing static digital photomicrography to send images for diagnosis to pathologists based in Germany. [27] Also in 2007, at the Kuluva Hospital in the Arura district of northwest Uganda, a microscope eyepiece mounted Motic camera was utilized in conjunction with a laptop to E-mail static digital photomicrographs to a pathologist in Kampala, Uganda. [28],[29] Finally in 2007, at the Kahuzi-Biéga National Park in the eastern Democratic Republic of the Congo, the Centre de Recherches de Sciences Naturelles, with the collaboration of the Spanish government, started a human and veterinary telepathology service utilizing a satellite Internet connection. [30]

In March of 2008, a pilot telepathology service known as Remote Access for Health Professionals was established with the objective of promoting evidence-based medicine in developing countries. An asynchronous static telepathology program was created in collaboration between four hospitals throughout Tanzania and Kenya and the Massachusetts General Hospital (MGH) (Boston, MA, USA) to provide dermatopathology consultation to local pathologists, using skin histopathology images captured by microscope-mounted digital cameras in conjunction with iPath. The authors of this work identified limitations with static telepathology that could as they posited, be overcome with increased training. [31] Later in 2008, an initiative in Ghana to use microscopes with attached digital cameras to allow quick consultations failed due to the lack of adequate bandwidth, as well as the high cost of the required equipment. [2] Finally in 2008, the Indian government initiated a project known as the Pan African e-Network (http://www.panafricanenetwork.com/). The objective of this project was to provide tele-education and telemedicine services (including all necessary medical and computer equipment) to 53 remote hospitals in Africa via satellite (International Telecommunications Satellite Organization (INTELSAT), European Telecommunications Satellite Organization (EUTELSAT), Regional African Satellite Communication Organization (RASCOM)) and fiber optic links to 12 super-specialty hospitals in India. [16]

In 2009, the French association Pathology, Cytologie, Développement (PCD) installed a telepathology service in Brazzaville, Congo, with the cooperation of the Francophone Digital University. [32] Also in 2009, a Zeiss Mirax Live RT system - a combination robotic microscope and WSI scanner - was installed in the National Health Laboratory in Gaborone, Botswana as part of the Africa Teledermatology Project. [33]

More recent telepathology events in Africa date to 2010. In this year, static telepathology was applied to vaginal cytology at the APOF projects in Zambia, Madagascar, and Tanzania for quality control purposes. [34] Also during this year, the French branch of Alliance Mondiale Contre le Cancer, International Network for Cancer Treatment and Research Programs began development of a telepathology network in sub-Saharan Africa for diagnostic, pedagogic, and research purposes, initially for lymphomas (which has now been expanded to a broad range of diseases). Partners in this endeavor were the French National Cancer Institute INCa, the PCD Association, and the Groupe Franco-Africain d'Oncologie Pediatrique. Pilot centers for telepathology have been established in the Kenyatta National Hospital in Nairobi, Kenya, in Dar-es-Salaam, Tanzania, and in Ile-Ife, Nigeria, with the following objectives: [35]

  • Online consultations, using iPath, for subspecialty sign-out
  • Online support to improve histologic/cytologic techniques
  • Online case discussion and lectures
  • Support for preparation of publications
Finally in 2010, phase one of the Pan African e-Network went live in 29 African countries. [16]

Telepathology in South Africa

Computers with various applications, some of them specifically designed to support laboratory operations, we increasingly introduced into many pathology laboratories around South Africa. For example, in the pathology laboratory of Mthatha General Hospital, these computers were originally supplied by the University of Transkei (now re-named Walter Sisulu University). This allowed pathologists to develop a database using the DataEase software package, which allowed for limited statistical computations to take place. These statistics were used for cancer registries and research. The first computers networked to the Internet were installed at Mthatha General Hospital's pathology laboratory by the health systems trust project (funded by the Henry J. Keyser Foundation, USA) in 1995. These computers - connected to the Internet via analog modems over ordinary telephone lines with the central dial-in node set in Durban, South Africa - were primarily used for sending and receiving E-mail. E-mail attachments were used to transmit histology images and pathology reports (both anatomic and clinical). Health workers from rural hospitals and clinics around this region of South Africa were able to thereby receive their lab results via E-mail. This dial-up system would see enthusiastic uptake and active use until 1998, at which point it was replaced by a web-based information site with online discussion groups (http://www.healthlink.org.za/).

Later in 1995, these computers - now with dedicated modem-based links between the Department of Pathology of the University of Transkei and the Department of Anatomic Pathology of the Medical University of Southern Africa - were used to send still images (microscopy, X-rays, computed tomography (CTs), ultrasounds) to the Telepathology Services of the Armed Forces Institute of Pathology (AFIP) in Washington DC, USA, via the Internet. At first, only static photomicrographs were sent; later, radiology and dermatology images were sent along with the photomicrographs [Figure 1]. Initially, all files were compressed for send-out using the program ISSA (Med Tech, Zagreb), which was installed at both Mthatha General Hospital and the AFIP. Later on, the AFIP introduced a more user-friendly web-based online attachment system for further ease of use. It should be noted that all cameras used in this project at this time were analog and as such scanning/digitization was necessary as an intermediate step before the images were sent along to the AFIP. This project would eventually extend into a larger initiative to connect smaller remote hospitals in South Africa and to similarly provide them with remote pathology, cytology, and hematology consultation. [2],[36]
Figure 1: The telepathology project between the Armed Forces Institute of Pathology (left) and Mthatha General Hospital (right)

Click here to view


The National Committee on Telemedicine and Tele-education was formed in 1998; this committee developed a National Telemedicine Strategic Plan that included several telepathology projects under its umbrella. Phase I of the National Telemedicine Strategic Plan was implemented between March 1999 and September 2000, establishing 28 telemedicine sites in six of the nine provinces of South Africa. Modem-based connectivity was replaced with ISDN (256 kbps) lines, which provided sufficient bandwidth for real-time video conferencing, teleradiology, and telepathology [Figure 2]. Unfortunately, because there was initially relatively low usage of this telemedicine system by pathologists, the software packages used were optimized for teleradiology, not telepathology. As such, the telepathology portions of this system would later migrate to the iPath platform (see section: Data Management Platforms). [14],[37],[38]
Figure 2: The South African Telemedicine System at St. Elizabeth Hospital, Lusikisiki

Click here to view


In 1999, a teledermatology project was initiated in Port St. Johns, South Africa, with the aim of improving access to dermatologic care for patients and for the education of family practitioners. In 2002, this project also migrated to the iPath platform. By 2003, this project was connected to a telemedicine network run by the Telemedicine Unit of the University of Transkei in Umtata. [17]

In 2001, as part of an e-health learning initiative, the Free State Department of Health in South Africa set up an interactive satellite broadcasting system that was offered to 40 health and training venues. This initiative extensively utilized iPath for telepathology purposes - with a link between Switzerland, South Africa, and other developing countries - and achieved over 18,000 consultations over the next 4 years. Discussion groups included topics about HIV/AIDS treatment, renal pathology, dermatology, and other topics. This system - which is still in operation today - is now also used to support problem-based e-learning for the medical students at Walter Sisulu University by digitizing exhibits (X-rays, lab results, etc.) and presenting them online. [13],[14] 2001 is also significant as it was the year that the National Health Laboratory Service (NHLS) was formed in South Africa, with the purpose of incorporating and electronically connecting all the state laboratories around the country (http://www.nhls.ac.za/). All results from these laboratories are now computerized, stored in a central system, and made electronically available to practitioners around the country. [39]

A mobile pathology laboratory was designed by the South African national Defence Force in 2004, equipped with a remote-controlled Zeiss microscope that could be manipulated via satellite or landline. Operation of this Zeiss microscope is still supported by a dedicated technologist. [40] By 2008, three Nikon Coolscopes had been installed in NHLS laboratories in the cities Mthatha, East London, and Port Elisabeth and connected via local area network (LAN), allowing remote control of the microscopes from any personal computer (PC) on the NHLS network. These laboratories are run by a small number of pathologists, without access to full immunohistochemical studies for some surgical pathology cases, which occasionally makes final diagnosis difficult. This system of Coolscopes is mostly supported by the pathologists located at Stellenbosch University in Cape Town - where it is mostly employed for dermatopathology and oral pathology cases. In 2008, a Zeiss Mirax WSI scanner was installed at the NHLS branch of Mthatha, which is currently utilized primarily for teaching purposes. [39]

Data Management Platforms

A clinical and research database was used in 1997 to standardize HIV studies in South Africa. This database utilized the systematized nomenclature of medicine (SNOMED) as its coding system and had both client-server and wide area network (WAN) mappings. This system is significant for being the first medical data management system reported in the African medical literature. [41] The implementation and widespread success of iPath servers in Africa, as described in section: Telepathology (Africa) above, provided a powerful platform to manage pathology data in Africa for several reasons:

  • Ease of use
  • Built atop a LAMP stack using standard, open-source technologies
  • Inexpensive (essentially provided for free)
  • Minimal hardware requirements
Unlike other areas of the world such as the USA where computing hardware and software is relatively cheap and ubiquitous, in Africa these resources are comparatively scarce (limited vendors) and more expensive. Hence, in this kind of environment, software platforms that are free and that can run efficiently on older hardware - iPath being one example - can flourish. As such, open source software has made significant inroads in Africa; this trend is likely to continue in the future. [42]

Laboratory Information Systems (LISs)

As section: Telepathology in South Africa indicates, in South Africa, all pathology reports from the NHLS are managed and stored in a central system. [39] Several international data management companies (e.g., Afrosoft International, MEDITECH) also market pathology-centric software packages (e.g., Afrosoft VeriLIMS, MEDITECH LIS) in South Africa.

Many of the LIS installations in sub-Saharan African countries are international projects (usually executed with the help of international non-governmental organizations such as Baobab Health), and are mainly focused on tracking, diagnosing, and defeating common infectious diseases (e.g., AIDS, malaria). This is the case for the Pan-African e-Network, [16] and for collaboration between the University of North Carolina at Chapel Hill and the Malawi Ministry of Health to install a LIS in Malawi.

In many West African countries, pathology services are usually limited to major academic centers and tertiary care hospitals, and LISs are not usually available. Consequently, most pathology reports are still totally paper-based. [43]

Teaching and Continuing Medical Education (CME)

Medical informatics has been included as a standard part of the undergraduate medical education program in South Africa since 1984. [44] It has kept abreast of technologic innovations, utilizing resources from the country's nationwide telemedicine project and technologies such as WSI scanners as they have become available. [39] In recent years, for instance, telepathology platforms like iPath have been used to facilitate problem-based learning at the University of Transkei/Walter Sisulu University. [38],[45] Since 1992, an annual health informatics workshop for various categories of healthcare providers has been held by the Teaching Hospitals Complex and the Computer Sciences Department of Obafemi Awolowo University in Nigeria. This workshop has been a great success, with attendance increasing each year. Workshops like this have been proposed as a model for health informatics training in low-resource countries. [46]

A study at the University of Natal Medical School in South Africa was published in 1996. This study divided students in a histology course into two groups: One was given access to a computer aided instruction package along with standard microscopic learning, and the other was not. Members of the former group spent less time in the regular microscopy lab and showed a slight greater improvement in knowledge relative to students in the latter group. [47] Africa Calls is an annual series of audio teleconferences established by Dr. David Kaminsky in the USA, after he visited South Africa in 1997, with the support of the Annenberg Center for Health Sciences. Since 1999, audio teleconferences broadcast to centers in Botswana, Ghana, Namibia, Nigeria, South Africa, Sudan, Swaziland, Tanzania, Uganda, and Zimbabwe have formed the basis for customized educational programs in cytopathology, including informatics. These programs have been supplemented with downloadable learning material (e.g., PowerPoint slide decks) and other relevant educational material. [2],[48] Finally, the first histopathology course in the history of Bulawayo, Zimbabwe was implemented in 2009. This course utilized materials from the local hospital libraries, the Internet, and local clinicians. Response to the inaugural course was enthusiastic, and the course gains more participants every year it is offered. [49]

