{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T05:57:50Z","timestamp":1769925470303,"version":"3.49.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,9,26]],"date-time":"2018-09-26T00:00:00Z","timestamp":1537920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Atherosclerotic plaques constitute the primary cause of heart attack and stroke. However, we still lack a clear identification of the plaques. Here, we evaluate the feasibility of scanning acoustic microscopy (SAM) and time-resolved fluorescence spectroscopy (TRFS) in atherosclerotic plaque characterization. We perform dual-modality microscopic imaging of the human carotid atherosclerotic plaques. We first show that the acoustic impedance values are statistically higher in calcified regions compared with the collagen-rich areas. We then use CdTe\/CdS quantum dots for imaging the atherosclerotic plaques by TRFS and show that fluorescence lifetime values of the quantum dots in collagen-rich areas are notably different from the ones in calcified areas. In summary, both modalities are successful in differentiating the calcified regions from the collagen-rich areas within the plaques indicating that these techniques are confirmatory and may be combined to characterize atherosclerotic plaques in the future.<\/jats:p>","DOI":"10.1038\/s41598-018-32788-2","type":"journal-article","created":{"date-parts":[[2018,9,20]],"date-time":"2018-09-20T10:20:39Z","timestamp":1537438839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Scanning Acoustic Microscopy and Time-Resolved Fluorescence Spectroscopy for Characterization of Atherosclerotic Plaques"],"prefix":"10.1038","volume":"8","author":[{"given":"Bukem","family":"Bilen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belkis","family":"Gokbulut","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulku","family":"Kafa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emre","family":"Heves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet Naci","family":"Inci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet Burcin","family":"Unlu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,9,26]]},"reference":[{"key":"32788_CR1","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1161\/01.ATV.20.5.1262","volume":"20","author":"R Virmani","year":"2000","unstructured":"Virmani, R., Kolodgie, F. D., Burke, A. P., Farb, A. & Schwartz, S. M. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arter. Thromb. Vasc. Biol. 20, 1262\u20131275 (2000).","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"32788_CR2","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","volume":"114","author":"JF Bentzon","year":"2014","unstructured":"Bentzon, J. F., Otsuka, F., Virmani, R. & Falk, E. Mechanisms of plaque formation and rupture. Circ. Res. 114, 1852\u20131866 (2014).","journal-title":"Circ. Res."},{"issue":"1A","key":"32788_CR3","doi-asserted-by":"publisher","first-page":"s3","DOI":"10.1016\/j.amjmed.2008.10.013","volume":"122","author":"W Insull","year":"2009","unstructured":"Insull, W. The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. The Am. J. Medicine 122(1A), s3\u2013s14 (2009).","journal-title":"The Am. J. Medicine"},{"issue":"8","key":"32788_CR4","first-page":"51","volume":"18","author":"G Bailey","year":"2016","unstructured":"Bailey, G., Meadows, J. & Morrison, A. R. Imaging atherosclerotic plaque calcification: translating biology. The Am. J. Medicine 18(8), 51 (2016).","journal-title":"J. Medicine"},{"issue":"40","key":"32788_CR5","doi-asserted-by":"publisher","first-page":"14678","DOI":"10.1073\/pnas.0606310103","volume":"103","author":"Y Vengrenyuk","year":"2006","unstructured":"Vengrenyuk, Y. et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc. Natl. Acad. Sci. 103(40), 14678\u201314683 (2006).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"32788_CR6","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1161\/CIRCULATIONAHA.107.749655","volume":"116","author":"CM Shanahan","year":"2007","unstructured":"Shanahan, C. M. Inflammation ushers in calcification. Circ. 116, 2782\u20132785 (2007).","journal-title":"Circ."},{"key":"32788_CR7","doi-asserted-by":"publisher","first-page":"2841","DOI":"10.1161\/CIRCULATIONAHA.107.732867","volume":"116","author":"E Aikawa","year":"2007","unstructured":"Aikawa, E. et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circ. 116, 2841\u20132850 (2007).","journal-title":"Circ."