Pushing into routine oncology
The advantages of MALDI imaging have significant diagnostic potential. In-depth spatial proteomic, lipidomic, and metabolomic insights that complement traditional genomic and transcriptomic methods can, for example, help identify new predictive or prognostic biomarkers, and classify heterogeneous tumour subpopulations to give important contextual clues to tissue-level communication networks that are integral to cancer growth and treatment success.
Many recent studies demonstrate the advantage of integrating MALDI imaging with traditional techniques for tissue pathology applications. For example, Yagnik et al. reported the development of a new method based on novel photocleavable mass-tags (PC-MTs) for facile antibody labelling, which enables highly multiplexed IHC based on MALDI mass spectrometric imaging (MALDI-IHC ). Their conclusions were that the new combination shows promise for use in the fields of tissue pathology, tissue diagnostics, therapeutics, and precision medicine .
Work published in 2019 by Randall et al. demonstrated how MALDI imaging of lipids and metabolites in tissue samples accurately reflected a patient’s prostate cancer stage, as defined by traditional histologic evaluation using the Gleason score. This is the current standard of care; however, it is a time consuming process that is prone to intra-/inter-observer variability, and provides no information about altered metabolic pathways or altered tissue architecture. They concluded that MALDI imaging could be used as a potential clinical tool to support more objective and faster diagnosis .
To assess the suitability of MALDI imaging as a front-line technique, Basu et al. recently reported on ‘real-time’ assessment of tumour margins. Their goal was to discriminate surgical resection specimens from patients in a workflow that was rapid enough to be applied in clinical pathology . By adapting various stages of a conventional 30-minute protocol for MALDI imaging, they were able to develop a reliable and reproducible 5-minute workflow that they concluded placed MALDI imaging firmly in the realm of routine clinical decision-making. See Fig. 1 in Basu et al. for their comparison of conventional workflows and rapid MALDI imaging (https://doi. org/10.1038/s41698-019-0089-y) . Furthermore, they suggest that, by using an artificial intelligence (AI) step in the workflow, the MALDI imaging data could be analysed directly, without visual review, using previously established machine trained models.
Technology developments are continuing, and two recent breakthroughs are now also being applied to MALDI imaging. First, ion mobility separation (IMS) has greatly broadened the range of biomolecules that can be analysed by pre-separation ahead of mass analysis. Of the many IMS technologies that exist, TIMS offers a number of benefits for MALDI imaging as well as traditional omics, which was demonstrated in a joint project between Bruker and the University of Maastricht, The Netherlands, that illustrated how MALDI-guided spatial omics uncovers proteomic diversity in lipid-segmented subpopulations of breast cancer .
Second, novel laser-induced PI technology has delivered a quantum leap in MALDI imaging sensitivity, by up to three orders of magnitude. This has now been applied to a dual MALDI-electrospray ionization (ESI) mass spectrometer, combining high mass accuracy with advanced MALDI imaging for the separation and identification of analytes such as lipids and glycans in complex mixtures . Currently, this exciting development is being explored in research projects, but it is easy to see how this could, in time, offer next-level performance to pathology applications too.
Clinical research has led the way in utilizing MALDI imaging technology, capitalizing on the powerful label-free analytical tool that can fill in the broad gaps that spatial transcriptomics and genomics leaves in molecular investigations on tissue samples. It can provide valuable information about protein modifications after gene expression and visualizes additional compounds such as, for example, metabolites, glycans and lipids that all play a role in disease pathology.
Crucially, it maintains the spatial relationships of analytes in tissues, allowing improved translational and clinical insights. Recent literature provides a compelling body of evidence for the consideration of MALDI imaging in routine pathology applications, and many see the potential of this technology to provide a top-down, disease-centric pathological view of tissues that can inform therapeutic strategies, support diagnosis and improve patient outcomes.
Further developments to the technology will provide faster measurement speeds, increased sensitivity without compromising spatial resolution, and even deeper molecular content – important factors that look set to accelerate the adoption of MALDI imaging in the routine clinical environment.
Shannon Cornett PhD, Mass Spectrometry
Applications Development Manager, Bruker
Daltonics Bruker Corporation, MA 01821, USA
For further information visit Bruker MALDI