Obtaining 20 μm Spatial Resolution with a 2940 nm Laser by IR-MALDESI Mass Spectrometry Imaging.

High spatial resolution is a key parameter in mass spectrometry imaging (MSI), enabling a greater understanding of system biology and cellular processes. Using a novel IR laser with good Gaussian beam quality ( = 4) coupled with spatial filtering and a reflective objective, 20 μm spatial resolution was obtained by IR-MALDESI. The optical train was optimized on burn paper before demonstrating feasibility for imaging of liver tissue.

Improved detection in untargeted lipidomics through silver-doped infrared matrix-assisted laser desorption electrospray ionization.

Rationale: Silver doping of electrospray is known to increase the abundance of olefinic compounds detected by mass spectrometry. While demonstrated in targeted experiments, this has yet to be investigated in an untargeted study. Utilizing infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI-MSI), an untargeted lipidomics experiment on mouse liver was performed to evaluate the advantages of silver-doped electrospray.

Prototyping an ionization source for non-engineers.

Novel mass spectrometry (MS) based analytical platforms have enabled scientists to detect and quantify molecules within biological and environmental samples more accurately. Novel MS instrumentation starts as a prototype and, after years of development, can become a commercial product to be used by the larger MS community. Without the initial prototype, many MS-based instruments today would not be produced.

Metabolite Annotation Confidence Score (MACS): A Novel MSI Identification Scoring Tool.

Mass spectrometry imaging (MSI) is an analytical technique capable of measuring and visualizing the spatial distribution of thousands of ions across a sample. Measured ions can be putatively identified and annotated by comparing their mass-to-charge ratio (/) to a database of known compounds. For high-resolution, accurate mass (HRAM) imaging data sets, this is commonly performed by the annotation platform METASPACE.

Development of an object-based image analysis tool for mass spectrometry imaging ion classification.

Mass spectrometry imaging (MSI) is an analytical technique that can detect and visualize thousands of m/z values resolved in two- and three-dimensional space. These m/z values lead to hundreds of molecular annotations, including on-tissue and background ions. Discrimination of sample-related analytes from ambient ions conventionally involves manual investigation of each ion heatmap, which requires significant researcher time and effort (for a single tissue image, it can take an hour to determine on-tissue and off-tissue species).

Preclinical evaluation of new C-11 labeled benzo-1,4-dioxane PET radiotracers for brain α2C adrenergic receptors.

As one of the nine subtypes of adrenergic receptors (ARs) in the brain, α2C-ARs play essential roles in emotion and memory, and are implicated in neuropsychiatric disorders, including depression, Alzheimer's disease, substance use disorder, and schizophrenia. A recently developed α2C-AR specific positron emission tomography (PET) radiotracer, [C]ORM-13070, showed promise for imaging α2C-ARs in the brain. Herein, we prepared highly potent C-11 labeled benzo-1,4-dioxane derivatives and compared them with [C]ORM-13070, aiming to improve the specific binding signal, as evaluated by in vivo rodent brain PET imaging.

Naloxone's dose-dependent displacement of [C]carfentanil and duration of receptor occupancy in the rat brain.

The continuous rise in opioid overdoses in the United States is predominantly driven by very potent synthetic opioids, mostly fentanyl and its derivatives (fentanyls). Although naloxone (NLX) has been shown to effectively reverse overdoses by conventional opioids, there may be a need for higher or repeated doses of NLX to revert overdoses from highly potent fentanyls. Here, we used positron emission tomography (PET) to assess NLX's dose-dependence on both its rate of displacement of [C]carfentanil ([C]CFN) binding and its duration of mu opioid receptor (MOR) occupancy in the male rat brain.

Discovery of Highly Potent Adenosine A Receptor Agonists: Targeting Positron Emission Tomography Probes.

Adenosine receptor (AR) radiotracers for positron emission tomography (PET) have provided knowledge on the biodistribution of ARs in the central nervous system (CNS), which is of therapeutic interest for various neuropsychiatric disorders. Additionally, radioligands that can image changes in endogenous adenosine levels in different physiological and pathological conditions are still lacking. The binding of known antagonist adenosine A receptor (AR) radiotracer, [C]MDPX, failed to be inhibited by elevated endogenous adenosine in a rodent PET study.