{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:47:23Z","timestamp":1788058043312,"version":"build-2784847793"},"reference-count":36,"publisher":"IOP Publishing","issue":"20","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/page\/copyright"},{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"NIH","award":["R01 CA172336"],"award-info":[{"award-number":["R01 CA172336"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Med. Biol."],"published-print":{"date-parts":[[2024,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Subcutaneous microbubble administration in connection with contrast enhanced ultrasound (CEUS) imaging is showing promise as a noninvasive and sensitive way to detect tumor draining sentinel lymph nodes (SLNs) in patients with breast cancer. Moreover, there is potential to harness the results from these approaches to directly estimate cancer burden, since some microbubble formulas, such as the Sonazoid used in this study, are rapidly phagocytosed by macrophages, and the macrophage concentration in a lymph node is inversely related to the cancer burden. This work presents a mathematical model that can approximate a rate constant governing macrophage uptake of Sonazoid, <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic>, given dynamic CEUS Sonazoid imaging data. Twelve healthy women were injected with 1.0 ml of Sonazoid in an upper-outer quadrant of one of their breasts and SLNs were imaged in each patient immediately after injection, and then at 0.25, 0.5, 1, 2, 4, 6, and 24 h after injection. The mathematical model developed was fit to the dynamic CEUS data from each subject resulting in a mean \u00b1 sd of 0.006 \u00b1 0.005 h<jats:sup>\u22121<\/jats:sup> and 0.4 \u00b1 0.1 h<jats:sup>\u22121<\/jats:sup> for relative lymphatic flow (<jats:italic>EF<jats:sub>l<\/jats:sub>\n                  <\/jats:italic>) and <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic>, respectively. Furthermore, the roughly 25% sd of the <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic> measurement was similar to the sd that would be expected from realistic noise simulations for a stable 0.4 h<jats:sup>\u22121<\/jats:sup> value of <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic>, suggesting that macrophage concentration is highly consistent among cancer-free SLNs. These results, along with the significantly smaller variance in <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic> measurement observed compared to relative lymphatic flow suggest that <jats:italic>k<jats:sub>i<\/jats:sub>\n                  <\/jats:italic> may be a more precise and promising approach of estimating macrophage abundance, and inversely cancer burden. Future studies comparing tumor-free to tumor-bearing nodes are planned to verify this hypothesis.<\/jats:p>","DOI":"10.1088\/1361-6560\/ad7f1c","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T23:00:25Z","timestamp":1727218825000},"page":"205006","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Macrophage uptake rate of Sonazoid in breast lymphosonography is highly conserved in healthy controls"],"prefix":"10.1088","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-3026","authenticated-orcid":true,"given":"Kenneth M","family":"Tichauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscilla","family":"Machado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A S Chalmika","family":"Sarathchandra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Stanczak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter K","family":"Kraft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-1371","authenticated-orcid":true,"given":"Flemming","family":"Forsberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"pmbad7f1cbib1","doi-asserted-by":"publisher","first-page":"e351","DOI":"10.1016\/S1470-2045(13)70590-4","article-title":"Novel techniques for sentinel lymph node biopsy in breast cancer: a systematic review","volume":"15","author":"Ahmed","year":"2014","journal-title":"Lancet Oncol."},{"key":"pmbad7f1cbib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1137\/S1064827595289108","article-title":"A subspace, interior, and conjugate gradient method for large-scale bound-constrained minimization problems","volume":"21","author":"Branch","year":"1999","journal-title":"SIAM J. Sci. Comput."},{"key":"pmbad7f1cbib3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2024.102441","article-title":"Recent advances in ratiometric fluorescence imaging of enzyme activity in vivo","volume":"80","author":"Cosco","year":"2024","journal-title":"Curr. Opin. Chem. Biol."},{"key":"pmbad7f1cbib4","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.jamcollsurg.2007.08.024","article-title":"Significance of sentinel lymph node micrometastases in human breast cancer","volume":"206","author":"Cox","year":"2008","journal-title":"J. Am. Coll. Surg."},{"key":"pmbad7f1cbib5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.suronc.2020.06.005","article-title":"New technologies in breast cancer sentinel lymph node biopsy; from the current gold standard to artificial intelligence","volume":"34","author":"Cykowska","year":"2020","journal-title":"Surg. Oncol."