Image Analysis

Image analysis papers that stem from Africa are rare. Only a single example could be found. In 1994, the Institut Pasteur de Madagascar in Antananarivo, Madagascar, studied the in-situ cellular immune response and associated fibrosis in mucocutaneous leishmaniasis due to Leishmania braziliensis utilizing automatic image analytic methods. [50]


   The Americas Top


Canada and The United States of America

Canada


University and Government Infrastructure

The first few decades of pathology informatics in Canada were dominated by three influential National Health Informatics Organizations. The oldest of these is the Canadian Organization for the Advancement of Computers in Health (COACH). This member-supported organization was founded in 1975 and currently boasts over 1,500 members. As its name suggests, COACH has primarily focused on the use of computer technology in healthcare as well as the effective use of health information for decision-making. COACH holds national conferences and offers a professional certification in health informatics. [51] The second historically significant Canadian organization is the Canadian Institute for Health Information (CIHI). CIHI was founded in 1994 by federal, provincial and territorial governments as a not-for-profit corporation with a mandate that included setting national standards for health information technology and collecting, processing, and maintaining health related databases and registries. [52] The third organization, Canada Health Infoway, is a federally funded corporation created by the Premiers of Canada's provinces in 2001. Since its creation, this organization has been a primary driver of health informatics in Canada, providing partial funding for numerous informatics related initiatives. Although the primary goal of the Canada Health Infoway is to accelerate the development of electronic health records (EHR) across Canada, five of the 193 projects it has funded up to 2011 have focused on LISs. [53] Additionally, the Alberta Netcare portal represents a significant milestone in Canadian pathology informatics. Created in 2003, Netcare is a repository for essentially all laboratory data generated in the province of Alberta as well as for radiology, clinic notes, allergies and medication information. A secure login is available to healthcare providers in the province. [54] More recently, the province of Saskatchewan implemented a similar database, called the eHealth Portal. [55] In the province of British Columbia patients can directly access their own laboratory test results through a secure website called MyeHealth. [56] The province of Alberta has a similar website, part of their myHealth web service, in the planning stages. [57]

LISs

Despite the influence of these organizations, many laboratories in Canada were slow to adopt LISs. The first generation systems began to appear in Canadian hospitals in the 1980's, but some anatomic pathology services in smaller communities still relied on type writers and carbon paper as late as 2005. With the exception of a large home-grown LIS in Ontario, Canadian Laboratories have tended to adopt the best North American LIS. Meditech has installations in a number of provinces including British Columbia, Alberta, Ontario and Nova Scotia and is particularly popular in rural and community hospital settings. Cerner has LIS installations in several major Canadian population centers and academic teaching centers as does Sunquest. Sysmex has a large installation in the province of Manitoba. Like the United States, analyzer-LIS interfaces are a mixture of homegrown solutions and vender-supplies middleware. However, increasingly laboratories are moving toward commercial/vender-supplied software to fill this need. Overall, the relatively slow uptake of computer technology in Canadian laboratories may be seen as a reflection of the generally slow adoption of computer technology by Canadian physicians in general. Even in 2012, many primary care physician offices do not use computers at all, much less electronic medical records.

In recent years, there has been an interest in enhancing the functionality of LIS systems to support additional operational and research objectives. A major area of interest in this regard is synoptic reporting for anatomic pathology. In 2012, the non-profit group Canadian Partnership against Cancer with the support of the Canadian Association of Pathologists launched an initiative to implement synoptic reporting across Canada by 2017. [58]

The second area of interest is in using the LIS to assist in utilization management of laboratory tests Predictably, in light of its publically funded health care system, Canada has a long history of interest in utilization management, dating back to 1965. [59] Historically, interest in using the LIS to aid in utilization management has been centered at the University of Ottawa, [60],[61],[62] and the University of Edmonton [63] as well as other centers. [64],[65] In 2013, the Alberta government established a provincial laboratory utilization office with the intent of using LIS systems in the province to support utilization management initiatives.

Education and Training Opportunities

In academic circles, it is only in the past several years that pathology informatics has begun to have a voice in Canada independent of health informatics in general. In July 2009, the Canadian Association of Pathologists added a Special Interest Group in Pathology Informatics. This group has been chaired alternately by Dr. C. Naugler from the University of Calgary and Dr. G. Yousef from the University of Toronto. This group presents a series of short talks each year at the Canadian Association of Pathologists Annual Scientific Meeting. In 2010, the University of Calgary became the first Canadian Institution to offer an official pathology informatics training experience opportunity when it launched a 1 month pathology informatics elective open to laboratory medicine residents. In 2011, the University of Toronto launched a virtual rotation in pathology informatics for the anatomical pathology residents. Currently, academic pathology informatics is centered in three Canadian university departments (Dalhousie University, University of Toronto and the University of Calgary), all of which have academic pathology informatics faculty. However, as of 2013, there are no pathology informatics fellowships available in Canada. A number of other universities have very strong research and teaching programs in bioinformatics including the University of British Columbia and Dalhousie University.

Telepathology

The geography of Canada with cities separated by vast distances suggests that telepathology may have a particularly promising future in this country. Despite this, Canada has been relatively slow to embrace telepathology, with the University Health Network in Toronto establishing the first operational system in 2010. This system links several remote northern hospitals to subspecialist pathology support at University Health Network hospitals. [66] It is likely that this model will be repeated in a number of geographically isolated regions in the coming years. Indeed, the necessary infrastructure is gradually accumulating, with whole slide imagers now in routine use for teaching at a number of academic pathology departments. In hematopathology, several large scale installations of the CellaVision system are in use in Nova Scotia, Ontario and Alberta.

In 2011, General electric (GE) Healthcare opened its Pathology Innovation Centre of Excellence as part of the Toronto MaRS Discovery District of technology companies. The facility includes a digital laboratory to facilitate training, research and development on the Omnyx Integrated Digital Pathology platform.

The United States of America

This history of pathology informatics - especially in the USA - resembles a train station from which multiple tracks have emerged and intermittently crossed paths. Historical events are presented chronologically in [Figure 3]. However, for ease of reading, the history of each area of study within pathology informatics is discussed separately where possible, allowing for the fact that some of these categories have overlap.
Figure 3: Major events in the history of pathology informatics in the USA

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Pathology Informatics as a Term and a Medical Subspecialty

Informatics, including pathology informatics, in the USA began in the early 1950's. The word "Informatik" was first coined in a German publication and likely arose from a combination of "information" and the suffix "-atics," which is derived from Greek and means "the science of". [67] This was shortly followed by use of "informatique" by the French, "informatika" (информатиwка) by the Russians, and finally "informatics" in English-speaking countries including the USA. [67],[68],[69],[70] Subsequently, the first definitions of medical informatics as a clinical and research medical subspecialty appeared in the Journal of the American Medical Association (JAMA). [71]

During the same year that clinical informatics was introduced to the medical literature (1990), Dr. Bruce Friedman is first credited with using the term "pathology informatics" while concomitantly advocating for the development of separate divisions of pathology informatics within pathology departments. He described the key benefits of having such a division, which included: (i) enhanced productivity and efficiency in application development, (ii) better management of pathology information with oversight by informaticists (also called informaticians), (iii) increased departmental political power, and (iv) increased awareness and sophistication among departmental leaders in information technology. [72] These advantages continue to be true today. Informatics as a recognized subspecialty within pathology was further championed by others who declared that pathology informaticists should play a key role in defining, selecting and implementing all information systems in a pathology department, in addition to being involved in information systems planning for a healthcare enterprise. [73]

Recognition of informatics as a bona fide academic medical subspecialty lagged behind actual practice of informatics (information management) for a time, despite the above efforts. Lack of reimbursement for clinical informatics service likely contributed to limited publication options and research funding as well as recognition from peers. [74] Similarly, clinical wards, outpatient offices and clinics still relied heavily, if not entirely, on paper records, including printouts of laboratory results and reports. This was probably related, in part, to the fact that hospitals were spending an average of only 2% of their budget on information systems. [75] However, as federal legislation surrounding cost accounting, delivery of healthcare and quality laboratory practices began to increase in the late 1980s, including but not limited to the Clinical Laboratory Improvements Act of 1988, [76] more attention was paid to the use of computer systems in healthcare as a whole. Compounded by the promulgation of PCs with graphical user interfaces and the advent of interfaced communications (vide infra), the use of computers in the hospital setting began to skyrocket. As human-computer interactions in medicine began a sharp ascent, the need for physicians to act as medical information specialists (informaticists) was more widely accepted. [71],[75],[77]

In 1992, the American Board of Pathology (ABP) sent a letter of intent to create an informatics subspecialty to the American Board of Medical Specialties (ABMS). Subsequently, a five-member informatics test committee was convened to write questions for the examination. This effort was unsuccessful at that time for two reasons. Much of informatics involves medical knowledge and complex managerial skills which are difficult to adequately represent in written questions with multiple choice answers, and questions on technical topics were considered insufficient for a clinical informatics board exam. [78] However, beginning in 2009, renewed interest in a board-certifiable subspecialty in clinical informatics spurred the publication of several papers describing criteria for a fellowship in clinical informatics in the Journal of the American Medical Informatics Association. [79],[80],[81] In September of 2011, the ABMS announced its approval of clinical informatics as a board-certifiable medial subspecialty. The application was brought forth by the American Board of Preventive Medicine with co-sponsorship by the ABP. This board examination breaks new ground because, unlike most other board examinations which are only open to a few medical specialties, any qualified candidate with primary certification in any ABMS primary specialty may sit for the clinical informatics board examination. Currently, the first examination is anticipated to take place in the fall of 2013. This will hopefully spawn more fellowships in clinical informatics that accredited by the American Council on Graduate Medical Education. At present, however, practicing pathologists may still sit for this board exam under the by-experience pathway, at least for the first five years that the board examination is available.

Use of Computers in Laboratories

Shortly after informatics was defined as a term in the early 1950's, the earliest evidence of data processing in the medical laboratory was reported. Dr. Arthur E. Rappoport presented his experience with the "McBee manual punch card for laboratory data" at the 1952 meeting of the American Society for Clinical Pathology (ASCP). [70] During the next decade, a number of events took place which demonstrated the need for information technology in the laboratory space. At the 1962 meeting of the ASCP, Dr. Rappoport demonstrated the use of IBM punch card systems in the laboratory. [70] In 1964, JAMA published the first article describing a laboratory computer system. This system, called the Laboratory Instrument Computer, was developed by the Massachusetts Institute of Technology. [82],[83] Several other early publications in the field, including a monograph, were contributed by Dr. Donald Lindberg. [84],[85],[86],[87]

By the 1970's, computer systems were in widespread use in clinical laboratories. [74] [Figure 4] illustrates the Spear CLAS-300, an early LIS from circa 1971. The first commercially supported LIS, from a vendor which still today provides such laboratory systems, was implemented at Cape Cod Hospital in 1972 by Meditech. The quantitative nature (i.e., numerical data) of clinical laboratory results and the necessity of performing repetitive calculations helped incentivize laboratories to computerize their processes. These aspects of clinical laboratory data also facilitated automation more quickly than in anatomic pathology laboratories and other areas of healthcare. The first laboratory audio response system - DIVOTS - was developed by Dr. Rappoport at the Youngstown Hospital Association in 1975. CAPER, the first online surgical pathology information system was implemented in 1976 and served as the inspiration for successive generations of anatomical pathology systems, including Surepath (1978, Tufts), and in 1983 CoPath (descendants of CoPath remain market leaders today). Likewise, the structured textual data used in microbiology proved challenging to implement, but the model created by Peebles and Ryan in 1979 continues to be a crucial component of the Sunquest LIS. Until the late 1980's, information technology in laboratories and other ancillary care areas such as the pharmacy and radiology continued to progress, but most hospital information systems (HIS) were focused on capturing charges rather than the delivery of patient care. [75],[77] By contrast, automation, with its concomitant reduction in cost per test, furthered the laboratory's strength as a revenue center for the hospital. [74],[75]
Figure 4: The CLAS-300. Top left: CLAS-300 with central alpha - numeric display keyboard and three remote universal data entry terminals. Top right: data entry on the CLAS-300 (note the large size of the computer components, as well as the magnetic tape-based storage). Bottom left: the CLAS-300's line printer; this particular model, which featured a speed of 300 lines per minute, was considered an incredibly fast printer by 1970's standards. Bottom right: the CLAS-300's central input station; though a large unit, this station was - like the smaller remote data entry terminals: A "dumb" terminal that merely reflected the state of the mainframe that powered it. Photographs reproduced with permission

