{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:54:22Z","timestamp":1791860062146,"version":"4.3.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Birefringent crystals such as monosodium-urate (MSU) and cholesterol crystals (CC) likely contribute to the progression of coronary artery disease (CAD) due to their potential to exacerbate inflammation through inflammatory cytokine activation. Here, we present cross-polarized micro-optical coherence tomography (CP-\u00b5OCT) for visualizing individual birefringent crystals in human coronary arteries.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Human cadaver coronary arteries with a history of CAD with or without gout were dissected for CP-\u00b5OCT imaging. Specimens were processed for histological identification of birefringence under polarization light microscopy (PLM). CP-\u00b5OCT visualized needle-crystals that appeared as long projections in orthogonal planes, and PLM confirmed that CP-\u00b5OCT-delineated needle-crystals demonstrated negative birefringence. The needle-crystals were dissolved after immersion in uricase (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05), and thus were MSU. CP-\u00b5OCT was three-dimensionally volume-rendered for counting MSU and CCs in 79 regions of interest sized [750 (\n                      <jats:italic>x<\/jats:italic>\n                      )\u2009\u00d7\u2009500 (\n                      <jats:italic>y<\/jats:italic>\n                      )\u2009\u00d7\u2009400 (\n                      <jats:italic>z<\/jats:italic>\n                      ) \u00b5m]. Crystal counts were normalized by the total coronary length utilized. The relationship between CP-\u00b5OCT-delineated MSU counts and those seen in corresponding histology, and the difference in coronary MSU amongst gout vs. non-gout patients was analyzed. CP-\u00b5OCT-delineated MSU counts were significantly correlated with MSU counted by PLM-based histology (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.98,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.01), and with histology-derived intimal thickening (\n                      <jats:italic>R<\/jats:italic>\n                      \u2009=\u20090.51,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.01). MSU and CCs were both significantly greater in gout patients compared with non-gout patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These results demonstrate a significant increase in CP-\u00b5OCT-delineated crystals in gout vs. non-gout patients, suggesting that this technology can be used to improve our understanding of crystal-driven coronary pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2024.1433227","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T07:13:11Z","timestamp":1730099591000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Imaging human coronary cholesterol\/urate crystals with cross-polarized micro-optical coherence tomography"],"prefix":"10.3389","volume":"11","author":[{"given":"Kensuke","family":"Nishimiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gargi","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwarpal","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman O.","family":"Ahsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Gardecki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo J.","family":"Tearney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1093\/eurheartj\/ehaa505","article-title":"Cholesterol crystals and atherosclerosis","volume":"41","author":"Baumer","year":"2020","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/nature08938","article-title":"NLRP3 Inflammasomes are required for atherogenesis and activated by cholesterol crystals","volume":"464","author":"Duewell","year":"2010","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2178","DOI":"10.1039\/c8cc10050k","article-title":"Structure and cleavage of monosodium urate monohydrate crystals","volume":"55","author":"Molloy","year":"2019","journal-title":"Chem Commun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"452","DOI":"10.7326\/0003-4819-54-3-452","article-title":"Identification of urate crystals in gouty synovial fluid","volume":"54","author":"Mccarty","year":"1961","journal-title":"Ann Intern Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"756","DOI":"10.7326\/0003-4819-131-10-199911160-00007","article-title":"Synovial fluid analysis for diagnosis of intercritical gout","volume":"131","author":"Pascual","year":"1999","journal-title":"Ann Intern Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.atherosclerosis.2017.12.027","article-title":"The NLRP3 inflammasome and the emerging role of colchicine to inhibit atherosclerosis-associated inflammation","volume":"269","author":"Mart\u00ednez","year":"2018","journal-title":"Atherosclerosis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and safety of low-dose colchicine after myocardial infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1056\/NEJMoa2021372","article-title":"Colchicine in patients with chronic coronary