“Digitizing is Believing” with the New Microscope
Safety Assessment
Daniel Rudmann

“Digitizing is Believing” with the New Microscope

Whole Slide Imaging has the potential to transform how pathologists diagnose disease  

In 2017, the US Food and Drug Administration (FDA) granted marketing clearance for the first Whole Slide Imaging (WSI) System for use in human disease diagnosis. This FDA clearance was an important step for the acceptance of digital pathology by regulatory agencies, which for years was slowed by the challenges of demonstrating equivalence between what appears visually through the microscope eyepiece and on the computer monitor screen.

WSI systems consist of a digital slide scanner and visualization software that create digital images of pathology slides. These digitized slides can be viewed, managed, and stored electronically, promoting collaboration in nonclinical and clinical research as well as improving diagnostic accuracy and precision. Similar systems have been used successfully by physicians for many years to evaluate radiographs and cancer screening tests like the PAP smear. Veterinarians also began using WSI recently for the primary diagnosis of animal disease, especially cancer.

WSI systems are critical for the rapidly advancing area of digital image analysis (IA). IA increases the power of the pathologist’s microscope by transforming what a pathologist sees through their objectives into quantitative data that can be integrated with other data sets, as this article in Toxicologic Pathology discusses. IA techniques are already being used by pathologists in agrochemical, medical device, and pharmaceutical research settings. Continued innovation in the application of IA for nonclinical toxicology is an exciting area of interest for toxicology and pathology organizations across the private and public sectors.  

A valuable immunology tool

WSI and IA pathology workflows should further advance the pathologist’s impact on non-regulated Good Laboratory Practice (nGLP) and regulated (GLP) preclinical studies including those done for immunotoxicology. WSI and IA have already demonstrated an impact in immuno-oncology research, where similar types of preclinical and clinical questions are asked at the tissue level. In immuno-oncology, IA is used by the pathologist to study the interactions between cancer and immune cells in digital images created by WSI systems. For immunotoxicology studies, WSI and IA could also aid the pathologist in deciphering potential drug-mediated effects on the immune system and its many effector cells. The pathologist assesses these potential drug-related effects by examining hundreds of immune tissues, including multiple lymph nodes and local lymphoid structures such as the intestinal Peyer’s Patch as well as the spleen, bone marrow, and thymus. Pathologists can use WSI systems as a collaboration tool by accessing a global network of peers for consultation and review of potential effects in these tissues.   

Bridging Pathology to the World of Big Data

IA can also be incredibly useful in transforming more qualitative data sets into formats that can integrate effectively with other quantitative data. Often the pathologist uses simple ordinal, non-continuous scoring systems (e.g. 1= minimal to 5= severe) for measuring an observed change. These qualitative data sets are more difficult to integrate with other more quantitative data sets that are commonly produced as part of preclinical and clinical studies. Yet, the pathologist, in partnership with other scientists, must effectively integrate immunopathology data with data from clinical pathology, flow cytometry, and other ex vivo and in vitro assays into an expert nonclinical report. Augmenting pathology data sets using IA could enable a pathologist to analyze tissue-based histopathology more quantitatively, increase the ease of data integration and analysis, and in effect expand the impact of the histopathology data when combined with these other data sets.

Challenges OF WSI and IA

Advancements like WSI and IA strengthen a pathologist’s ability to partner with other scientists and ensure a thorough understanding of a drug’s effect on the immune system. Long-term, we’ll see scientific and operational advances by using both WSI and IA in diagnostic and toxicology settings. However it will be key to make WSI and IA user friendly to the pathologist and ensure that the machine (WSI/IA) and human (pathologist) work in a way that is synergistic and not simply additive or worse, antagonistic. Also pathologists will need to engage with key scientific and information technology (IT) partners to harness the full potential of these technologies. It is an exciting time to be a pathologist and WSI and IA will be at the forefront in helping our data increase its impact on medicine and drug development for years to come.

You can learn more about Charles River's pathology services, including its use of whole slide scanner systems, here.