Ron M A Heeren

Maastricht University | UM · M4I, The Maastricht MultiModal Molecular Imaging institute

Background The differential diagnosis of Rheumatoid Arthritis (RA) and Psoriatic arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical biomarkers. Molecular alterations have been suggested to contribute to the pathophysiological processes in the knee joint, and it is known that chronic infl...

Radical resection for patients with oral cavity cancer remains challenging. Rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical vapors has been reported for real-time classification of normal and tumor tissues for numerous surgical applications. However, the infiltrative pattern of invasion of oral squamous cell carcinomas (OS...

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular fatty acids (FA) and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hithe...

Human cells produce thousands of lipids that change during cell differentiation and can vary across individual cells of the same type. However, we are only starting to characterize the function of these cell-to-cell differences in lipid composition. Here, we measured the lipidomes and transcriptomes of individual human dermal fibroblasts by couplin...

Celecoxib, a non-steroidal anti-inflammatory drug and selective cyclooxygenase-II inhibitor, is used to reduce pain and inflammation in knee osteoarthritis patients. However, its potential protective effect on cartilage degeneration is disputed. In this study, we aimed to investigate the chondroprotective effect of celecoxib on cartilage-secreted m...

The molecular pathology of breast cancer is challenging due to the complex heterogeneity of cellular subtypes. The ability to directly identify and visualize cell subtype distribution at the single-cell level within a tissue section enables precise and rapid diagnosis and prognosis. Here, we applied mass spectrometry imaging (MSI) to acquire and vi...

In addition to individual imaging techniques, the combination and integration of several imaging techniques, so-called multimodal imaging, can provide large amounts of anatomical, functional, and molecular information accelerating drug discovery and development processes. Imaging technologies aid in understanding the disease mechanism, finding new...

Introduction The main goal of brain tumour surgery is to maximize tumour resection while avoiding neurological deficits. Accurate characterization of tissue and delineation of resection margins are, therefore, essential to achieve optimal surgical results. Objectives The primary objective of this study was to develop and validate a mass spectromet...

Human hair absorbs numerous biomolecules from the body during its growth. This can act as a fingerprint to determine substance intake of an individual, which can be useful in forensic studies. The cocaine concentration profile along the growth axis of hair indicates the time evolution of the metabolic incorporation of cocaine usage. It could be eit...

Background: Fracture healing is a complex process, involving cell-cell interactions, various cytokines, and growth factors. Although fracture treatment improved over the last decades, a substantial part of all fractures shows delayed or absent healing. The fracture hematoma (fxh) is known to have a relevant role in this process, while the exact mec...

Time‐of‐flight (TOF) systems are one of the most widely used mass analyzers in native mass spectrometry (nMS) for the analysis of non‐covalent multiply charged bio‐macromolecular assemblies (MMAs). Typically, microchannel plates (MCPs) are employed for high mass native ion detection in TOF MS. MCPs are well known for their reduced detection efficie...

Organoid culture systems are self-renewing, three-dimensional (3D) models derived from pluripotent stem cells, adult derived stem cells or cancer cells that recapitulate key molecular and structural characteristics of their tissue of origin. They generally form into hollow structures with apical–basolateral polarization. Mass spectrometry imaging (...

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 tiss...

The analysis of samples with large height variations remains a challenge for mass spectrometry imaging (MSI), despite many technological advantages. Ambient sampling and ionization MS techniques allow for the molecular analysis of sample surfaces with height variations, but most techniques lack MSI capabilities. We developed a 3D MS scanner for the...

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-t...

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...

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...

Infectious diseases, including those of viral, bacterial, fungal, and parasitic origin are often characterized by focal inflammation occurring in one or more distinct tissues. Tissue-specific outcomes of infection are also evident in many infectious diseases, suggesting that the local microenvironment may instruct complex and diverse innate and ada...

Prostate cancer is the fourth most common cancer worldwide with definitive diagnosis reliant on biopsy and human-graded histopathology. As with other pathologies, grading based on classical haematoxylin and eosin (H&E) staining of formalin fixed paraffin-embedded material can be prone to variation between pathologists, prompting investigation of bi...

