MALDI Imaging Research Articles

A Streamlined Workflow for Microscopy-Driven MALDI Imaging Mass Spectrometry Data Collection.

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a rapidly advancing technology for biomedical research. As spatial resolution increases, however, so do acquisition time, file size, and experimental cost, which increases the need to perform precise sampling of targeted tissue regions to optimize the biological information gleaned from an experiment and minimize wasted resources. The ability to define instrument measurement regions based on key tissue features and automatically sample these specific regions of interest (ROIs) addresses this challenge. Herein, we demonstrate a workflow using standard software that allows for direct sampling of microscopy-defined regions by MALDI IMS. Three case studies are included, highlighting different methods for defining features from common sample types─manual annotation of vasculature in human brain tissue, automated segmentation of renal functional tissue units across whole slide images using custom segmentation algorithms, and automated segmentation of dispersed HeLa cells using open-source software. Each case minimizes data acquisition from unnecessary sample regions and dramatically increases throughput while uncovering molecular heterogeneity within targeted ROIs. This workflow provides an approachable method for spatially targeted MALDI IMS driven by microscopy as part of multimodal molecular imaging studies.

Membrane-based preparation for mass spectrometry imaging of cultures of bacteria.

The study of the dialogue between microorganisms at the molecular level is becoming essential to understand their relationship (antagonist, neutral, or beneficial interactions) and its impact on the organization of the microbial community. Mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) is a technique that reveals the spatial distribution of molecules on a sample surface that may be involved in interactions between organisms. An experimental limitation to perform MALDI MSI is a flat sample surface, which in many cases could not be achieved for bacterial colonies such as filamentous bacteria (e.g., Streptomyces). In addition, sample heterogeneity affects sample dryness and MALDI matrix deposition prior to MSI. To avoid such problems, we introduce an additional step in the sample preparation. A polymeric membrane is interposed between the microorganisms and the agar-based culture medium, allowing the removal of bacterial colonies prior to MSI of the homogeneous culture medium. A proof of concept was evaluated on Streptomyces ambofaciens (a soil bacterium) cultures on solid media. As the mycelium was removed at the same time as the polymeric membrane, the metabolites released into the medium were spatially resolved by MALDI MSI. In addition, extraction of the recovered mycelium from the membrane confirmed the identification of the metabolites by ESI MS/MS analysis. This approach allows both the spatial distribution of metabolites produced by microorganisms in an agar medium to be studied under well-controlled sample preparation and their structure to be elucidated. This capability is illustrated using desferrioxamine E, a siderophore produced by S. ambofaciens.

Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids.

Recent research linking choline-containing lipids to degeneration of basal forebrain cholinergic neurons in neuropathological states illustrates the challenge of balancing lipid integrity with optimal acetylcholine levels, essential for memory preservation. The endocannabinoid system influences learning and memory processes regulated by cholinergic neurotransmission. Therefore, we hypothesised that activation of the endocannabinoid system may confer neuroprotection against cholinergic degeneration. We examined the neuroprotective potential of sub-chronic treatments with the cannabinoid agonist WIN55,212-2, using ex vivo organotypic tissue cultures including nucleus basalis magnocellularis and cortex and in vivo rat models of specific cholinergic damage induced by 192IgG-saporin. Levels of lipids, choline and acetylcholine were measured with histochemical and immunofluorescence assays, along with [35S]GTPγS autoradiography of cannabinoid and muscarinic GPCRs and MALDI-mass spectrometry imaging analysis. Learning and memory were assessed by the Barnes maze and the novel object recognition test in rats and in the 3xTg-AD mouse model. Degeneration, induced by 192IgG-saporin, of baso-cortical cholinergic pathways resulted in memory deficits and decreased cortical levels of lysophosphatidylcholines (LPC). WIN55,212-2 restored cortical cholinergic transmission and LPC levels via activation of cannabinoid receptors. This activation altered cortical lipid homeostasis mainly by reducing sphingomyelins in lesioned animals. These modifications were crucial for memory recovery. We hypothesise that WIN55,212-2 facilitates an alternative choline source by breaking down sphingomyelins, leading to elevated cortical acetylcholine levels and LPCs. These results imply that altering choline-containing lipids via activation of cannabinoid receptors presents a promising therapeutic approach for dementia linked to cholinergic dysfunction.