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Automated Capture and Exchange of Laboratory Data

Laboratories enabled with computer technology quickly realized the need to automate transfer of data from the specimen to the instrument to the LIS, and later to the EHR. One of the first aspects of such automated data transfer was realized in the use of barcodes. Concomitantly with the birth of the term informatics and the use of computers in the laboratory, Bernard Silver and Joseph Woodland of Drexel University were granted the first barcoding technology patent in 1952. Adoption of barcodes was initially slow. While the first use of early barcodes in the commercial setting was in 1966, widespread use did not become reality until the mid-1970s. [88] Again, laboratories seemed to be ahead of their medical counterparts in the adoption of new technologies into healthcare. Dr. Arthur Rappoport implemented many creative uses of barcodes in his laboratory in the 1960's and 1970's. While many clinical applications did not utilize barcodes until the 1990s, transfusion medicine made far earlier calls for the use of barcodes for transfused products. In 1977, The American Blood Commission's Committee for Commonality in Blood Banking Automation recommended the adoption of Codabar barcodes for blood product labels. The use of Codabar on blood products was mandated by the United States Food and Drug Administration (FDA) in 1985. In 1994, a new barcode system based on Code 128 symbology was approved by the International Society for Blood Transfusion called ISBT 128. [89] ISBT 128 has been very slowly adopted over the last 17 years as transfusion laboratories are only just now being required to comply with this new standard. By the early 1980's, many laboratory instruments accepted barcode-labeled specimen tubes, and laboratories took advantage of this capability for more rapid, accurate specimen identification as well as automation.

Exchange of data over network lines came later. Health Level 7 (HL7) was formed in 1987 to provide standards for communication of health information between different systems, thereby improving the efficiency of interface implementation and accuracy of data transfer. The formation of several working groups including laboratory, anatomic pathology and genomics took place in the years that followed. In 1997, an organization called Integrating the Healthcare Enterprise (IHE) was formed with subsequent formation of laboratory and anatomic pathology working groups. The overall goal of IHE is to promote the coordinated use of established standards such as HL7 to address specific clinical needs in support of optimal patient care. Just prior to this in 1996, recognition of the importance of automation in the clinical setting increased as the National Committee for Clinical Laboratory Standards (NCCLS) formed an Area Committee on Automation to provide additional technical standards for all aspects of laboratory automated data exchange and workflow including barcoding, interface implementation and robotic lines that move specimens between different instruments for testing. [90],[91],[92] In 2005, the NCCLS changed its name to the Clinical and Laboratory Standards Institute (CLSI), to which it is now referred.

Additional discoveries by pathology informaticists furthered automation in several areas. Development of a single system to electronically collect, analyze and manage point-of-care testing data across devices from multiple vendors can be attributed to pathology informatics, [93] and pathology informatics often still leads the way in the implementation of Lean, six sigma, and automation systems for laboratories, resulting in workflow efficiencies and improvements in patient safety. [94],[95],[96],[97] Similarly, automated reporting of critical laboratory values with streamlined tracking of communication hand-offs have been generated through the work of pathology informatics. [98]

Ontologies, Terminologies and Coding Systems

Shortly after the advent of computer technology in the laboratory, the College of American Pathologists (CAP) recognized the need to define an ontology surrounding pathology concepts. The systematized nomenclature of pathology (SNOP) was published by the CAP Committee on Nomenclature and Classification under the direction of Dr. Arthur Walls in 1965. Under the long-term leadership of Dr. Roger Cote, SNOP evolved into the SNOMED. The first edition of SNOMED was published in 1976, the 2 nd edition in 1979, 3 rd (international) edition in 1998, Reference Terminology in 2002 (when Dr. Kent Spackman took up the baton), then following a merger with the British nomenclature Read codes, SNOMED-Clinical Terminology was published in 2004. The CAP with perfect foresight funded and supported the development of SNOMED for almost 30 years. Since then, SNOMED has transitioned to a truly international code, now co-sponsored and funded by 18 countries It is now owned and licensed by the International Health Terminology Standards Development Organization. [99] It is anticipated that the international classification of diseases, 11 th revision will be based on SNOMED. It is rewarding to witness how a pathology-inspired terminology initiative has become the world-wide standard for standardized and structured medical terminology.

SNOMED-CT today is the most comprehensive, multilingual clinical healthcare terminology in the world. Dr. Donald Lindberg, a pathologist and informaticist who has been the long-term head of the National Library of Medicine (NLM) started another terminology project called the unified medical language system in 1986 to facilitate the creation of more effective and interoperable biomedical information systems and services, including EHRs. [100] As the availability of automated data exchange grew, so did the scope of that exchange. Laboratories that once only used such technology for transfer of data between the test instrument and the LIS began to expand into the transfer of data between different laboratories. They quickly realized that gaps in the HL7 standard led to challenges associated with transferring test results for the same analyte, but with different methods and reference ranges. Rather than, continue with dependence on idiosyncratic test codes developed in each laboratory independently, the Regenstrief Institute at Indiana University, in cooperation with laboratorians from Utah and the USA and Canada developed a standard coding system for tests and their methods called logical observation identifiers names and codes (LOINC) in 1994. [101] LOINC facilitates the exchange and pooling of results for clinical care, outcomes management, and research and may be used in conjunction with HL7 to ensure correct mapping of test results within a database. Current draft proposals for the Health Insurance Portability and Accountability Act [102] electronic claim attachment standards are based on LOINC codes. [103] Also, the ability to send and receive laboratory results encoded with LOINC codes are an important part of the meaningful use regulations now being implemented by the US Office of the National Coordinator for Health Information Technology.

LIS Vendors

The use of LISs in USA laboratories has depended almost entirely on supply of such software by commercial vendors who install and support these systems. There have been isolated instances of home-grown/self-developed software being used in hospital laboratories, but there have been probably fewer than two dozen long-term survivors. On the other hand, long-term installations of vendor-supported systems have numbered in the thousands.

The history of the LIS is replete with many instances of vendors either going out of business or being absorbed or acquired by other entities. Interestingly, it has been the larger, non-laboratory specific companies that have had the shortest "lifetimes" as LIS providers. Examples include General Electric, International Business Machines, Digital Equipment Corporation, Honeywell, Beckman, Technicon, and Control Data Corporation among others. In contrast, the smaller, laboratory-dedicated firms experienced longer lifetimes, and although often acquired, their LISs were usually continued in use. The USA firm with the longest longevity in the LIS domain is Meditech who installed its first LIS in 1972, and is today still one of the market dominant vendors. Other firms with long, continuous histories as LIS providers include Mckesson, Sunquest (Misys), Cerner (PGI), Computer Programs and Systems Incorporated, Diamond Computing, Comp Pro Med, Psyche (SAC), and Soft Computer Consultants. Of 64 LIS firms in business in 1988, only 15 remain in business today. Over the years, despite competition for a dwindling number of potential customers, new firms have entered the market. As of 2011, 33 companies offer complete LIS solutions. [Figure 5] offers a reasonably complete timeline of LIS vendors serving the US market from the late 1960's to the present.
Figure 5: A timeline of selected Laboratory Information Systems (LIS) vendors from 1960's to the present. It is important to note that this is a sampling and not an exact account of the full history of LIS vendors. ALS = Advanced Laboratory Systems; BSL = Berkeley Scientific Laboratories; CCA = Creative Computing Applications; CDC = Control Data Corporation; CHC = Community Health Computing; DEC = Digital Equipment Corporation; DHT = Dynamic Health Technologies; DNA = Diversified Numeric Applications; FF = Fletcher-Flora; HBOC = Huff, Barrington and Owens; IDX = IDX Systems (acquired by GE in 2006); KDS = Knowledge Data Systems; LCI = Laboratory Consulting, Inc.; MCK = McKesson; MJS = Michael J. Selner Systems; NLFC = New Lab Force Corporation; PGI = Patterson, Gorup, Illig; SAC = System Analysis Corporation; SCC = Soft Computer Consultants; SMS = Shared Medical systems; T and T = T and T Technology (Peter Tong). Image courtesy Weiner Consulting Services and Dennis Winsten and Associates

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Digital Pathology, Telepathology and Image Analysis

The use of digital images in pathology was a latecomer to the pathology informatics scene. In 1968, analog video-based telepathology was first demonstrated by Ronald Weinstein and colleagues in Boston via a link between Logan International Airport and MGH [Figure 6] and [Figure 7]. This showcased the potential for image-based pathology informatics to have a positive effect on the practice of surgical pathology, cytopathology and hematology. With the advent of increasingly affordable digital imaging technologies, such early analog efforts paved the way for the emergence of digital pathology. The first publication describing the use of dynamic robotic telepathology occurred in 1986 [Figure 8], and an early publication describing a "virtual microscope" prototype which included the concept of WSI was published 10 years later. This publication forecast correctly that digital slides would not only conveniently emulate a physical microscope for clinical interpretations and teaching, but also that digital images would be used to better screen and characterize malignancies, generate three-dimensional (3D) reconstructions, and permit image analysis using various special stains that revealed the presence or absence of biochemical markers. [104],[105] Over the ensuing years the field of digital pathology continued to evolve with faster and better whole slide scanning technologies and computational algorithms to analyze the images. The first national course on digital pathology led by Mariano Alvira, Peter Shireman and John Minarcik was presented by the ASCP both at its national meetings and at its Chicago headquarters beginning in the early 1990's. Early efforts in image analysis can also be attributed to researchers in pathology informatics. [106],[107] Automated slide scanners with image analysis algorithms on board were designed to screen cervical cytology smears for abnormal cells. Such instruments first began to receive clearance for clinical use by the FDA in 1995. [108] FDA clearance for image analysis algorithms enabling quantitative analysis of immunohistochemical cancer markers for estrogen receptor, progesterone receptor and others first occurred in 2003. [109] Research continues with extensions into parallel and grid-based systems capable of supporting digital slide sign out in routine surgical pathology practice, computer-aided diagnosis, content-based image retrieval, and 3D image reconstruction. [104],[110],[111],[112] As the use of WSI evolved, the need for imaging standards specific to pathology emerged. The Digital Imaging and Communications in Medicine (DICOM) standard was initially developed to house radiological images, but in 2005, the Working Group 26 (Pathology) was added to specifically incorporate WSI into the specification. Since that time, Working Group 26 has published two supplements to the DICOM standard. [113],[114]
Figure 6: The live telepathology system connecting Boston Logan Airport and the Massachusetts general hospital in action. This is widely considered the first working telepathology system in history

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Figure 7: Examples of the video streams the first telepathology system could generate. Left: peripheral blood smear; right: Urine cytology

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Figure 8: Live demonstration (in 1986) of the first operational robotic telemicroscopy system in history. Top left: Dr. Alexander Miller and associate operating the robotic telemicroscopy system; top right: example of the video feed from the system; bottom left: Close-up of videoconferencing gear worn by participants; bottom right: Close-up demonstrating keyboard control of remote robotic microscope

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Education Efforts in Pathology Informatics

Approximately 10 years after the first reports of computer use in a laboratory, the CAP established the first computer course for pathologists at their annual meeting. [99] In 1979, the ASCP began offering the first regularly scheduled course in pathology informatics entitled "The ABCs of LIS." This was offered at every ASCP national meeting, fall and spring, from 1979-1986. Fellowships in medical informatics (this was general informatics - not pathology informatics) began to appear in the early 1980's, funded by the NLM and again spearheaded by Dr. Donald Lindberg. [115] In 1986, the first journal article, which called for pathologists to be medical information specialists appeared in the literature. [116] The first pathology informatics book, called "The ABCs of LIS", was published by Dr. Frank Elevitch and Dr. Ray Aller (based on their ASCP course) in 1986, with a revised edition published in 1989, [117] In 1980, the first article was published on training pathology residents in informatics, [118]],[ but subsequent articles did not appear until a decade later. In 1984, Dr. Frank Elevitch was appointed Chair of the CAP Lab Computer Committee (LCC), subsequently termed the Informatics Committee and more recently the Diagnostic Intelligence and Health Information Technology Committee. Under his leadership, the members of the LCC proposed, prepared, and presented an enormous number of CAP national meeting seminars on pathology informatics. Indeed, for much of the ensuing decade, more than 50% of the courses at the CAP National Meeting were focused on informatics. Although this strengthened informatics expertise at many community practices, academic centers did not appoint sufficient faculty, or permit them sufficient focus, to strengthen residency training. Because of ongoing gaps in pathology informatics expertise at many residency training programs at that time, the CAP began to develop several informatics mini-fellowships in the late 1990's to early 2000's. In 1995, the first formal pathology informatics fellowship in the nation was established by Dr. Michael Becich at the University of Pittsburgh Medical Center. [119] Today there are many more training opportunities (http://www.pathologyinformatics.org/content/training-opportunities-pathology-informatics), but still not enough to meet the emerging demand for skilled informaticists.

