Research

16 pages, 28615 KiB

Open AccessArticle

Enhancement of Ambient Mass Spectrometry Imaging Data by Image Restoration

by Yuchen Xiang, Martin Metodiev, Meiqi Wang, Boxuan Cao, Josephine Bunch and Zoltan Takats

Metabolites 2023, 13(5), 669; https://doi.org/10.3390/metabo13050669 - 19 May 2023

Viewed by 1301

Mass spectrometry imaging (MSI) has been a key driver of groundbreaking discoveries in a number of fields since its inception more than 50 years ago. Recently, MSI development trends have shifted towards ambient MSI (AMSI) as the removal of sample-preparation steps and the [...] Read more.

Mass spectrometry imaging (MSI) has been a key driver of groundbreaking discoveries in a number of fields since its inception more than 50 years ago. Recently, MSI development trends have shifted towards ambient MSI (AMSI) as the removal of sample-preparation steps and the possibility of analysing biological specimens in their natural state have drawn the attention of multiple groups across the world. Nevertheless, the lack of spatial resolution has been cited as one of the main limitations of AMSI. While significant research effort has presented hardware solutions for improving the resolution, software solutions are often overlooked, although they can usually be applied in a cost-effective manner after image acquisition. In this vein, we present two computational methods that we have developed to directly enhance the image resolution post-acquisition. Robust and quantitative resolution improvement is demonstrated for 12 cases of openly accessible datasets across laboratories around the globe. Using the same universally applicable Fourier imaging model, we discuss the possibility of true super-resolution by software for future studies. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Figure 1

17 pages, 2871 KiB

Open AccessArticle

Metabolically Active Zones Involving Fatty Acid Elongation Delineated by DESI-MSI Correlate with Pathological and Prognostic Features of Colorectal Cancer

by Martin Kaufmann, Natasha Iaboni, Amoon Jamzad, David Hurlbut, Kevin Yi Mi Ren, John F. Rudan, Parvin Mousavi, Gabor Fichtinger, Sonal Varma, Antonio Caycedo-Marulanda and Christopher J. B. Nicol

Metabolites 2023, 13(4), 508; https://doi.org/10.3390/metabo13040508 - 31 Mar 2023

Cited by 2 | Viewed by 2092

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer deaths. Despite recent advances, five-year survival rates remain largely unchanged. Desorption electrospray ionization mass spectrometry imaging (DESI) is an emerging nondestructive metabolomics-based method that retains the spatial orientation of small-molecule profiles on tissue [...] Read more.

Colorectal cancer (CRC) is the second leading cause of cancer deaths. Despite recent advances, five-year survival rates remain largely unchanged. Desorption electrospray ionization mass spectrometry imaging (DESI) is an emerging nondestructive metabolomics-based method that retains the spatial orientation of small-molecule profiles on tissue sections, which may be validated by ‘gold standard’ histopathology. In this study, CRC samples were analyzed by DESI from 10 patients undergoing surgery at Kingston Health Sciences Center. The spatial correlation of the mass spectral profiles was compared with histopathological annotations and prognostic biomarkers. Fresh frozen sections of representative colorectal cross sections and simulated endoscopic biopsy samples containing tumour and non-neoplastic mucosa for each patient were generated and analyzed by DESI in a blinded fashion. Sections were then hematoxylin and eosin (H and E) stained, annotated by two independent pathologists, and analyzed. Using PCA/LDA-based models, DESI profiles of the cross sections and biopsies achieved 97% and 75% accuracies in identifying the presence of adenocarcinoma, using leave-one-patient-out cross validation. Among the m/z ratios exhibiting the greatest differential abundance in adenocarcinoma were a series of eight long-chain or very-long-chain fatty acids, consistent with molecular and targeted metabolomics indicators of de novo lipogenesis in CRC tissue. Sample stratification based on the presence of lympovascular invasion (LVI), a poor CRC prognostic indicator, revealed the abundance of oxidized phospholipids, suggestive of pro-apoptotic mechanisms, was increased in LVI-negative compared to LVI-positive patients. This study provides evidence of the potential clinical utility of spatially-resolved DESI profiles to enhance the information available to clinicians for CRC diagnosis and prognosis. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Figure 1

5 pages, 3201 KiB

Open AccessArticle

Targeted Desorption Electrospray Ionization Mass Spectrometry Imaging for Drug Distribution, Toxicity, and Tissue Classification Studies

by Andreas Dannhorn, Maria Luisa Doria, James McKenzie, Paolo Inglese, John G. Swales, Gregory Hamm, Nicole Strittmatter, Gareth Maglennon, Sadaf Ghaem-Maghami, Richard J. A. Goodwin and Zoltan Takats

Metabolites 2023, 13(3), 377; https://doi.org/10.3390/metabo13030377 - 03 Mar 2023

Cited by 5 | Viewed by 2314

Abstract

With increased use of mass spectrometry imaging (MSI) in support of pharmaceutical research and development, there are opportunities to develop analytical pipelines that incorporate exploratory high-performance analysis with higher capacity and faster targeted MSI. Therefore, to enable faster MSI data acquisition we present [...] Read more.