Spatially heterogeneous lipid dysregulation in tuberculous meningitis

Tuberculous (TB) meningitis is the deadliest form of extrapulmonary TB which disproportionately affects children and immunocompromised individuals. Studies in pulmonary TB have shown that Mycobacterium tuberculosis can alter host lipid metabolism to evade the immune system. Cholesterol lowering drugs (i.e., statins) reduce the risk of infection, making them a promising host-directed therapy in pulmonary TB. However, the effect of M. tuberculosis infection on the young or adult brain lipidome has not been studied. The brain is the second-most lipid-rich organ, after adipose tissue, with a temporally and spatially heterogeneous lipidome that changes from infancy to adulthood. The young, developing brain in children may be uniquely vulnerable to alterations in lipid composition and homeostasis, as perturbations in cholesterol metabolism can cause developmental disorders leading to intellectual disabilities. To begin to understand the alterations to the brain lipidome in pediatric TB meningitis, we utilized our previously published young rabbit model of TB meningitis and applied mass spectrometry (MS) techniques to elucidate spatial differences. We used matrix assisted laser desorption/ionization-MS imaging (MALDI-MSI) and complemented it with region-specific liquid chromatography (LC)-MS/MS developed to identify and quantify sterols and oxysterols difficult to identify by MALDI MSI. MALDI-MSI revealed several sphingolipids, glycerolipids and glycerophospholipids that were downregulated in brain lesions. LC-MS/MS revealed the downregulation of cholesterol, several sterol intermediates along the cholesterol biosynthesis pathway and enzymatically produced oxysterols as a direct result of M. tuberculosis infection. However, oxysterols produced by oxidative stress were increased in brain lesions. Together, these results demonstrate significant spatially regulated brain lipidome dysregulation in pediatric TB meningitis.

Methodological aspects of correlative, multimodal, multiparametric breast cancer imaging: from data acquisition to image processing for AI-based radioproteomics in a preclinical setting

Preclinical high-field magnetic resonance imaging (MRI) systems offer a diverse array of MRI techniques, providing rich multiparametric MRI (mpMRI) platforms for studying numerous biological parameters. mpMRI platforms prove particularly indispensable when investigating tumors that exhibit profound intratumoral heterogeneity, such as breast cancer. A thoughtful comprehension of the origins of intratumoral heterogeneity is imperative for the judicious assessment of new targeted therapies and treatment interventions. Furthermore, when data from mpMRI are complemented with data from other in vivo imaging modalities, such as positron emission tomography (PET), and correlated with data from ex vivo modalities, such as matrix-assisted laser desorption imaging mass spectrometry (MALDI IMS), the in vivo parameters can be further elucidated at a molecular level and microscopic scale. Nevertheless, extracting meaningful scientific insights from such complex datasets necessitates the utilization of machine learning (ML) approaches to discern region-specific radiomic features. The development of correlative, multimodal imaging (CMI) workflows, such as one incorporating MRI, PET and MALDI IMS, is inherently challenging, given the many technological and methodological challenges related to multimodal data acquisition as well as the physiological limitations of the laboratory mice of the investigation. Standardization efforts in image acquisition and processing are required to increase the reproducibility and translatability of CMI data. To address the challenges of developing standardized CMI workflows and stimulate dialog regarding this area of need, we present a practical workflow to investigate tumor heterogeneity in breast cancer xenografts across various spatial scales. Our workflow entails simultaneous functional MRI and PET acquisitions in living mice, followed by correlation with post-imaging MALDI IMS and histologic data. Additionally, we propose data preprocessing steps for potential ML applications. We illustrate the feasibility of this workflow through two examples, showcasing its effectiveness in comparing in vivo and ex vivo images to evaluate tumor metabolism and hypoxia in mice with breast cancer xenografts.

