A Survey of Methods for 3D Histology Reconstruction

Histology permits the observation of otherwise invisible structures of the internal topography of a specimen. Although it enables the investigation of tissues at a cellular level, it is invasive and breaks topology due to cutting. Three-dimensional (3D) reconstruction was thus introduced to overcome the limitations of single-section studies in a dimensional scope. 3D reconstruction finds its roots in embryology, where it enabled the visualisation of spatial relationships of developing systems and organs, and extended to biomedicine, where the observation of individual, stained sections provided only partial understanding of normal and abnormal tissues. However, despite bringing visual awareness, recovering realistic reconstructions is elusive without prior knowledge about the tissue shape. 3D medical imaging made such structural ground truths available. In addition, combining non-invasive imaging with histology unveiled invaluable opportunities to relate macroscopic information to the underlying microscopic properties of tissues through the establishment of spatial correspondences; image registration is one technique that permits the automation of such a process and we describe reconstruction methods that rely on it. It is thereby possible to recover the original topology of histology and lost relationships, gain insight into what affects the signals used to construct medical images (and characterise them), or build high resolution anatomical atlases. This paper reviews almost three decades of methods for 3D histology reconstruction from serial sections, used in the study of many different types of tissue. We first summarise the process that produces digitised sections from a tissue specimen in order to understand the peculiarity of the data, the associated artefacts and some possible ways to minimise them. We then describe methods for 3D histology reconstruction with and without the help of 3D medical imaging, along with methods of validation and some applications. We finally attempt to identify the trends and challenges that the field is facing, many of which are derived from the cross-disciplinary nature of the problem as it involves the collaboration between physicists, histolopathologists, computer scientists and physicians.