Parade of hopefuls in digital pathology
You know a new technology is catching on when the talk becomes less about whether it will be adopted and more about how and why. That shift appears to be taking place in the digital pathology world where the focus today is on how to make digital work for pathologists and laboratories. The digital pathology market itself is changing, too, as more vendors surface with different business agendas and strategies.
Two major companies are banking on high-volume surgical pathology labs making the leap to completely digital surgical pathology sometime soon.
Omnyx, a joint venture between GE Healthcare and the University of Pittsburgh Medical Center, has designed an integrated digital pathology solution that will be on the market for research use in the second quarter of this year, says Omnyx CEO Gene Cartwright.
Cartwright estimates that labs overall today use digital for 10 percent of their work and says, “We have designed a system that is capable of doing 100 percent of the work by digital.” He predicts the entire market will adopt digital pathology over a seven- to 10-year period.
Philips Healthcare is also developing a comprehensive digital pathology solution intended for clinical use, which includes primary diagnosis in the future, says Guido du Pree, vice president of worldwide marketing and sales for Philips Digital Pathology. Philips installed its first systems at beta sites last year; clinical studies are set to begin soon.
The Omnyx system will not include cytology and hematopathology, which require more of a three-dimensional view, a feature that a future version will include. But the current product itself is a strong one, Cartwright says, and the company’s leaders want to begin recouping the considerable investment.
Philips’ first products will also focus initially only on histopathology, du Pree says.
Both companies plan to pursue FDA approval for use of their systems in making routine pathologic diagnoses. Ditto for Aperio, which the company’s CEO, Dirk Soenksen, says has become the only “pure play” digital pathology company in the market since Roche-owned Ventana acquired BioImagene last year.
Despite the competition, Soenksen is enthusiastic about Omnyx and Philips pushing the market toward full adoption. He believes that approach will encourage more places to try digital for one or two applications, which is how he has long seen adoption occurring and predicts it will continue to do so.
“There’s a big difference between adopting digital pathology for some uses versus adopting it for all uses,” Soenksen says. When Aperio talks to potential customers about its digital system, the customers assume “we are talking about full adoption, and they say the scanners aren’t fast enough and they cost too much, and they worry that once everything is digital, maybe their jobs aren’t so sacred.”
Admittedly, the road to more complete adoption has impediments.
First, there are the technological requirements. The scanners in a high-throughput setting have to be fast so the workflow is not interrupted, says Cartwright. “Either you have to have a very fast scanner or so many scanners to keep up that it’s not really tenable to do.”
You also need a high-quality image, which most scanners today can produce, Cartwright says. “But technology hasn’t yet allowed us to create a high-quality image within a minute.” Omnyx has demonstrated that speed during its product development, he says.
The system also has to provide fast imaging streaming to compete with how pathologists are able to move glass under the microscope. “When the pathologist navigates around the digital image, there cannot be any image latency or pixilation,” Cartwright says. And “the streaming cannot hog the hospital’s network. It can’t take up all the bandwidth at the hospital or require the hospital to invest heavily in redoing its network.”
In addition, “it is very important for the pathologists to know when a case is ready for review.”
The Omnyx system, says pathologist Andrew Evans, MD, PhD, of University Health Network in Toronto, a beta test site for Omnyx, “organizes full cases in digital form.” Pathologists use a dual-screen system, reviewing clinical and gross pathology information on one screen and digital slides on the other. A virtual slide tray contains all of the slides for a particular case. “Using a mouse, you click on the slides and pull them up for review on the screen. This becomes your digital workflow,” says Dr. Evans, who has been a go-to person for beta testing of the Omnyx software.
The Omnyx system, Cartwright says, accepts images from the Aperio scanner, which is what University Health Network uses.
Philips’ system is set up to exchange data with other systems that comply with the new DICOM (Digital Imaging and Communication in Medicine) standard, du Pree says.
