A new approach to the computer-assisted quantitative analysis of nuclear shape.

In recent years, researchers have explored the use of computer-assisted morphometric analysis to evaluate nuclear shape. Most of these studies use nuclear shape factors which are based on circumference/surface measurement ratios, such as variations of the nuclear contour index, the form factor, and the nuclear roundness factor. Here we present a new method for the objective evaluation of nuclear shape, involving a simple computer-assisted determination of nuclear area (N) divided by the area of a rectangular figure (F) with sides tangent to the nuclear margin and parallel to the frame of a video monitor. Following calculation of N/F for individual nuclei, our method generates statistical parameters for quantitating nuclear irregularity directly at the population level: the mean N/F ratio; standard deviation; and coefficient of variation. Our use of surface/surface measurement ratios makes our method independent of both magnification and nuclear size. Our method is applied first to normal lymphocytes and neutrophils to manifest the parameters for nuclear irregularity which are generated by our method. The sensitivity of our method is demonstrated using lymphoblasts from patients with acute lymphoblastic leukemia (ALL). Our objective ranking of nuclear irregularity for 20 cases of ALL correlates well with the subjective ranking of two pathologists. Because our method scores irregularity on a population basis and independently of other morphological criteria, it is compatible for use with the French-American-British (FAB) classification system (1981) for ALL.