Professional Activities for Pathology Informaticists

The first national foci of pathology informatics began with the CAP courses of Rappaport and others in the 60's and 70's, then the ASCP course series of Elevitch and Aller 1979-1986, followed by the CAP seminars from the mid-1980's to 2000. A large amount of focused information was presented at user groups of various LIS vendors, such as Meditech, Sunquest, Cerner, and Kontron.

The first national pathology informatics conference in the USA took place in 1983 in Ann Arbor, Michigan, entitled Automated Information Management in the Clinical Laboratory (AIMCL). One year later, the American Association for Clinical Chemistry formed a division of the organization dedicated to LIS. [120] A journal called "Informatics in Pathology" was launched that same year, but was unfortunately discontinued 1 year later due to poor subscription and insufficient contributions. [78] In contrast, the AIMCL meeting was quite successful, taking place annually for 21 years. Beginning in 1996, a second conference known as advancing pathology informatics, imaging and the internet (APIII), later renamed Advancing Practice, Instruction and Innovation through Informatics (still APIII), began to be held each fall, usually in Pittsburgh, Pennsylvania. While the theme of AIMCL tended to be weighted toward clinical pathology, APIII was initially more focused on anatomic pathology and digital imaging. The driving forces behind each of these conferences were Dr. Bruce Friedman and Dr. Michael Becich, respectively. As a result of their efforts and those of many others, the first professional organization specifically oriented to pathology informatics called the Association of Pathology Informatics (API) was chartered in 2000. Since its inception, the API has been a driving force behind a number of conferences and activities for pathology informaticists (http://www.pathologyinformatics.org/).

In 2004, AIMCL was replaced by the Lab InfoTech Summit which was held annually in Las Vegas, Nevada from 2004-2009. During this time, several international meetings related to pathology informatics were held including the First World Congress on Pathology Informatics in Australia organized by Michael Legg, Ulysses Balis, and Vitali Sintchenko, and conferences in Europe hosted by the European Congress on Telepathology and International Congress on Virtual Microscopy. The Digital Pathology Association subsequently formed in 2009. Toward the end of 2010, both the APIII conference and the Lab InfoTech Summit combined, in concert with the Histology Image Analysis group, to produce a single pathology informatics mega-event in Boston, Massachusetts, named Pathology Informatics 2010. That same year, a new open-access journal entitled "Journal of Pathology Informatics" was launched under the editorship of Dr. Liron Pantanowitz and Dr. Anil Parwani. [121] Most recently, in August 2011, the first-ever nationwide retreat for pathology informatics fellows was organized by and held at the MGH in Boston, MA.

Mexico, South America, Central America, and the Caribbean

1958-1989


Telepathology

In 1974, static black-and-white images of tissues, peripheral blood and bone marrow smears were transmitted via satellite from a hospital ship docked in Brazil to Washington DC, USA. It was the first time that still images of microscopic slides were transmitted by satellite communication. [122] The same year, Dr. Moacyr Domingos Novelli from the University of Sγo Paulo published a report on the SACI Project (Advanced System in Educational Communication), which broke new ground in the usage of satellite communication in telemedicine in Brazil. [123] In 1981, the same group described its experiences with rendering remote histopathologic diagnosis from analog images obtained with optical microscopes that were then digitized and finally transmitted via satellite communication. [124],[125] In 1985, the Mexican Centre for Health Education by Television (CEMESATEL) began transmitting clinicopathologic conferences from the Hospital Infantil Federico Gσmez to 18 remote Mexican health institutions via satellite. [126]

Data Management

Computer data analysis in pathology was first reported in the South American literature by Friedrich et al. in 1977; their report describes a postoperative staging system for vulvar carcinoma. [127] One year later, Novelli et al. published their work on computerized data analysis in oral pathology. [128] Novelli's group would, 4 years later, also report on their research on terminology coding and database management in surgical pathology. [129] In 1985, a group of pathologists and engineers developed an information system for pathology and reported their experiences. [130] The same year, a team of researchers from the Universidad Nacional Autσnoma in Zargoza, Mexico described an information system for oral histopathology. [131]

Image Processing and Analysis

Throughout the 1980's, Brazil was a hotbed for microscopic image processing and analysis (mainly focusing on oral pathology) as evidenced by the creation of the Laboratory of Informatics Dedicated to Odontology at the University of Sγo Paulo in 1980. [132] In 1987 in Cuba, the first computer-based morphometric studies were performed on atherosclerotic lesions of the aorta at the Higher Institute of Medical Science of La Habana. In these studies, data was gathered with a digitizer interfaced with a NEC 9801 personal microcomputer. These data were then processed on a GDR EC-1040 minicomputer using SPSS (a statistical software package). [133] In 1989, studies on computer-aided morphometric analysis were published by the Laboratory for Cell Biology and Pathology of the University of Sγo Paulo. [134]

Teaching and CME

In 1958, the University of Santa Maria (Rνo Grande do Sul, Brazil) utilized closed-circuit television for undergraduate pathology education. [135] This was considered a pioneering use of that technology in the worldwide literature at the time. In 1986, Dr. Fernando Augusto Soares of the Ribeirγo Preto Medical School of the University of de Sγo Paulo published practical recommendations for pathologists on the use of computers. [136]

1990-1999

Telepathology

In 1993, the Department of Pathology of the Hospital of Hermosillo, Mexico (Roberto de Leσn Caballero, Jorge Platt Garcia, and Minor Cordero Bautista) participated in 63.5% of all cases processed by the Arizona International Telemedicine Network that year. This network utilized static telepathology methods to reach hospitals across the world. Even with the technological limitations (static telepathology only; relatively low-resolution images), an 88.3% absolute concordance between telepathologic diagnosis and glass slide diagnosis was seen - with an astonishing 96.5% concordance for clinically significant diagnoses. [36],[137]

Brazil and Mexico were avid users of the AFIP's Telepathology Service between 1994 and 1999. This service - described in section: Telepathology in South Africa - utilized static telepathology only in that time period and recorded a telepathology-to-glass concordance rate similar to that of the Arizona International Telemedicine Network (73% absolute concordance; 97% concordance for clinically significant diagnoses). These early static telepathology experiences highlighted the need for increased technical expertise on the part of both the referring pathologist and the telepathology consultant and increased training in the selection of appropriate regions of interest on the part of the referring pathologist. [138],[139]

In 1994, RESINTEL's TRANSPATH network - briefly described in section: Telepathology (Africa) - had operational telepathology sites in Martinique and Guadeloupe Island. Unfortunately, by 1998 this network had to be shut down due to lack of funding. The ultimate fate of these sites is not known, but they are thought to be currently non-operational. [7]

On October 11 th , 1996, Dr. Sergio Gonzαlez (Department of Pathology, Hospital Clνnico of the Pontificia Universidad Catσlica de Chile) reported on the usage of a telepathology station that connected his institution with the Hospital Dr. Sσtero del Rνo, also in Chile. This study concluded that the 10 Mbps connections afforded by their network offered good image quality for online S-video transmission from microscopes using a Silicon Graphics workstation to digitize and compress video signal from a Sony DXC-C1 camera mounted on the Olympus BH-2 light microscope. [141],[142]

South America experienced a wellspring of telepathology activity in 1997. That year, the "Europe-Latin America Telepathology Initiative" - a pilot telepathology exercise - was funded by the European Union, with the participation of the Netherlands and the Belgrano Public Hospital in Buenos Aires, Argentina. It employed ISDN technology for its network connectivity. [143] Also in 1997, the Hospital de Clνnicas de Porto Alegre in Brazil conducted a comparison study on tele-consultation in cytopathology of serous effusions. [144] Finally for 1997, the Enlace Hispano Americano de Salud (EHAS) Project as created to offer low cost radio (HF and VHF) links, with solar energy systems, in rural areas and other areas in South America where conventional telephony was not available. For instance, in the province of Alto Amazonas, Peru, this allowed for sending and receiving of E-mails between healthcare providers - a first for that geographically isolated province. [141]

Telepathology in South America continued to be strongly developed in 1998 and 1999. A videoconference session on telepathology, using three ISDN telephone lines (384 Kbits/s), between Santiago de Chile and Buenos Aires took place in 1998, during a Congress organized by the Hospital de Clνnicas de Buenos Aires. [145] In October of 1998, a telepathology workshop was organized in Peru, between Lima (Universidad Federico Villarreal) and Arequipa (Universidad San Agustνn). Its subject matter included tele-consultations, Internet, as well as image capture and processing. [146] Finally, in 1999, the Universidad Nacional de Colombia (UNC) implemented a remotely-managed robotic microscope - a first for this region of the world. [147]

Data Management

There were two notable events in pathology data management in South/Central America and the Caribbean, both of which took place in 1995. The Mexican National Epidemiological Surveillance System (SINAVE) was created that year, including an information system for the histopathologic records of malignant neoplasia. [148] Meanwhile, in Cuba, SARCAP - an automated registry and control system for pathology - was developed by the pathology department of the Hospital "Dr. Luis Dνaz Soto." It was initially designed as an information system for both autopsies and biopsies but has since then expanded into a national database for registry and coding clinical autopsies in Cuba. [149]

Image Processing and Analysis

An Argentinian group from the Medical School of the University of Buenos Aires published a digital pathology image processing study in 1990. [150] In the same timeframe, another Argentinian group studied the morphometric determination of AgNORs in breast carcinoma. [151] Also in 1990, Novelli et al. created software called IMAGELAB for image processing and analysis of microscopic images. [152] Though Novelli's group was the most prolific it was far from the only Brazilian effort in digital pathology image analysis at the time; there were also active research groups at the Evangelical Faculty of Medicine of Parana, Brazil and the Adolfo Lutz Institute, Sγo Paulo, Brazil. [153],[154] In 1993, The Institut Pasteur de Guyane, Hopital Jean Martial, Cayenne, French Guiana published a paper on the use of computer-aided image analysis in the study of inflammatory cells in skin lesions of chromomycosis. [155] Finally, in 1994, the Department of Biomedical Engineering of the Universidad Nacional de Asunciσn (Paraguay) began a full-blow research initiative on biomedical images and cancer pathology. [156]

Teaching and CME

In 1994, Infomed - a Cuban health telecommunication network that supports Internet connectivity and web editing - was brought online. It became a very popular resource for anatomic pathology in that country and still enjoys considerable activity today (http://www.sld.cu/sitios/scap/). The first Virtual Hispano-American Congress of Pathology (http://www.conganat.org/) took place in 1997, with the participation of Argentina, Brazil, Cuba, Dominican Republic, and Mexico. [157] Since then, there have been 10 further convocations of this virtual Internet congress. Dr. Gyφrgy Miklσs Bφhm, a Professor of the Department of Pathology, Faculty of Medicine, University of Sγo Paulo, created the first Brazilian Telemedicine and Medical Research Laboratory in 1998. [158] Finally, a multinational virtual health library known as Biblioteca Virtual en Salud (http://regional.bvsalud.org/) was created in March 1998 as an initiative of the Pan-American Health Organization (a WHO affiliate). Its mission was to improve access to reliable, locally relevant information on health and health sciences. Pathology journals from Ibero-American countries were included as part of this library.

