Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds.

Multimodal imaging analyses of dosed tissue samples can provide more comprehensive insights into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multimodal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging.

Enhancing Spatial Resolution in Tandem Mass Spectrometry Ion/Ion Reaction Imaging Experiments through Image Fusion.

We have recently developed a charge inversion ion/ion reaction to selectively derivatize phosphatidylserine lipids via gas-phase Schiff base formation. This tandem mass spectrometry (MS/MS) workflow enables the separation and detection of isobaric lipids in imaging mass spectrometry, but the images acquired using this workflow are limited to relatively poor spatial resolutions due to the current time and limit of detection requirements for these ion/ion reaction imaging mass spectrometry experiments. This trade-off between chemical specificity and spatial resolution can be overcome by using computational image fusion, which combines complementary information from multiple images.

Formation of multiple ion types during MALDI imaging mass spectrometry analysis of Mitragyna speciosa alkaloids in dosed rat brain tissue.

Mitragyna speciosa, more commonly known as kratom, has emerged as an alternative to treat chronic pain and addiction. However, the alkaloid components of kratom, which are the major contributors to kratom's pharmaceutical properties, have not yet been fully investigated. In this study, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry was used to map the biodistribution of three alkaloids (corynantheidine, mitragynine, and speciogynine) in rat brain tissues.

A multi-modal image fusion workflow incorporating MALDI imaging mass spectrometry and microscopy for the study of small pharmaceutical compounds.

Multi-modal imaging analyses of dosed tissue samples can provide more comprehensive insight into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multi-modal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging.

Relative Quantification of Lipid Isomers in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions and Infrared Multiphoton Dissociation.

Accurate structural identification of lipids in imaging mass spectrometry is critical to properly contextualizing spatial distributions with tissue biochemistry. Gas-phase charge inversion ion/ion reactions alter the ion type prior to dissociation to allow for more structurally informative fragmentation and improve lipid identification at the isomeric level. In this work, infrared multiphoton dissociation (IRMPD) was interfaced with a commercial hybrid Qh-FT-ICR mass spectrometer to enable the rapid fragmentation of gas-phase charge inversion ion/ion reaction products at every pixel in imaging mass spectrometry experiments.

Imaging and Structural Characterization of Phosphatidylcholine Isomers from Rat Brain Tissue Using Sequential Collision-Induced Dissociation/Electron-Induced Dissociation.

The chemical complexity of biological tissues creates challenges in the analysis of lipids via imaging mass spectrometry. The presence of isobaric and isomeric compounds introduces chemical noise that makes it difficult to unambiguously identify and accurately map the spatial distributions of these compounds. Electron-induced dissociation (EID) has previously been shown to profile phosphatidylcholine (PCs) -isomers directly from rat brain tissue in matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry.

Quantification of pharmaceutical compounds in tissue and plasma samples using selective ion accumulation with multiple mass isolation windows.

Quantification of pharmaceutical compounds using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) is an alternative to traditional liquid chromatography (LC)-MS techniques. Benefits of MALDI-based approaches include rapid analysis times for liquid samples and imaging mass spectrometry capabilities for tissue samples. As in most quantification experiments, the use of internal standards can compensate for spot-to-spot and shot-to-shot variability associated with MALDI sampling.