Stereology going mainstream

Lars Peterson discusses how whole slide stereology is beginning to make an impact in the biopharmaceutical industry.

What was the main reason for pharmaceutical companies not to employ stereology based methods in their pre-clinical research?

Lars Peterson. From a position as an esoteric discipline in the hinterlands of purely academic research, stereology has become a recognized best-practice approach to obtain critical histomorphometric information about tissues. Applications range from efficacy pharmacology to toxicological pathology, and in some cases, even clinical studies. Increasingly, scientific societies, biopharmaceutical companies and even the regulatory authorities are adopting stereological principles whenever data are used as a basis for critical business or scientific decisions.
 
Decision-makers in the biopharmaceutical industry, and with regulatory authorities, are increasingly aware of the limitations of manual scoring, ranking, grading and 2-D image analysis approaches. But the load of manual labor, as well as the complexity of the stereological approach, has made the proposition of stereology unrealistic in an environment with relentless demands for data and throughput.
 
Robust, high-quality whole slide imaging devices and novel technology for automating stereology are rapidly changing both adoption and regulatory awareness.
 
What other factors influence the penetration of whole slide stereology into the pharmaceutical pre-clinical research market?

LP. Whole slide stereology is a powerful research tool, allowing a researcher to ask critical questions, such as fx number of dopaminergic neurons in substantia nigra, number of proliferating hepatocytes, number of alveoli in a lung, etc – and get a statistically unbiased answer, with a known precision. Additionally, whole slide stereology is substantially reducing or eliminating bottlenecks associated with manual labor.
 
Slides from whole slide imaging systems, like the Olympus VS110 (for research and educational purposes only), can be used with the patent protected software tools from Visiopharm, and demonstrate improvements in efficiency between 20 and 40 times, compared to the traditional methods.
 
Whole slide stereology is efficiently addressing other critical issues as well. The stereological sampling approach at every level provides better precision in estimates of tissue properties at study unit level, which is typically translated into the ability to detect smaller group differences with the same number of study units.

By virtue of being whole slide based, all end-points are fully traceable from study unit, down to the individual structures that formed the basis for quantification; and based on thin sections, a whole range of time-consuming and expensive issues with tissue preparation (shrinkage, penetration of staining reagents, etc.) can be eliminated.

How does your partnership with Olympus America Inc. bring increased value to your customers?

LP. The results delivered by image analysis software rely on high-quality images. Olympus is a recognized leader in optical technologies and has had many years of experience bringing microscopic imaging and image analysis to the pharmaceutical industry. This expertise has allowed Olympus to develop high-resolution whole slide imaging systems like its VS110 scanner.

Working together to bring our knowledge of advanced image analysis and histo-informatics with the Olympus whole slide scanning technology, we can offer our customers imaging solutions today, like automated whole slide stereology, that were not previously possible, giving them tools that deliver better quality results, easier and faster. For pharmaceutical drug discovery and development, this can mean significant reductions in time to market, which potentially can lead to decreased costs and increased revenue.

What do you see the future holding for whole slide stereology?

LP. An increasing number of scientific societies adopt guidelines requiring use of stereology whenever reporting findings are based on quantitative morphometry. Examples are neuroscience and nephrology, where leading scientific journals impose such requirements for publications. Recently, the field of respiratory research agreed on an official statement on quantitative assessment of lung structure using stereology published as a joint statement from the American Thoracic Society and the European Respiratory Society.

Also regulatory authorities are familiarizing themselves with and educating themselves on methods and technological advances in the field. Although this is not likely to result in immediate changes in regulatory guidelines, there is little doubt that companies engaged in pharmaceutical R&D will be faced with new types of questions and expectations from regulatory reviewers. These types of questions can be efficiently addressed with whole slide stereology.

Biography

Lars Pedersen, PhD, Director of Professional Services, joined Visiopharm in 2002 after completing his doctoral training in Informatics and Mathematical Modeling at the Technical University of Denmark. His strong academic background in digital image analysis and statistical pattern recognition, combined with several years of experience in stereology, allows Pedersen to master and teach the complete range of Visiopharm software products.