2000-Present

Telepathology, WSI, and Image Analysis

The year 2000 was a highly significant year for telepathology in South America. Early that year, the UNC, the Instituto Tecnolσgico de Electrσnica y Comunicaciones and TELECOM (National Company of Telecommunications in Colombia) began a pilot study on telemedicine. This study connected the San Andres Islands, Amazonas, Bogotα and other centers. Telepathology services were based on the use of the Nikon Coolpix 995 digital camera and Nikon and Leica microscopes. [141] The inaugural Telemedicine Meeting in Panama took place in August 2000, with the collaboration of Dr. Ronald Weinstein. In this meeting, the National Program of Telemedicine, with the participation of the Medical School of the Universidad de Panamα presented a telepathology project led by Dr. Silvio Vega that connected the Universidad de Panamα with the Hospital El Vigia in Chitrι. [159],[160] Finally, in October 2000, an international randomized telepathology study was performed between Instituto Materno Infantil de Pernambuco in Brazil and St. Jude Children's Research Hospital in Memphis, Tennessee, USA. The main objective of this project was to improve the diagnostic accuracy of pediatric cancer using static telemicroscopy. It was concluded that telepathology is an efficient second opinion method and that it also allows for an improvement of quality and speed of diagnosis, resulting in a better treatment of cancer in children. [161]

In 2001, tele-consultations utilizing static telepathology only were performed between the Arias-Stella Pathology and Molecular Biology Institute in Peru and the Instituto Nazionale per lo Studio e la Cura dei Tumore in Milano, Italy. These tele-consultations were a success, with concordance rates similar to previous studies on static telepathology. [162] The Arias-Stella group continues to be a driving force for telepathology in South America to the present day.

Between 1 st October 2003 and 30 th September 2006, the European Union funded the T@lemed project. This project - which promoted evidence based telemedicine for remote and rural underserved regions in Latin America using e-health platforms - included fast transmission of microscopy images from local hospitals to high-level referral hospitals, in order to improve the diagnosis of malaria. There were 14 institutions from many different countries that participated in this project, notably the Universidad Santiago de Cali, Universidad Nacional, Centro Internacional de Vacunas and Cαmara de Industrνa y Comercio Colombo-Alemana of Colombia and the Fraunhofer Society of Germany. [163]

In 2004, Dr. Mauricio Ribeiro Borges of the Pontifνcia Universidade Catσlica do Rio de Janeiro published a comprehensive thesis on telepathology. [164] This thesis would later be recognized as a classic in the field, and now serves as one of the cornerstone texts in the understanding of telepathology in Latin America.

In 2005, the ABC Hospital of Mexico was formally recognized as a private institution with one of the highest technological levels in telepathology and digital medical imaging services in the Latin American sphere. It has remained a regional superhub for pathology informatics endeavors ever since. [148] Also in 2005, two microscopes with attached digital cameras were installed at the National Cytology Program of El Salvador, allowing quick consultations between pathologists in remote areas of the country and experts in San Salvador. [4]

In 2005 in Colombia, a telemedicine network between Cali (Universidad Santiago de Cali) and Costa Pacνfica was developed for the tracking of infectious diseases. Microscopic images containing blood and urine samples were exchanged utilizing a custom store-and-forward architecture. This network is still in operation today. [165]

In 2006, the Amazon Telemedicine Project developed a tele-health system using satellite-based networking to reach Amazon Indians in Northern Brazil, with applications in the areas of telecardiology, teleradiology, teledentistry, telepathology, and videoconferences. The telepathology component of this project largely focused on the transmission of high-resolution static images of  Pap smear More Detailss. The satellite communication system - said by its creators to be highly robust, and cost-effective - is still in operation and actively use today. [166]

In 2007, a Peruvian project known as PAMAFRO (Control of Malaria in Border Areas of the Andine Region) began installation of wide-area networks utilizing IEEE 802.11 (Wi-Fi) technology in remote areas of the country. One of the networks - which spans a 447 Km segment along the Napo river, allowing an uplink to the Hospital Regional de Iquitos - is notable as being the single longest known Wi-Fi network in the world. [167]

In 2007, the BioIngenium Research Group of the UNC in Bogotα, Colombia was formed. It has since then made virtual microscopy, image compression, and image analysis its main research foci. [168] One of its notable projects has been on the automatic programmatic detection of malaria parasites in thick blood films stained with haematoxylin-eosin. [169]

In 2008 in Cuba, a national network for telediagnosis in anatomic pathology was established by a National Reference Center for Anatomic Pathology (CENRAP) in the Hospital "Hermanos Ameijeiras" in La Habana, Cuba. [170] That same year, in Cuenca, Ecuador, a private hospital known as the SOLCA Institute began to utilize a WSI scanner for tele-consultation and primary remote diagnosis. To the best of our knowledge, this is the first - or at least one of the first - mentions in the South American literature of WSI for primary diagnosis. [171]

Finally, in 2009, a telepathology pilot using digital slides created with Aperio ScanScope was performed with the participation of the Arias-Stella Pathology and Molecular Biology Institute in Peru, the Department of Pathology of University of Sao Paulo in Brazil, the Hospital Britαnico de Buenos Aires in Argentina, and Centro Consulenze Anatomia Patologica in Milano, Italy. [172]

Teaching and CME

In 2000, a website containing a comprehensive collection of histopathologic images with a special focus on oral pathology was published by the Fundaηγo Odontolσgica de Ribeirγo Preto, Universidade de Sγo Paulo. [173] Also in 2000, the University of Cauca served as a mirror site for the 6 th Internet World Congress for Biomedical Sciences, organized by the Pathology Department of Hospital de Ciudad Real in Spain. [174] Since June 2002, autopsies have been broadcast online on a weekly basis, with the participation of 12 Brazilian medical schools. [175]

In 2004 in Uruguay, the Pathology Department of the Medical School of the Hospital de Clνnicas "Dr. Manuel Quintela" in Montevideo, Uruguay started publishing online study material for medical students. [176] In 2005, the Virtual Hispano-American Congress of Pathology began utilizing WSIs instead of static images in its presentations. Finally, at present, iPath hosts the Telemedicina Sur telemedicine network, active in South-American countries for medical discussions, including pathology CME and consultations.

LISs

In the last 5 years, significant improvements have been made in data management in pathology departments in Central and South America. Several commercial vendors (e.g., Labsoft Tecnologia Ltda.) are distributing products in Argentina, Brazil, and other countries. System integration and interoperability solutions for pathology are also available in products like data innovations (Austria and Brazil), Tesi Pathox (Italy and Brazil), CSC Patwin, Vitro Novopath and Esblada Gesapath (Spain and Ibero-America). Tracking and laboratory connectivity solutions from Dako (DaloLink, TPID) are also distributed in Brazil and other Ibero-American countries.


   Asia Top


The progress of pathology informatics in Asia has been much like the phenomenon of watching ripples spread across the surface of a once-placid pond after a pebble has been thrown into it. The pond in this metaphor is Asia; the pebble represents progress in telepathology and WSI from the West. Although this historical review of informatics in Asia is focused largely on advances in digital imaging, much progress has been achieved in these countries utilizing computers to establish LISs. In general, development of digitized telepathology was supported by the development of computers, and improvements in the performance of digital cameras. In the modern era, WSI have been a primary focus of pathology informatics activity across the world. Asia is no different in this respect. In some Asian countries (e.g., Japan), where network infrastructure and high-speed Internet-based telemedicine are well-developed WSI systems are in heavy use. In other Asian countries (e.g., China), there are significant bottlenecks to further penetration of telepathology, including (i) low levels of understanding in society in general about the importance of pathological diagnosis, (ii) physical constraints, including infrastructure development not keeping up in large geographic areas, (iii) high prices of WSI systems, (iv) lack of mutual trust between pathologists in different areas, and (v) regulatory issues.

The story of digital imaging in pathology was, in its earliest years, confined largely to the USA and Europe. With the development of the Internet came the possibility of sending and receiving digital images across the world; most historians of our still-nascent field trace the lion's share of the evolution of the current state of telepathology - and indeed pathology at large - to this singularly disruptive event. Many organizations - such as the AITN - sprang up in the so-called "Web 1.0" era, providing platforms for diagnoses and consultations based on international telepathology involving not only the USA, but also many other nations, including China and Japan. [177] While these early efforts uniformly used static telepathology as their primary diagnostic modality, in the modern era we have seen a shift to the usage of WSI instead. [178] In Asia, the story of true digital pathology has just begun; it currently lags far behind the more developed state of digital pathology among the Western nations. However, Asian nations - particularly those with advanced network infrastructures like Japan and South Korea - are making more and more use of digital pathology as broadband saturation in these countries have reached (and indeed by now have exceeded) 100%. More recently, fast-growing economies like China and India have been pushing forward with digitization. Iran and Uzbekistan are also promoting digital pathology. [179],[180]

Telepathology options differ from country to country: Offerings run the gamut from relatively slow transfer of static images taken by digital cameras via digital subscriber line to nearly-instantaneous transfer of WSIs via fiber optic networks. [181],[182],[183] Governmental support for telepathology and digital pathology is also quite variable - some countries have embraced these new technologies as quickly as they are introduced, whereas others have applied heavy regulation that has effectively stifled the growth of digital pathology in those nations. A case in point is the comparison between Japan and South Korea: Although both countries have impressive network infrastructures (South Korea's broadband penetration approached 100% as of 2012), the uptake of digital pathology in South Korea has been relatively slow due to an onerous regulatory environment. Compare this to the governmental policies of Japan, which openly promote a "standardization of cancer medical services" based on WSIs as well as other medical advances. It should therefore, come as no surprise that Japan's growth in telepathology and WSI adoption is outstanding as compared to that of South Korea - a nation that not only has a smaller landmass, but also an arguably better-developed network infrastructure [Figure 9]. [184]
Figure 9: Growth in Japanese telepathology installations, 2004-2010

Click here to view


Japan

Japan's network infrastructure is among the best-developed in the world. Population coverage and network speeds also rank among the highest in the world-it is worth noting that fiber optics is a common connectivity option even among general households! High-speed network-based telemedicine has been developed to such a level that intraoperative rapid diagnosis and consultation take place actively in the field of pathological diagnosis. The first reports of digital pathology in Japan date from the first half of the 1990's. At first, static images were the major telepathology modality; now, real-time remote control of robotic microscopes and access to WSI is the norm. The essential driver of this change is widely accepted to have been the government's policymaking.

