Digital Pathology at the Crossroads of Major Health Care Trends: Corporate Innovation as an Engine for Change
Dirk G. Soenksen · Archives of Pathology & Laboratory Medicine · 2009
As the founder and chief executive officer of Aperio Technologies, Inc (Vista, California), I am pleased to share with you our view of the rapidly emerging digital pathology market.Fundamentally, digital pathology is an information-management play. It is an environment for managing and interpreting information. This is not patient information but information that is enabled by being able to deal with an entire digital slide. The reason digital pathology is exciting is that, for the first time, it is possible to digitize an entire glass slide in such a way that the resolution of the digital slide displayed on the computer monitor is essentially equivalent to what you can see under the microscope. That opens up a number of possibilities and opportunities for using digital pathology to address some of the challenges that pathologists are having today.I want to take the definition of digital pathology a little bit further and explain the way we think about it. Digital pathology comprises 4 key elements. First, there is slide scanning technology, which is basically required to be “in the game.” You need to have a scanner that can digitize the entire slide in a reasonable amount of time and you want to have high enough resolution so that you are comfortable that the information on the glass slide is represented accurately in the digital slide. If you want to do hematology, you need ultra-high resolution scanning with oil immersion. If you just do typical biopsies, you can usually scan at ×20 and ×40. If you want to do cytology, you need to go up and down through focus. If you want to do fluorescence, you are going to need to have different types of light sources and so forth for that.You then need to be able to manage all the digital slide images. As we know in the radiology world, this has the name of picture archiving and communication system (PACS), but essentially you need software that is going to allow you to manage these digital slide images in the same way that you manage your e-mail with Microsoft Outlook. You just need image management software and, of course, you can make such software very sophisticated. Fundamentally you need a way to organize digital slides and related images by case and by project and to be able to give access to various users in a secure way to share images through the Web and do all that in a way that actually makes sense and is integrated into the workflow.I think the opportunities in digital pathology for clinical algorithms and computer-aided diagnosis or diagnostics is really immense. Being able to do pattern recognition and doing quantitative immunohistochemistry and a variety of other things is going to be part of digital pathology and will add a lot of value.Finally, there is the element of advanced visualization. The ability to simultaneously view a hematoxylin-eosin slide and an immunohistochemistry slide, whether it's an estrogen receptor or a progesterone receptor digital slide, and to be able to move all of these digital slide images synchronously is a new way of looking at pathology information. It precludes you having to take one slide, look at it, find a cell, put the slide away, look at another microscope slide, and look for the same cells on a different slide. This can all be integrated to provide a much more powerful environment for visualization.The way we think about digital pathology is analogous to the 4 legs of the stool: scanning, image management, clinical algorithms, and then advanced visualization.Digital pathology is well positioned at the crossroads of major health care trends. A closer examination of the sources of value that digital pathology brings to health care provides further insights into the strategic value of digital pathology.One area of value for digital pathology that has been identified in the article by Gene Cartwright, PhD, in this issue is the ability to “bolt” digital pathology onto existing digital modalities, for example, radiology and cardiology PACS. What would that do for you? You would get a more complete enterprise-wide imaging solution and you could presumably get a more complete electronic medical record. Pathology PACS is clearly 1 dimension of value generation and you can see in Figure 1 that digital pathology is really at the crossroads of getting to a more complete solution, which includes a pathologist's cockpit where you can have all the disparate sources of information used by pathologists at your fingertips.Another “orthogonal” value proposition that has been described by others in this issue involves the use of biomarkers in tissue to help develop companion diagnostics for personalized medicine. HER2 is a good example of that. Digital pathology is well suited to perform the protein expression of biomarkers applied to tissue sections. The ability to digitize the glass slide and the ability to apply image analysis algorithms to digital slides are going to be critical to realize the vision of personalized medicine, to the extent that the biomarker is deployed on tissue.Then, of course, digital pathology can use automation to improve lab quality and efficiency. All the things that you see on the clinical side of the pathology lab, where you have all these wonderful instruments that run multiple assays and really drive quality and efficiency, digital pathology can do for the anatomical side of the pathology lab. For example, you could digitize a slide and then look for rare events. Instead of spending 20 minutes looking for an acid-fast bacillus on a slide, you could ask a computer to do that and you would probably save 20 minutes per case. You can easily imagine a number of other rare event or rare pathogen applications that you routinely look for that could be addressed by digital pathology.There is considerable interest in understanding why digital pathology is at the center of a number of major health care trends. Based on the number of participants in the College of American Pathologists' 2008 Futurescape meeting, it is easy to see that different venues or different strategies of how to use the technology are going to be important to different parties. For example, if your goal is a more complete electronic medical record, you can “bolt” digital pathology onto your radiology and cardiology PACS. Alternatively, if you want to go into the companion diagnostics business, you can use digital pathology to apply image analysis algorithms to new biomarkers, or you can use digital pathology to automate your laboratory.Aperio has invested large sums of venture capital money in advancing the digital pathology market. We openly describe the success we have had in installations, largely to highlight that the market is moving today and that digital pathology has value today. We have about 400 systems placed in 25 countries today. We will have more than 500 systems placed by the end of the year. That is a large number of systems. Our sales pipeline is more than $100 million, which is about 1000 people who have indicated that they have a need for digital pathology today. This is not in the future, but this is the situation today.For publications, there are more than 130 publications thus far describing applications of digital pathology (Figure 2). By the end of the year, we expect that to be close to 200 publications, which is a dramatic increase in the number of peer-reviewed