AUTHOR=Hartnell David , Andrews Wendy , Smith Nicole , Jiang Haibo , McAllum Erin , Rajan Ramesh , Colbourne Frederick , Fitzgerald Melinda , Lam Virginie , Takechi Ryusuke , Pushie M. Jake , Kelly Michael E. , Hackett Mark J. TITLE=A Review of ex vivo Elemental Mapping Methods to Directly Image Changes in the Homeostasis of Diffusible Ions (Na+, K+, Mg2 +, Ca2 +, Cl–) Within Brain Tissue JOURNAL=Frontiers in Neuroscience VOLUME=Volume 13 - 2019 YEAR=2020 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2019.01415 DOI=10.3389/fnins.2019.01415 ISSN=1662-453X ABSTRACT=Diffusible ions (Na+, K+, Mg2+, Ca2+, Cl-) are vital for healthy function of all cells, especially brain cells. Unfortunately, the diffusible nature of these ions renders them difficult to study with traditional microscopy approaches. This mini-review examines the recent progress in the field, using direct elemental mapping techniques to study ion homeostasis during normal brain physiology and pathophysiology. The mini-review examines the advantages and limitations of specific techniques: proton induced X-ray emission (PIXE), X-ray fluorescence microscopy (XFM), secondary ion mass spectrometry (SIMS), laser-ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and the sample preparation requirements to study diffusible ions with these methods.