Introduction: Knee osteoarthritis (OA) is a joint disease, affecting multiple tissues in the joint. Early detection and intervention may delay OA development and avoid total knee arthroplasty. Specific biomarker profiles for early detection and guiding clinical decision-making of OA have not yet been identified. One technique that can contribute to...

Mass spectrometry imaging (MSI) of lipids within tissues has significant potential for both biomolecular discovery and histopathological applications. Conventional MSI technologies are, however, challenged by the prevalence of phospholipid regioisomers that differ only in the location(s) of carbon-carbon double bonds and/or the relative position of...

Introduction In addition to the well-known cartilage extracellular matrix-related expression of Sox9, we demonstrated that chondrogenic differentiation of progenitor cells is driven by a sharply defined bi-phasic expression of Sox9: an immediate early and a late (extracellular matrix associated) phase expression. In this study, we aimed to determin...

Background Failure of fascial healing in the abdominal wall can result in incisional hernia, one of the most common complications occurring in 13% of patients after a laparotomy at two years. Revealing the molecular healing process of abdominal fascia may provide lipid markers of incisional hernia or therapeutic targets that allow prevention or tre...

Osteoarthritis (OA) is a multifactorial pathology and comprises a wide range of distinct phenotypes. In this context, the characterization of the different molecular profiles associated with each phenotype can improve the classification of OA. In particular, OA can coexist with type 2 diabetes mellitus (T2DM). This study investigates lipidomic and...

Lead halide perovskites are among the most exciting classes of optoelectronic materials due to their unique ability to form high‐quality crystals with tunable bandgaps in the visible and near‐infrared using simple solution precipitation reactions. This facile crystallization is driven by their ionic nature; just as with other salts, it is challengi...

We present a novel probe design for ambient laser-based mass spectrometry imaging combining electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) in a single probe, compatible with a commercial laser ablation electrospray ionization (LAESI) instrument. Here we describe the probe design considerations and features, as wel...

Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools...

Human cells produce thousands of lipids that impact a wide range of biological processes in ways we are only starting to characterize. The cellular composition in lipids changes during differentiation events and also varies across individual cells of the same type. Yet, the precise differences in lipid composition that directly affect cell phenotyp...

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 investig...

Canonical fatty acid metabolism describes specific enzyme-substrate interactions that result in products with well-defined chain lengths, degree(s), and positions of unsaturation. Deep profiling of lipids across a range of prostate cancer cell lines reveals a variety of fatty acids with unusual site(s) of unsaturation that are not described by cano...

Objective Synovial inflammation is one of the most characteristic events in different types of arthritis, including Osteoarthritis (OA). Emerging evidence also suggests the involvement of lipids in the regulation of inflammatory processes. The aim of this study was to elucidate the heterogeneity and spatial distribution of lipids in the OA synovial...

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 th...

Real-time tissue classifiers based on molecular patterns are emerging tools for fast tumor diagnosis. Here, we used rapid evaporative ionization mass spectrometry (REIMS) and multivariate statistical analysis (principal component analysis–linear discriminant analysis) to classify tissues with subsequent comparison to gold standard histopathology. W...

Local delivery to the lower gut to treat diseases of the colon has become a topic of special attention. Tissue exposure of locally acting agents is not represented by plasma concentrations. Therefore, reliable methods to measure tissue uptake at the primary site of action (e.g., epithelial layer or lamina propria) are vital. This work investigates...

Intestinal ischemia-reperfusion (IR) injury is associated with high mortality rates, which have not improved in the past decades despite advanced insight in its pathophysiology using in vivo animal and human models. The inability to translate previous findings to effective therapies emphasizes the need for a physiologically relevant in vitro model...

Mass spectrometry imaging (MSI) combines molecular and spatial information in a valuable tool for a wide range of applications. Matrix‐assisted laser desorption/ionization (MALDI) is at the forefront of MSI ionization due to its wide availability and increasing improvement in spatial resolution and analysis speed. However, ionization suppression, l...

Mass spectrometry imaging (MSI) visualises molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labelling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many...