Neither Omnyx nor Philips is releasing pricing information at this time. Du Pree says Philips is “looking into flexible pricing models, just like we have in radiology, meaning everything from capital purchase to leasing/rental as well as service models similar to our iSite radiology PACS offering.”
Generally speaking, the price tag for a full digital solution is known to sometimes cause sticker shock.
J. Mark Tuthill, MD, division head of pathology informatics at Henry Ford Health System in Detroit, says the expense involved in implementing digital pathology systems also includes outfitting pathologists with new computers and monitors. And that, combined with a small number of scanners, would cost a health care system like Henry Ford about $1 million, he says.
While the digital pathology systems will work on a current 20-inch monitor, “in reality we are talking about people having at least two high-resolution monitors like the ones used in radiology,” Dr. Tuthill says. “You’d also have to have new computer workstations, which are $5,000 to $6,000 each.”
There are also significant digital data management requirements. And while Dr. Tuthill believes the majority of digital pathology companies know all about anatomic pathology lab workflow, he sees them being “somewhat naïve in some cases” in understanding the quantity of data flowing through an AP lab.
“If we were to digitize all our slides right now with the X, Y, and Z axis, it would require two petabytes [uncompressed image files] of data to be stored and transited,” or 2,000 terabytes, he says as a case in point. Yet the entire hospital data center has only 200 terabytes. Removing the Z axis from the image and compressing files would reduce the data feed to 100 terabytes, which would still take up half of the hospital data center’s storage space, he says.
In preparation for moving to whole-slide imaging, the pathology department last year bought a PathPACS from Apollo of Falls Church, Va. The system can “not only store the whole-slide images but provide the patient demographic data to and from systems,” says Dr. Tuthill. The system can also link the image back to CoPath for workflow support.
In addition to the data management challenges to going digital, there are also the “soft features of what we might call optical or visual ergonomics,” Dr. Tuthill says. And digital pathology companies may be a bit naïve, too, in some instances, he adds, about the quality of clinical microscopy. He compares using light microscopy to watching a sports event on high-definition TV. Digital is like viewing it on a regular TV. You can watch the game on the regular TV, “but you aren’t going to be happy, especially if you flip back and forth.”
People who read a lot of digital slides on a computer have been known to complain of eyestrain. “Yes, you can make a diagnosis using whole-slide imaging,” he says, “but would you use that tool all day long, and how comfortable would you feel if you did?” There’s also an issue with lighting. “In radiology, everything is dim for a reason,” he points out. “Your eyes have to accommodate to seeing things on the screen, and if you have bright lights on, everything washes out.”
“These are hurdles,” Dr. Tuthill concludes, “and clearly they will be overcome.”
Christopher Cestaro, life cycle leader for advanced workflow at Ventana Medical Systems, which has integrated digital pathology into a single team since acquiring BioImagene, says Ventana sees additional opportunity for making the digital interface more like handling glass slides under a microscope.
“Ventana is looking at several ways to do this,” he says, “including touchscreens and other interfaces to optimize the experience for a pathologist well trained in using the microscope.”
Even without that change in place, Ventana’s recent workflow studies show that digital pathology boosts a pathologist’s efficiency overall by 10 to 20 percent when used for the entire case sign-out process, Cestaro says.
Omnyx, too, conducted a time-and-motion study that found “pathologists can gain 14 to 15 percent efficiency by using our system in doing their normal work,” Cartwright says.
Keith Kaplan, MD, pathologist and chief information officer at Carolinas Pathology Group, Charlotte, NC, can’t help but wonder whether the increased efficiency afforded by digital means he’ll be working smarter or simply harder.
“One of the greatest examples of that is e-mail,” he says. “It was touted as helping us get more done and communicate better and be more connected. Yet for a lot of us, e-mail has become a burden in terms of responding to it and managing it.”
Dr. Kaplan understands being able to work more efficiently with the same quality and “squeezing 15 percent more out of your people” to improve the bottom line, saying, “I can get all of that.”
