Highlighting Functional Mass Spectrometry Imaging Methods in Bioanalysis

Abstract

Most mass spectrometry imaging (MSI) methods provide a molecular map of tissue content but little information on tissue function. Mapping tissue function is possible using several well-known examples of “functional imaging” such as positron emission tomography and functional magnetic resonance imaging that can provide the spatial distribution of time-dependent biological processes. These functional imaging methods represent the net output of molecular networks influenced by local tissue environments that are difficult to predict from molecular/cellular content alone. However, for decades, MSI methods have also been demonstrated to provide functional imaging data on a variety of biological processes. In fact, MSI exceeds some of the classic functional imaging methods, demonstrating the ability to provide functional data from the nanoscale (subcellular) to whole tissue or organ level. This Perspective highlights several examples of how different MSI ionization and detection technologies can provide unprecedented detailed spatial maps of time-dependent biological processes, namely, nucleic acid synthesis, lipid metabolism, bioenergetics, and protein metabolism. By classifying various MSI methods under the umbrella of “functional MSI”, we hope to draw attention to both the unique capabilities and accessibility with the aim of expanding this underappreciated field to include new approaches and applications.

Correlative Chemical Imaging and Spatial Chemometrics Delineate Alzheimer Plaque Heterogeneity at High Spatial Resolution

“…Thereby, the spectral values j of each individual pixel i were summed up. (6) Multivariate analyses of MSI data were performed in SIMCA 17 (Sartorius Stedim Biotech, Umeå, Sweden) and comprised PCA and multiblock orthogonal projections to latent structures based on the OnPLS algorithm. 59,60 OnPLS components describe variation in globally joint, locally joint, and unique parts for each data block as follows:…”

“…Over the last years, mass spectrometry imaging (MSI) has emerged as a powerful tool for chemical imaging to increase understanding of spatial biochemical distribution dynamics in tissue that are associated with histopathological processes. − Moreover, acquisitions of multiple chemical imaging modalities contribute with complementary molecular information, specifically multimodal MSI or the integration of MSI with histological microscopy, vibrational spectroscopy, magnetic resonance imaging, as well as fluorescence microscopy. − The acquisition of imaging data in multiple modalities yields datasets that may be spatially misaligned. In order to combine such datasets, the imaging data need to be registered to one another, meaning precisely geometrically aligned and image distortion-corrected .…”

Mass spectrometry imaging advances and application in pharmaceutical research

“…These bio-informative connections could provide insight into the drug-phenotype interaction, and spatially resolved molecular composition-environment-biological function. It is believed that MSI can also become a functional imaging tool to visualize biological events, such as proliferation, metastasis, invasion, autophagy, ferroptosis [122,123], and biomolecular activity, such as enzyme catalysis [124][125][126][127], and biological tissue microenvironments, such as acidity [128], by analyzing and organizing the acquired big data.…”

Quasi‐continuous infrared matrix‐assisted laser desorption electrospray ionization source coupled to a quadrupole time‐of‐flight mass spectrometer for direct analysis from well plates

“…[20][21][22] This source has been extensively used for mass spectrometry imaging (MSI) applications. [23][24][25][26] Previously, the MSI source had been coupled to an ion mobility (IM) quadrupole time-of-flight (Q-TOF) instrument. 27 This instrument contains an ion trap to accumulate ions before entering the drift tube for gas phase separation.…”

“…Different versions of this source have been presented previously using trap‐based mass spectrometers 20–22 . This source has been extensively used for mass spectrometry imaging (MSI) applications 23–26 …”