Digital pathology: From microscope slide to virtual microscopy

The digitization of medicine moves on. Researchers, physicians and patients equally benefit from this development – thanks to improved diagnostics with highly sensitive devices, today findings can be comprehensively analyzed and treatment decisions made on a broadened basis. Digitization also offers the area of pathology interesting fields of application.

02/02/2015

 
Photo: Man working with microscope ©panthermedia.net/ luchschen

Virtual microscopy facilitates the workflow of pathologists. It presupposes that the histological specimens is available in digital form, so that they were scanned with a scanner; © panthermedia.net/luchschen

The term "digital pathology" refers to an increasing use of information technology in pathology. The switch from histopathologic diagnosis with analog microscopic images to computer-aided diagnosis represents a major part of this change. In the broadest sense, the term also includes the introduction of digital techniques to process, analyze and archive slide preparations.

"Tissue sections are digitized using the computer. That is to say, the sections are scanned using high resolution so that an analog image is being created. The maximum resolution approximately corresponds to that of visible light," explains Dr. Gian Kayser, Chief physician at the Institute of Clinical Pathology at the University Medical Center Freiburg, Germany.

Automated capture technique and the data storage capacity challenge

A tissue section is placed into a so-called slide scanner and measured. The device identifies certain focal points in the tissue and scans them frame by frame. There are two different methods: the linear scanner technique comes from aerospace technology. It works similar to recording satellite images where the digital images are strung together in a linear fashion. The sensors in this case consist of a few strung together lines. There are also scanners that feature a rectangular chip we know from the setup in commercial film cameras. The technology works similar to the panorama function in cell phones or film cameras: several overlapping images are taken at specific intervals and are then stitched together into one overall picture.
Photo: Server Room © panthermedia.net/scanrail

The digital data storage allows access to all desired scans or patient reports. A comparison of scans with archive images is possible at any time, but at the moment images need very much storage volume; © panthermedia.net/scanrail

"A slice that measures about 1x1 cm generates approximately 6 gigabytes of uncompressed data. Even though you can compress the data to 0.5 -1 GB, it also needs to be processed," says Kayser. To optimize data flow, the slices are filed in so-called pyramidal format. The entire section is not loaded all at once for viewing, but just the image sections or tiles the pathologist wants to look at. This ensures that the data transfer is kept as minimal as possible and the typical bandwidths of the existing network infrastructures are generally sufficient for digital pathology. Google Earth also uses the pyramidal format principle for instance.

Besides the automated capture of slices, data storage is another area of digital pathology. Even though advanced computer technology makes it possible to collect and process large amounts of data, the slices also need to be archived and made available. Kayser explains: "A medium-sized institute produces approximately 300-700 slide preparations per day, about 300 to 1000 GB of data daily. The legal data retention period for analog slides ranges between 10 and 30 years. This is likely to be carried over for digital slices in the same way. When you extrapolate the memory requirements to 300 workdays per year you quickly reach the petabyte range that needs to be held available for archiving image data. This equates to one billion GB. These archives need additional corresponding server capacities that require adequate data bandwidth and (still) involve very large investments." For small-sized pathology institute and facilities, this is presently one of the main reasons not to switch to digital pathology.

Economizing sequences

The benefits of digital pathology are obvious: it is much faster and doesn’t necessitate additional personnel costs to make comparative diagnostic findings, since pathologists access a digital archive. Slide preparations are no longer manually exchanged at the microscopy. Comparative positions within a preparation can thus be located easier and several preparations can be examined under the microscope in parallel at the same time. This is especially beneficial when there are only a few diagnostically relevant cells or cell systems in the charted tissue.

The digitization process with the image viewing software is not the only advantage of digital pathology. It also offers great potential for a national and international exchange of experts. Experts can compare notes on digitized histology preparations in real time and get a second opinion via telepathology consultation services and teleconferences. On the one hand, this promotes the skills of "local" pathologists, while it optimizes patient care through a faster availability of specialized knowledge on the other.

The work within the pathology field is also made a lot easier for the entire laboratory thanks to the integration of virtual microscopy. "Thanks to the intelligent integration of digital pathology into the quality assurance system, the quality management system and the error correction system, we pathologists can save resources and use our time more efficiently," Kayser adds.

Photo: histopathological picture of a thyroid

The slide scanner automatically scans and digitizes colored tissue sections. Several levels of a sample can be detected, so that all dimension of a tissue can be examined. In this case, you see the tissue section of the thyroid; © panthermedia.net/Norbert Dr. Lange

The "Digital Pathology" committee, which was initiated by the Professional Association of German Pathologists (German: Berufsverband der Deutschen Pathologen e. V.), is committed to utilizing the digital methodology capabilities for pathologists.

Kayser is also one of the members, who promote the development of this field. His own vision of digital pathology pertains especially to the further development of potential applications within morphometric digital pathology.

Pre-screening could also support the work of a pathologist in the future. That means a tissue section is first automatically analyzed and the computer marks diagnostically relevant areas. The pathologist is then able to specifically focus on a diagnosis. Thanks to the algorithms that are presently only tested in science, the diagnostic pathologist has more time for more complex cases with rare diagnoses.

"In the future, it will certainly be possible to use automated pre-screening. The further development of algorithms can create an automated diagnostics system that indicates potential differential diagnoses with the respective probability to the pathologist by including databases and neural networks." However, the diagnostic responsibility will always remain with the pathologist, but he subsequently has the added opportunity to amend and support his diagnosis through the automatic diagnostics data to ensure quality assurance.

However, it will still take some time before digital pathology also takes root in everyday clinical practice, especially in clinical diagnostics. At the moment, university and science institutes primarily use digital slice scanners and archiving systems, especially during training. What’s more, pathology suffers from a big recruitment problem. At the same time however, the demands of clinical diagnostics increase, so that pathologists are confronted with more and more tasks that also pertain to non-medical aspects. This is where digital pathology can contribute in assisting the pathologist.

Kayser is nevertheless optimistic. "The technology is definitely going to be more cost-effective and higher in quality in the foreseeable future. Within five to ten years, we are going to see more and more pathology departments that work entirely digitally."
Photo: Melanie Günther; Copyright: B. Frommann

© B. Frommann

The article was conducted by Melanie Günther and translated from German by Elena O'Meara.
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