Origins of ... image analysis in clinical pathology.

The term "image analysis" is reserved for a special discipline in pathology that aims to obtain diagnostically important information in an objective and reproducible manner, by measuring and counting. The origins of measuring microscopical images are almost as old as the microscope itself. Leeuwenhoek (fig 1) in the 17th century had developed a system to measure microscopic objects. As a reference he used sand grains of different sizes, and hairs from his head, beard or wig.' 2 Using this method, in 1674 he measured human erythro-cytes as 25 000 times smaller than a small sand grain, corresponding to 8.5 gm.3 Given the means at his disposal, this is amazingly precise. This review intends to give an overview of the developments that have led to image analysis as it is currently applied in routine diagnostic cytopathology and histopathology as well as in research. For the purpose of clarity we discriminate between three different areas of image analysis; however, they are not mutually exclusive. These areas are measuring morphological characteristics of tissues, cells, nuclei or even nucleoli; counting of cell or tissue components ; and cytometry and pattern recognition, which aims to measure cytochemical, histo-chemical, and molecular cell or tissue features Figure 1 Antoni van Leuwenhoek (1632-1723) in the 1 7th century had developed a system for measuring microscopic objects. (Courtesy the Antoni van Leeuwenhoek Hospital, Amsterdam.) such as the DNA content of nuclei, and to classify cells according to the distribution pattern of these features in cells or nuclei. Morphometry Morphometry is the quantitative description of geometric features of structures of any dimension.4 This includes planimetry, which refers to the measurement of geometric features of structures in two dimensions. Stereol-ogy denotes all techniques used to obtain quantitative information about geometric features of structures with a test system of lower dimension than the structure itself-for example , point or line grids. Measuring requires a reference or a probe. In 1777, Georges Louis Leclerc, Comte de Buffon, demonstrated that the chance that a needle of given length (a probe) dropped at random on a series of equidistal parallel lines would intersect one of these lines, depended on the distance between the lines.5 The concept of measuring distances by randomly dropping a probe was the cradle of stereology. In general, stereological techniques can be used to estimate fractions of different tissue components, inner and outer surface density, shape and volume. Delesse, a French geologist, …