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Here, phase\u2010changing peptide nanoemulsions are developed as theranostic contrast agents for synchronous ultrasound detection and therapy of at\u2010risk atherosclerotic lesions. By targeting lipids within atherogenic foam cells, and exploiting characteristic features of vulnerable plaques, these nanoemulsions preferentially accumulate within lesions and are retained by intraplaque macrophages. It is demonstrated that acoustic vaporization of intracellular nanoemulsions promotes lipid efflux from foam cells and generates echogenic microbubbles that provide contrast\u2010enhanced ultrasound identification of lipid\u2010rich anatomical sites. In Doppler mode, stably oscillating peptide nanoemulsions induce random amplitude and phase changes of the echo wave to generate transient color imaging features, referred to as \u2018twinkling\u2019. Importantly, acoustic twinkling is unique to these peptide emulsions, and not observed from endogenous tissue bubble nuclei, generating diagnostic features that offer unprecedented spatial precision of lesion identification in 3D.<\/jats:p>","DOI":"10.1002\/adfm.202415609","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T10:01:32Z","timestamp":1734084092000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Twinkling Peptide Nanoemulsions Enable Precision Ultrasound Detection of Atherosclerotic Plaques"],"prefix":"10.1002","volume":"35","author":[{"given":"Inhye","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Pennsylvania State University  University Park PA 16802\u20104400 USA"}]},{"given":"Jacob C.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Graduate Program in Acoustics Pennsylvania State University  University Park PA 16802\u20104400 USA"}]},{"given":"Atip","family":"Lawanprasert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Pennsylvania State University  University Park PA 16802\u20104400 USA"}]},{"suffix":"III","given":"Anthony M.","family":"Koehle","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Pennsylvania State University  University Park PA 16802\u20104400 USA"}]},{"given":"Grace M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Graduate Program in Acoustics Pennsylvania State University  University Park PA 16802\u20104400 USA"}]},{"given":"Rita","family":"Castro","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences Pennsylvania State University  University Park PA 16802\u20104400 USA"},{"name":"Department of Pharmaceutical Sciences &amp; 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