Computerized extraction of the time dimension in histopathological sections

Most tissues in the organism renew their cells continuously. A renewing tissue consists of a progenitor compartment P and a functional compartment Q. Cells are first formed in P and only thcn enter Q. Such an arrangement is known as a two-compartment cell renewal system. The cells advance along a trajectory which is called tissue radius. The P compartment occupies the inner radius portion, while the Q compartment covers its outer part. Cell displacement on the radius depends solely on cell production by P cells. Following each mitosis one of the daughter cells replaces its parent, while the other is placed more distally. Concomitantly all distal cells advance by one position. A cell thus starts its existence at radius origin, and when reaching the periphery, it is eliminated. This motion is part of a stream including all tissue cells. Since cells advance along the radius in a single outward direction, they are ordered by their ages: the further a cell from radius origin, the older it is. Age of a cell is thus proportional to its distance from origin, and may be derived by measuring distance. The radius also summarizes the history of the entire system. Generally a cell at location J + 1 represents the future state of a cell at locationj, and its proximal neighbor at location j - 1 represents its past state. Thus, to extract the time dimension of a tissue, it has to be sampled along its radius. This approach is implemented in the software of our tissue analyzer, which sampled Feulgen-stained hepatocytes and determined their optical densities. The optical density of the hepatocyte increases with its age. Since it is generally accepted that the Feulgen stain binds to the DNA stoichiometrically, our experiments indicate that hepatocyte DNA content increases with its age.