Whole slide image (WSI) registration is an essential task for analyzing the tumor microenvironment (TME) in histopathology. It involves the alignment of spatial information between WSIs of the same section or serial sections of a tissue sample. The tissue sections are usually stained with single or multiple biomarkers before imaging, and the goal is to identify neighboring nuclei along the Z-axis for creating a 3D image or identifying subclasses of cells in the TME. This task is considerably more challenging compared to radiology image registration, such as magnetic resonance imaging or computed tomography, due to various factors. These include gigapixel size of images, variations in appearance between differently stained tissues, changes in structure and morphology between non-consecutive sections, and the presence of artifacts, tears, and deformations. Currently, there is a noticeable gap in the literature regarding a review of the current approaches and their limitations, as well as the challenges and opportunities they present. We aim to provide a comprehensive understanding of the available approaches and their application for various purposes. Furthermore, we investigate current deep learning methods used for WSI registration, emphasizing their diverse methodologies. We examine the available datasets and explore tools and software employed in the field. Finally, we identify open challenges and potential future trends in this area of research.
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