Unlabeled aspirin as activatable CEST MRI agent for imaging of inflammation - chemical exchange saturation transfer (CEST) MRI is currently emerging as promising alternative, allowing use of fully…

The National Institute of Biomedical Imaging and Bioengineering awarded the Hugo W. Moser Research Institute at Kennedy Krieger, Inc., $661,953 on July 1, 2026, under the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286) to develop unlabeled aspirin as an activatable contrast agent for chemical exchange saturation transfer (CEST) MRI imaging of inflammation.

The project optimizes CEST MRI protocols to evaluate signal dynamics in mouse kidneys following tail-vein injection of various aspirin concentrations, including toxicity assessment. The recipient will develop matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging approaches to detect aspirin metabolites and prostaglandins in brain, kidney, and liver tissue sections from mouse models of inflammation. The work tests the applicability of dynamic aspirin-enhanced in vivo CEST MRI and ex vivo MALDI imaging across multiple inflammation models, examining mechanistic relationships between inflammation markers, tumor microenvironment, blood vessel characteristics, cyclooxygenase-1/-2, aspirin-hydrolyzing carboxylesterases, and aspirin metabolites.

Preliminary data demonstrated that tail-vein aspirin injection into a mouse neuroinflammation model produced significantly enhanced signal in inflamed brain tissue regions and distributed salicylic acid and other aspirin metabolites through kidney, liver, and tumor sections while effectively inhibiting prostaglandin synthesis.

Performance occurs in Baltimore, Maryland through June 30, 2030. This is a project grant, the assistance type for individual investigator-initiated research.

Unlabeled aspirin as activatable CEST MRI agent for imaging of inflammation - chemical exchange saturation transfer (CEST) MRI is currently emerging as promising alternative, allowing use of fully biocompatible contrast agents without any heavy metal or other labels. We will develop the well-known precursor of salicylic acid (SA), acetyl salicylic acid, better known as aspirin, as a novel activatable contrast agent for detecting inflammation with CEST MRI. Our preliminary data show that tail-vein injection into a mouse model of neuroinflammation resulted in significantly enhanced signal in inflamed mouse brain tissue regions. Using innovative matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) approaches, we showed that SA and other aspirin metabolites are distributed through kidney, liver and tumor sections of the aspirin injected mice, and not in tissue sections of untreated controls. Several prostaglandins were detected in tissue sections from untreated control mice, and not in tissues from aspirin-injected mice, providing strong evidence that prostaglandin synthesis was effectively inhibited in the aspirin-injected mice. In aim 1, we will optimize a novel radial sampling CEST MRI protocol to evaluate CEST MRI signal dynamics in mouse kidneys following tail-vein injection of various concentrations of injectable aspirin, which includes a toxicity study. In aim 2, we will develop innovative MALDI imaging approaches for detecting aspirin metabolites and prostaglandins in thin tissue sections of brain, kidney and liver in mouse models of inflammation. In aim 3, we will broadly test the applicability of dynamic aspirin enhanced in vivo SA CEST MRI and EX vivo MALDI imaging in various mouse models of inflammation. We will comparatively perform mechanistic studies into the relationships between inflammation markers, tumor microenvironment, blood vessels, cyclooxygenase-1/-2, aspirin-hydrolyzing carboxylesterases, aspirin metabolites, and prostaglandins. Aspirin enhanced SA CEST MRI holds promise for future use in monitoring tissue inflammation. MALDI imaging for measuring the spatial distribution of aspirin metabolites and prostaglandins is broadly applicable for tissue imaging of inflammation, cancer, infection, and aspirin treatment effects. These new MALDI imaging methods are compatible with histology and immunohistochemistry (IHC) for use in pathology.