But “most of us can get through the daily case workload in six hours,” he adds. And if you take 15 percent off that, you have saved 45 minutes. “You have to compare that time savings to the cost to produce the scanned slide and store the image, etc.”
The 15 percent time savings, however, doesn’t tell the whole story, in the view of Michael Becich, MD, PhD, professor and chair of the Department of Biomedical Informatics at the University of Pittsburgh and a member of Omnyx’s scientific board.
He says the improvement in efficiency of 15 percent or more is because “you don’t have the time tracking down missing slides or looking for slides that aren’t available.” And “digital gives you capability to do comparisons you can’t do with regular glass.”
In addition, “When pathologists do IHC quantitative analysis they can bill a kicker code” for reimbursement, Dr. Becich adds. “The problem is that most pathologists don’t get involved in doing quantitative analysis because it occurs outside their workflow.” But if you gave them a digital platform, he says, they could choose to make quantitative analysis a regular part of what they do. Then when they perform the analysis, they can use the higher paying codes.
Beyond that reimbursement, however, Charles Root, PhD, president of CodeMap, Barrington, Ill., doesn’t predict digital pathology will generate any extra payment for digitizing glass slides and looking at those on a computer screen to make diagnoses. “Not unless it produces some unique benefit that you can’t possibly have unless you use very expensive software.
“If the relative value units get revalued, and it turns out there is a more expensive component related to digital pathology, then CMS could adjust the payment,” Dr. Root says. A mechanism exists where you can value the RVUs to be more in step with expensive technology. But he doesn’t see that as important considering that in the long-term, the technology will become less expensive.
Dr. Kaplan sees another potential obstacle to full adoption of digital pathology by smaller private pathology practices: They really don’t need a high-volume scanner. He does think pathologists in such settings would be interested in using a personal scanner that fits on a desktop. “You can really start to have some discussions about where that could take you.”
A desktop whole-slide-imaging system could even be the beginning of “the killer app,” he says—that must-have thing that could drive pathologists to adopt digital, a topic he’s written about on his blog (www.tissuepathology.com).
MikroScan Technologies, Vista, Calif., a new company on the digital block, is now offering a personal scanner. Since it began marketing the system a couple of months ago, interest has been brisk, says Victor Casas, MikroScan’s chief technology officer.
MikroScan determined that a group of pathologists could use a scanner in their office to produce a single slide immediately for collaboration or archiving, Casas says.
“The second area where we have found digital pathology actually growing, and where there is a real financial need for it, is in frozen section rooms,” Casas adds. “Rural and other remote medical centers are another really big market for us.”
MikroScan’s system costs about $35,000, compared with the typical price of $150,000 to $200,000 and higher per unit for full digital pathology systems, he says. The MikroScan product gives people “a taste of what digital pathology can do,” allowing them “to affordably enter the digital pathology field.” Competing with the big systems is not the aim. “We feel that we strongly complement them,” Casas says.
The system, which includes a computer, monitor, scanner, and software, scans one slide at a time. The scanner can hold two 1 × 3 slides or one 3 × 2 slide.
To perform the scan, the paddle accessory that holds the slides is loaded and automatically pre-scans the slide at a low magnification (2.5×). Then the region the pathologist wants to scan with high magnification of 20× or 40× is selected. “You can preview it to make sure it’s good to go, hit scan, and it scans,” Casas says. “It saves the low-magnification scan of the whole slide, as well as any regions on which you’ve scanned at higher magnification.”
The system transfers images to the server, or to any host of the images in the facility, for viewing. Anyone with Internet or private network access and a Web browser can view the images and have secure private access for diagnosis and consults. At this time, MikroScan doesn’t host the scanned images.
“The file size of a whole-slide–scanned image varies a lot,” Casas says, “but you could store hundreds to thousands of images on a standard image server with a few high-capacity hard drives.”
