TuBaFrost 6: Virtual microscopy in virtual tumour banking

doi:10.1016/j.ejca.2006.04.033

European Journal of Cancer

Volume 42, Issue 18, December 2006, Pages 3110-3116

https://doi.org/10.1016/j.ejca.2006.04.033 Get rights and content

Abstract

Many systems have already been designed and successfully used for sharing histology images over large distances, without transfer of the original glass slides. Rapid evolution was seen when digital images could be transferred over the Internet. Nowadays, sophisticated Virtual Microscope systems can be acquired, with the capability to quickly scan large batches of glass slides at high magnification and compress and store the large images on disc, which subsequently can be consulted through the Internet. The images are stored on an image server, which can give simple, easy to transfer pictures to the user specifying a certain magnification on any position in the scan. This offers new opportunities in histology review, overcoming the necessity of the dynamic telepathology systems to have compatible software systems and microscopes and in addition, an adequate connection of sufficient bandwidth. Consulting the images now only requires an Internet connection and a computer with a high quality monitor. A system of complete pathology review supporting bio-repositories is described, based on the implementation of this technique in the European Human Frozen Tumor Tissue Bank (TuBaFrost).

Introduction

Telepathology is the practice of ‘pathology’ at a distance, using telecommunications technology as a medium to facilitate transfer of images concerning pathology data between remote locations for the purposes of diagnosis, education and research.1, 2 Traditionally, telepathology is the practice of diagnostic pathology by a remote pathologist utilising images of tissue specimens transmitted over a telecommunications network. However, uses of telepathology also include remote discussion from pathologist to pathologist and from clinicians to pathologist, remote quality assurance involving pathologists and referral labs and research collaboration between research teams.1, 2

Telepathology systems have been traditionally defined as either dynamic or static. Dynamic systems allow a telepathologist to view images transmitted in real time from a remote robotic microscope that permits complete control of the field of view and magnification.3, 4 Static (or store- and -forward) telepathology involves the capture and storage of images followed by transmission over the Internet via e-mail attachment, file transfer protocol, or a Web page, or distribution via CD-ROM. Dynamic hybrids also exist, which incorporate aspects of both technologies.⁴

Today, telepathology systems are divided into three major types: static image-based systems, real-time systems and virtual slide systems. To overcome problems attributable to sampling bias and interpretation resulting from limited field selection, telepathologists must be able to navigate to any field of view, at magnifications comparable to that of a conventional microscope, using images of sufficient resolution to render a correct diagnosis.5, 6, 7 Real-time systems and virtual slide systems (the Virtual Pathology Slide)8, 9 meet these criteria. The Virtual Pathology Slide mimics the use of a microscope in both the stepwise increase in magnification and in lateral motion in the X and Y Cartesian directions. This permits a pathologist to navigate to any area on a slide, at any magnification, similar to a conventional microscope. This is discussed further in the next section.

Static image systems have the significant drawback in only being able to provide selected microscopic fields. Conversely, both real-time and virtual slide systems provide a consultant pathologist the opportunity to evaluate the entire microscopic slide. With real-time systems, the consultant actively operates a microscope located at a distant site, whereas virtual slide systems utilise an automated scanner that takes a virtual image of the entire slide, which can then be forwarded to another location.

While real-time and virtual slide systems appear ideal for telepathology, there are certain drawbacks to each. Real-time systems perform best on local area networks, but performance may suffer if employed during periods of high network traffic. The scanning of virtual slides can be a time-intensive operation requiring anywhere from minutes to hours to accurately scan a single slide. Also the large data size of the virtual slide means that a large data storage space is required as well as adequate archival and backup systems.

However, recent developments in virtual slide systems have resulted in a dramatic reduction of the time required for scanning a single slide, and also auto slide feeding technology has been developed in conjunction with these systems to allow batch slide scanning of a number of slides without the user having to manually feed a single slide one at a time onto the stage. Developments in software applications and compression methods have also allowed for a smaller data size compared to what was possible in the past.

Telepathology can also be classified according to the technologies employed. Each has its own characteristics: video conferencing (high cost, satellite or large bandwidth line, expertise); telepathology with motorised microscopy (high tech, costly, large bandwidth, internet speed limiting factor); full digitised image as movie (high tech, costly, large bandwidth, efficient connection); selected static images by e-mail/web (low cost, e-mail capability, speed is not critical, less accurate, repeat sending may be necessary).