},{"issue":"3","key":"32788_CR8","first-page":"71","volume":"23","author":"J Hjortnaes","year":"2013","unstructured":"Hjortnaes, J., New, S. E. P. & Aikawa, E. Visualizing novel concepts of cardiovascular calcification. Trends Cardiovasc. Medicine 23(3), 71\u201379 (2013).","journal-title":"Medicine"},{"issue":"1","key":"32788_CR9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1089\/ten.teb.2014.0180","volume":"21","author":"SY Nam","year":"2015","unstructured":"Nam, S. Y., Ricles, L. M., Suggs, L. J. & Emelianov, S. Y. Imaging strategies for tissue engineering applications. Tissue Eng. 21(1), 88\u2013102 (2015).","journal-title":"Tissue Eng."},{"key":"32788_CR10","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s10396-008-0183-1","volume":"35","author":"N Kamiyama","year":"2008","unstructured":"Kamiyama, N., Okomura, Y., Kakee, A. & Hashimoto, H. Investigation of ultrasound image processing to improve perceptibility of microcalcifications. J. Med. Ultrason. 35, 97\u2013105 (2008).","journal-title":"J. Med. Ultrason."},{"key":"32788_CR11","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1038\/s41598-017-01649-9","volume":"7","author":"J Hui","year":"2017","unstructured":"Hui, J. et al. Real-time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque in human coronary artery at 16 frames per second. Sci. Reports 7, 1417 (2017).","journal-title":"Sci. Reports"},{"issue":"7","key":"32788_CR12","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/pin.12288","volume":"65","author":"K Miura","year":"2015","unstructured":"Miura, K. et al. Microscopic observation of chemical modification in sections using scanning acoustic microscopy. Pathol. Int. 65(7), 355\u2013366 (2015).","journal-title":"Pathol. Int."},{"issue":"8","key":"32788_CR13","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1109\/TUFFC.2007.427","volume":"54","author":"Y Saijo","year":"2007","unstructured":"Saijo, Y. et al. Ultrasonic tissue characterization of atherosclerosis by a speed-of-sound microscanning system. IEEE Transactions on Ultrason. Ferroelectr. Freq. Control. 54(8), 1571\u20131577 (2007).","journal-title":"IEEE Transactions on Ultrason. Ferroelectr. Freq. Control."},{"key":"32788_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.artres.2015.11.001","volume":"13","author":"R Akhtar","year":"2016","unstructured":"Akhtar, R., Cruickshank, J. K., Zhao, X., Derby, B. & Weber, T. A pilot study of scanning acoustic microscopy as a tool for measuring arterial stiffness in aortic biopsies. Artery Res. 13, 1\u20135 (2016).","journal-title":"Artery Res."},{"key":"32788_CR15","doi-asserted-by":"publisher","first-page":"e51","DOI":"10.1016\/j.ultras.2006.06.050","volume":"44","author":"Y Saijo","year":"2006","unstructured":"Saijo, Y. et al. Ultrasonic speed microscopy for imaging of coronary artery. Ultrason. 44, e51\u2013e55 (2006).","journal-title":"Ultrason."},{"key":"32788_CR16","doi-asserted-by":"publisher","first-page":"6125204","DOI":"10.1155\/2016\/6125204","volume":"2016","author":"K Miura","year":"2016","unstructured":"Miura, K. & Katoh, H. Structural and histochemical alterations in the aortic valves of elderly patients: a comparative study of aortic stenosis, aortic regurgitation, and normal valves. Biomed Res. Int. 2016, 6125204 (2016).","journal-title":"Biomed Res. Int."},{"key":"32788_CR17","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/j.ultras.2013.04.015","volume":"54","author":"MP Brewin","year":"2014","unstructured":"Brewin, M. P., Srodon, P. D., Greenwald, S. E. & Birch, M. J. Carotid atherosclerotic plaque characterization by measurement of ultrasound sound speed in vitro at high frequency, 20\u2009MHz. Ultrason. 54, 428\u2013441 (2014).","journal-title":"Ultrason."},{"key":"32788_CR18","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/j.ultras.2003.11.023","volume":"42","author":"Y Saijo","year":"2004","unstructured":"Saijo, Y., Miyakawa, T., Sasaki, H., Tanaka, M. & Nitta, S. Acoustic properties of aortic aneurysm obtained with scanning acoustic microscopy. Ultrason. 42, 695\u2013698 (2004).","journal-title":"Ultrason."},{"key":"32788_CR19","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1114\/1.1424912","volume":"29","author":"Y Saijo","year":"2001","unstructured":"Saijo, Y. et al. Application of scanning acoustic microscopy for assessing stress distribution in atherosclerotic plaque. Annals Biomed. Eng. 29, 1048\u20131053 (2001).","journal-title":"Annals Biomed. Eng."