},{"key":"pmbad7f1cbib6","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1364\/BOE.6.001304","article-title":"Nodal lymph flow quantified with afferent vessel input function allows differentiation between normal and cancer-bearing nodes","volume":"6","author":"DSouza","year":"2015","journal-title":"Biomed. Opt. Express"},{"key":"pmbad7f1cbib7","doi-asserted-by":"publisher","first-page":"7258","DOI":"10.1021\/acs.analchem.1c00469","article-title":"Protease secretion visualization and metastatic lymph nodes imaging","volume":"93","author":"Fang","year":"2021","journal-title":"Anal. Chem."},{"key":"pmbad7f1cbib8","doi-asserted-by":"publisher","first-page":"S405","DOI":"10.21037\/tcr.2018.02.07","article-title":"New techniques for sentinel node biopsy in breast cancer","volume":"7","author":"Ferrucci","year":"2018","journal-title":"Transl. Cancer Res."},{"key":"pmbad7f1cbib9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.7863\/jum.2011.30.4.441","article-title":"Contrast-enhanced ultrasound imaging of sentinel lymph nodes after peritumoral administration of Sonazoid in a melanoma tumor animal model","volume":"30","author":"Goldberg","year":"2011","journal-title":"J. Ultrasound Med."},{"key":"pmbad7f1cbib10","doi-asserted-by":"publisher","first-page":"953","DOI":"10.7863\/jum.2005.24.7.953","article-title":"Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes","volume":"24","author":"Goldberg","year":"2005","journal-title":"J. Ultrasound Med."},{"key":"pmbad7f1cbib11","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1148\/radiol.2303021440","article-title":"Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US","volume":"230","author":"Goldberg","year":"2004","journal-title":"Radiology"},{"key":"pmbad7f1cbib12","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.1245\/s10434-010-1155-4","article-title":"Morbidity of sentinel node biopsy in breast cancer: the relationship between the number of excised lymph nodes and lymphedema","volume":"17","author":"Goldberg","year":"2010","journal-title":"Ann. Surg. Oncol."},{"key":"pmbad7f1cbib13","doi-asserted-by":"publisher","first-page":"5894","DOI":"10.1007\/s00330-020-07639-2","article-title":"Percutaneous Sonazoid-enhanced ultrasonography combined with in vitro verification for detection and characterization of sentinel lymph nodes in early breast cancer","volume":"31","author":"Hao","year":"2021","journal-title":"Eur. Radiol."},{"key":"pmbad7f1cbib14","doi-asserted-by":"publisher","first-page":"774","DOI":"10.2353\/ajpath.2007.060761","article-title":"Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis","volume":"170","author":"Harrell","year":"2007","journal-title":"Am. J. Pathol."},{"key":"pmbad7f1cbib15","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.hepres.2006.04.016","article-title":"Ultrasound contrast agent, Levovist microbubbles are phagocytosed by Kupffer cells-in vitro and in vivo studies","volume":"35","author":"Iijima","year":"2006","journal-title":"Hepatol. Res."},{"key":"pmbad7f1cbib16","first-page":"90","article-title":"Size- and surface-dependent uptake of colloid particles into the lymphatic system","volume":"32","author":"Ikomi","year":"1999","journal-title":"Lymphology"},{"key":"pmbad7f1cbib17","first-page":"1285","article-title":"Differentiation of benign and malignant lymph nodes with contrast-enhanced echolymphography using endoscopic ultrasound-guided puncture","volume":"50","author":"Kojima","year":"2003","journal-title":"Hepatogastroenterology"},{"key":"pmbad7f1cbib18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.jim.2010.06.016","article-title":"Functional lymphatic imaging in tumor-bearing mice","volume":"360","author":"Kwon","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"pmbad7f1cbib19","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1002\/jso.25124","article-title":"Noninvasive detection of cancer spread to lymph nodes: a review of molecular imaging principles and protocols","volume":"118","author":"Li","year":"2018","journal-title":"J. Surg. Oncol."},{"key":"pmbad7f1cbib20","doi-asserted-by":"publisher","first-page":"7191","DOI":"10.7150\/thno.78085","article-title":"Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes","volume":"12","author":"Li","year":"2022","journal-title":"Theranostics"},{"key":"pmbad7f1cbib21","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1097\/eus.0000000000000001","article-title":"Identification of sentinel lymph nodes in esophageal cancer patients using contrast-enhanced EUS with peritumoral injections","volume":"12","author":"Liu","year":"2023","journal-title":"Endosc. Ultrasound"},{"key":"pmbad7f1cbib22","doi-asserted-by":"publisher","first-page":"939","DOI":"10.7863\/ultra.33.6.939","article-title":"Contrast-enhanced sonography for detection of secondary lymph nodes in a melanoma tumor animal model","volume":"33","author":"Liu","year":"2014","journal-title":"J. Ultrasound Med."},{"key":"pmbad7f1cbib23","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1016\/j.ultrasmedbio.2022.10.020","article-title":"Sentinel lymph node identification in patients with breast cancer using lymphosonography","volume":"49","author":"Machado","year":"2023a","journal-title":"Ultrasound Med. Biol."