MALDI MSI Protocol for Spatial Bottom-Up Proteomics at Single-Cell Resolution.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) started with spatial mapping of peptides and proteins. Since then, numerous bottom-up protocols have been developed. However, achievable spatial resolution and sample preparation with many wet steps hindered the development of single cell-level workflows for bottom-up spatial proteomics. This study presents a protocol optimized for MALDI-MSI measurements of single cells within the context of their 2D culture. Sublimation of CHCA, followed by a dip in ice-cold ammonium phosphate monobasic (AmP), produced peptide-rich mass spectra while maintaining matrix crystal sizes around 400 nm. This enables MALDI-MSI imaging of proteins in single cells grown on an ITO slide with a throughput of approximately 7800 cells per day. 89 peptide-like features corresponding to a single MDA-MB-231 breast cancer cell were detected. Furthermore, by combining the MALDI-MSI data with LC-MS/MS data obtained on cell pellets, we have successfully identified 24 peptides corresponding to 17 proteins, including actin, vimentin, and transgelin-2.

Single-colony MALDI mass spectrometry imaging reveals spatial differences in metabolite abundance between natural and cultured Trichodesmium morphotypes.

Trichodesmium, a globally significant N2-fixing marine cyanobacterium, forms extensive surface blooms in nutrient-poor ocean regions. These blooms consist of a dynamic assemblage of Trichodesmium species that form distinct colony morphotypes and are inhabited by diverse microorganisms. Trichodesmium colony morphotypes vary in ecological niche, nutrient uptake, and organic molecule release, differentially impacting ocean carbon and nitrogen biogeochemical cycles. Here, we assessed the poorly studied spatial abundance of metabolites within and between three morphologically distinct Trichodesmium colonies collected from the Red Sea. We also compared these results with two morphotypes of the cultivable Trichodesmium strain IMS101. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) coupled with liquid extraction surface analysis (LESA) tandem mass spectrometry (MS2), we identified and localized a wide range of small metabolites associated with single-colony Trichodesmium morphotypes. Our untargeted MALDI-MSI approach revealed 80 unique features (metabolites) shared between Trichodesmium morphotypes. Discrimination analysis showed spatial variations in 57 shared metabolites, accounting for 62% of the observed variation between morphotypes. The greatest variations in metabolite abundance were observed between the cultured morphotypes compared to the natural colony morphotypes, suggesting substantial differences in metabolite production between the cultivable strain IMS101 and the naturally occurring colony morphotypes that the cultivable strain is meant to represent. This study highlights the variations in metabolite abundance between natural and cultured Trichodesmium morphotypes and provides valuable insights into metabolites common to morphologically distinct Trichodesmium colonies, offering a foundation for future targeted metabolomic investigations.IMPORTANCEThis work demonstrates that the application of spatial mass spectrometry imaging at single-colony resolution can successfully resolve metabolite differences between natural and cultured Trichodesmium morphotypes, shedding light on their distinct biochemical profiles. Understanding the morphological differences between Trichodesmium colonies is crucial because they impact nutrient uptake, organic molecule production, and carbon and nitrogen export, and subsequently influence ocean biogeochemical cycles. As such, our study serves as an important initial assessment of metabolite differences between distinct Trichodesmium colony types, identifying features that can serve as ideal candidates for future targeted metabolomic studies.

Exploring the medicinal potential of Dendrobium: Uncovering the spatial distribution of flavonoids and alkaloids in 15 species of Dendrobium using MALDI-MSI

