Evaluation of Inlet Temperature with Three Sprayer Designs for Desorption Electrospray Ionization Mass Spectrometry Tissue Analysis.

Mass spectrometry imaging (MSI) allows for the spatially resolved detection of endogenous and exogenous molecules and atoms in biological samples, typically prepared as thin tissue sections. Desorption electrospray ionization (DESI) is one of the most commonly utilized MSI modalities in preclinical research. DESI ion source technology is still rapidly evolving, with new sprayer designs and heated inlet capillaries having recently been incorporated in commercially available systems.

Visualisation of drug distribution in skin using correlative optical spectroscopy and mass spectrometry imaging.

A correlative methodology for label-free chemical imaging of soft tissue has been developed, combining non-linear optical spectroscopies and mass spectrometry to achieve sub-micron spatial resolution and critically improved drug detection sensitivity. The approach was applied to visualise the kinetics of drug reservoir formation within human skin following in vitro topical treatment with a commercial diclofenac gel. Non-destructive optical spectroscopic techniques, namely stimulated Raman scattering, second harmonic generation and two photon fluorescence microscopies, were used to provide chemical and structural contrast.

NECTAR: A New Algorithm for Characterizing and Correcting Noise in QToF-Mass Spectrometry Imaging Data.

A typical mass spectrometry imaging experiment yields a very high number of detected peaks, many of which are noise and thus unwanted. To select only peaks of interest, data preprocessing tasks are applied to raw data. A statistical study to characterize three types of noise in MSI QToF data (random, chemical, and background noise) is presented through NECTAR, a new NoisE CorrecTion AlgoRithm.

Metabolic profiling stratifies colorectal cancer and reveals adenosylhomocysteinase as a therapeutic target.

The genomic landscape of colorectal cancer (CRC) is shaped by inactivating mutations in tumour suppressors such as APC, and oncogenic mutations such as mutant KRAS. Here we used genetically engineered mouse models, and multimodal mass spectrometry-based metabolomics to study the impact of common genetic drivers of CRC on the metabolic landscape of the intestine. We show that untargeted metabolic profiling can be applied to stratify intestinal tissues according to underlying genetic alterations, and use mass spectrometry imaging to identify tumour, stromal and normal adjacent tissues.

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

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.

Exploring New Methods to Study and Moderate Proton Beam Damage for Multimodal Imaging on a Single Tissue Section.

Characterizing proton beam damage in biological materials is of interest to enable the integration of proton microprobe elemental mapping techniques with other imaging modalities. It is also of relevance to obtain a deeper understanding of mechanical damage to lipids in tissues during proton beam cancer therapy. We have developed a novel strategy to characterize proton beam damage to lipids in biological tissues based on mass spectrometry imaging.

Correlative Imaging of Trace Elements and Intact Molecular Species in a Single-Tissue Sample at the 50 μm Scale.

Elemental and molecular imaging play a crucial role in understanding disease pathogenesis. To accurately correlate elemental and molecular markers, it is desirable to perform sequential elemental and molecular imaging on a single-tissue section. However, very little is known about the impact of performing these measurements in sequence.

Implications of Peak Selection in the Interpretation of Unsupervised Mass Spectrometry Imaging Data Analyses.

Mass spectrometry imaging can produce large amounts of complex spectral and spatial data. Such data sets are often analyzed with unsupervised machine learning approaches, which aim at reducing their complexity and facilitating their interpretation. However, choices made during data processing can impact the overall interpretation of these analyses.