disease","volume":"383","author":"Nidorf","year":"2020","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/nm.2409","article-title":"Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography","volume":"17","author":"Liu","year":"2011","journal-title":"Nat Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e102669","DOI":"10.1371\/journal.pone.0102669","article-title":"Feasibility of the assessment of cholesterol crystals in human macrophages using micro optical coherence tomography","volume":"9","author":"Kashiwagi","year":"2014","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41377-019-0211-5","article-title":"3D cellular-resolution imaging in arteries using few-mode interferometry","volume":"8","author":"Yin","year":"2019","journal-title":"Light Sci Appl"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1016\/j.jcmg.2019.01.021","article-title":"Micro-optical coherence tomography for endothelial cell visualization in the coronary arteries","volume":"12","author":"Nishimiya","year":"2019","journal-title":"J Am Coll Cardiol Cardiovasc Img"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1364\/ol.23.001060","article-title":"Cross-polarized backscatter in optical coherence tomography of biological tissue","volume":"22","author":"Schmitt","year":"1998","journal-title":"Opt Lett"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1038\/s41598-019-38493-y","article-title":"Quantitative nontumorous and tumorous human brain tissue assessment using microstructural co- and cross-polarized optical coherence tomography","volume":"9","author":"Yashin","year":"2019","journal-title":"Sci Rep"},{"key":"B16","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat Methods"},{"key":"B17","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.jcmg.2008.06.007","article-title":"Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging","volume":"1","author":"Tearney","year":"2008","journal-title":"J Am Coll Cardiol Cardiovasc Img"},{"key":"B18","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1161\/ATVBAHA.119.312934","article-title":"Feasibility and clinical significance of in vivo cholesterol crystal detection using optical coherence tomography","volume":"40","author":"Katayama","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B19","first-page":"2320","article-title":"Not water, but formalin, dissolves urate crystals in tophaceous tissue samples","volume":"21","author":"Simkin","year":"1994","journal-title":"J Rheumatol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1002\/jemt.22560","article-title":"Role of cholesterol crystals in atherosclerosis is unmaskedby altering tissue preparation methods","volume":"78","author":"Nasiri","year":"2015","journal-title":"Microsc Res Tech"},{"key":"B21","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1001\/jama.203.7.508","article-title":"Compensated polarized light microscopy. Identification of crystals in synovial fluids from gout and pseudogout","volume":"203","author":"Phelps","year":"1968","journal-title":"JAMA"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e005308","DOI":"10.1136\/bmjopen-2014-005308","article-title":"Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study","volume":"4","author":"Park","year":"2014","journal-title":"BMJ Open"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1001\/jamacardio.2019.3201","article-title":"Dual-energy computed tomography detection of cardiovascular monosodium urate deposits in patients with gout","volume":"4","author":"Klauser","year":"2019","journal-title":"JAMA Cardiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jacl.2010.03.003","article-title":"Cholesterol crystals piercing the arterial plaque and intima trigger local and systemic inflammation","volume":"4","author":"Abela","year":"2010","journal-title":"J Clin Lipidol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2688","DOI":"10.1002\/art.22014","article-title":"Gout and the risk of acute myocardial infarction","volume":"54","author":"Krishnan","year":"2006","journal-title":"Arthritis Rheum"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/S0140-6736(22)01657-9","article-title":"Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial","volume":"400","author":"Mackenzie","year":"2022","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1016\/j.jcis.2005.09.013","article-title":"Growth of calcium hydroxyapatite (Ca-HAp) on cholesterol and cholestanol crystals from a simulated body fluid: a possible insight into the pathological calcifications associated with atherosclerosis","volume":"295","author":"Laird","year":"2006","journal-title":"J Colloid Interface Sci"},{"key":"B28","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3390\/gucdd1030017","article-title":"Does monosodium urate crystal vascular deposition exist? Review of the evidence","volume":"1","author":"Pascart","year":"2023","journal-title":"Gout Urate Cryst Dis"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2024.1433227\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T07:13:14Z","timestamp":1730099594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2024.1433227\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":28,"alternative-id":["10.3389\/fcvm.2024.1433227"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2024.1433227","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]},"article-number":"1433227"}}