Dendrobium, the second largest genus in the Orchidaceae family, has been regarded as a valuable medicinal plant throughout Chinese history. Secondary metabolites present in the stem of Dendrobium, including alkaloids and flavonoids, confer significant pharmacological effects such as anti-inflammatory, antibacterial, immunomodulatory, antitumor, and antioxidant properties. To our knowledge, this study is the first to apply matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology to comprehensively identify the spatial distribution of secondary metabolites, particularly flavonoids and alkaloids, in the mature stems of 15 common Dendrobium species. By analyzing the matching scores and relative concentrations of compounds, 20 flavonoids and 19 alkaloids with high identification credibility were identified, along with 4 sesquiterpenoid compounds. Their spatial distributions and compositions were analyzed, and the results revealed that despite the similar structural basis of the stems in the 15 Dendrobium species, significant differences existed in the distribution of secondary metabolites among different species. Flavonoids and alkaloids with different medicinal effects exhibited certain specific distribution patterns; for instance, flavonoids with antioxidant effects were mostly concentrated in the outer circle of thin-walled cells of Dendrobium stems, whereas those with antitumor effects were found in higher concentrations in the central areas of some Dendrobium species than in the periphery. Alkaloids with antitumor properties typically exhibited a higher concentration in peripheral thin-walled cells than in central regions. Furthermore, statistical analysis was conducted on the content of secondary metabolites with different effects among the 15 Dendrobium species to identify species with greater medicinal potential in terms of antioxidant and antitumor effects. The findings of this study not only enhance our understanding of the distribution patterns of flavonoids and alkaloids within Dendrobium stems but also offer valuable insights for the medicinal development and quality assessment of Dendrobium.

Visualizing the transdermal delivery of berberine loaded within chitosan microneedles using mass spectrometry imaging.

Berberine (BR), an alkaloid isolated from theChinese traditional medicine Coptidis rhizoma, exhibits therapeutic effects on several diseases including bacterial infections, diabetes, and hyperlipidemia, but the oral availability is poor. In this work, we prepared the chitosan microneedle array-loaded BR (BR-CS MNAs) to transdermally deliver BR, and the spatial distribution of BR in heterogeneous skin tissues was analyzed and imaged by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Some endogenous phospholipids with specific spatial distribution were used to differentiate the epidermis and dermis regions of the skin. The results showed that BR was effectively delivered and could permeate to both epidermis and dermis regions of the skin. This demonstrated the feasibility of MALDI-MSI to evaluate the transdermal delivery efficiency of microneedle arrays and suggested BR could be transdermally delivered by CS MNAs.

Tissue derivatization for visualizing lactate and pyruvate in mouse testis tissues using matrix-assisted laser desorption/ionization-mass spectrometry imaging

Pyruvate and lactate are the final metabolites of the glycolytic system that are formed under oxygen-rich and anaerobic conditions, respectively. They play an important role in energy metabolism. Obtaining a tissue distribution image of pyruvate and lactate holds great significance in molecular biology because the glycolytic system plays an essential role in diseases, such as tumors and diabetes; microbial activities, such as alcohol production and lactic acid fermentation; and maintaining homeostasis in the gut environment. However, it is difficult to obtain images of the distribution of in vivo metabolites because of the low detection sensitivities of current methods. In this study, a novel derivatization method for pyruvate and lactate was developed using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to detect pyruvate and lactate in vivo and obtain biodistribution images. We investigated derivatization methods using readily available 3-nitrophenylhydrazine (3NPH), the addition of which improves the sensitivity of pyruvate detection, and the distribution of pyruvate in mouse testes was successfully visualized. Furthermore, the distribution of lactate in the mouse testes could be visualized, and improved detection sensitivity for the main metabolites of the tricarboxylic acid cycle was demonstrated. This derivatization method can be used to detect carboxyl-containing metabolites, including pyruvate, via MALDI-MSI. Furthermore, 3NPH forms amide bonds with carbonyl, phosphate, and carboxyl groups, suggesting the possibility of visualizing its distribution in many metabolites.Graphical

Matrix-assisted laser desorption/ionization mass spectrometry imaging as a new tool for molecular histopathology in epilepsy surgery.

Epilepsy surgery is a treatment option for patients with seizures that do not respond to pharmacotherapy. The histopathological characterization of the resected tissue has an important prognostic value to define postoperative seizure outcome in these patients. However, the diagnostic classification process based on microscopic assessment remains challenging, particularly in the case of focal cortical dysplasia (FCD). Imaging mass spectrometry is a spatial omics technique that could improve tissue phenotyping and patient stratification by investigating hundreds of biomolecules within a single tissue sample, without the need for target-specific reagents. An insitu proteomic technique called matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is here investigated as a potential new tool to expand conventional diagnosis on standard paraffin brain tissue sections. Unsupervised and region of interest-based MALDI-MSI analyses of sections from 10 FCD type IIb (FCDIIb) cases were performed, and the results were validated by immunohistochemistry. MALDI-MSI identified distinct histopathological features and the boundaries of the dysplastic lesion. The capability to visualize the spatial distribution of well-known diagnostic markers enabling multiplex measurements on single tissue sections was demonstrated. Finally, a fingerprint list of potential discriminant peptides that distinguish FCD core from peri-FCD tissue was generated. This is the first study that explores the potential application of MALDI-MSI in epilepsy postsurgery fixed tissue, by utilizing the well-characterized FCDIIb features as a model. Extending these preliminary analyses to a larger cohort of patients will generate spectral libraries of molecular signatures that discriminate tissue features and will contribute to patient phenotyping.