With increased use of mass spectrometry imaging (MSI) in support of pharmaceutical research and development, there are opportunities to develop analytical pipelines that incorporate exploratory high-performance analysis with higher capacity and faster targeted MSI. Therefore, to enable faster MSI data acquisition we present analyte-targeted desorption electrospray ionization–mass spectrometry imaging (DESI-MSI) utilizing a triple-quadrupole (TQ) mass analyzer. The evaluated platform configuration provided superior sensitivity compared to a conventional time-of-flight (TOF) mass analyzer and thus holds the potential to generate data applicable to pharmaceutical research and development. The platform was successfully operated with sampling rates up to 10 scans/s, comparing positively to the 1 scan/s commonly used on comparable DESI-TOF setups. The higher scan rate enabled investigation of the desorption/ionization processes of endogenous lipid species such as phosphatidylcholines and a co-administered cassette of four orally dosed drugs—erlotininb, moxifloxacin, olanzapine, and terfenadine. This was used to enable understanding of the impact of the desorption/ionization processes in order to optimize the operational parameters, resulting in improved compound coverage for olanzapine and the main olanzapine metabolite, hydroxy-olanzapine, in brain tissue sections compared to DESI-TOF analysis or matrix-assisted laser desorption/ionization (MALDI) platforms. The approach allowed reducing the amount of recorded information, thus reducing the size of datasets from up to 150 GB per experiment down to several hundred MB. The improved performance was demonstrated in case studies investigating the suitability of this approach for mapping drug distribution, spatially resolved profiling of drug-induced nephrotoxicity, and molecular–histological tissue classification of ovarian tumors specimens. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Graphical abstract

18 pages, 7253 KiB

Open AccessArticle

Assessing the Effectiveness of Chemical Marker Extraction from Amazonian Plant Cupuassu (Theobroma grandiflorum) by PSI-HRMS/MS and LC-HRMS/MS

by Nerilson M. Lima, Gesiane S. Lima, Gabriel F. dos Santos, Gagan Preet, Lanaia I. L. Maciel, Teresinha de Jesus A. S. Andrade, Marcel Jaspars, Andrea R. Chaves and Boniek G. Vaz

Metabolites 2023, 13(3), 367; https://doi.org/10.3390/metabo13030367 - 01 Mar 2023

Cited by 1 | Viewed by 1775

Abstract

Employing a combination of liquid chromatography electrospray ionization and paper spray ionization high-resolution tandem mass spectrometry, extracts from cupuassu (Theobroma grandiflorum) pulp prepared with either water, methanol, acetonitrile or combinations thereof were subjected to metabolite fingerprinting. Among the tested extractors, 100% [...] Read more.

Employing a combination of liquid chromatography electrospray ionization and paper spray ionization high-resolution tandem mass spectrometry, extracts from cupuassu (Theobroma grandiflorum) pulp prepared with either water, methanol, acetonitrile or combinations thereof were subjected to metabolite fingerprinting. Among the tested extractors, 100% methanol extracted preferentially phenols and cinnamic acids derivatives, whereas acetonitrile and acetonitrile/methanol were more effective in extracting terpenoids and flavonoids, respectively. And while liquid chromatography- mass spectrometry detected twice as many metabolites as paper spray ionization tandem mass spectrometry, the latter proved its potential as a screening technique. Comprehensive structural annotation showed a high production of terpenes, mainly oleanane triterpene derivatives. of the mass spectra Further, five major metabolites with known antioxidant activity, namely catechin, citric acid, epigallocatechin-3′-glucuronide, 5,7,8-trihydroxyflavanone, and asiatic acid, were subjected to molecular docking analysis using the antioxidative enzyme peroxiredoxin 5 (PRDX5) as a model receptor. Based on its excellent docking score, a pharmacophore model of 5,7,8-trihydroxyflavanone was generated, which may help the design of new antioxidants. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Graphical abstract

14 pages, 6692 KiB

Open AccessArticle

A Multimodal Desorption Electrospray Ionisation Workflow Enabling Visualisation of Lipids and Biologically Relevant Elements in a Single Tissue Section

by Catia Costa, Janella De Jesus, Chelsea Nikula, Teresa Murta, Geoffrey W. Grime, Vladimir Palitsin, Véronique Dartois, Kaya Firat, Roger Webb, Josephine Bunch and Melanie J. Bailey

Metabolites 2023, 13(2), 262; https://doi.org/10.3390/metabo13020262 - 11 Feb 2023

Cited by 1 | Viewed by 1624

Abstract

The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative [...] Read more.