articles about digital pathology. We track only the publications that are related to Aperio, so these numbers would be higher if you included publications that involve other companies.Integration with laboratory information systems also has to happen. Aperio has integrated with a number of commercially available laboratory information systems. There are also efforts underway at a number of customer sites for laboratory information system integration. We have integrated with home-grown laboratory information systems at various reference labs and are involved in other integration efforts with PACS and with electronic medical records. Integration with other information systems is one of the major things that has to occur for digital pathology to move forward; so efforts to interface with other information management systems are actively underway and in some cases are commercially available today.Figure 3 is a list of the niches in which adoption has happened. It is intended to be overwhelming to highlight the many applications where current customers are using this technology. Digital pathology systems are deployed in applications ranging from education to research to biopharma to clinical. What is interesting is that there is no “killer” application. Adoption is really happening in niches. The value of this technology, today, is being driven by using it in specific applications. This insight is very, very important when you think about strategy, and Aperio's strategy has always been to focus on niche applications, which are areas where pathologists have challenges today, and to deliver solutions that address those needs. This long-term vision of full adoption, one in which you digitize all the slides and have fully integrated digital pathology into the workflow, is not our aim today. Our strategy is to aim for those niches where you have needs today, where you can see value today. I think it will be a long time until you see full adoption. Not because we do not have the technology to scan fast enough or to efficiently view the images but because it is simply going to take time to overcome the regulatory hurdles, the information technology hurdles, and the adoption challenges to drive the market to full adoption. It will happen.Figure 3 shows a few applications (highlighted in red) that I actually want to describe in a little more detail.Aperio was involved in a study to evaluate digital pathology for something as simple as tumor boards. We asked a number of clinicians about the tumor board preparation process. Looking at Figure 4, what you see in orange are the scores given for items such as overall experience, ease of hardware use, and how they are currently doing tumor boards, and the scores in blue are the improvements achieved as a result of using digital pathology for tumor boards. As you can see, there is a dramatic improvement in the scores that pathologists and administrators gave regarding preparation for a tumor board. In the presentation of the actual tumor board itself, you also see dramatic increases in the scores. The low-power image has always been a problem in a tumor board. Now with digital pathology you can get beautiful, high-quality, low-power images, so everybody said that is as good as you could possibly expect. All categories, including ease of presentation, received much higher scores in the tumor board using digital pathology. We also evaluated clinician satisfaction. We actually went to the tumor boards and we polled the clinicians. The radiologists, the oncologists, the surgeons, and other clinicians were asked, “Is this an improvement? Is this good?” You can see that 97% of the clinicians actually said that the digital pathology as applied on a tumor board is a dramatic improvement over what they had seen before.The key findings of the study indicated we saved 50% of the tumor board preparation time. Think about it. If you are spending 4 to 5 hours on a tumor board preparation in a large institution, you could probably cut that in half. That is a real return on investment today for this technology.The summary findings were that digital slides were judged to convey more information. Also, for preparation, the process was much more smooth and seamless and less chaotic and everybody liked it a lot more. The clinicians actually saw more value in what the pathologists were talking about and the time spent on the tumor board went from about 80% radiology, 20% pathology, to about 50:50, once you had digital pathology in there. It was quite remarkable.There are also applications in quality assurance, such as facilitating interfacility random reviews using digitized slides for doing quality assurance overreads.Another quality assurance application using digital pathology is to retrieve mandatory digital slides when you have an abnormal case. You can save yourself a lot of time and effort and chaos in having to retrieve slides. And, of course, in those cases for which you are being sent glass slides for a consultation and you make a report and send the slide back, you have no record of what you actually did. With digital pathology you can digitize a slide so you have a record that can be used to engage in a digital slide conference when you are asked a question later or worst case, risk management, in the event your diagnosis comes into question. These are quality assurance uses today for this technology.I think the first area in the workflow in which you will see complete adoption is in the area of immunohistochemistry. Aperio has developed a complete solution for digital immunohistochemistry including reading digital immunohistochemistry slides on a monitor. We have a US Food and Drug Administration clearance for reading HER2 digital slides on a monitor. That is the first clearance of its kind. As a vendor we cannot tell you to read any other type of digital slide on a monitor for making a diagnosis, so the regulatory hurdles in demonstrating compliance with a digital slide on the microscope are quite high. We have clearance for immunohistochemistry and we are on a path for obtaining clearance for hematoxylin-eosin, so sometime next year we hope to be able to report that we have done the first clinical studies to demonstrate that you can make a primary diagnosis from an hematoxylin-eosin. We definitely think this clearance will happen. The idea of being able to simultaneously look at an hematoxylin-eosin, an estrogen receptor, a progesterone receptor, and a HER2 digital slide all synchronized is quite valuable. Of course, the HER2 image analysis itself is going to be more accurate and more quantitative and more reproducible.You all have an invitation to attend Pathology Visions in San Diego, California, in October 2008. This year will be the 4th Annual Pathology Visions Conference. It is a conference dedicated entirely to digital pathology. Last year we had about 250 people in attendance; this year we expect an attendance of about 350 people, all coming to learn about digital pathology. There will be about 44 speakers. Most of those faculty are different from last year's speakers. They will talk about the use of this technology in research, in clinical, and in veterinary pathology applications. I am pleased to say that Richard Friedberg, MD, PhD, is going to be one of the keynote speakers at this meeting. If you are interested in digital pathology, I encourage you to consider attending Future Visions conferences. We are very pleased that the CAP Foundation is cohosting this conference. Thank you very much.