},{"key":"pmbad7f1cbib24","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1002\/jum.16164","article-title":"Sentinel lymph node identification in post neoadjuvant chemotherapy breast cancer patients undergoing surgical excision using lymphosonography","volume":"42","author":"Machado","year":"2023b","journal-title":"J. Ultrasound Med."},{"key":"pmbad7f1cbib25","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1002\/jum.14502","article-title":"Subdermal ultrasound contrast agent injection for sentinel lymph node identification: an analysis of safety and contrast agent dose in healthy volunteers","volume":"37","author":"Machado","year":"2018","journal-title":"J. Ultrasound Med."},{"key":"pmbad7f1cbib26","doi-asserted-by":"publisher","first-page":"1544","DOI":"10.3390\/medicina59091544","article-title":"Future directions in the assessment of axillary lymph nodes in patients with breast cancer","volume":"59","author":"Pesapane","year":"2023","journal-title":"Medicina"},{"key":"pmbad7f1cbib27","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.pathophys.2009.11.003","article-title":"Lymphangiogenesis and lymphatic metastasis in breast cancer","volume":"17","author":"Ran","year":"2010","journal-title":"Pathophysiology"},{"key":"pmbad7f1cbib28","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.copbio.2009.01.009","article-title":"Lymphatic imaging in humans with near-infrared fluorescence","volume":"20","author":"Rasmussen","year":"2009","journal-title":"Curr. Opin. Biotechnol."},{"key":"pmbad7f1cbib29","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1158\/0008-5472.CAN-12-2969","article-title":"Real-time in vivo molecular detection of primary tumors and metastases with ratiometric activatable cell-penetrating peptides","volume":"73","author":"Savariar","year":"2013","journal-title":"Cancer Res."},{"key":"pmbad7f1cbib30","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1002\/cam4.1142","article-title":"Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with Sonazoid in patients with breast cancer: a feasibility study in three hospitals","volume":"6","author":"Shimazu","year":"2017","journal-title":"Cancer Med."},{"key":"pmbad7f1cbib31","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1016\/j.ultrasmedbio.2019.07.005","article-title":"Real-time visualization of lymphatic flow to sentinel lymph nodes by contrast-enhanced ultrasonography with sonazoid in patients with breast cancer","volume":"45","author":"Shimazu","year":"2019","journal-title":"Ultrasound Med. Biol."},{"key":"pmbad7f1cbib32","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.ultrasmedbio.2007.11.006","article-title":"Physicochemical characteristics of Sonazoid, a new contrast agent for ultrasound imaging","volume":"34","author":"Sontum","year":"2008","journal-title":"Ultrasound Med. Biol."},{"key":"pmbad7f1cbib33","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1097\/00004647-199812000-00011","article-title":"An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: I. theoretical derivation","volume":"18","author":"St. Lawrence","year":"1998","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"pmbad7f1cbib34","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1038\/nm.3732","article-title":"Microscopic lymph node tumor burden quantified by macroscopic dual-tracer molecular imaging","volume":"20","author":"Tichauer","year":"2014","journal-title":"Nat. Med."},{"key":"pmbad7f1cbib35","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1021\/acs.nanolett.3c03719","article-title":"Multiplex ultrasound imaging of perfluorocarbon nanodroplets enabled by decomposition of postvaporization dynamics","volume":"24","author":"Van Namen","year":"2024","journal-title":"Nano Lett."},{"key":"pmbad7f1cbib36","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1097\/SLA.0b013e3181c0e92a","article-title":"Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study","volume":"251","author":"Veronesi","year":"2010","journal-title":"Ann. Surg."}],"container-title":["Physics in Medicine &amp; Biology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T09:15:10Z","timestamp":1728033310000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ad7f1c"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":36,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2024,10,4]]},"published-print":{"date-parts":[[2024,10,21]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6560\/ad7f1c","relation":{},"ISSN":["0031-9155","1361-6560"],"issn-type":[{"value":"0031-9155","type":"print"},{"value":"1361-6560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]},"assertion":[{"value":"Macrophage uptake rate of Sonazoid in breast lymphosonography is highly conserved in healthy controls","name":"article_title","label":"Article Title"},{"value":"Physics in Medicine & Biology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2024-05-29","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-09-24","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2024-10-04","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}