A System for Computer-based Reconstruction of 3-Dimensional Structures from Serial Tissue Sections: an Application to the Study of Normal and Neoplastic Mammary Gland Biology

Abstract

Tissue heterogeneity and three-dimensionality are generally neglected by most traditional analytical microscopy methods in Biology. These often disregard contextual information important for understanding most biological systems. in breast cancer, which is a tissue level disease, heterogeneity and three dimensionality are at the very base of cancer initiation and clonal progression. Thus, a three dimensional quantitative system that allows low resolution virtual reconstruction of the mammary gland from serial sections, followed by high resolution cell-level reconstruction and quantitative analysis of the ductal epithelium emerges as an essential tool in studying the disease. We present here a distributed microscopic imaging system which allows acquiring and registering low magnification (1 pixel = 5 μm) conventional (bright field or fluorescence) images of entire tissue sections; then it allows tracing (in 3D) the ducts of the mammary gland from adjacent sections, to create a 3D virtual reconstruction of the gland; finally it allows revisiting areas of interest for high resolution (1 pixel = 0.5 μm) imaging and automatic analysis. We illustrate the use of the system for the reconstruction of a small volume of breast tissue.