The use of FFPE Tissues in Digital Pathology

Digital pathology has come a long way for more than two decades since, its birth in the late 1990s. Using whole-slide images (WSIs) created from traditional glass microscopy slides with specialized scanners, digital pathology enables easier sharing of samples between pathologists. It also helps with the application of a new generation of machine learning and artificial intelligence tools to aid in diagnosis. Thanks in part to U.S. regulatory approval of digital pathology tools for the primary diagnosis of disease, some analysts expect the market to grow to more than $1.3 billion by 2026.

The history and development of digital pathology

Digital pathology has its origins in the development of digital microscopy and, perhaps surprisingly, earth imaging data science in the 1990s.

In 1997, Dr. Joel Saltz — then a PhD computer scientist and M.D. Pathologist at the University of Maryland — had been developing software to process the large databases of spatio-temporal data generated by earth imaging satellites, developing new methods of accurate spatial indexing across large datasets. After a conversation about the possibility of employing computers in place of light microscopes with then Duke University Pathology Chair Dr. Sal Pizzo, Saltz hit on the idea of applying the data processing tools his team had developed for satellite data to WSIs, leading to the joint Johns Hopkins and University of Maryland Virtual Microscope project. This was the first software to emulate the functions of high powered light microscopes, allowing the projection of a high quality WSIs from a central server to multiple workstations.

Digital microscopy would have had little to work with if it had not been for a concurrent developing of the scanner technologies that could convert a glass specimen slide into a WSI file. That work was pioneered by Bacus Laboratories, which offered the Bacus Laboratories, Inc. Slide Scanner, or “BLISS,” the first commercial slide scanner beginning in the late 1990s (Bacus was purchased by Olympus in 2006). The BLISS utilized a tile scanning approach to digitizing a slide, imaging smaller rectangular “tiles” of the whole slide and then stitching these together to create a WSI. In 2000, Aperio, developed a competing approach, scanning across a slide as if reading a line of text and then combining those image strips to compose the full WSI.

While early WSI scanners could take hours to scan a single slide, the past 20 years have seen significant advances in robotics, processing, optics and other slide handling accoutrement allowing for efficient and automatic creation of high resolution WSI for virtual microscopy and digital pathology. Most WSI systems today have integrated both the scanner, which acquires the WSI from the sample, and a workstation with a monitor for viewing the WSI, into one unit.

The biggest recent development in digital pathology came in April 2017, when the FDA granted de novo approval to the first WSI system for use in pathology diagnosis, the Philips IntelliSite Pathology Solution (PIPS) WSI system. This has allowed other players to bring digital pathology systems to market without FDA premarket approval, using the 510(k) application process, expanding the market and pathologist interest in the systems.

As none other than Joel Saltz put it in a 2017 post on LinkedIn, “A vision realized at last — FDA approval interpretation of digital surgical pathology slides,” he wrote. “This will represent a sea change in Pathology, a huge boost to precision medicine and the birth of a new area of data science.”

The global digital pathology market was estimated at $767 million in 2019, by analysts at Grand View Research, and is projected to grow to more than $1.3 billion by 2026. Major players include Phillips Healthcare, Danaher, F. Hoffmann-La Roche and Leica. In the U.S., Phillips has been joined by Leica and Aperio which saw FDA approvals for their WSI scanning systems in 2019.

Advantages of DP

Digital pathology has a number of advantages over conventional light microscopy, and some labs have already gone fully digital, ditching their glass slides altogether in a version of the paperless office — the slide less digital pathology laboratory.

The most immediate advantages come in the form of increased pathologist and lab efficiency, and decreased diagnosis turnaround time, with less need to sort, handle and store physical slides, and digging into archival images similarly less difficult. Digital storage can even impact real estate decisions for some labs, since physical storage space is no longer necessary, and pathologists need not be physically on site to view specimens.

And by removing the need for a pathologist to be physically present to view a slide, WSIs also enable more efficient consultations. Without physical slides to be shipped, other specialists can weigh in on a case faster and there is no risk of slides being lost or damage in transit.

In educational and academic settings, WSI allow students to view the same, high quality sample from multiple workstations. Historically, the large collections of glass slides used for training pathologists were not always of the same quality — slides can fade, degrade or become broken with time — and by the mid-2000s some institutions had ditched their collections of slides and gone completely digital.

Perhaps the biggest advantages of WSI pathology is the ability to use computer assisted image analysis algorithms to identify structures of interest. The application of artificial intelligence and machine learning techniques to digital pathology image analysis is an area of active research.

Challenges in Digital Pathology

With the advantages of digital pathology comes a unique set of challenges as well, primary among them being data management. WSIs are data hungry, with a single WSI file ranging from 1 to 4+ GB in size, and many institutions, medical schools in particular, may store thousands of WSIs. Additionally, there is, at present, a lack of a common image file format for WSIs. While there is a Digital Imaging and Communications in Medicine, (DICOM) extension specified for digital pathology images, most WSI scanners are not DICOM compliant, which could hinder the most efficient integration of WSI and digital pathology workflows with radiology and electronic health records systems.

And to fully realize the advantages of digital pathology, laboratories must have the information infrastructure to support and process the large file sizes, not only ample storage but reliably high-speed internet connectivity and processing power. This infrastructure along with the high cost of WSI scanner devices can make the initial capital investment another challenge for smaller institutions hoping to transition to digital pathology.

The Future of Digital Pathology

What’s next in digital pathology? Some of the most immediate developments will be in integrating WSIs with other forms of pathology and electronic health information systems and workflows. Saltz, for instance, is still involved in digital pathology research, and his group at SUNY Stone Brook is exploring combined radiomics and pathomics, the processing of digital pathology and radiology images within the same information pipelines.

As digital pathology technology advances, artificial intelligence and machine learning techniques will find more and more applications in detecting regions of interest or structures in WSIs, as well as parsing which areas of an image are of the highest quality and those that are impacted by artifacts or noise. A number of startups — such as Prosaic, DeepLens and PathAI — are exploring the use of AI digital pathology tools in the detection and diagnosis of cancers.

Further advances in imaging technology may move digital pathology beyond the concept of slides altogether, as techniques such as open-top light sheet microscopy create 3D renderings of tissues samples and move digital pathology beyond 2D scanners.

But it is still early days yet for digital pathology, and to get to a more advanced future requires manufacturers fully taking advantage of regulatory easing to fully develop the market today. As Harvard Medical School pathologists Dr. Richard Huang and Veronica Klepeis noted in an article for The Pathologist appropriately titled “Midas Tech or Fool’s Gold,” despite the Phillips PIP system’s pioneering de novo approval by the FDA in 2017, many WSI scanner  makers are still pursuing de novo approval for their devices rather than taking advantage of more efficient routes to approval. “Companies have not kept up-to-date with future pathways that are being considered, developed, or even piloted,” the pair write. “If digital pathology is to thrive in the booming digital health market, companies need to be at the forefront of adapting to new regulatory changes.”

BioChain and Digital Pathology

BioChain offers several digital pathology products and services for pathology labs and their applications, beginning with a Whole Slide Imaging service for digitizing existing glass slide collection.

BioChain also offers tissue section and array products, which can also be digitized with BioChain’s Whole Slide Imaging service when placing an order.

To learn more about BioChain’s digital pathology products, click here!

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Author: Franklin Chin

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