The diversity in telepathology systems reflects growing technological advances in this area and the increasing importance of telepathology in education, training, quality assurance and teleconsultation.10, 11, 12, 13, 14, 15 Numerous pathology archives abound on the Internet, providing links to both educational and commercial telepathology websites. These offer access to either static or dynamic image delivery systems.13, 14, 15

Section snippets

Virtual microscopy

Traditional histopathology diagnosis uses the standard microscope to observe prepared tissue sections on glass slides. If second opinion is required for the original diagnosis, it would be necessary to send the glass slides by post to another pathologist. This method takes time, risks permanent damage to the glass slides and incurs transport costs.

Classroom viewing of microscope slides in an educational environment would require an optical microscope with a projector operated by an instructor

Application of telepathology and virtual microscopy in routine pathology

Current telepathology applications include intra-operative frozen sections services, routine surgical pathology services, second opinions, and subspeciality consultations. In this context, diagnostic accuracy of telepathology is comparable with that of conventional light microscopy for most diagnoses. Rapid and ultrarapid virtual slide processors may further expand the range of telepathology applications. Next-generation digital imaging light microscopes may make virtual slide processing a

Virtual microscope system components

Fig. 3 portrays a general setup for a virtual microscope and telepathology system. The glass slide is placed on the microscope stage and the digital camera (3-chip 24 bit) takes high quality ‘field of view’ single images (usually at 20× objective but 40× is possible) as the motorised stage moves the glass slide left-to-right and up and down. Eventually, a collection of ‘field of view images’ are taken representing the entire glass slide. These images are saved to the PC that is connected to the

Investigation of commercial virtual microscope systems

During 2003–2004, as part of the TuBaFrost Project, 20 companies involved in virtual microscope (VM) systems around Europe were consulted and their systems evaluated.

From this evaluation the criteria for a good virtual microscope system were determined:

1.
Good quality images (good resolution, focus and sharpness).
2.
Adequate range of objectives/magnification.
3.
Accurate focusing.
4.
Fast scan speeds/low scan times.
5.
Best compression rates and low image sizes (but maintaining good quality images – e.g. JPEG

Application of virtual microscopy in the TuBaFrost network

The addition of the virtual microscope tool to the tissue bank model was primarily to assist when tissues with a difficult diagnosis are selected for experimental purposes. In this way, the user is aware of the exact constitution of the sample so samples are not transported unnecessarily at cost to the requestor and samples are not unjustifiably unavailable. In addition, for very problematic cases a diagnosis review system can be easily established.

As detailed in the associated article ‘Central

Conclusion and future prospects

A relevant application for virtual slide technology is the documentation of tissue samples in tissue banks. This technology in the tissue bank can enhance traditional sample annotation, assist in ensuring that remote tissue bank clients receive appropriate tissue for their research, and form the basis of quality assurance systems.¹⁸ In this paper, the TuBaFrost methods for integration of whole slide imaging into the tissue bank workflow and information systems have been reported.

An additional

Conflict of interest statement

None declared.

Acknowledgements

The European human frozen tumor tissue bank or TuBaFrost project was funded by the European Commission within the 5th framework of the division ‘Quality of life and living resources’ under project number QLRI-CT-2002-01551, with the aid and commitment of the involved scientific officers J. Namorado, M. Vidal, O. Kelm and S. Jungblud. The authors greatly appreciate the many collaborators (pathologists, technicians, health documentation experts, etc.) involved in the Tumor Banks of the TuBaFrost

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^☆: Grants: European Commission 5th framework Quality of life and living resources QLRI-CT-2002-01551.

^m: The TuBaFrost Consortium.

ⁿ: Present address: Instituto Nazionale Tumori, Via Venezian 1, 20133 Milano, Italy.

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TuBaFrost 6: Virtual microscopy in virtual tumour banking☆

Abstract

Introduction

Section snippets

Virtual microscopy

Application of telepathology and virtual microscopy in routine pathology

Virtual microscope system components

Investigation of commercial virtual microscope systems

Application of virtual microscopy in the TuBaFrost network

Conclusion and future prospects

Conflict of interest statement

Acknowledgements

Hum Pathol

Hum Pathol

Prospects for telepathology (editorial)

Hum Pathol

Telepathology. Long-distance diagnosis

Am J Clin Pathol

Experience and present status of telepathology in the National Cancer Center Hospital, Tokio

Zentralbl Pathol

Telepathology clinical utility and methodology

Digital storage of glass slides for quality assurance in histopathology and cytopatholgy

J Telemed Telecare

The virtual pathology slide. A new internet telemicroscopy tool for tracing the process of microscopic diagnosis and evaluating pathologist behaviour (abstract)

Arch Pathol Lab Med

Evaluation of the virtual pathology slide: using breast needle core biopsy specimens

Br J Cancer Suppl

Telemicroscopy by the Internet revisited

J Pathol