Transparent Window Models and Intravital Microscopy: Imaging Gene Expression, Physiological Function and Therapeutic Effects in Tumors

Abstract

Currently, gene expression, physiological function and treatment efficacy are typically determined by techniques that are either destructive or have poor spatial resolution (millimeter to centimeter). The former have limited ability to provide insight into the dynamics and the latter preclude visualization at the cellular and sub-cellular levels (1-10 micrometers). Intravital microscopy of tumors growing in various organs overcomes these limitations and offers powerful insight into tumor pathophysiology and treatment. Furthermore, the recent availability of in vivo reporters such as GFP as well as transgenic mice and cell lines is likely to present new opportunities for discoveries. There are three broad categories of tissue preparations, which can accommodate intravital microscopopy: chronic-transparent chambers, acute (exteriorized) tissue preparations and in situ preparations. Each of these preparations can be used to study normal tissue, an implanted tumor or a tissue construct containing growth factor(s) or engineered cells to study angiogenesis. In this chapter, we will briefly describe historical perspective, surgical procedures and strengths and weaknesses for various tissue preparations. We then outline various intravital microscopy techniques and the computer-assisted image analyses. Finally, we highlight key insights obtained from such approaches and the possibilities that lay ahead.