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. 2019 Jul;411(17):3709-3720.
doi: 10.1007/s00216-019-01780-8. Epub 2019 Apr 12.

Trends in mass spectrometry imaging for cardiovascular diseases

Stephanie T P Mezger  1   2   3 , Alma M A Mingels  2   3 , Otto Bekers  2   3 , Berta Cillero-Pastor  1 , Ron M A Heeren  4
Affiliations

Trends in mass spectrometry imaging for cardiovascular diseases

Stephanie T P Mezger et al. Anal Bioanal Chem. 2019 Jul.

Abstract

Mass spectrometry imaging (MSI) is a widely established technology; however, in the cardiovascular research field, its use is still emerging. The technique has the advantage of analyzing multiple molecules without prior knowledge while maintaining the relation with tissue morphology. Particularly, MALDI-based approaches have been applied to obtain in-depth knowledge of cardiac (dys)function. Here, we discuss the different aspects of the MSI protocols, from sample handling to instrumentation used in cardiovascular research, and critically evaluate these methods. The trend towards structural lipid analysis, identification, and "top-down" protein MSI shows the potential for implementation in (pre)clinical research and complementing the diagnostic tests. Moreover, new insights into disease progression are expected and thereby contribute to the understanding of underlying mechanisms related to cardiovascular diseases.

Keywords: Cardiovascular diseases; Lipids; MALDI; Mass spectrometry imaging; Proteins; SIMS.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic overview of the workflow for MSI. First, the organ is harvested, then either snap-frozen or fixed, with or without embedding. Next, the tissue is cut and mounted on a slide. Then, optional and depending on the analyte of choice, washing steps, antigen retrieval, and digestion protocols are performed. For MALDI, a matrix is applied on top of the tissue, and a laser beam generates the ions for detection. For SIMS, an ion beam generates the secondary ions for detection. For DESI, a charged solvent extracts the ions from the tissue. Afterwards, a histological stain can still be done
Fig. 2
Fig. 2
Sagittal sections of a rat hearts imaged using metal-assisted SIMS. Anatomical features are visualized in SIMS ion images, specific for the aorta wall (a–d), ventricles (h and n), and pericardium (m). Localization of the main cholesterol ions (m/z 369 and m/z 385) shows localization in the aorta wall, aorta valve, right coronary artery, and right and left atria, image e and i respectively. Scale bar = 100 μm. Reprinted with permission from Springer Nature Customer Service Centre GmbH: Springer Anal Bioanal Chem. Fornai L, Angelini A, Klinkert I, Giskes F, Kiss A, Eijkel G et al. Three-dimensional molecular reconstruction of rat heart with mass spectrometry imaging. Anal Bioanal Chem. 2012;404(10):2927–38, copyright 2012. [31]
Fig. 3
Fig. 3
Peptide MALDI-MSI analysis of cardiac tissue. The left column contains H&E staining and orientation (endocardium and pericardium) of the samples. Other columns contain ion images of the identified proteins including m/z values or the corresponding immunohistochemistry as indicated above the images. The “*” represents the coronary artery. [12]
Fig. 4
Fig. 4
Distribution of cardiac metabolites in an ischemic mouse heart. a Optical image of the section indicates the ischemic region in red using NADH as metabolic indicator. The other columns show the ion images of the glucose-derived metabolites and adenine nucleotides as indicated above the images. b Energy charge (E.C.) values per pixel were calculated based on MALDI-MSI and normalized using CE-MS-based quantitative analysis. This is presented for the LAD ligated (left) and sham (right) mouse hearts. c The E.C. values for the three distinct areas in the LAD ligated heart (ischemic, penumbra, and normoxic regions) and the sham heart. d Correlation between adenosine elevation and ischemic severity was detected (left), adenosine overflow in the penumbra region (arrow in the middle panel) from the ischemic core (right panel) was seen. Adapted from Sugiura et al. [63]
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