Bacteria from the Amycolatopsis genus associated with a toxic bird secrete protective secondary metabolites

Uropygial gland secretions of birds consist of host and bacteria derived compounds and play a major sanitary and feather-protective role. Here we report on our microbiome studies of the New Guinean toxic bird Pachycephala schlegelii and the isolation of a member of the Amycolatopsis genus from the uropygial gland secretions. Bioactivity studies in combination with co-cultures, MALDI imaging and HR-MS/MS-based network analyses unveil the basis of its activity against keratinolytic bacteria and fungal skin pathogens. We trace the protective antimicrobial activity of Amycolatopsis sp. PS_44_ISF1 to the production of rifamycin congeners, ciromicin A and of two yet unreported compound families. We perform NMR and HR-MS/MS studies to determine the relative structures of six members belonging to a yet unreported lipopeptide family of pachycephalamides and of one representative of the demiguisins, a new hexapeptide family. We then use a combination of phylogenomic, transcriptomic and knock-out studies to identify the underlying biosynthetic gene clusters responsible for the production of pachycephalamides and demiguisins. Our metabolomics data allow us to map molecular ion features of the identified metabolites in extracts of P. schlegelii feathers, verifying their presence in the ecological setting where they exert their presumed active role for hosts. Our study shows that members of the Actinomycetota may play a role in avian feather protection.

Spatial Metabolomics via Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) Identifies Bioenergetic and Tricarboxylic Acid (TCA) Cycle Metabolites as Pharmacodynamic Biomarkers of Losartan for Diabetic Kidney Disease

Spatial Metabolomics via Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) Identifies Bioenergetic and Tricarboxylic Acid (TCA) Cycle Metabolites as Pharmacodynamic Biomarkers of Losartan for Diabetic Kidney Disease

MALDI and MALDI-2 mass spectrometry imaging contribute to revealing the alternations in lipid metabolism in germinating soybean seeds

MALDI and MALDI-2 mass spectrometry imaging contribute to revealing the alternations in lipid metabolism in germinating soybean seeds

The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer

Around 13% of women will likely develop breast cancer during their lifetime. Advances in cancer metabolism research have identified a range of metabolic reprogramming events, such as altered glucose and amino acid uptake, increased reliance on glycolysis, and interactions with the tumor microenvironment (TME), all of which present new opportunities for targeted therapies. However, studying these metabolic networks is challenging in traditional 2D cell cultures, which often fail to replicate the three-dimensional architecture and dynamic interactions of real tumors. To address this, organoid models have emerged as powerful tools. Tumor organoids are 3D cultures, often derived from patient tissue, that more accurately mimic the structural and functional properties of actual tumor tissues in vivo, offering a more realistic model for investigating cancer metabolism. This review explores the unique metabolic adaptations of breast cancer and discusses how organoid models can provide deeper insights into these processes. We evaluate the most advanced tools for studying cancer metabolism in three-dimensional culture models, including optical metabolic imaging (OMI), matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), and recent advances in conventional techniques applied to 3D cultures. Finally, we explore the progress made in identifying and targeting potential therapeutic targets in breast cancer metabolism.