Infrastructure

Telepathology in Japan was first conducted on an analog system. It started shifting to digital modalities in approximately 1996 by using the ISDN protocol, which was the first step toward full implementation. In 2001 and 2002, asymmetric digital subscriber line (ADSL) and fiber optics, respectively, were implemented in telepathology. The advances in transmission technology combined with wide spread digitization made it possible to transfer still images and videos of tissues for pathological diagnosis. With the more recent addition of Hi-Vision (HDTV) technology, intraoperative rapid diagnosis is performed utilizing dynamic methods with full remote control of a robotic microscope. [185],[10] WSI is also utilized for consultation and second opinions while their application in medical education is expanding. In 2009 and 2010, the high-speed satellite "Kizuna" was used for the first-ever Japanese fully dynamic/WSI telepathology study via satellite; this study allowed for simultaneous live telepresence across three sites (Iwate, Tokyo, and Okinawa). [186]

Digitization

In Japan, the static, dynamic (live video feed without control of the microscope), fully dynamic (live video feed with direct control of robotic microscope), and WSI methods of digital pathology are all in use. As of today, two Japanese providers offer fully dynamic and/or WSI methods. The Ministry of Health, Labour and Welfare has provided (and continues to provide) half of the funds necessary to procure WSI scanners and other such equipment at institutes and hospitals across the nation. The total number of WSI systems deployed in Japan is approximately 400, most of which are provided by Hamamatsu Photonics and Olympus. The use of WSI has taken root not only for pathological diagnosis, but also for education. The usage rate in medical faculties of Japanese universities for teaching histology and pathology is 46%. [187] Most of the universities utilize WSI in combination with existing microscopes; however, depending on the content of the lectures, some have fully shifted to WSI. [188] Although a complete shift from microscopes to WSI still requires validation of their educational effectiveness, WSI has been highly praised by students and researchers alike as they allow more than one user to look at a specimen simultaneously and to conduct discussions among themselves. WSI is also more flexible compared with traditional microscopes.

China

Expectations for telemedicine including telepathology are very high in China, which is a country with an extensive national territory. Telepathology, however, is not currently actively practiced because (i) the infrastructure has not developed fast enough to cover all areas, (ii) hardware cost is still high, (iii) digital imagery is not fully trusted, (iv) people have a strong attachment to traditional optical microscopic diagnoses, (v) not enough physicians engage in telepathology, and (vi) state regulations concerning remote diagnosis are inadequate. In terms of infrastructure, digital subscriber line (DSL) is still the dominant technology, but more recently some cases of telepathology are reported as using fiber optics and WSI.

Infrastructure and Equipment

Along with its recent outstanding economic growth, China has been rapidly expanding its infrastructure. The speed of development can be exemplified by the number of Internet users reaching 400 million in 2011 and the number of cell phone users reaching 900 million. [189],[190] Nevertheless, China's overall network infrastructure remains less developed than that of the USA, Japan, and South Korea. Although the absolute number of people who have access to the Internet is the highest in the world, if divided by China's large population, the penetration rate remains as low as 36.3% as opposed to 100% in South Korea, 78.3% in North America, and 78.4% in Japan. [191] Moreover, the digital divide in terms of Internet use between urban and rural areas is significant.

Digitization and Telepathology

Pathologists are scarce in China, particularly in the southwest region. To ascertain the telepathology situation in the country, we performed a PubMed search with the keywords, '"Telepathology" and "China."' There were five hits, three of which were related to consultation using the AITN as reported by Weinstein. These telepathology cases utilized static telemicroscopy over the Internet. Telepathology efforts indigenous to China, however, began in the first half of the 1990's. [177] Since the early 2000's, telepathology studies have been conducted based mainly on employing digitized still images and live video feeds without direct microscope control. These two diagnostic modalities appear to be the current mainstream in China. More recently, however, telepathology using fiber optics and WSI has tentatively begun between Peking University and its first hospital. The most popular way of currently conducting telepathology in China is to either share WSI on a server with a trusted partner or to send an E-mail with a WSI as an attached file in the file transaction hub (FTH) format via DSL. In this format, the sender observes an image enlarged by a factor of four, extracts his/her area of interest into a 40-times-larger WSI, attaches the image as an FTH file to an E-mail, and sends it to the consulting pathologist. The advantage of this process is that the WSI files are of relatively small size, between 2 MB and 30 MB. This represents a middle ground between WSI-based and static image-based approaches. The attempt started with validating the result of this mode of telepathology by comparing it to conventional optical microscopy using biopsy cases; the diagnoses were reported to show good agreement for all cases. [182],[183] Nevertheless, the use of static telepathology still remains more prevalent than dynamic methods. In addition, the issue of disparity between urban and rural areas remains unsolved in terms of limited infrastructure development and utilization of Information Technology (IT) in hospital facilities. As such, the practice of telepathology in China is currently limited to certain institutes only.

India

Telepathology in India is generally limited to static telemicroscopy utilizing the Internet. [181] Similar to China, constraints include the size of the country, the gap between urban and rural areas, startup cost, a power grid electrical supply system that is subject to occasional blackouts, and also the complex human relations among several groups.

Infrastructure

Due to India's historical background, the Indian people exhibit a high level of proficiency in English and mathematics, and the implementation of IT, mainly in enterprises, has been well positioned in a global society since the 1990's due to the government's policies. As of June 2010, the number of subscribers to wired Internet services was 16.72 million and that to broadband services was 9.47 million. The most popular connectivity type is DSL. [192] At the same time, the number of cell phone users reached around 635 million. The (what?) coverage was approximately 53.8% in 2010. [193] The country is pushing forward the construction of a wireless communications infrastructure in rural areas, with increasing adoption of third-generation (3G) wireless telecommunication and WiMAX technology.

The implementation of IT in medical settings is observed in the connection of the three major municipal hospitals in New Delhi with their affiliated hospitals, and communication with local cities was experimentally attempted in the Hyderbad District in the Southern part of the country. [194] Transmission of surgery-related images and other interactions on remote images in other districts have not been reported.

Digitization

According to the 50 th Annual Conference of the Indian Association of Pathologists and Microbiologists held in Mumbai in 2001, the static (store-and-forward) method of telepathology relying on the Internet was used for consultation. [181] This static approach is still the mainstream method of practicing telepathology, but is used only by very few pathologists. Desai et al. successfully obtained effective tele-consultation outcomes by connecting the Tertiary Cancer Center (Tata Memorial Hospital) and the Rural Cancer Hospital (Nargis Dutt Memorial Cancer Hospital). However, these consultations were performed with a 56 kbps modem, which is not broadband. Still, concordance rates from this trial were 90.2%, and such time- and labor-consuming efforts are contributing to the rise in the level of confidence in telepathology. [195] In 2011, Kanthraj reported the application of store-and-forward teledermatology and mobile teledermatology. [196] The scope of this application, however, mainly covered macroscopic observation and treatment and addressed pathology images only in part. The promotion and utilization of WSI in the country awaits better infrastructure and other issues are overcome.

South Korea

The adoption of IT in South Korea is characterized by the highest levels of high-speed Internet coverage in the world, cloud computing, and active applications in the medical sphere. Conversely, due to a heavy regulatory environment and the high number of diagnostic pathologists to the number of hospitals, social need for and interest in telepathology seem marginal. The number of WSI scanners is approximately 30, which is fewer than Japan has, and most are being used for educational purposes.

Infrastructure

The country has been developing its infrastructure for high-speed Internet based on advanced DSL technology, as part of its initiative promoting IT projects since the mid-1990's. A great portion of the South Korean population is concentrated in Seoul and its metropolitan area, where many people reside in housing complexes. This is an appropriate environment for ADSL, and its coverage has expanded due to its low pricing, which since its introduction has fallen even further as a result of fierce competition among providers. Today, more than one-half of wired broadband subscribers use fiber to the home and optical LAN with sustained transfer speeds of greater than 50 Mbps. [197]

In general medicine, receipts (medical fee bills) and other documents have been increasingly digitized, such that the nationwide digitization rate for medical billing was already 88% in 2006 and almost 100% of this information has been made available online at dispensing pharmacies. [198] Nevertheless, telemedicine is observed only in the government's primary-level research and not in practical settings due to legal constraints.

South Korea is a rapidly aging society, just like Japan. Thus, the "u-healthcare" industry, which combines information and communication technology with medicine, garners much attention for future healthcare services. This concept includes telemedicine and also remote health control. It is most likely that, once the regulations are relaxed, services at an international standard will immediately be available in South Korea, where the IT infrastructure is well established.

Digitization

Though the number of WSI systems in South Korea is smaller than that in other Asian nations, WSI is being applied in educational conferences, but rarely for telepathology. Factors contributing to this include the South Korean medical laws and also the perceived lack of need for telemedicine considering the relatively large scale of South Korean hospitals and the presence of local pathologists. WSI for educational applications, on the other hand, are widely observed and enthusiastically adopted in the hands-on training of students and for self-study. WSI is highly appreciated by students and positioned as an important tool for pathological education. [199] It is likely that the WSI-based learning style will be common in the country, where onsite LAN is well developed in educational settings.


   Australia Top


Australia's Council for Scientific and Industrial Research Automated Computer Mark 1 (CSIR MK1), which ran its first program in 1949, was the fourth stored program computer in the world. This and the replacement machines in Sydney, SILLIAC and KDF9 were used for medical and pathology research including Fourier analysis of pressure and displacement waves to understand the elasticity of arteries. Between 1969 and 1971 three Australian preventive healthcare organizations began using computers for EHRs. All these systems included a pathology LIS. Those organizations were Medicheck and Preventicare in Sydney and the Shepherd Foundation in Melbourne. Medicheck, modeled on the Kaiser Permanente Multiphasic Health Screening Centre led by Morris Collen (after whom the American College of Medical Informatics Prize is named), had its own pathology laboratory and installed the IBM 1800 while Preventicare, which developed into New South Wales' largest private pathology laboratory, used the IBM Call 360 time-share service. Both developed their own software. This was front-page news at the time and seen as a threat to good medicine. Around the same time an LIS written in assembler on ICL hardware (Hospro) was developed and became the dominant system in private pathology practices in Australia. These LISs were later replaced by one of the world's first LISs that used a high transaction relational database-Triple G's Ultra (so-called after the three Australian developers who called one another George but were actually Mike, Peter and Brian). Triple G sold in Canada and the USA, and the company was subsequently acquired by GE.

Other LISs developed in Australia of note are:

  • MGH Utility Multi Programming System (MUMPS) based system first developed by Dιtente in 1970's and now known as ISS-Omni-Lab installed in the United Kingdom and New Zealand. This was redeveloped by Sonic into their Apollo system which is now in use in their laboratories around the world.
  • Pick based system from last resort support which is sold into the United Kingdom.
  • Delphi and HL7 based kestral and medical objects LISs-both organizations at the vanguard of informatics standards development and recognized for having contributed significantly, especially to HL7.
The first electronic transfer of pathology reports from laboratories in Australia was in 1969 using teletypes on the Preventicare IBM Call 360 network. In the early 1970's, this network got as large as 250 sites in four states and was reputed to be the third biggest network of its kind in the world.

The first pathology transfer using the Internet was in the early 1990's, but the most common method then was modem to modem communication. In 1993, a de facto standard for this purpose was introduced with an agreement between two dominant Queensland laboratories. This was a FORTRAN like message called Pathology Information Transfer (PIT) that was and still remains in wide use. In 1996, a Standards Australia Committee (IT 14-6-5) was established ostensibly to answer which was the best Standard for Australia to adopt for pathology results reporting-PIT, EDIFACT or HL7?

In 1997, Standards Australia established a relationship with HL7.org (and later HL7 Australia) and in 1998 Australian Implementation Standards AS4700.1 ADT and AS4700.2 for Pathology Orders and Results were published. A detailed handbook for pathology messaging (HB262) followed in 2002. The Standard pointed to a subset of LOINC codes as the recommended terminology for the test name (OBX3). This standard for electronic communication was taken up in the National Pathology Accreditation Advisory Council "Requirements for Information Communication" publication in 2007, and so forms an integral part of the requirements for laboratory accreditation in Australia. It is estimated that there are around 100 million pathology messages a year and it is now the usual manner for delivering a report, and in some places now also used for ordering.

