3D Whole-Brain Imaging Approaches to Study Brain Tumors

Simple Summary Brain tumors integrate into the brain and consist of tumor cells with different molecular alterations. During brain tumor pathogenesis, a variety of cell types surround the tumors to either inhibit or promote tumor growth. These cells are collectively referred to as the tumor microenvironment. Three-dimensional and/or longitudinal visualization approaches are needed to understand the growth of these tumors in time and space. In this review, we present three imaging modalities that are suitable or that can be adapted to study the volumetric distribution of malignant or tumor-associated cells in the brain. In addition, we highlight the potential clinical utility of some of the microscopy approaches for brain tumors using exemplars from solid tumors. Although our understanding of the two-dimensional state of brain tumors has greatly expanded, relatively little is known about their spatial structures. The interactions between tumor cells and the tumor microenvironment (TME) occur in a three-dimensional (3D) space. This volumetric distribution is important for elucidating tumor biology and predicting and monitoring response to therapy. While static 2D imaging modalities have been critical to our understanding of these tumors, studies using 3D imaging modalities are needed to understand how malignant cells co-opt the host brain. Here we summarize the preclinical utility of in vivo imaging using two-photon microscopy in brain tumors and present ex vivo approaches (light-sheet fluorescence microscopy and serial two-photon tomography) and highlight their current and potential utility in neuro-oncology using data from solid tumors or pathological brain as examples.