Insights into Tissue-Specific Specialized Metabolism in Wampee (Clausena lansium (Lour.) Skeels) Varieties

Wampee (Clausena lansium (Lour.) Skeels) has natural bioactive components with diverse health benefits, but its detailed metabolism and tissue distribution are not fully understood. Here, widely targeted metabolomics analysis methods were employed to analyze the wampee fruit (peel, pulp, and seed) of 17 different varieties. A total of 1286 metabolites were annotated, including lipids, flavonoids, polyphenols, carbazole alkaloids, coumarins, and organic acids, among others. The quantitative analysis and matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI) analysis indicated remarkable variations in metabolite categories and content in the peel, pulp, and seed of wampee fruit. Additionally, the difference analysis found that the metabolic components of peel contributed dominantly to the differences among varieties, and 7 potential biomarkers were identified. In this study, a comprehensive metabolome landscape of wampee fruit was established, which provided important information for the isolation and identification of functional components, food industry application, and nutritional improvement breeding.

Experimental and Computational Evaluation of Lipidomic In-Source Fragmentation as a Result of Postionization with Matrix-Assisted Laser Desorption/Ionization.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can provide spatially resolved molecular information about a sample. Recently, a postionization approach (MALDI-2) has been commercially integrated with MALDI-MSI, allowing for bettered sensitivity and consequent improved spatial resolution. While advantages of MALDI-2 have previously been established, we demonstrate here statistically increased in-source fragmentation (ISF) results from postionization with a commercial instrument. Via lipid standard analyses, known MALDI ISF pathways (e.g., loss of trimethylamine) were statistically increased in MALDI-2 compared to MALDI-1 (65-172% increase in fragmentation). Gas phase molecular modeling with density functional theory estimated that the most-weighted virtual orbitals to excite within lipids involve ester and phosphate bonds. Protonated lipid excitation energies are furthermore red-shifted compared to those of other adduct types [e.g., 254 nm for protonated PC(16:0/18:1)] and approach the MALDI-2 laser energy (266 nm). Analysis of rat brain homogenate detected statistically more positive-ion mode peaks with MALDI-2 (1090) than that with MALDI-1 (719), where Kernel density estimations showed that the majority of this enhancement occurs with low m/z ions (i.e., m/z 75-500). Taken together with the lipid standard data, these observations may indicate ISF due to postionization. While artifact contributions from matrix blanks were also noted, both experimental and computational data sets suggest that the overall extent of ISF is statistically increased in MALDI-2 compared to MALDI-1.

Spatial Metabolomic Profiling of Pinelliae Rhizoma from Different Leaf Types Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Pinelliae Rhizoma (PR), a highly esteemed traditional Chinese medicinal herb, is widely applied in clinical settings due to its diverse pharmacological effects, including antitussive, expectorant, antiemetic, sedative-hypnotic, and antitumor activities. Pinellia ternata exhibits morphological variation in its leaves, with types resembling peach, bamboo, and willow leaves. However, the chemical composition differences among the corresponding rhizomes of these leaf phenotypes remain unelucidated. This pioneering research employed Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) to conduct the in situ identification and spatial profiling of 35 PR metabolites in PR, comprising 12 alkaloids, 4 organic acids, 12 amino acids, 5 flavonoids, 1 sterol, and 1 anthraquinone. Our findings revealed distinct spatial distribution patterns of secondary metabolites within the rhizome tissues of varying leaf types. Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) effectively differentiated between rhizomes associated with different leaf morphologies. Furthermore, this study identified five potential differential biomarkers-methylophiopogonanone B, inosine, cytidine, adenine, and leucine/isoleucine-that elucidate the biochemical distinctions among leaf types. The precise tissue-specific localization of these secondary metabolites offers compelling insights into the specialized accumulation of bioactive compounds in medicinal plants, thereby enhancing our comprehension of PR's therapeutic potential.

Maldi-ms imaging in niftp diagnosis: an alternative approach

Maldi-ms imaging in niftp diagnosis: an alternative approach

Hydrazide-based reactive matrices for the sensitive detection of aldehydes and ketones by MALDI mass spectrometry imaging.

A one-step, on-tissue chemical derivatisation method for MALDI mass spectrometry imaging was found to improve the detectability of aldehydes and ketones by charge-tagging. The developed reactive matrices, containing a UV-chromophore, ionisable moiety and hydrazide group, showed an equal or higher detection efficiency than Girard's reagent P, enabling improved imaging of brain metabolites without the need for additional co-matrices.