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Quantitative positron emission tomography (PET) allows noninvasive assessment of myocardial blood flow and identification of CMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate the association between PET-assessed coronary microvascular dysfunction (CMD), coronary plaque burden, and vascular remodeling, integrating microvascular resistance reserve (MRR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This post hoc analysis of the PACIFIC-1 trial included coronary arteries from symptomatic patients with suspected stable CAD who underwent [\n                      <jats:sup>15<\/jats:sup>\n                      O]water PET, coronary CT angiography (CTA), and invasive fractional flow reserve (FFR). Coronary arteries were categorized into three groups: non-ischemic vessels (normal FFR and hyperemic myocardial blood flow [hMBF],\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009352), CMD vessels (normal FFR but impaired hMBF,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200988), and epicardial flow-limiting vessels (abnormal FFR,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009159). MRR was calculated by integrating PET-derived coronary flow reserve with invasive FFR. AI-based CTA quantified plaque burden and remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Diameter stenosis and plaque burden increased progressively from non-ischemic to CMD to epicardial flow-limiting vessels (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). CMD vessels demonstrated the largest lumen volume (583.75 mm\n                      <jats:sup>3<\/jats:sup>\n                      [IQR 337.02\u2013754.30]) and lumen area (4.63 mm\n                      <jats:sup>2<\/jats:sup>\n                      [IQR 3.77\u20136.67]) among the three groups (both\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). In non-ischemic vessels, noncalcified plaque burden was associated with worse microvascular function detected by MRR (B\u2009=\u2009-0.12, 95%CI [-0.21, -0.04],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.006). In CMD vessels, remodeling index was independently associated with higher MRR after adjustment (B\u2009=\u20090.10, 95%CI [0.05, 0.15],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CMD is associated with an intermediate atherosclerotic burden and paradoxical lumen enlargement, representing a distinct functional-structural phenotype defined by PET-derived microvascular dysfunction and CT-based plaque characteristics.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Clinical Trial Registration:<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.clinicaltrials.gov\" ext-link-type=\"uri\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT01521468.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p>Abbreviations: CMD, coronary microvascular dysfunction; FFR, fractional flow reserve; MBF, myocardial blood flow; MRR, microvascular resistance reserve; PET, positron emission tomography-computed tomography.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08054-3","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T03:05:24Z","timestamp":1783307124000},"page":"7573-7583","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PET-based assessment of coronary microvascular dysfunction and its relation to plaque burden and vascular remodeling: integration with microvascular resistance reserve"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5188-2558","authenticated-orcid":false,"given":"Yipu","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Hoek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri Annisa","family":"Kamila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Danad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick S.","family":"Nurmohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruurt A.","family":"Jukema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter G.","family":"Raijmakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel S.","family":"Driessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pepijn A.","family":"van Diemen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Knaapen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J.","family":"Bax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"van Rosendael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on the behalf of the PACIFIC-1 Investigators.","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel S.","family":"Driessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pepijn","family":"van Diemen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruurt","family":"Jukema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Meijboom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhani","family":"Knuuti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Saraste","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter G.","family":"Raijmakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Knaapen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Danad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"8054_CR1","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1056\/NEJMoa0907272","volume":"362","author":"MR Patel","year":"2010","unstructured":"Patel MR, Peterson ED, Dai D, Brennan JM, Redberg RF, Anderson HV, et al. 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