Recent Advances and Applications of Ambient Mass Spectrometry Imaging in Cancer Research: An Overview

Abstract

Cancer metabolic variability has a significant impact on both diagnosis and treatment outcomes. The discovery of novel biological indicators and metabolic dysregulation, can significantly rely on comprehension of the modified metabolism in cancer, is a research focus. Tissue histology is a critical feature in the diagnostic testing of many ailments, such as cancer. To assess the surgical margin of the tumour on patients, frozen section histology is a tedious, laborious, and typically arbitrary method. Concurrent monitoring of ion images in tissues facilitated by the latest advancements in mass spectrometry imaging (MSI) is far more efficient than optical tissue image analysis utilized in conventional histopathology examination. This article focuses on the "desorption electrospray ionization (DESI)-MSI" technique's most recent advancements and uses in cancer research. DESI-MSI can provide wealthy information based on the variances in metabolites and lipids in normal and cancerous tissues by acquiring ion images of the lipid and metabolite variances on biopsy samples. As opposed to a systematic review, this article offers a synopsis of the most widely employed cutting-edge DESI-MSI techniques in cancer research.

Keywords: DESI-MSI; ambient mass spectrometry; cancer studies; carcinoma; mass spectrometry imaging.

Fig. 1. Schematic illustration of typical MSI workflow. MS, mass spectrometric; MSI, mass spectrometry imaging.

Fig. 2. Schematic illustration of DESI source. DESI, desorption electrospray ionization; MS, mass spectrometric.

Fig. 3. Representative DESI-MS ion images of normal kidney, RO, and RCC tissues. To better visualize the differences among the three tissue types for the six ions selected, the scale bars used are in unit of absolute intensity and were amplified by a factor of 4 (0–500 absolute intensity) for m/z 391.260, m/z 656.574, and m/z 835.530 of all the samples. (Reproduced with permission from Zhang et al., Cancer Research PMC.) Cer, ceramide; CL, cardiolipin; DESI, desorption electrospray ionization; H&E, hematoxylin and eosin; MG, monoradylglycerolipids; MS, mass spectrometric; PI, glycerophosphoinositol; PS, glycerophosphoserine; RCC, renal cell carcinoma; RO, renal oncocytoma.

Fig. 4. Distinct nerve metabolic profiles in oral cavity tissues by DESI-MSI. (A) Histology surrounding tissue defects of needle electrode sampling for REIMS analysis surrounded by nerve features delineated in yellow on one resected specimen. (B) Segmentation analysis discriminating nervous tissue from the rest of the imaged areas based on DESI-MS profiles. (C) Principal component analysis score plot of DESI-MS profiles (55 nerves, 54 muscles, and 53 tumors) from tissue provided by six patients on the mass range m/z 600−1000 (PC1, which explains 80.3% of the variance of the data; PC2, 7.8%). (Reproduced with permission from Vaysse et al., ACS.) DESI, desorption electrospray ionization; MS, mass spectrometric; MSI, mass spectrometry imaging; PC1, principal component 1; PC2, principal component 2; REIMS, rapid evaporative ionization mass spectrometry.

Fig. 5. Positive ion mode DESI-MSI study with excision specimens obtained from lumpectomy of breast cancer patients. (A) Box−Whisker plot showing the age distribution of patients (n = 73) enrolled in this study. (B) Average mass spectral data collected from cancer (red spectrum) and adjacent normal (blue spectrum) specimens across all patients. Spectral averaging was performed using a total of 40,277 cancer pixels and 130,094 normal pixels across all MSI data of 73 patients. (C) Representative MSI showing spatial distributions of a PC, a PE, a Cer, an SM, and four DG molecules in a typical breast specimen that contains both cancer (red outline) and normal (green outline) areas as presented by the adjacent H&E-stained tissue (upper left). (D) Box−Whisker plots showing significant upregulation of those lipids in breast cancer compared to the adjacent normal tissue (p-values). (Reproduced with permission from Mondal et al., ACS). Cer, ceramide; DG, diacylglycerol; DESI, desorption electrospray ionization; H&E, hematoxylin and eosin; MSI, mass spectrometry imaging; PC, phosphatidylcholine; PE, phosphatidylethanolamine; SM, sphingomyelin; TIC, total ion current.

Fig. 6. (A) MSI workflow, (B) schematic illustration of DESI technique, and (C) distribution of gemcitabine and its metabolites, and AZD6738, in KPC PDAC mouse tumor no. 15908 by MSI. (A) H&E staining with different histological regions annotated, and (B−H) MSI composite images (AZD6738, panel B; dFdC, panel C; dFdU, panel D; dFdCMP, panel E; dFdCDP, panel F; dFdCTP, panel G; and AMP, ADP, and ATP composite image, panel H. (Reproduced with permission from Strittmatter et al., ACS.) ADP, adenosine diphosphate; AMP, adenosine monophosphate; ATP, adenosine triphosphate; DESI, desorption electrospray ionization; H&E, hematoxylin and eosin; KPC, pancreatic cancer; MSI, mass spectrometry imaging; PDAC, pancreatic ductal adenocarcinoma.