The colocation of elemental species with host biomolecules such as lipids and metabolites may shed new light on the dysregulation of metabolic pathways and how these affect disease pathogeneses. Alkali metals have been the subject of extensive research, are implicated in various neurodegenerative and infectious diseases and are known to disrupt lipid metabolism. Desorption electrospray ionisation (DESI) is a widely used approach for molecular imaging, but previous work has shown that DESI delocalises ions such as potassium (K) and chlorine (Cl), precluding the subsequent elemental analysis of the same section of tissue. The solvent typically used for the DESI electrospray is a combination of methanol and water. Here we show that a novel solvent system, (50:50 (%v/v) MeOH:EtOH) does not delocalise elemental species and thus enables elemental mapping to be performed on the same tissue section post-DESI. Benchmarking the MeOH:EtOH electrospray solvent against the widely used MeOH:H₂O electrospray solvent revealed that the MeOH:EtOH solvent yielded increased signal-to-noise ratios for selected lipids. The developed multimodal imaging workflow was applied to a lung tissue section containing a tuberculosis granuloma, showcasing its applicability to elementally rich samples displaying defined structural information. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Graphical abstract

15 pages, 7020 KiB

Open AccessArticle

In Vivo Low-Temperature Plasma Ionization Mass Spectrometry (LTP-MS) Reveals Regulation of 6-Pentyl-2H-Pyran-2-One (6-PP) as a Physiological Variable during Plant-Fungal Interaction

by Rosina Torres-Ortega, Héctor Guillén-Alonso, Raúl Alcalde-Vázquez, Enrique Ramírez-Chávez, Jorge Molina-Torres and Robert Winkler

Metabolites 2022, 12(12), 1231; https://doi.org/10.3390/metabo12121231 - 08 Dec 2022

Cited by 4 | Viewed by 1582

Abstract

Volatile organic compounds (VOCs) comprises a broad class of small molecules (up to ~300 g/mol) produced by biological and non-biological sources. VOCs play a vital role in an organism’s metabolism during its growth, defense, and reproduction. The well-known 6-pentyl-

α

-pyrone (6-PP) molecule [...] Read more.

Volatile organic compounds (VOCs) comprises a broad class of small molecules (up to ~300 g/mol) produced by biological and non-biological sources. VOCs play a vital role in an organism’s metabolism during its growth, defense, and reproduction. The well-known 6-pentyl-

α

-pyrone (6-PP) molecule is an example of a major volatile biosynthesized by Trichoderma atroviride that modulates the expression of PIN auxin-transport proteins in primary roots of Arabidopsis thaliana during their relationship. Their beneficial relation includes lateral root formation, defense induction, and increased plant biomass production. The role of 6-PP has been widely studied due to its relevance in this cross-kingdom relationship. Conventional VOCs measurements are often destructive; samples require further preparation, and the time resolution is low (around hours). Some techniques enable at-line or real-time analyses but are highly selective to defined compounds. Due to these technical constraints, it is difficult to acquire relevant information about the dynamics of VOCs in biological systems. Low-temperature plasma (LTP) ionization allows the analysis of a wide range of VOCs by mass spectrometry (MS). In addition, LTP-MS requires no sample preparation, is solvent-free, and enables the detection of 6-PP faster than conventional analytical methods. Applying static statistical methods such as Principal Component Analysis (PCA) and Discriminant Factorial Analysis (DFA) leads to a loss of information since the biological systems are dynamic. Thus, we applied a time series analysis to find patterns in the signal changes. Our results indicate that the 6-PP signal is constitutively emitted by T. atroviride only; the signal shows high skewness and kurtosis. In A. thaliana grown alone, no signal corresponding to 6-PP is detected above the white noise level. However, during T. atroviride-A. thaliana interaction, the signal performance showed reduced skewness and kurtosis with high autocorrelation. These results suggest that 6-PP is a physiological variable that promotes homeostasis during the plant-fungal relationship. Although the molecular mechanism of this cross-kingdom control is still unknown, our study indicates that 6-PP has to be regulated by A. thaliana during their interaction. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Figure 1

