Interactive system for registering adjacent tissue sections

The molecular and structural analysis of cells within their tissue context helps us understand disease mechanisms, such as carcinogenesis. Standard analysis of cutting specimens into thin (4 μm) sections, followed by labeling and visual microscopic analysis, has the limitation that tissue properties can only be studied within the section plane, and not perpendicular to the plane. We solved these limitations by building a system for registering images of adjacent sections. In addition, the system enables analysis of many molecular markers in a specific tissue volume, by labeling different sections with different markers, followed by using the system to locate the relevant tissue volume in each section. The system has three stages. First, it automatically images each entire section and two fiducial markers per slide. After this stage, the slides can be removed from the microscope. In stage two, pairs of images of adjacent sections are registered. This is done by interactively marking several points that are common to both images, which are used to calculate the translation and rotation of the images relative to each other. Different registrations can be performed on different parts of the images to account for differential stretching, tearing and folding of sections. In stage three, a slide is placed on the microscope stage and the analyst can bring a specific location into the field of view by referring to it in the previously acquired image. Accuracy is ≈10 μm.