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At the bedside, the lesion that precipitates infarction is seldom the tightest but rather the most unstable. This review integrates the mechanistic chain, from endothelial dysfunction and retention\/oxidation of apolipoprotein B lipoproteins to maladaptive innate and adaptive immunity, failed efferocytosis with necrotic core expansion, and biomechanical forces that thin and fatigue the fibrous cap, with their corresponding in vivo imaging phenotypes. Thus, this study aimed to examine how intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near-infrared spectroscopy (NIRS), alongside coronary computed tomography angiography (CCTA), cardiac magnetic resonance (CMR), and positron emission tomography (PET), characterize these processes and enable longitudinal tracking of disease activity. Moreover, we briefly discuss emerging therapeutic implications of plaque imaging, focusing on how improved identification of vulnerable plaque features may inform risk stratification. Finally, we evaluate therapies that extend beyond lipid-lowering to modulate inflammatory and immune pathways, reinforce cap stability, and support a risk-adapted, trajectory-based pathway in which serial imaging and biomarkers guide treatment intensity. Together, these advances support a shift in clinical practice from stenosis-centered revascularization to imaging-guided, vulnerability-centered prevention.<\/jats:p>","DOI":"10.31083\/rcm48015","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:31:56Z","timestamp":1777458716000},"source":"Crossref","is-referenced-by-count":0,"title":["Plaque Progression and Rupture in Obstructive Coronary Artery Disease: A Review of Current Imaging Modalities"],"prefix":"10.31083","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-2901","authenticated-orcid":true,"given":"Francesco Antonio","family":"Veneziano","sequence":"first","affiliation":[{"name":"Division of Cardiology, South Padova General Hospitals, 35043 Monselice, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4981-3777","authenticated-orcid":true,"given":"Nino","family":"Cocco","sequence":"additional","affiliation":[{"name":"Operative Research Unit of Emodinamica, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7453-3748","authenticated-orcid":true,"given":"Francesco","family":"Gentile","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Gabriele Monasterio, Division of Cardiovascular Medicine, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-282X","authenticated-orcid":true,"given":"Francesco","family":"Chietera","sequence":"additional","affiliation":[{"name":"Cardiology Unit, IRCCS University Hospital of Bologna, Policlinico S. Orsola, 40138 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-1272","authenticated-orcid":true,"given":"Leonardo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Global Burden of Cardiovascular Diseases and Risks 2023 Collaborators. Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990\u20132023. Journal of the American College of Cardiology. 2025; 86: 2167\u20132243.","DOI":"10.1016\/j.jacc.2025.08.015"},{"key":"ref2","doi-asserted-by":"publisher","unstructured":"Townsend N, Kazakiewicz D, Lucy Wright F, Timmis A, Huculeci R, Torbica A, et al. 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