Intravital Correlative Microscopy: Imaging Life at the Nanoscale

Studying key biological events within complex model systems relies on dynamic and functional imaging at optimum spatial and temporal resolutions. Intravital correlative light and electron microscopy (intravital CLEM) combines imaging living multicellular model systems with electron microscopy, and offers full ultrastructural details of dynamic or transient events in vivo. However, routine use of intravital CLEM is hindered by multiple technological challenges faced when targeting a micron-size object (e.g., single cells or organelles) in a complex living organism. Recently, various approaches have been developed to overcome these limitations. In this review we outline the current methods and present the power of intravital CLEM in different fields of research. Finally, we describe approaches that will make intravital CLEM a routine, quantitative method for high-resolution cell biology in vivo.