Karreman, M.A. et al. J. Cell Sci. 129, 444–456 (2016).

Intravital imaging of cancer cells can yield important insights into processes such as metastasis. However, metastatic events are rare, and thus it is a challenge to identify them with high-resolution imaging. Karreman et al. describe a multimodal correlative microscopy approach that enables rapid and precise targeting of cancer cells for high-resolution imaging by 3D electron microscopy (3DEM). In their approach, a cell of interest is first identified by fluorescence microscopy. Next, the precise position of the cell is determined by registration with X-ray computed tomography data. Finally, the cell is imaged using 3DEM. To demonstrate the method, they injected fluorescently labeled cancer cells into a mouse heart and imaged cells that metastasized to the brain. Their approach improves the throughput of rare cell ultrastructural analysis by allowing experiments to be completed from start to finish in around two weeks.