Virtual Double Staining Using Elastic Image Registration

Double staining techniques are often used to analyze the colocalization of different antibodies on a tissue sample. In this process the first stain is applied to the tissue which is then washed before the second stain is applied likewise. However, multiple staining of tissue has disadvantages. Different stains can interfere and crossreact making the analysis more difficult. Even worse, the multiple chemical treatment of the tissue can lead to tissue loss. With the increasing availability of whole slide scanners, high resolution scans of histological samples can be obtained and analyzed digitally. Adjacent, differently stained slides can be combined in an analysis, which is often referred to as virtual double staining. However, spatial correspondence between adjacent slides is lost during the sectioning process and various distortions are introduced to the tissue, such that a naïve overlay of the slides is not possible.