Native mass spectrometry (native MS) has emerged as a powerful technique to study the structure and stoichiometry of large protein complexes. Traditionally, native MS has been performed on modified time-of-flight (TOF) systems combined with detectors that do not provide information on the arrival coordinates of each ion at the detector. In this stu...

Mass spectrometry imaging (MSI) can analyze the spatial distribution of hundreds of different molecules directly from tissue sections usually placed on conductive glass slides to provide conductivity on the sample surface. Additional experiments are often required for molecular identification using consecutive sections on membrane slides compatible...

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 disprop...

The Cover Feature shows a single laser ablation electrospray ionisation event for mass spectrometric analysis of protein complexes. The infrared laser ejects intact protein complexes containing droplets from a sample surface, to interact with an orthogonal nebula of charged electrospray droplets. These charges are transferred to the protein complex...

Achieving radical tumor resection while preserving disease-free tissue during breast-conserving surgery (BCS) remains a challenge. Here, mass spectrometry technologies were used to discriminate stromal tissues reported to be altered surrounding breast tumors, and build tissue classifiers ex vivo. Additionally, we employed the approach for in vivo a...

We present a novel method enabling the infrared laser desorption and electrospray ionisation (ESI) of protein complexes in their native state. Using this method, we demonstrate the surprising generation of intact, multiply charged ions of myoglobin, non‐covalent haemoglobin complex and intact immunoglobulin G antibody in their native state. The obs...

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging provides molecular speciation at the micrometer scale, while the penetration depth of the primary ion beam is limited to the top-layers of a sample. These combined properties make TOF-SIMS potentially an ideal technique to study oil–gas interfaces. TOF-SIMS spectra of three crude oil...

Mass spectrometry imaging (MSI) visualises molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labelling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many...

Mass spectrometry imaging (MSI) enables the visualization of molecular distributions on complex surfaces. It has been extensively used in the field of biomedical research to investigate healthy and diseased tissues. Most of the MSI studies are conducted in a 2D fashion where only a single slice of the full sample volume is investigated. However, bi...

Rationale: Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is routinely employed to monitor the distribution of compounds in tissue sections and generate 2D images. Whilst informative the images do not represent the distribution of the analyte of interest through the entire organ. The generation of 3D images is an...

In the past decades, matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has been applied to a broad range of biological samples, e.g., forensics and preclinical samples. The use of MALDI-MSI for the analysis of bone tissue has been limited due to the insulating properties of the material but more importantly the absen...

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...

In the last decade, Matrix Assisted Laser Desorption Ionisation Mass Spectrometry (MALDI MS) has proven to be a valuable analytical tool in forensic research as it can detect and map molecular information of forensic relevance in trace evidence such as fingermarks and hair. The first published proof of concept demonstrating that it was possible to...

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. Matrix-...

Understanding how cells regulate their bioenergetic demands, adjust to the microenvironment, or respond to stimuli is the aim of molecular biology. Yet, methods able to describe the molecular content, histological identity, and spatial context of a single cell do not exist. The presented method integrates morphometric image analysis to delineate an...

The large‐scale and unlabeled molecular characterization of single cells inside 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 new means t...

Fast, accurate and sensitive detection of drugs in human tissue is of crucial importance in an investigation of a suspicious death. Here, we aimed to screen cocaine, diazepam, methadone and morphine in post-mortem muscle samples without sample preparation and in quasi-real time using rapid evaporative ionisation mass spectrometry (REIMS). REIMS ena...

Fatty acid (FA) modifications, such as enzymatic desaturation and elongation, have long been thought to involve sequential and highly specific enzyme-substrate interactions, which result in canonical products that are well-defined in their chain lengths, degree of unsaturation and double bond positions. These products act as a supply of building bl...

Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a scree...

Background Osteoarthritis (OA) is mainly characterized by the progressive deterioration of articular cartilage. Recent studies support that type 2 diabetes (TD2) is a risk factor to develop OA [1, 2]. However, the molecular cartilage profile of patients combining these two diseases remains unclear, and a better understanding of the different OA phe...