A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry

Abstract

Mass spectrometry imaging (MSI) has evolved into a valuable tool across many fields of chemistry, biology, and medicine. However, arguably its greatest disadvantage is the difficulty in acquiring quantitative data regarding the surface concentration of the analyte(s) of interest. These difficulties largely arise from the high dependence of the ion signal on the localized chemical and morphological environment and the difficulties associated with calibrating such signals. The development of quantitative MSI approaches would correspond to a giant leap forward for the field, particularly for the biomedical and pharmaceutical fields, and is thus a highly active area of current research. In this review, we outline the current progress being made in the development and application of quantitative MSI workflows with a focus on biomedical applications. Particular emphasis is placed on the various strategies used for both signal calibration and correcting for various ion suppression effects that are invariably present in any MSI study. In addition, the difficulties in validating quantitative-MSI data on a pixel-by-pixel basis are highlighted.

Matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for direct visualization of plant metabolites in situ

“…Quantification in MSI is still a major hurdle, which is not easy to overcome because of the complexity of this problem; e.g., local environment or tissue specific ion suppression, differential extraction efficiency, and lack of understanding of MALDI mechanisms. Some progress has been made in the last few years [41], and improvements are likely to continue in the near future. With all the progress and trends, it would not be surprising within the next decade to find this technology become a routine and essential tool that is commonly available to a wide range of plant biologists.…”

The Use of Auxin Quantification for Understanding Clonal Tree Propagation

“…These techniques provide simultaneous high-resolution identification and imaging of compounds to visualize their distribution in plant tissue [144][145][146][147]. They have been applied extensively to study the distribution of drugs and their metabolites in human and animal tissues [145,148].…”

Insights into organic-aerosol sources via a novel laser-desorption/ionization mass spectrometry technique applied to one year of PM<sub>10</sub> samples from nine sites in central Europe

“…Although this type of ionization is considered softer than electron ionization, the observed ions are typically still fragments of their parent molecules (De Hoffmann and Stroobant, 1999). Furthermore, the measured intensity of one compound does not only depend on its concentration but also on the concentration of all other compounds present (the so-called matrix effect) making quantification challenging (Ellis et al, 2014;Borisov et al, 2013). 20 We recorded the mass spectra of 819 filter samples (m/z range 65-500, ion gate at m/z 60) using a laserdesorption/ionization-ToF MS (Shimadzu Axima Confidence, Shimadzu-Biotech Corp., Kyoto, Japan) equipped with an N 2 laser (wavelength 337 nm, frequency 50 Hz, laser pulse width 3 ns) in the positive reflectron mode.…”