Technological advances now allow high resolution scanning of whole microscope slides (“whole slide images” or WSI) and the use of secure web-based viewing applications that can link those images to clinical information to facilitate remote interpretation on a computer monitor.
These technological advances have been paralleled by an increasing demand for digital pathology information in general throughout healthcare networks with the expectation by some for eventual integration of digital pathology images and information with the laboratory information system and electronic medical record.
One of the most obvious attributes of digital pathology is to facilitate the interpretation of surgical pathology cases at a distance. This has the potential of helping distribute workload within a complicated healthcare system, as well as the ability to provide subspecialty pathology interpretations of difficult cases with rapid turnaround time. With those long-term goals in mind, the Center for ePathology at The Cleveland Clinic has validated the use of WSI for primary surgical pathology diagnosis and for consultation case. We are now regularly receiving consultation cases from several institutions in the People’s Republic of China, as well as from clients and affiliated partners in Hawaii, Cleveland Clinic Abu Dhabi and elsewhere. To date we have completed 266 consultation cases with an average turnaround time of two days, excluding waiting time for additional stains or information and weekends.
Following in part the experience of the University Health Network experience in Toronto, we also validated the use of WSI to interpret frozen sections and are gradually implementing the remote interpretation of frozen sections from 12 different sites within the Cleveland Clinic Health Network. It is anticipated that this process will significantly increase thereby increasing productivity and efficiency by allowing the pathologist to stay in his or her office rather than traveling to numerous sites.
Outside consult cases are obtained via two cloud-based platforms; one offshore, one domestic. The system provides email notification and workflow management between main campus and our international clients. Additional in-network consultations and frozen section interpretation among affiliated regional hospitals and ambulatory surgery centres are performed by directly accessing eSlideManager. Users log into a web front end that controls access to the database. Access to whole slide images is controlled by individual or group permissions that are configured by the ePathology manager. Slides are organised into cases, courses and research projects within the application database.
In addition to consultative support, the use of digital pathology has helped to reduce cost and facilitate better ordering practices for immunohistochemical and other special stains. Clients seeking special stains without interpretation can send paraffin blocks or unstained slides. Slides are scanned within a few hours of staining, so client pathologists can view the WSI and either proceed with diagnosis or request additional stains. This “eIHC” service allows for less upfront ordering and reduces the need to perform unneeded stains.
Our ePathology infrastructure has evolved significantly to support these activities (Fig. 2). As an overview, the digital slide system runs on an HP ProLiant DL360 GL7 Windows 2008 server with 2 quad core xenon E5620 processors and 16 GB RAM. This platform hosts eSlideManager (Leica Biosystems) software that performs the function of web server (user access), database server (SQl), image server and application server for the web-based viewer.
Digital slides are captured on Aperio AT Turbo scanners, capable of 20x and 40x magnification scanning at resolutions of 49um and 24um, respectively, with a load capacity of 400 slides. Images are stored in a non-proprietary format and viewed via a “bits on demand” type stream, similar to Google Earth. Barcoded slides are interfaced with and accessible from the Anatomic Pathology Laboratory Information System (LIS), Cerner CoPath, and case and demographics are populated and links are created. Typical 20x images range in size from 350 to 700mb per slide; 40x images can be as large as 2.4Gb. Images are streamed using a 1GB local network and stored on an EMC VNX5400 network attached storage array (NAS) at the Cleveland Clinic data centre offsite and backed up to a mirrored file system. Additionally, slides may be captured at 60x or 100x on an Olympus VS-120 scanner. These slides are converted and imported into the Aperio eSlideManager for general use. We currently have 72,000 individual images that occupy a total of 35 terabytes storage. In addition to the NAS located offsite, older images are stored on an Isilon storage area network (SAN) array. Smaller subsets of images can be downloaded to portable hard drives, primarily for resident and fellow educational use.
Tissue Microarray (TMA) and image analysis algorithms are supported, and access to the system for authenticated users outside the Cleveland Clinic firewall is provided through a Bluecoat reverse proxy. This allows off-site pathologists to temporarily view a designated subset of images. For example, if a Cleveland Clinic pathologist is giving an invited lecture on soft tissue tumours, then WSI of unknown cases can be made available to conference participants before and after the conference, no matter where the lecture takes place.
The FDA has not yet approved the use of WSI for primary diagnosis in the United States, but several manufacturers have clinical studies under way and hope to achieve clearance in the relatively near future. Already used for primary diagnosis in Europe, the Middle East and Canada, we anticipate that Cleveland Clinic will be well positioned to utilize digital pathology in a cost-effective way for primary diagnosis of selected types of cases once it is cleared by the FDA, and we anticipate continued growth of digital pathology for consultation cases as well as for education and research