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Electrochemical impedance spectroscopy (EIS) characterizes biological tissues by assessing impedance and phase delay responses to alternating current at multiple frequencies. We evaluated invasive 6\u2010point stretchable EIS sensors over a spectrum of experimental atherosclerosis and compared results with intravascular ultrasound (IVUS), molecular positron emission tomography (PET) imaging, and histology. Male New Zealand White rabbits (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916) were placed on a high\u2010fat diet, with or without endothelial denudation via balloon injury of the infrarenal abdominal aorta. Rabbits underwent in\u00a0vivo micro\u2010PET imaging of the abdominal aorta with\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010DOTATATE,\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010NaF, and\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010FDG, followed by invasive interrogation via IVUS and EIS. Background signal\u2010corrected values of impedance and phase delay were determined. Abdominal aortic samples were collected for histology. Analyses were performed blindly. EIS impedance was associated with markers of plaque activity including macrophage infiltration (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.813,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.008) and macrophage\/smooth muscle cell (SMC) ratio (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.813,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.026). Moreover, EIS phase delay correlated with anatomic markers of plaque burden, namely intima\/media ratio (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.883,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.004) and %stenosis (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.901,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.002), similar to IVUS.\n                    <jats:sup>68<\/jats:sup>\n                    Ga\u2010DOTATATE correlated with intimal macrophage infiltration (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.861,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.003) and macrophage\/SMC ratio (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.831,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.021),\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010NaF with SMC infiltration (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009\u2212.842,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.018), and\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010FDG correlated with macrophage\/SMC ratio (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u2009.787,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u2009.036). EIS with phase delay integrates key atherosclerosis features that otherwise require multiple complementary invasive and non\u2010invasive imaging approaches to capture. These findings indicate the potential of invasive EIS to comprehensively evaluate human coronary artery disease.\n                  <\/jats:p>","DOI":"10.1096\/fj.202302544rr","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T11:46:51Z","timestamp":1716551211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Invasive electrochemical impedance spectroscopy with phase delay for experimental atherosclerosis phenotyping"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0694-6641","authenticated-orcid":false,"given":"Michael","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Neverova","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"},{"name":"Ronald Reagan UCLA Medical Center  Los Angeles California USA"},{"name":"West Los Angeles Veterans Affairs Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-8673","authenticated-orcid":false,"given":"Shili","family":"Xu","sequence":"additional","affiliation":[{"name":"Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine University of California  Los Angeles California USA"},{"name":"Jonsson Comprehensive Cancer Center University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6036-829X","authenticated-orcid":false,"given":"Krit","family":"Suwannaphoom","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-8993","authenticated-orcid":false,"given":"Gentian","family":"Lluri","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"},{"name":"Ronald Reagan UCLA Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3675-2904","authenticated-orcid":false,"given":"Mikayla","family":"Tamboline","sequence":"additional","affiliation":[{"name":"Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7671-2589","authenticated-orcid":false,"given":"Sandra","family":"Duarte","sequence":"additional","affiliation":[{"name":"Division of Laboratory and Animal Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-6306","authenticated-orcid":false,"given":"Michael C.","family":"Fishbein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, David Geffen School of Medicine University of California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-7495","authenticated-orcid":false,"given":"Yuan","family":"Luo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology Chinese Academy of Sciences  Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-5843","authenticated-orcid":false,"given":"Ren\u00e9 R. 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