In 1993, the Australasian Association of Clinical Biochemists sponsored a satellite meeting of the International Federation of Clinical Chemistry and Laboratory Medicine dedicated to pathology informatics at Uluru in the middle of Australia. Among the eminent invited speakers were Dr. Octo Barnett from the MGH, who was instrumental in designing and programming one of the first comprehensive HIS. This was followed by a meeting a decade later sponsored by the Health Informatics Society of Australia and in 2007 the first World Congress in Pathology Informatics co-sponsored by the API, the Health Informatics Society of Australia and the Royal College of Pathologists of Australasia (RCPA).

Pathology informatics research and projects reported at these meetings and subsequent ones included:

  • The application of ripple-down rules in pathology decision support (1993)
  • Privacy in community pathology (2002)
Government Quality Use of Pathology Committee Projects (2003-2007):

  • The chain of information custody
  • The role of pathology informatics in a quality framework
  • The influence of computers on ordering
  • Terminology
  • Electronic reporting and ordering
  • Natural language processing of surgical pathology reports
  • Evaluation of pathology order entry systems in hospitals
  • A seminal work on Infectious disease informatics (2009).
Unlike teleradiology, where Australia is a major player, telepathology has not yet become routine. Virtual microscopy, using Aperio, has however been a component of the RCPA Quality Assurance Programs since 2008. In 2007 a national workshop on safety and quality in pathology identified workforce and smart requesting and reporting as three of the top five issues that should be addressed in Australia. This set the agenda for funding through the Quality Use of Pathology Program of the Australian Department of Health and Ageing. The role of the health informaticist was recognized in the 2008 report entitled 'The Australian Pathology Workforce Crisis' and has been included in workforce considerations since. In 2012, the RCPA established a formal Informatics Advisory Committee of the same status as other sub-disciplines in pathology after having had ad-hoc taskforces for many years.


   Europe Top


Stereography and the Infancy of Pathology Informatics

In the infancy of pathology informatics in Europe (1945-1970), much effort was focused on measuring sizes and numbers of nuclei, cells, vessels, glands and nerves by projecting microscopic images on a light screen equipped with a suitable grid. [200] This technique - later to be called stereology - would allow three-dimensional approximations to be extrapolated from two-dimensional measurements. [201] The history of stereology in pathology can be traced back to the 1950's, when H. Elias analyzed the structure of the mammalian liver, [200] and Tomkeieff and Campbell investigated in the structure of the mammalian lung. [201],[202] Later, Cruz-Orieve applied rigorous mathematical algorithms to stereology, and Gundersen and Jensen published their ideas of the "fractionator", "nucleator" and "rotator" - statistical sampling techniques that allowed the observer to estimate particle volume and distribution in an unbiased manner. [203],[204],[205]

At that time, European research in pathology informatics was largely focused on attempting to associate stereological data with clinical findings, for example, morphological changes with cancer cell types, or to predict the survival of cancer patients. [206],[207] Although several significant associations were reported initially, clinicostereologic correlation never made it past the experimental phase. On the other side, such experiments promoted further investigation and understanding of semi-quantitative methods in image evaluation, as well as research in classification, coding, and nomenclature.

Coding Standards and Natural Language Processing

Once the first computers became available, two important areas of research and development emerged: The standardization and codification of clinical nomenclatures (e.g., SNOMED, ICD) and natural language processing (and auto-coding) of free-text pathology reports. [208],[209],[210],[211],[212],[213] These efforts quickly bore fruit and were integrated into routine pathology services. At the Institute of Pathology at the University of Heidelberg, for instance, there were projects to (a) enable "just-in-time" free text translation of autopsy findings and (b) pursue complete digitalization of all autopsy records back to 1841. [214]

The advent of computerized tomography technology in the 1980's induced a sharp decrease of autopsies. For instance, at the Institute of Pathology at the University of Heidelberg, the number of autopsies dropped down from 1200/year in 1970 to approximately 350/year in 2000; other European and German Institutes of Pathology displayed a similar trend. [215] It was around this time that interest in natural language processing for the automation of pathology reports waned, instead being supplanted by research in molecular biology and genetics. [216],[217],[218]

The drop in autopsies did not diminish the workload of pathologists. In fact, the concurrent rise in biopsies, fine needle aspirations, and surgical specimens created an overwhelmingly heavy workload for pathology departments throughout Europe, along with the need for sophisticated logistics, financial analysis, and clinician-facing electronic communication tools in the laboratory.

Laboratory and HIS

In Europe, the increase in biopsies induced research in different aspects of pathology informatics. Questions on to handle the enormous number of biopsies and other specimens, how to classify the obtained diagnoses, and how to correctly manage issues of reimbursement arose, [219] eventually resulting in the need for the first precursors of modern LISs. [220] Advanced tissue testing modalities, most notably immunohistochemistry and DNA sequencing, drastically increased the complexity of routine tissue handling, in turn requiring a standardization of laboratory techniques and performance. [221] It was soon recognized that LISs themselves require regulation and standardization, which gave rise to formal certification of LISs. Such certification is now considered to be mandatory since the beginning of this century. [222],[223]

At the same time, similar factors in the health care industry at large forced hospitals to introduce electronic record-keeping systems, and thus HIS were increasingly adopted in the 1990s. [224] In Germany, LIS and HIS are strongly controlled by obligatory insurance companies: employees who earn less than a certain salary per month are mandatorily insured by one of these companies. These companies provide reimbursement for care which is calculated by so-called reimbursement codes (codes for diseases, therapeutic and diagnostic examinations, all of which correspond to a flexible, fixed amount of Euros). The financial value of each code is locally and periodically regulated and depends mainly upon the local and momentary contribution of the insured workers to the insurance company. Thus, the management and maintenance of LIS and HIS in combination with the demands of certification is highly region-specific. Commonly, these systems require an update every 3 months.

With only a few exceptions, all patients in Europe have been equipped with an insurance card. These cards commonly integrate a solid-state electronic storage component that contains the patient's personal identifiers and the patient's insurance company. While these cards have carried no medical records up until now, trials are now underway to include comprehensive medical records on insurance cards. [225] In most cases, these data can be electronically transferred into the HIS, and afterwards into the LIS in hospitals, or into the local administration system of private pathology institutions. This allows for true portability of a patient's personal health records, as well as easy billing and reimbursement on the part of the institution. [225]

LIS and HIS are well developed in nearly all Western European countries including Belgium, Denmark, Finland, France, Great Britain, Iceland, Ireland, Italy, Norway, Portugal, Spain, Sweden, and the Netherlands. Those in former socialistic EU countries such as Estonia, Latvia, Lithuania, and Poland have introduced well developed LIS and HIS in combination with the mandatory renovation of their bigger hospitals.

The implementation and maturation of LIS and HIS was forced by the demands of public health and the government. Standardization of image transfer (in radiology) and medical records inside and in between different hospitals were considered to be prerequisites for success. The implementation of PACS and that of DICOM standards occurred in the middle to end of the 1990's. At present, more than 80% of hospitals and private institutions (radiology practices) are assumed to be equipped with such systems to the best of our knowledge.

Image Analysis

The development of measurements at a light microscopic magnification was characterized by three milestones in the 1980's-1990's, namely the development, implementation and standardization of DNA cytometry, syntactic structure analysis, and communication in diagnostic pathology.

DNA cytometry was the first and to our knowledge only pathology measure that introduced fixed, reliable, and commonly agreed measurement standards and error limitations, for example, a standard deviation of less than 5%, and others. [226],[227],[228],[229] It is a crude measurement procedure of genetic abnormalities in a nucleus (total amount of DNA) and is based upon the stoichiometric light absorption of Feulgen stained DNA. The analyzed parameters include ploidy, S-phase, and 5C exceeding rate. [226],[227],[228],[229] In recent years, DNA cytometry has been replaced by genetic examinations that permit a more detailed insight into chromosome, genes, DNA sequences, and proteins.

Syntactic structure analysis is a measure of structures present in cells (or nuclei). It utilizes graph theory to successfully analyse and annotate properties between nodes (edges) in combination with properties of nodes (vertices). It can be considered as a direct successor to DNA cytometry. [230],[231],[232],[233],[234] The reported results and derived data (e.g., Structural Entropy) have been shown to be of prognostic significance for certain patient populations, most notably lung cancer patients with intra-pulmonary metastases. [235],[236],[237] At present, the technique has been expanded to IHC images, and reported being suitable for determination of so-called areas of interest in WSI. [238],[239],[240],[241]

Telepathology

Early Events Prior to the Internet


The history of telemedicine is closely associated with the technological development and progress in medical diagnosis and treatment. [242],[36] Most efforts focused on diagnosis (teleradiology, telepathology, teledermatology, tele-endoscopy, etc.), and only a few investigations were devoted to teletreatment such as telesurgery. [242],[36],[243],[244],[245],[246],[178],[247] The floodgates of telemedicine were opened by the National Aeronautics and Space Administration of the USA in the 1960's. [245],[178],[248],[249],[250],[251],[177],[252],[253],[254],[255] Telemonitoring systems had to be implemented in order to monitor the health condition of astronauts. [256],[257],[258],[259],[260],[261],[262],[263] These included continuous monitoring of cardiovascular functions as well as those of brain functionality. [242],[253],[264],[265] Based upon these experiences, earth-bound telemedicine trials were performed in the USA first. One of the earliest events was the video transmission of black and white blood smears from the Logan International Airport, Boston to the MGH by W. Beck and K. Bird in 1968. [245],[254],[266],[267] Despite some tele-education and distant cytology consultations done at John Hopkins Hospital, Baltimore, USA (J. Frost) [268],[269],[270],[271] in 1979, it took about another 20 years until further investigations in telemedicine followed. They started with USA-based trials. [266],[140],[272],[273] European investigations followed about 3-4 years later. [248],[274],[275],[276],[277],[278],[279] At that time, telemedicine was based mainly upon still images, and those that were performed using the remote control systems (mainly for intra-operative frozen section). These considerations are based upon the three different types of tissue-based diagnostic needs (pre-, intra- and post-operative diagnostics. [36],[280],[281],[282],[283],[284],[285],[286] With the exception of cardiology, most investigations regarding telemedicine trials included still images. [247],[248],[252],[287],[288],[289],[290],[291],[292],[293],[294],[295],[296],[297],[298],[299] Still images for telemedicine investigations were seen also in radiology (including ultrasound examinations), surgical pathology, and dermatology. [247],[276],[277],[278],[295],[298],[300],[301],[302],[303],[304],[305],[306],[307],[308],[309],[310],[311]

Telecardiology, however, did not include still images, as it relied on the transmission of analogue signals. In fact, the first telecardiology trial was reported by Wilhelm Einthofen (1860-1924), who in 1905 transmitted heart beats by telephone. [312],[313],[314],[315]

This historical event remained silent for more than 50 years until the need for bridging long distances of inaccessible heart functions was evident for astronauts. In Europe, the electronic transmission of electrocardiogram signals to specialized clinics took place in the 1980's. The analogue signals were acquired by specific electronic devices (frame grabbers) and the patient could be monitored for at least 24 h. [295],[313],[314],[315],[316] Ultrasound telemedicine devices had already been suggested in 1978. [313],[314],[315],[316],[317],[318],[319],[320] However, it was only in the 1990's that these emergency devices were available for patient care in Europe. [250],[264],[265],[310]

The common telecardiologic devices included ambulatory Holter monitors and loop event recorders, or event-triggered monitors. Similar to other telemedicine fields the preferred solutions have been an end to end connections, i.e., a fixed client - observer line. [250],[265] In addition to telecardiology, the development of telemedicine applications in Europe was formed by other medical fields that use images for diagnosis, such as dermatology, pathology, and radiology. [177],[316],[321],[322],[323],[324],[325],[327],[328],[329],[330],[331],[332],[333],[334],[335],[336],[337],[338],[339],[340],[341]

Intensive research to explore the potency of this new technology was remarkably enhanced by the on-going technological development. Here, three different "coordinates" have to be mentioned:

  • Velocity and the kind of line (telephone) connections available,
  • Systems of image acquisition and display, and
  • Electronic communication systems.
To start with, telecommunication in Europe was characterized by a unique situation in which state owned telecommunication companies dominated the market. Private telephone companies did not exist at the beginning of the telemedicine era. Therefore, the analogue lines could be replaced by digital line connections without major difficulties or without dealing with (intra-state) different digital standards. The ISDN was created by the European Telecommunication Standards Institute in 1989 and implemented as a European Telecommunication Standard in 1993. [342]

European efforts with telepathology started, however, prior to this development. Of particular interest was the immediate transfer of a (primary) diagnosis in surgical pathology during frozen section. This involved the replacement of specimen transportation from smaller hospitals, which were not equipped with an Institute of Pathology, by the electronic transfer and remote control of microscopic images. [121],[343],[344],[345],[346],[347],[348],[349],[350],[351] Several specific telepathology systems have been developed for this purpose. [343],[350],[352],[353],[354],[355],[356],[357]

In 1988, a routine telemedicine service was started by T. Eide and I. Nordrum to provide three smaller hospitals with an intra-operative frozen section service. [334],[350],[358] The hospitals were located at a distance of 300-400 km from the Institute of Pathology of the University of Tromsφ, Norway. A specific end-to-end user (store-and-forward) system was developed. By 1993, more than 150 intra-operative frozen section diagnoses had been reported through this service. [275],[122],[359] At the same time, the University Hospital of North-Norway performed trials in teleradiology, teledermatology, tele-otorhinolaryngology (remote endoscopy), remote gastroscopy, tele-echocardiography, remote transmission of electrocardiograms, telepsychiatry, teleophthalmology, teledialysis, tele-emergency medicine, tele-oncology, telecare, telegeriatrics, teledentistry, and maritime telemedicine. [291]

Telepathology trials confirmed the following:

Intra-operatively obtained microscopic images could be acquired with an image quality that was sufficient for reliable diagnostic purposes.

