Digital Pathology in a Web-based System to Study Renal Disease in Animals

To improve standards for diagnosis of renal diseases in animals by integrating pathologic findings from histologic, ultrastructural, and immunostaining examinations of specimens with clinical information in a way that facilitates collecting, analyzing, and sharing information.

Combine digital pathology imagery using Aperio ScanScope® with Prelude Dynamics' Vision software system, designed for electronic data capture of medical records in clinical trials. The result is an integrated web-based system that provides an innovative and efficient solution that is extensible, accessible, and affordable.

Nephropathology is unique among sub-specialties of anatomic pathology for its routine use of ultrastructural (transmission electron microscopic) examinations together with histologic (light microscopic) findings and immunostaining (immunofluorescence microscopy) for the diagnosis of common diseases, especially those affecting glomeruli. Findings must be carefully integrated with information derived from the clinical investigation of the patient’s illness in order to formulate the correct diagnosis.

Veterinary nephropathology confronts several additional problems. Well-established standards for diagnosis of kidney diseases in animals (particularly in dogs and cats) are lacking, especially for disorders that affect glomeruli. Most veterinary laboratories that perform pathologic evaluations of kidney never perform ultrastructural examinations or immunostaining; indeed, thorough histologic evaluations (using appropriately thin sections, special stains, etc.) often are not performed. Those reading slides rarely have access to detailed clinical case information. Additionally, veterinarians with expertise in nephropathology are very few in number and widely scattered.

Veterinarians largely do not adequately integrate the clinical and pathologic features of the disorders when identifying specific renal disease entities that afflict their patients.

To address the challenges, the International Veterinary Renal Pathology Initiative was organized under the auspices of the World Small Animal Veterinary Association beginning in January, 2005. The organizers established the following strategies:

• Study a sufficiently large number of cases prospectively and include cases from geographically diverse origins.
• Establish “Diagnostic Renal Pathology Centers,” DRPC, to perform thorough pathologic evaluations of specimens (LM, TEM, and IF).
• Initially focus on standards for glomerular diseases in dogs.
• Build an extensible hardware/software processing infrastructure for more distant goals.
• Collect appropriate clinical information in concert with the pathologic evaluation.
• Render all tissue sections in digital formats with sufficient detail for diagnostic assessment on widely available viewing platforms.
• Enable investigators to review and discuss evaluations regardless of geographic location (web-based).
• Ultimately to build consensus about disease classifications, diagnostic criteria, and nomenclature, i.e., the standards.

In 2005, Dr. George Lees, DVM, MS, Small Animal Clinical Sciences, Texas A&M University started a prototype DRPC at TAMU, and in 2006 began adapting Prelude Dynamics' Vision software product (designed principally for electronic data capture for clinical trials) to support the center’s work. The result was a web-based “pathology component” for communication with specialty colleagues and collaborators, communication among front-line providers, and database and image archive in which LM, TEM, & IF images were uploaded and associated with cases. The prototype allowed referral veterinarians to enter cases, track shipping of specimens, and view final reports from the pathologist(s) from any geographic location. The prototype provided a measure of digital image sharing and case-by-case electronic data management. However, the Vision system was not intended as a digital image processing system, and it did not meet the goal of easily sharing and annotating digital specimens.

In 2007, financial support  provided through the WSAVA enhanced Dr. Lees' prototype and established two initial DRPCs; one located at Texas A&M University for North America and the other at Utrecht University, the Netherlands, for Europe. This step included three major improvements to the prototype:

• Procurement of Aperio's ScanScope systems to produce, manage, and view digital pathology images using Spectrum Plus for LM images, plus uploaded TEM and IF images. With Aperio's ImageScope for viewing, the imagery is readily available to all users and includes digital slide conferencing.
• Enhancement of the Vision system to expand the clinical data collection component to complement the previously-developed renal pathology component;
• Implementation of an interface between Vision and Spectrum Plus that automatically and seamlessly links the imagery and clinical data for all pathology cases.

Users now have a web-based mechanism to enter detailed case information that is globally accessible and shareable using Vision; and includes “direct” access to all digital pathology imagery and image management and viewing capabilities of Spectrum Plus and ImageScope. Image thumbnails and key entries from the slide tables are integrated in a view of the case information. When users click thumbnails, the system launches ImageScope, which then deploys the images from the TAMU or Utrecht server where the images are located.

Key functional needs have been successfully addressed: multi-center data capture, digital pathology, and on-line conferencing. The project integrated separate technology solutions with complementary strengths:

• Vision is a robust platform for gathering and managing data about every case that is examined from multiple contributing study sites (> 50 sites so far) worldwide.
• Aperio’s digital pathology system effectively delivers high-resolution images that are suitable for diagnostic purposes and facilitates collaborative evaluation of study cases by widely dispersed investigators

During the ‘proof-of-concept’ and ‘start-up’ phases of this initiative, the project developed and tested the processes required to operate a DRPC and evaluated more than 280 cases, constructing a database of results and reports that can be analyzed in a variety of ways to address best practices in combating renal disease in animals

The project has built a core infrastructure that can readily be expanded by creating additional DRPCs and can function as a simple ‘registry’ of all renal pathology cases submitted for evaluation, as well as a means to study cases entered in sponsored studies or prospective clinical trials that have specific study protocols (e.g., entry criteria, prescribed follow-up exams, etc.).

Prelude Dynamics is a global provider of customized web-based software systems for data collection, analysis and management of clinical trials, studies and registries. We streamline eClinical operations through our unique and innovative Vision software system, which allows us to rapidly configure data collection solutions for pharmaceutical, CRO, medical device, animal health, and university organizations.

Aperio is digitizing pathology. We provide systems and services for digital pathology, which is a digital environment for the management and interpretation of pathology information that originates with a digital slide. Aperio's award-winning ScanScope® slide scanning system and SpectrumTM digital pathology information management software improve the efficiency and quality of pathology services for patholgists and other professionals. Applications include education, remote viewing, archival and retrieval, basic research, and image analysis.