},{"key":"32788_CR20","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/srep01255","volume":"3","author":"K Miura","year":"2013","unstructured":"Miura, K., Nasu, H. & Yamamoto, S. Scanning acoustic microscopy for characterization of neoplastic and inflammatory lesions of lymph nodes. Sci. Reports 3, 1255 (2013).","journal-title":"Sci. Reports"},{"key":"32788_CR21","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1038\/labinvest.2012.135","volume":"92","author":"K Miura","year":"2012","unstructured":"Miura, K. & Yamamoto, S. Pulmonary imaging with a scanning acoustic microscope discriminates speed-of-sound and shows structural characteristics of disease. Lab. Investig. 92, 1760\u20131765 (2012).","journal-title":"Lab. Investig."},{"key":"32788_CR22","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1016\/j.ultras.2014.04.007","volume":"54","author":"K Kobayashi","year":"2014","unstructured":"Kobayashi, K., Yoshida, S., Saijo, Y. & Hozumi, N. Acoustic impedance microscopy for biological tissue characterization. Ultrason. 54, 1922\u20131928 (2014).","journal-title":"Ultrason."},{"key":"32788_CR23","first-page":"181","volume":"2016","author":"K Hatori","year":"2016","unstructured":"Hatori, K. et al. Acoustic diagnosis device for dentistry. Interface Oral Heal. Sci. 2016, 181\u2013201 (2016).","journal-title":"Interface Oral Heal. Sci."},{"issue":"10","key":"32788_CR24","doi-asserted-by":"publisher","first-page":"2293","DOI":"10.1109\/TUFFC.2010.1690","volume":"57","author":"EM Strohm","year":"2010","unstructured":"Strohm, E. M., Czarnota, G. J. & Kolios, M. C. Quantitative measurements of apoptotic cell properties using acoustic microscopy. IEEE Transactions on Ultrason. Ferroelectr. Freq. Control. 57(10), 2293\u20132304 (2010).","journal-title":"IEEE Transactions on Ultrason. Ferroelectr. Freq. Control."},{"key":"32788_CR25","doi-asserted-by":"crossref","unstructured":"Shelke, A., Brand, S., Kundu, T., Bereiter-Hahn, J. & Blase, C. Mechanical property quantification of endothelial cells using scanning acoustic microscopy. Proc. SPIE 8348, 83481T (2012).","DOI":"10.1117\/12.917512"},{"issue":"2005","key":"32788_CR26","first-page":"882","volume":"2","author":"S Brand","year":"2005","unstructured":"Brand, S., Czarnota, G. J., Kolios, M. C., Weiss, E. C. & Lemor, R. Visualization of apoptotic cells using scanning acoustic microscopy and high frequency ultrasound. Proc. IEEE Ultrason. Symp. 2(2005), 882\u2013885 (2005).","journal-title":"Proc. IEEE Ultrason. Symp."},{"issue":"10","key":"32788_CR27","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1177\/000331979905001008","volume":"50","author":"H Masugata","year":"1999","unstructured":"Masugata, H. et al. Tissue characterization of myocardial cells by use of high-frequency acoustic microscopy: differential myocyte sound speed and its transmural variation in normal, pressure-overload hypertrophic, and amyloid myocardium. Angiol. 50(10), 837\u2013845 (1999).","journal-title":"Angiol."},{"key":"32788_CR28","doi-asserted-by":"publisher","first-page":"15243","DOI":"10.1038\/srep15243","volume":"5","author":"K Miura","year":"2015","unstructured":"Miura, K. & Yamamoto, S. A scanning acoustic microscope discriminates cancer cells in fluid. Sci. Reports 5, 15243 (2015).","journal-title":"Sci. Reports"},{"key":"32788_CR29","first-page":"11208710","volume":"2009","author":"EM Strohm","year":"2009","unstructured":"Strohm, E. M. & Kolios, M. C. Quantifying the ultrasonic properties of cells during apoptosis using time resolved acoustic microscopy. IEEE Int. Ultrason. Symp. 2009, 11208710 (2009).","journal-title":"IEEE Int. Ultrason. Symp."},{"key":"32788_CR30","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/S0041-624X(99)00200-0","volume":"38","author":"Y Saijo","year":"2000","unstructured":"Saijo, Y., Sasaki, H., Sato, M., Nitta, S. & Tanaka, M. Visualization of human umbilical vein endothelial cells by acoustic microscopy. Ultrason. 38, 396\u2013399 (2000).","journal-title":"Ultrason."},{"key":"32788_CR31","doi-asserted-by":"publisher","first-page":"07JF15","DOI":"10.7567\/JJAP.56.07JF15","volume":"56","author":"TTK Soon","year":"2017","unstructured":"Soon, T. T. K. et al. Effects of anticancer drugs on glia-glioma brain tumor model characterized by acoustic impedance microscopy. Jpn. J. Appl. Phys. 56, 07JF15 (2017).","journal-title":"Jpn. J. Appl. Phys."},{"issue":"9","key":"32788_CR32","doi-asserted-by":"publisher","first-page":"096018","DOI":"10.1117\/1.3626865","volume":"16","author":"J Phipps","year":"2011","unstructured":"Phipps, J. et al. Fluorescence lifetime imaging for the characterization of the biochemical composition of atherosclerotic plaques. J. Biomed. Opt. 16(9), 096018 (2011).","journal-title":"J. Biomed. Opt."