Dr. Becich sees the approach of selling small scanners as “a very positive sign.” For example, without a practice becoming completely digital, two pathologists in the same group working at different locations could scan and share a slide for quality assurance. And that’s “a powerful use case,” he says.
The wild card for digital pathology is the Food and Drug Administration in terms of how quickly it issues guidance on how manufacturers must proceed to get their devices approved for primary diagnosis, and how stringent that guidance proves to be.
The FDA held an information-gathering advisory panel meeting on digital pathology in fall 2009 (CAP TODAY, “Where will FDA land on whole-slide digital?” December 2009). And since that meeting, Soenksen says, “nothing has happened.”
Aperio conducted a study showing that digital and glass slides were equivalent for making a primary diagnosis in breast cancer. Though Aperio followed the FDA’s recommendations in conducting the study, Soenksen says, now the FDA “tells us they want more, but are not being clear about exactly what they want to see.”
Couldn’t a lab under CLIA simply take a digital pathology system, validate it, and then use it for primary diagnosis? The short answer, says Jared Schwartz, MD, PhD, chief medical officer for Aperio, is yes. And that answer, he says, applies to any diagnostic test system. “The FDA clearance and/or approval is of much more importance to the manufacturer than it is to the lab user. The manufacturer needs it in order to promote a product for a specific clinical use.”
Soenksen notes, however, that “depending on the risk profile of a [digital pathology] application, some labs and pathologists may not be comfortable adopting it without FDA support.”
As clinical trials are conducted for full use of whole slides for primary diagnosis, Dr. Becich predicts that major barriers to full adoption of digital pathology will start to come down. “That’s when digital pathology will move from niche to mainstream,” he says.
Companion diagnostics will become increasingly important for health care cost savings and patient safety. “And a lot of the companion diagnostics will be done on tissue,” requiring image analysis, Soenksen says. That makes digital pathology the “enabling technology that allows you to quantify biomarkers, which is what HER2 testing does. So I think we will see more and more interest in digital pathology as the platform for image-based technology.”
Ventana’s Cestaro says Roche’s interest in digital pathology is fueled in part by interest in “novel future tests for personalized health care.”
“We use digital imaging/ pathology internally as part of Roche pharmaceutical development activities,” Cestaro says, “but we’re primarily focused as a business on making digital pathology successful in clinical practice.”
Digital pathology has definitely come a long way since the startup days.
The players come from different backgrounds and have various core businesses, says du Pree of Philips: “Roche has pharma/IVD and Ventana; GE and Philips have strong information or data-management capabilities. It’ll be interesting to see which core capabilities are leveraged by these different companies and how they are integrated into their businesses’ portfolios.”
Cartwright of Omnyx says digital pathology is a “natural evolution” for any digital radiology or digital cardiology company. “It’s a very adjacent field and a very natural progression for companies like GE, Philips, and Siemens, although we haven’t seen activity from Siemens.”
Dr. Tuthill notes the small size of the pathology market. “Unless you are going to get these on the desktop of every pathologist or some large percentage of them, it’s going to be hard to make money and recoup your investment,” he points out.
“As the technology becomes less and less expensive, the market share will increase and penetration will occur more rapidly,” he adds. “But companies in the space are making a huge investment, and it does cause you to scratch your head a bit.”
Aperio’s Soenksen says he may not fully understand the steps the large companies have taken related to digital pathology. But, he asks, “Is it important for them to get closer to pathology and understand molecular diagnostics? Absolutely.”
Dr. Schwartz foresees the digital pathology market continuing to attract new players, some of which “we don’t even know the names of yet.” Over time, he says, all the companies will produce ever more powerful scanners, software, and computer-assisted diagnostic tools. And one day, “we will look back and realize that pathologists today are having the same kinds of discussion as bankers had when they wondered if people would actually use ATMs or online banking.”
Karen Lusky is a writer in Brentwood, Tenn.