Gadolinium deposition: Is it chelated or dissociated gadolinium? How can we tell?

The methodology and published work aimed at speciation of gadolinium based contrast agents in tissues is reviewed. The discussion focusses on the context of Gd deposited long term in tissue following administration of the contrast agents. Detection of Gd without identification of the chemical form detected is simple and straight forward using a variety of methods. Determination of the chemical form of Gd detected is far more complex and most methods require inherently imperfect extraction steps that can alter the Gd chemical species detected. Control studies wherein Gd is not deposited biologically or is deposited in animal tissues are also inherently imperfect. Strengths and weaknesses of the various methods used and examples are demonstrated. It is concluded that a combination of spatially resolved mass spectral based methods, combined with extraction/HPLC analysis methods can provide sufficient sensitivity, spatial resolution and chemical species specificity to address the title question on ex vivo tissue samples. (C) 2016 Elsevier Inc. All rights reserved.