},{"key":"32788_CR33","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/lsm.22059","volume":"44","author":"JE Phipps","year":"2012","unstructured":"Phipps, J. E., Sun, Y., Fishbein, M. C. & Marcu, L. A fluorescence lifetime imaging classification method to investigate the collagen to lipid ratio in fibrous caps of atherosclerotic plaque. Lasers Surg. Medicine 44, 564\u2013571 (2012).","journal-title":"Lasers Surg. Medicine"},{"key":"32788_CR34","doi-asserted-by":"publisher","first-page":"754839","DOI":"10.1117\/12.842724","volume":"7548","author":"J Phipps","year":"2010","unstructured":"Phipps, J. et al. Endoscopic fluorescence lifetime imaging microcopy (FLIM) images of aortic plaque: an automated classification method. Proc. SPIE 7548, 754839 (2010).","journal-title":"Proc. SPIE"},{"issue":"1","key":"32788_CR35","doi-asserted-by":"publisher","first-page":"011106","DOI":"10.1117\/1.3327279","volume":"15","author":"L Marcu","year":"2010","unstructured":"Marcu, L. Fluorescence lifetime in cardiovascular diagnostics. J. Biomed. Opt. 15(1), 011106 (2010).","journal-title":"J. Biomed. Opt."},{"issue":"4","key":"32788_CR36","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/jbio.201400142","volume":"8","author":"R Cicchi","year":"2015","unstructured":"Cicchi, R. et al. Non-linear imaging and characterization of atherosclerotic arterial tissue using combined SHG and FLIM microscopy. J. Biophotonics 8(4), 347\u2013356 (2015).","journal-title":"J. Biophotonics"},{"key":"32788_CR37","first-page":"910","volume":"16","author":"JA Jo","year":"2015","unstructured":"Jo, J. A. et al. Simultaneous morphological and biochemical endogeneous optical imaging of atherosclerosis. Cardiovasc. Imaging 16, 910\u2013918 (2015).","journal-title":"Cardiovasc. Imaging"},{"key":"32788_CR38","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/jbio.201500341","volume":"9","author":"S Dochow","year":"2016","unstructured":"Dochow, S. et al. Comparing raman and fluorescence lifetime spectroscopy from human atherosclerotic lesions using a bimodal probe. J. Biophotonics 9, 958\u2013966 (2016).","journal-title":"J. Biophotonics"},{"key":"32788_CR39","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s12265-015-9627-3","volume":"8","author":"H Fatakdawala","year":"2015","unstructured":"Fatakdawala, H. et al. Fluorescence lifetime imaging combined with conventional intravascular ultrasound for enhanced assessment of atherosclerotic plaques: an ex vivo study in human coronary arteries. J. Cardiovasc. Transl. Res. 8, 253\u2013263 (2015).","journal-title":"J. Cardiovasc. Transl. Res."},{"issue":"5","key":"32788_CR40","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/jbio.201200220","volume":"7","author":"J Bec","year":"2014","unstructured":"Bec, J. et al. Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries. J. Biophotonics 7(5), 281\u2013285 (2014).","journal-title":"J. Biophotonics"},{"issue":"7","key":"32788_CR41","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1161\/01.CIR.103.7.934","volume":"103","author":"AP Burke","year":"2001","unstructured":"Burke, A. P. et al. Healed plaque ruptures and sudden coronary death: evidence that subclinical rupture has a role in plaque progression. Circ. 103(7), 934\u2013940 (2001).","journal-title":"Circ."},{"key":"32788_CR42","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.colsurfb.2014.07.043","volume":"122","author":"X Wang","year":"2014","unstructured":"Wang, X. et al. Multifunctional graphene quantum dots for simultaneous targeted cellular imaging and drug delivery. Colloids Surfaces B: Biointerfaces 122, 638\u2013644 (2014).","journal-title":"Colloids Surfaces B: Biointerfaces"},{"issue":"4","key":"32788_CR43","first-page":"465","volume":"38","author":"Y Naganuma","year":"2017","unstructured":"Naganuma, Y. et al. A basic study on the application of ultrasound microscope to the diagnosis of dental caries. J. Jpn. Soc. for Disabil. Oral Heal. 38(4), 465\u2013470 (2017).","journal-title":"J. Jpn. Soc. for Disabil. Oral Heal."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32788-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T09:52:30Z","timestamp":1671616350000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-32788-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,26]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["32788"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-32788-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,26]]},"assertion":[{"value":"8 May 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"14378"}}