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Quantitative mass spectrometry imaging (MSI) is an effective technique for determining the spatial distribution of molecules in a variety of sample types; however, the quality of the ion signals is related to the chemical and morphological properties of the tissue and the targeted analyte(s). Issues may arise with the incorporation of standards into the tissue at repeatable, well-defined concentrations, as well as with the extraction and incorporation of endogenous analytes versus standards from tissue into the matrix. To address these