Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS

Abstract

Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15–60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung tissue samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z 885.6 as a marker of PAH in human lung tissue. The m/z 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI­(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.

Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review

“…Schaepe et al compared the use of ToF-SIMS, atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization (AP-SMALDI) Orbitrap MSI, and OrbiSIMS for the chemical imaging of lipids in native human bone sections. 114 Van Nuffel et al combined MALDI-ToF, ToF-SIMS, and Hybrid SIMS to identify markers for pulmonary arterial hypertension in human lung tissue 115 .…”

Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging

“…In the area of MALDI MSI, adoption of unsupervised ML approaches for data processing, pattern recognition and exploration has been successfully applied to elucidate molecular signatures, as reviewed in [6]. Examples of prior applications of unsupervised learning to MALDI data include the characterization of epithelial ovarian cancer histotypes [9], white/grey brain tissue [10], renal cancer [7], pulmonary arterial hypertension (PAH) [11].…”

Streamlined Multimodal DESI and MALDI Mass Spectrometry Imaging on a Singular Dual-Source FT-ICR Mass Spectrometer

“…This has created many combined imaging approaches-known in the field as multimodal or multimode imaging, providing a secondary or tertiary round of analysis of the same (or serial) section [6]. Many have identified the tandem utility of comprehensive mapping of biomolecules from MSI, with targeted assays having incorporated multiple ionization sources or MSI methods [7][8][9][10], combination of MSI with microscopy and spectroscopy [11][12][13][14][15][16], and subsequent microdissection and extraction for liquid chromatography [17,18]. In light of these developments, two techniques of MSI have become predominant in the field, matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI), both of which are morphologically compatible [7,19].…”