13 pages, 11136 KiB

Open AccessArticle

Harmonization of Rapid Evaporative Ionization Mass Spectrometry Workflows across Four Sites and Testing Using Reference Material and Local Food-Grade Meats

by Martin Kaufmann, Pierre-Maxence Vaysse, Adele Savage, Ala Amgheib, András Marton, Eftychios Manoli, Gabor Fichtinger, Steven D. Pringle, John F. Rudan, Ron M. A. Heeren, Zoltán Takáts, Júlia Balog and Tiffany Porta Siegel

Metabolites 2022, 12(11), 1130; https://doi.org/10.3390/metabo12111130 - 17 Nov 2022

Viewed by 1344

Abstract

Rapid evaporative ionization mass spectrometry (REIMS) is a direct tissue metabolic profiling technique used to accurately classify tissues using pre-built mass spectral databases. The reproducibility of the analytical equipment, methodology and tissue classification algorithms has yet to be evaluated over multiple sites, which [...] Read more.

Rapid evaporative ionization mass spectrometry (REIMS) is a direct tissue metabolic profiling technique used to accurately classify tissues using pre-built mass spectral databases. The reproducibility of the analytical equipment, methodology and tissue classification algorithms has yet to be evaluated over multiple sites, which is an essential step for developing this technique for future clinical applications. In this study, we harmonized REIMS methodology using single-source reference material across four sites with identical equipment: Imperial College London (UK); Waters Research Centre (Hungary); Maastricht University (The Netherlands); and Queen’s University (Canada). We observed that method harmonization resulted in reduced spectral variability across sites. Each site then analyzed four different types of locally-sourced food-grade animal tissue. Tissue recognition models were created at each site using multivariate statistical analysis based on the different metabolic profiles observed in the m/z range of 600–1000, and these models were tested against data obtained at the other sites. Cross-validation by site resulted in 100% correct classification of two reference tissues and 69–100% correct classification for food-grade meat samples. While we were able to successfully minimize between-site variability in REIMS signals, differences in animal tissue from local sources led to significant variability in the accuracy of an individual site’s model. Our results inform future multi-site REIMS studies applied to clinical samples and emphasize the importance of carefully-annotated samples that encompass sufficient population diversity. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Figure 1

14 pages, 11436 KiB

Open AccessArticle

Interrogating the Metabolomic Profile of Amyotrophic Lateral Sclerosis in the Post-Mortem Human Brain by Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry Imaging (MSI)

by Alexandria L. Sohn, Lingyan Ping, Jonathan D. Glass, Nicholas T. Seyfried, Emily C. Hector and David C. Muddiman

Metabolites 2022, 12(11), 1096; https://doi.org/10.3390/metabo12111096 - 10 Nov 2022

Cited by 3 | Viewed by 1719

Abstract

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS [...] Read more.

Amyotrophic lateral sclerosis (ALS) is an idiopathic, fatal neurodegenerative disease characterized by progressive loss of motor function with an average survival time of 2–5 years after diagnosis. Due to the lack of signature biomarkers and heterogenous disease phenotypes, a definitive diagnosis of ALS can be challenging. Comprehensive investigation of this disease is imperative to discovering unique features to expedite the diagnostic process and improve diagnostic accuracy. Here, we present untargeted metabolomics by mass spectrometry imaging (MSI) for comparing sporadic ALS (sALS) and C9orf72 positive (C9Pos) post-mortem frontal cortex human brain tissues against a control cohort. The spatial distribution and relative abundance of metabolites were measured by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI for association to biological pathways. Proteomic studies on the same patients were completed via LC-MS/MS in a previous study, and results were integrated with imaging metabolomics results to enhance the breadth of molecular coverage. Utilizing METASPACE annotation platform and MSiPeakfinder, nearly 300 metabolites were identified across the sixteen samples, where 25 were identified as dysregulated between disease cohorts. The dysregulated metabolites were further examined for their relevance to alanine, aspartate, and glutamate metabolism, glutathione metabolism, and arginine and proline metabolism. The dysregulated pathways discussed are consistent with reports from other ALS studies. To our knowledge, this work is the first of its kind, reporting on the investigation of ALS post-mortem human brain tissue analyzed by multiomic MSI. Full article

(This article belongs to the Special Issue Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Advances in Ambient Ionization Techniques for Mass Spectrometry Volume 2

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI