Inhibition of intracellular versus extracellular cathepsin D differentially alters the liver lipidome of mice with metabolic dysfunction-associated steatohepatitis.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) progressing to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatic inflammation, has significantly increased in recent years due to unhealthy dietary practices and sedentary lifestyles. Cathepsin D (CTSD), a lysosomal protease involved in lipid homeostasis, is linked to abnormal lipid metabolism and inflammation in MASH. Although primarily intracellular, CTSD can be secreted extracellularly.

Inflammation-associated intramyocellular lipid alterations in human pancreatic cancer cachexia.

Background: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia.

Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation.

Background: The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation.

State-of-the-art mass spectrometry imaging applications in biomedical research.

Mass spectrometry imaging has advanced from a niche technique to a widely applied spatial biology tool operating at the forefront of numerous fields, most notably making a significant impact in biomedical pharmacological research. The growth of the field has gone hand in hand with an increase in publications and usage of the technique by new laboratories, and consequently this has led to a shift from general MSI reviews to topic-specific reviews. Given this development, we see the need to recapitulate the strengths of MSI by providing a more holistic overview of state-of-the-art MSI studies to provide the new generation of researchers with an up-to-date reference framework.

Tumor ratio of unsaturated to saturated sulfatide species is associated with disease-free survival in intrahepatic cholangiocarcinoma.

Purpose: Cholangiocarcinoma (CCA) is a malignancy arising from the bile duct epithelium and has a poor outcome. Sulfatides are lipid components of lipid rafts, and are implicated in several cancer types. In the liver, sulfatides are specifically present in the bile ducts.

Integrating multiplex immunofluorescent and mass spectrometry imaging to map myeloid heterogeneity in its metabolic and cellular context.

Cells often adopt different phenotypes, dictated by tissue-specific or local signals such as cell-cell and cell-matrix contacts or molecular micro-environment. This holds in extremis for macrophages with their high phenotypic plasticity. Their broad range of functions, some even opposing, reflects their heterogeneity, and a multitude of subsets has been described in different tissues and diseases.

An optimized MALDI MSI protocol for spatial detection of tryptic peptides in fresh frozen prostate tissue.

MALDI MS imaging (MSI) is a powerful analytical tool for spatial peptide detection in heterogeneous tissues. Proper sample preparation is crucial to achieve high quality, reproducible measurements. Here we developed an optimized protocol for spatially resolved proteolytic peptide detection with MALDI time-of-flight MSI of fresh frozen prostate tissue sections.

An overview of image registration for aligning mass spectrometry imaging with clinically relevant imaging modalities.

Mass spectrometry imaging (MSI) is used in many aspects of clinical research, including pharmacokinetics, toxicology, personalised medicine, and surgical decision-making. Maximising its potential requires the spatial integration of MSI images with imaging data from existing clinical imaging modalities, such as histology and MRI. To ensure that the information is properly integrated, all contributing images must be accurately aligned.

Combined Quantitative (Phospho)proteomics and Mass Spectrometry Imaging Reveal Temporal and Spatial Protein Changes in Human Intestinal Ischemia-Reperfusion.

Intestinal ischemia-reperfusion (IR) injury is a severe clinical condition, and unraveling its pathophysiology is crucial to improve therapeutic strategies and reduce the high morbidity and mortality rates. Here, we studied the dynamic proteome and phosphoproteome in the human intestine during ischemia and reperfusion, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to gain quantitative information of thousands of proteins and phosphorylation sites, as well as mass spectrometry imaging (MSI) to obtain spatial information. We identified a significant decrease in abundance of proteins related to intestinal absorption, microvillus, and cell junction, whereas proteins involved in innate immunity, in particular the complement cascade, and extracellular matrix organization increased in abundance after IR.

Examination of lipid profiles in abdominal fascial healing using MALDI-TOF to identify potential therapeutic targets.

Background: Failure of fascial healing in the abdominal wall can result in incisional hernia, which is one of the most common complications after laparotomy. Understanding the molecular healing process of abdominal fascia may provide lipid markers of incisional hernia or therapeutic targets that allow prevention or treatment of incisional hernias.

Purpose: This study aims to investigate temporal and in situ changes of lipids during the normal healing process of abdominal fascia in the first postoperative week.

Metabolic tumor constitution is superior to tumor regression grading for evaluating response to neoadjuvant therapy of esophageal adenocarcinoma patients.

The response to neoadjuvant therapy can vary widely between individual patients. Histopathological tumor regression grading (TRG) is a strong factor for treatment response and survival prognosis of esophageal adenocarcinoma (EAC) patients following neoadjuvant treatment and surgery. However, TRG systems are usually based on the estimation of residual tumor but do not consider stromal or metabolic changes after treatment.

Machine learning for grading and prognosis of esophageal dysplasia using mass spectrometry and histological imaging.

Background: Barrett's esophagus (BE) is a precursor lesion of esophageal adenocarcinoma and may progress from non-dysplastic through low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and cancer. Grading BE is of crucial prognostic value and is currently based on the subjective evaluation of biopsies. This study aims to investigate the potential of machine learning (ML) using spatially resolved molecular data from mass spectrometry imaging (MSI) and histological data from microscopic hematoxylin and eosin (H&E)-stained imaging for computer-aided diagnosis and prognosis of BE.

Mass spectrometry imaging of L-[ring-C]-labeled phenylalanine and tyrosine kinetics in non-small cell lung carcinoma.

Background: Metabolic reprogramming is a common phenomenon in tumorigenesis and tumor progression. Amino acids are important mediators in cancer metabolism, and their kinetics in tumor tissue are far from being understood completely. Mass spectrometry imaging is capable to spatiotemporally trace important endogenous metabolites in biological tissue specimens.

Batch Effects in MALDI Mass Spectrometry Imaging.

Mass spectrometry imaging (MSI) has become an indispensible tool for spatially resolved molecular investigation of tissues. One of the key application areas is biomedical research, where matrix-assisted laser desorption/ionization (MALDI) MSI is predominantly used due to its high-throughput capability, flexibility in the molecular class to investigate, and ability to achieve single cell spatial resolution. While many of the initial technical challenges have now been resolved, so-called batch effects, a phenomenon already known from other omics fields, appear to significantly impede reliable comparison of data from particular midsized studies typically performed in translational clinical research.

Spatial differentiation of metabolism in prostate cancer tissue by MALDI-TOF MSI.

Background: Prostate cancer tissues are inherently heterogeneous, which presents a challenge for metabolic profiling using traditional bulk analysis methods that produce an averaged profile. The aim of this study was therefore to spatially detect metabolites and lipids on prostate tissue sections by using mass spectrometry imaging (MSI), a method that facilitates molecular imaging of heterogeneous tissue sections, which can subsequently be related to the histology of the same section.

Methods: Here, we simultaneously obtained metabolic and lipidomic profiles in different prostate tissue types using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI.

Multilabel Per-Pixel Quantitation in Mass Spectrometry Imaging.

In quantitative mass spectrometry imaging (MSI), the gold standard adds a single structural homologue of the target compound at a known concentration to the sample. This internal standard enables to map the detected intensity of the target molecule against an external calibration curve. This approach, however, ignores local noise levels and disproportional ion suppression effects, which might depend on the concentration of the target compound.

Atheroma-Specific Lipids in and Mice Using 2D and 3D Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Atherosclerosis is the major contributor to cardiovascular diseases. It is a spatially and temporally complex inflammatory disease, in which intravascular accumulation of a plethora of lipids is considered to play a crucial role. To date, both the composition and local distribution of the involved lipids have not been thoroughly mapped yet.

MS Imaging-Guided Microproteomics for Spatial Omics on a Single Instrument.

Mass spectrometry imaging (MSI) allows investigating the spatial distribution of chemical compounds directly in biological tissues. As the analytical depth of MSI is limited, MSI needs to be coupled to more sensitive local extraction-based omics approaches to achieve a comprehensive molecular characterization. For this, it is important to retain the spatial information provided by MSI for follow-up omics studies.

Morphometric Cell Classification for Single-Cell MALDI-Mass Spectrometry Imaging.

The large-scale and label-free molecular characterization of single cells in their natural tissue habitat remains a major challenge in molecular biology. We present a method that integrates morphometric image analysis to delineate and classify individual cells with their single-cell-specific molecular profiles. This approach provides a new means to study spatial biological processes such as cancer field effects and the relationship between morphometric and molecular features.

Simultaneous Detection of Zinc and Its Pathway Metabolites Using MALDI MS Imaging of Prostate Tissue.

Levels of zinc, along with its mechanistically related metabolites citrate and aspartate, are widely reported as reduced in prostate cancer compared to healthy tissue and are therefore pointed out as potential cancer biomarkers. Previously, it has only been possible to analyze zinc and metabolites by separate detection methods. Through matrix-assisted laser desorption/ionization mass spectrometry imaging (MSI), we were for the first time able to demonstrate, in two different sample sets ( = 45 and = 4), the simultaneous spatial detection of zinc, in the form of ZnCl, together with citrate, aspartate, and -acetylaspartate on human prostate cancer tissues.

Cellular resolution in clinical MALDI mass spectrometry imaging: the latest advancements and current challenges.

Mass spectrometry (MS) is the workhorse of metabolomics, proteomics and lipidomics. Mass spectrometry imaging (MSI), its extension to spatially resolved analysis of tissues, is a powerful tool for visualizing molecular information within the histological context of tissue. This review summarizes recent developments in MSI and highlights current challenges that remain to achieve molecular imaging at the cellular level of clinical specimens.

Precise co-registration of mass spectrometry imaging, histology, and laser microdissection-based omics.

Mass spectrometry imaging (MSI) is an analytical technique for the unlabeled and multiplex imaging of molecules in biological tissue sections. It therefore enables the spatial and molecular annotations of tissues complementary to histology. It has already been shown that MSI can guide subsequent material isolation technologies such as laser microdissection (LMD) to enable a more in-depth molecular characterization of MSI-highlighted tissue regions.

Integrative Clustering in Mass Spectrometry Imaging for Enhanced Patient Stratification.

Scope: In biomedical research, mass spectrometry imaging (MSI) can obtain spatially-resolved molecular information from tissue sections. Especially matrix-assisted laser desorption/ionization (MALDI) MSI offers, depending on the type of matrix, the detection of a broad variety of molecules ranging from metabolites to proteins, thereby facilitating the collection of multilevel molecular data. Lately, integrative clustering techniques have been developed that make use of the complementary information of multilevel molecular data in order to better stratify patient cohorts, but which have not yet been applied in the field of MSI.

Round robin study of formalin-fixed paraffin-embedded tissues in mass spectrometry imaging.

Mass spectrometry imaging (MSI) has provided many results with translational character, which still have to be proven robust in large patient cohorts and across different centers. Although formalin-fixed paraffin-embedded (FFPE) specimens are most common in clinical practice, no MSI multicenter study has been reported for FFPE samples. Here, we report the results of the first round robin MSI study on FFPE tissues with the goal to investigate the consequences of inter- and intracenter technical variation on masking biological effects.