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. 2023 Jun:163:117055.
doi: 10.1016/j.trac.2023.117055. Epub 2023 Apr 13.

High-Throughput Mass Spectrometry Imaging of Biological Systems: Current Approaches and Future Directions

Li-Xue Jiang  1 , Manxi Yang  1 , Syeda Nazifa Wali  1 , Julia Laskin  1
Affiliations

High-Throughput Mass Spectrometry Imaging of Biological Systems: Current Approaches and Future Directions

Li-Xue Jiang et al. Trends Analyt Chem. 2023 Jun.

Abstract

In the past two decades, the power of mass spectrometry imaging (MSI) for the label free spatial mapping of molecules in biological systems has been substantially enhanced by the development of approaches for imaging with high spatial resolution. With the increase in the spatial resolution, the experimental throughput has become a limiting factor for imaging of large samples with high spatial resolution and 3D imaging of tissues. Several experimental and computational approaches have been recently developed to enhance the throughput of MSI. In this critical review, we provide a succinct summary of the current approaches used to improve the throughput of MSI experiments. These approaches are focused on speeding up sampling, reducing the mass spectrometer acquisition time, and reducing the number of sampling locations. We discuss the rate-determining steps for different MSI methods and future directions in the development of high-throughput MSI techniques.

Keywords: Continuous scanning; MSI; Multimodal; Sparse sampling; Throughput.

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Conflict of interest statement

Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Schematics of the two different approaches to macromolecular imaging mass spectrometry. Microprobe mode imaging (A) collects mass spectra from an array of designated positions to reconstruct a molecular image after completion of the experiment. In microscope imaging (B), magnified images of the ion distributions are directly acquired using a two-dimensional detector. Reprinted from Ref. [13] with permission from ACS.
Figure 2.
Figure 2.
Top: Schematic diagram of the MALDI source used for laser scanning mode. Reprinted from Ref. [23] with permission under the ACS AuthorChoice License. Bottom: Images of one spheroid with a diameter 0.8 mm. (a) Photograph and ion images of (b) cholesterol fragment [M−H2O+H]+ and (c) perifosine. The sample size is 1.0 × 1.3 mm2 and the spatial resolution is 10 μm. The total acquisition time is around 100 s with a speed of 130 pixel/s. Adapted from Ref. [24] with permission from ACS.
Figure 3.
Figure 3.
(A) A photograph of a capillary-based nano-DESI probe placed onto a tissue sample. (B) A schematic diagram of the iMFP. (C) Representative line profiles of PC 34:1 (m/z 782.568) across a mouse brain tissue section at different scan rates. (D) Optical images of tissue sections used at (i) 0.04, (ii) 0.2, and (iii) 0.4 mm/s scan rates. Representative positive mode ion images obtained for [M + Na]+ ions of PC 34:1, PC 38:3, and PC 36:1 along with image acquisition times. The following regions are labeled in the optical image: cortex, dentate gyrus (DG), and corpus callosum (CC). Scale bar: 2 mm. The intensity scale: black (low); yellow (high). Adapted from Ref. [34] with permission from ACS.
Figure 4.
Figure 4.
Subspace-based imaging for FT-ICR MSI. The subspace model starts with randomly sampling 10% of the transients with the long transient duration (0.734 s) to construct the transient set. The left pixels are acquired by shorter transient time (0.11s). The shorter transient time data are reconstructed to long transient data based on subspace method. This acquisition and reconstruction strategy can improve the data acquisition efficiency without compromising the spectral resolution and mass accuracy. Reprinted from Ref. [50] with permission from ACS.
Figure 5.
Figure 5.
Concept of multimodal FTIR-guided MALDI mass spectrometry imaging. In a two-modality workflow, FTIR imaging is used as the first modality to record a variable (Var) set of p vibrational bands that represent molecular distribution patterns at a pixel size limit of 6.25 × 6.25 μm2. By applying segmentation, FTIR spectra of all acquired pixels are separated into a defined number of subgroups based on spectral similarities. The membership of each FTIR pixel to one of the defined groups is expressed by assigning an exclusive index number (IDX). The spatial properties of a segment belonging to a given IDX (SIDX) are automatically registered to the second modality, MALDI-MSI, allowing for a targeted acquisition of a greater number of q mass variables for the region of interest predefined by the FTIR subgroup. FTIR and MS imaging measure different properties of the examined tissue specimen, thus complementing contours of spatial accuracy that exceed MALDI-MSI capabilities with chemically specific mass information while reducing data load and acquisition time. Reprinted from Ref. [64] with the permission from authors.
Figure 6.
Figure 6.
Simulated DLADS dynamic sampling and reconstruction in the pointwise and linewise modes, using a fully measured mouse kidney tissue MSI data. An optical image and ground-truth ion images of m/z 840.5854 and m/z 880.5693 are shown in the first column. DLADS sampling locations and reconstructed ion images at different simulation conditions are shown in columns 2–5. The results are shown for 10% and 30% sampling in the spot-by-spot mode and 40% and 60% sampling in the continuous line scan mode. Reprinted from Ref. [59] with the permission from authors.
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