September 2005
Feature Story

Ed Finkel

Used until now mostly for research, academic conferences, and secondary consultations, the field of telepathology is gaining acceptance as a primary diagnostic tool in the wake of the March merger of InterScope and Trestle, say leaders of the new Trestle firm, who are seeking FDA clearance of their combined platform.

Trestle’s Xcellerator suite of digital workflow products, launched in June and based on a melding of InterScope’s digital imaging technology and Trestle’s work in live microscopy, is aimed at the complementary clinical and biopharmaceutical markets, says Anthony Taddey, former CEO of InterScope and executive vice president of Trestle.

"What was actually very convenient, and why we went forward with [the merger], was there was very little duplication and thus very few costs to be eliminated" between the two firms, Taddey says. "It’s a nice combination of market segments."

Previously, he says, Trestle’s system made it possible for pathologists in two different places to simultaneously view a slide through a robotic microscope that transmitted the image, which provided the ability for motorized panning and zooming using a remote mouse. But this did not create a permanent digitized image (also known as a whole-slide image, or WSI), thereby limiting the potential use-cases of digital imaging technology.

The ability to create whole-slide images moves functionalities forward on a number of fronts. Among the features Trestle cites in its literature for Xcellerator are the ability to pan and zoom on an image, bookmark regions of interest, compare multiple images simultaneously, and display patient history and case information alongside images.

"The critical results from the merger are a combining of the telepathology business with a whole-slide scanning business, and the emergence of a workflow management environment," says Maurizio Vecchione, CEO of Trestle. "We are setting out to significantly improve the image quality with next-generation scanning capabilities, while at the same time enhance the ability to use those images in clinical practice." He says image quality can be enhanced with no, or minimal, penalty in speed.

The way Vecchione sees it, InterScope brought a "traditionally hardware-grounded technical team" that was "pushing the envelope in what we’re starting to call ’surface scanning’ technology. They also had made a very big push in clinical workflow applications. Trestle, on the flip side, had done a lot of work in FDA compliance on the clinical and biopharmacological side."

The integrated digital whole-slide scanning and clinical workflow platform and the prospect of FDA clearance are the two most important developments in the new firm, says Michael J. Becich, MD, PhD, vice chairman of pathology informatics at the University of Pittsburgh Medical Center and Shadyside/Hillman Cancer Center, where InterScope was incubated.

"Before the merger, there wasn’t a company that could provide an end-to-end solution," he says. "I think that rapid adoption of these instruments is now happening. What had been an early-adopted market is converting into, now, kind of a technology-leveraging tool. Folks are going to say, ’We can’t continue the practice as it is, currently, without these additions.’ That’s an exciting thing from my perspective."

What will take it to that level will be government clearance, which Dr. Becich believes the hardware platform will earn given the whole-slide capability. "This is the watermark for the FDA," he says. "These imagers will be validated along with the software tools. That’s when the floodgates for using this for clinical applications are really going to be moving to the next step."

Dr. Becich says that until now, companies have "skated around" the need for FDA clearance by asserting that their products’ whole-slide capabilities would be used for secondary diagnostics, noting the time, energy, and risk involved in seeking FDA clearance. "If you don’t get the answer you want, that could hurt your business," he says. "We’ve taken the approach to the FDA, ’Hey, we want your guidance.’ We think that’s going to be an important part of making this a standardized part of using this for clinical diagnostic purposes."

Upon FDA clearance, and with the use of an integrated-use case-specific workflow application, the newly combined system will provide laboratories with the ability to bill for the use of this technology, Vecchione says. "Then you combine the efficiencies that are introduced by the digital workflow with the ability to enhance revenues," he says. "A lot of our work has been putting together ingredients that are necessary not only to get FDA clearance but to deliver CPT billable tests both for quantitative scoring and teleconsultations." He adds, "Digital pathology has the promise to deliver on both."

The Xcellerator software that InterScope incubated is the cornerstone of the evolution of pathology best practices into the digital workflow environment. These applications provide the pathologist with the desktop tools needed to manage patient caseload data and generate whole-slide image-enhanced patient pathology reports, Vecchione says, and supporting "data mining and case management across a wide range of tissue types and disease states." Versions of this software are available for the anatomic pathologist, cytologist, laboratory histotechnician, and the educational market, he says, with toxicology to come soon.

"It allows for the archiving, manipulation, annotating, and sharing of the data," Taddey says, providing "a whole host of database management tools and functions you would want to do if you were a doctor dealing with a whole pile of caseload information that has no context to it."

Built into these applications is "a very rich amount of data management and user interface," says Jack Zeineh, MD, Trestle’s chief technology officer. "If you look at how people do workflow now, you have what’s essentially an analog data set" with glass slides and paper reports that aren’t bound to one another, Dr. Zeineh says. "It requires a lot of analog management by the pathologist or the technologist. Once you get them digital, it allows you to more efficiently manage them. It also gives you a lot of capabilities that you can’t easily do from a microscope."

Dr. Zeineh adds that pathologists can compare two different parts of the same slide or different slides at the same time, view "a lot more data" at the same time, zoom in while remaining at a fixed point in the larger scale to which the user can return, and take a snapshot to insert into a PowerPoint report or to archive for later use.

And images are less likely to get misplaced, he says. "You have full audit trail capability. You can assure that when an image is snapped and attached, because of the implicit linkage between the text data or image ... you can better form a hard linkage between the different elements of the case."

Another critical component is being able to "volume scan," a patent-pending technique that captures multiple images at once to produce a more accurate image rather than estimating optimal focus and essentially averaging out focal planes on different fields, the technique used in most scanning today, Vecchione says. "You may be missing details. We think that’s not an acceptable long-term solution for anybody who’s going to use this," he says. "We’re capturing, simultaneously, a whole stack of focal planes and then we create a composite of all that data that is perfectly focused and in perfect registration. This technique is fast and delivers 40¥-plus resolution."

A significant group of focal planes ensures that the area of interest can be perfectly focused. "You end up with a much clearer, crisper, more focused image," Vecchione says. "At the same time, you don’t have to rely on interpretation to guess what the focus is."

Being able to essentially scan the "Z" axis in addition to "X" and "Y" is far superior to acquiring five or 10 individual planes through multiple passes of an X/Y scanner, Dr. Zeineh says. "You’re presenting the system a lot more data to create a single plane," he says. "It becomes very fast to scan the slide as well as review the resulting image, and it’s a much smaller file."

InterScope and Trestle had whole-slide digital scanners before the merger, Taddey says. InterScope’s scanner provided higher speed and Trestle’s produced better images. "We took the best of the best," he says, and incorporated them into a combined platform. "It will expedite the transformation into digital anatomic pathology best practices."