We propose the engineering of responsive microbubbles that can be used as biomolecular contrast agents in US imaging to stratify inflamed fibrotic tissue in IBD due to protease activity. Gas-filled microbubbles are frequently used in US imaging to enhance contrast because of their ability to efficiently scatter ultrasound. The Protease Responsive US Contrast Agent (PRUCA) concept we developed is based on gas-filled microbubbles with a lipid shell crosslinked with peptides and equipped with molecular anchors. Once injected into the blood stream, PRUCAs are design to reside in the vessels of fibrotic tissues and the peptide linkers will be broken down by certain targeted protease if the tissue is inflamed. This in turn softens the shell and creates a bright US image that should inform clinicians about the state of inflammation.