The velocity (bandwidth) of the (analogue) telephone line connections permitted a stable transfer of images.

The diagnostic error rate of this technology was in the same range as that of conventional light microscopy frozen section technology, which served as the gold standard.

Patients greatly benefited from this technology by being treated in accordance with the latest guidelines, by avoiding the need to be transported over a long distance, and minimizing their risk of potential repeat surgical treatment.

The costs of this technology could be compensated by using reliable intra-operative diagnostic statements that translated into potential financial reimbursement.

The impact of the Tromsφ trials on the development of European telemedicine (pathology) cannot be overstated. [242],[360],[361],[362],[363] Several telepathology teams followed suit with their own investigations on the use of this technology to support a remote frozen section service, and reported similar results. [298],[332],[343],[346],[351],[357],[364],[365],[366],[367],[368],[369],[370],[371],[372],[373],[374],[375],[376],[377],[378],[379],[380],[381] This applied technology seemed to be promising, and was considered to increase the reputation of smaller hospitals, helped to establish larger institutes of pathology which would take over the services of smaller institutions, and provided patients with the latest technology for medical diagnosis and treatment. At about the same time, in 1990, Kayser et al. reported on different aspects of telepathology. [36],[249],[285],[338],[360],[382] They performed the first expert consultation trials in Germany between Darmstadt, Heidelberg, and Mainz, three cities each with about 120,000 inhabitants [Figure 10], which was followed by the first quality control board examination of lung cancer cases using telemedicine in 1992. [36],[362],[383] The year 1992 can be considered to be one of the milestones of early telemedicine in Europe because:

  • The Tromsφ telepathology group reported their successful trials
  • A unique telepathology network was installed in France by E. Martin, P. Dussere, and G. Brugal
  • The first European conference on telepathology was held in Heidelberg
  • The first international conference of telemedicine took place in Tromsφ, Norway.
Figure 10: Demonstration of image quality of first expert telepathology trials in Germany, 1990. Note the breaks of line connections

Click here to view


These two aforementioned conferences solidified the acknowledgement of telemedicine in Europe, and all subsequent annual national conferences of pathology since 2002 included telepathology in their themes. Bi-annual European telepathology conferences were held without exception in:

  • Heidelberg (Germany, 1992)
  • Paris (France, 1994)
  • Zagreb (Croatia, 1996)
  • Udine (Italy, 1998)
  • Aurich (Germany, 2000)
  • Heraclion (Crete, Greece, 2002)
  • Poznan (Poland, 2004)
  • Budapest (Hungary, 2006)
  • Toledo (Spain, 2008)
  • Vilnius (Lithuania, 2010)
  • Venice (Italy, 2012)
During the decade 1990-2000, there were several innovative European trials, some of which were successful, others not. Innovation by itself, however, does not assure success. The technological environment has to be mature in order to accept disruptive efforts, and to provide the "soil of success". [384] One successful application was the implementation of telepathology in a modern pathology laboratory in Cambodia, where a Cambodian-Thai-German pathologist team formed a working group (DIAG_AID) and trained Cambodian colleagues in diagnostic surgical pathology. [242],[380],[385] Only three experienced Cambodian pathologists were working in Cambodia at that time. A telepathology system was implemented at the Sihanouk Hospital Center of HOPE in 2002. It relied on the iPATH servers and was in use until the termination of the overarching iPATH system. [14],[386],[387] This infrastructure served for both assistance with immediate diagnoses and continuous education of young colleagues. The European assistance was continuously accompanied by Thai colleagues. The first double blinded study on intra-operative frozen section telepathology was performed by H. Guski at the Institute of Pathology, Charite. [242],[383],[394],[395] This study confirmed that digital images could be judged with the same diagnostic accuracy as conventional microscopic images. An additional innovative successful trial was the European founded Europath project headed by Dr. G. Brugal and Dr. K. Kunze. [388],[389],[390],[391],[392],[393] To our knowledge, this was the first telemeasurement system in cytology (using static DNA analysis of Feulgen stained nuclei). It was started in 1996 and was fully implemented in 1999. It was employed for determining individual measurements, as well as analysis of measurement accuracy of both submitted microscopic images and commercial DNA measurement systems. A less successful trial was the introduction of the PARIS project (pathology and anatomy review international score) in 1999. The focus of this project was to peer review potential scientific articles and to provide the authors with an internationally acknowledged score independently from the journal in which the authors wanted to publish their article. Only a few authors participated in this free service. The project resulted in the first solely electronically published medical journal (the electronic Journal of Pathology and Histology), which was eventually cancelled due to lack of subscribership. [36],[328]

The Internet Era

The advent of the Internet significantly influenced the development of telepathology in Europe. [344] Contemporary with the development and implementation of the Internet, preliminary development of the first WSI scanners started. [327],[396],[397],[398],[399],[400],[401],[402],[403] Both technologies impacted the application and distribution of telepathology; the Internet made telepathology easy to use which levelled the playing field between expert and non-expert computer telecommunication users. [242],[327],[368],[404],[405],[406],[407],[408],[409] Whereas in the pre-Internet era the implementation and maintenance of a telepathology network required high technical expertise and financial investment - thus sharply limiting the number of sites that could support telepathology - the Internet changed this allowing groups to implement telepathology platforms built from open-standards roots.

iPATH - developed by Brauchli and Oberholzer at the Institute of Pathology, University of Basel - is perhaps the most successful of these platforms. [387],[14],[13],[410] It was first implemented in 2002, and has served over 150 user groups around the world. More than 15,000 telepathology cases have been examined using this system. Its success can be attributed to the basic operating principle or iPATH: the development of an easy to use system optimized for diagnostic consultation in pathology that also permits the creation of individual "working groups" (for example, specialized for cytology, lymphomas, or countries such as Cambodia, etc.). [386],[387],[13] Participating experts were notified about a client's request to remotely view a case via E-mail, and after rendering their opinion, the client was in turn notified via E-mail. The iPATH system was built using only open source software; due to this, local iPATH server installations were located all over the world. [39] Two similar Internet-based telepathology platforms were created during this time period, one in the USA at the AFIP (Washington, DC), [411],[412],[413],[414] and the other at the Institute of Pathology, Charite, Berlin, Germany, sponsored by the Union Internationale contre le Cancre (UICC), Lyon, France called UICC-TPCC (UICC Telepathology Consultation Center). [396],[407],[415],[416] All of these systems - including iPATH - have since been terminated. Two of them (iPATH, AFIP) have been replaced with commercial software packages. iPATH was the first telepathology platform to offer such tremendous flexibility, and as such enterprising individuals soon realized that it was possible to formulate something akin to a virtual department of pathology around it. [242],[36],[384] To accomplish this, administrators and pathologists were recruited; administration and duty plans were drawn up, and the first ever Virtual Pathology Institution (VPI) was born. [384] This VPI served the total tissue - based diagnostic needs of the Salomon Islands for several years. [417] Oberholzer and Brauchli implemented a pathology laboratory in the Solomon Islands and trained technicians to perform gross examinations on excised tissue create H and E glass slides and submit corresponding microscopic images to the VPI. Usually, a telediagnosis could be rendered within 24 h. [417] Prior to this solution, all tissue had to be sent to Australia, with an average turnaround time of roughly 2 months. This VPI was in operation for more than 5 years. It was, however, unfortunately terminated due to the fact that neither the Salomon Islands Government nor charity organizations were willing to consistently fund it. Nevertheless, this remarkable experience can be considered as proof that functional VPIs can be implemented. [384]

The recently (2011) released telepathology forum called Medical Electronic Consultation Expert System (MECES) is an example of a platform that has tapped into Web 2.0 and WSI technologies. [418] It focuses on performances experienced from iPATH and UICC-TPCC in combination automated electronic measurements (EAMUS TM ), still image acquisition, and WSI. In combination with an internationally well-known expert team, MECES will probably become a new milestone in the history of European telepathology.


   Conclusion Top


The history of clinical (medical) informatics, a relatively new domain of computers and information science in healthcare, has been previously described. [419],[420],[421] However, to the best of our knowledge, this article represents the first account of the history of pathology informatics from a global perspective. Significant progress in our field has occurred in many countries around the world, and this rate of progress seems to be increasing. Progress in pathology informatics has been tied closely to developments in technology, particularly the advent of computers, the Internet and more recently digital imaging. It is apparent that major drivers in the field included the need for pathologists to comply with national standards for health information technology and for telepathology applications to meet the scarcity of pathology services and trained people in certain countries or underserved regions. Our predecessors are acknowledged for their insight, enduring investigations and trials to show us what works and what failed, and helping us solidify the current field of pathology informatics. This is a time of great excitement and opportunity for our discipline. Advances in genomic, molecular, diagnostic, imaging, and data analytic techniques have allowed - perhaps for the first time - a glimpse into a future in which hidden patterns embedded in our visual (e.g., WSI) and numerical (e.g., laboratory tests) data will be brought to light and exploited for the benefit of patient care. For us to face the challenges, and capitalize on the opportunities the "digital decade" of personalized medicine, it is imperative that we face our challenges and overcome ever changing barriers with the same vigor and excitement displayed by those who have gone before us. The history of pathology informatics is the story of us all. Those who have gone before us have left a rich foundation for us to build upon, but this story is not yet finished. We can be visionary leaders, bold explorers, and drivers of positive change throughout our healthcare systems; in doing so, we have the opportunity to take the destiny of medicine into our hands. Or we can be content to be followers or even ignore the disruptive changes that this history so clearly points out are looming before us; this being the path of diminishment and relegation to eventual irrelevance. We have the ability to write the end to this story. Where we go from here, is up to us.


   Acknowledgements Top


Klaus Kayser gratefully acknowledges the financial support of the the Verein zur Fφrderung des medizinisch technologischen Fortschritts in der Medizin. Takashi Sawai gratefully acknowledges T. Matsumura, A. Kamataki, Y. Miura, and M. Uzuki for help in researching and editing the Asia section of this monograph. Marcial Garcia Rojo gratefully acknowledges Dr. Rodolfo Avila for contributing his knowledge of Cuban pathology informatics history to this monograph. Seung Park gratefully acknowledges Stephanie Park for her steadfast administrative support and proofreading skills.

 
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