{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:22:17Z","timestamp":1791285737176,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bone fractures are common injuries with reported non\u2010union rates of up to 9%. Current treatments for non\u2010union include surgery with complication rates of up to 17% and significant costs. Microbubbles are used clinically in ultrasonography as contrast agents and have been shown to deliver therapeutics to desired locations by noninvasive stimulation of cavitation using extracorporeal ultrasound in preclinical studies. Contrast enhanced ultrasound (CEUS) has been used to determine the cause of established fracture non\u2010unions, though this is not in widespread use clinically. This pilot study aimed to test the hypothesis that peripherally injected microbubbles are detectable in acute fracture sites. Adult patients (18\u201375\u2009yrs) with acute humeral shaft fractures were recruited to undergo CEUS within 28 days of injury. They underwent peripheral injection of SonoVue microbubbles with ultrasound imaging. B\u2010mode and contrast\u2010mode videos were collected and time\u2010intensity curve analysis was used to assess for the presence of microbubbles at the fracture site. Ten patients were recruited, 8 underwent humeral shaft fracture scans with 7 analysed. All fracture sites demonstrated increased contrast signal following injection. The wash\u2010in volume of microbubbles was greater than the wash\u2010out volume in all cases, with a mean difference of 1.4\u2009\u00d7\u200910\u207b\u2075 (\u00b1\u20091.7 \u00d7 10\u207b\u2075) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.015 Wilcoxon Test). There was a trend toward decreasing PI and TtP with fracture age, though not statistically significant (R\u00b2\u2009=\u20090.44,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.1; R\u00b2 = 0.24,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.26, respectively). This pilot study demonstrates that commercially available microbubbles perfuse acute fractures in ultrasonographically detectable quantities using commercially available equipment.\n                  <\/jats:p>","DOI":"10.1002\/jor.70100","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T12:49:29Z","timestamp":1765630169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Contrast\u2010Enhanced Ultrasound (CEUS) Reveals Perfusion of Human Bone in Acute Fracture Healing: A Pilot Study"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0169-5484","authenticated-orcid":false,"given":"D.","family":"Cadoux\u2010Hudson","sequence":"first","affiliation":[{"name":"Bone and Joint Research Group University of Southampton Southampton UK"},{"name":"Department of Trauma and Orthopaedic Surgery University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopaedic Surgery University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Hurst","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Group University of Southampton Southampton UK"},{"name":"Department of Trauma and Orthopaedic Surgery University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Schranz","sequence":"additional","affiliation":[{"name":"Southampton Centre for Biomedical Research University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Gerrish","sequence":"additional","affiliation":[{"name":"Southampton Centre for Biomedical Research University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Wallace","sequence":"additional","affiliation":[{"name":"GE Healthcare Niskayuna New York State USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Warwick","sequence":"additional","affiliation":[{"name":"Department of Trauma and Orthopaedic Surgery University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Carugo","sequence":"additional","affiliation":[{"name":"Botnar Research Institute University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Stride","sequence":"additional","affiliation":[{"name":"Botnar Research Institute University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Tilley","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Group University of Southampton Southampton UK"},{"name":"Department of Trauma and Orthopaedic Surgery University Hospital Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. D.","family":"Evans","sequence":"additional","affiliation":[{"name":"Bone and Joint Research Group University of Southampton Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1558259"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17453674.2017.1321351"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2020.0006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-1383(07)80012-X"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-42"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753193412451424"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2020.11.029"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-200101000-00002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3182aafe0d"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-006-0280-6"},{"issue":"5","key":"e_1_2_8_12_1","first-page":"673","article-title":"Measurement of Blood Flow in Tibial Fracture Patients Using Positron Emission Tomography","volume":"74","author":"Ashcroft G. P. N. T.","year":"1992","journal-title":"The Journal of Bone and Joint Surgery. British Volume"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.12659\/PJR.894548"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21490"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/b809517p"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.4142\/jvs.2020.21.e10"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics8030055"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.7863\/ultra.15.06107"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jse.2011.04.001"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2483071400"},{"key":"e_1_2_8_21_1","article-title":"Low Intensity Pulsed Ultrasound for Bone Healing: Systematic Review of Randomized Controlled Trials","volume":"1","author":"Schandelmaier S.","year":"2017","journal-title":"BMJ"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.19.00790"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcot.2019.10.009"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.langmuir.8b03779"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113847"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-71831-3"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191788"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0637-1679"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05376.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13244-022-01335-z"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani11020284"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20210189"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70100","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.70100","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.70100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:57:44Z","timestamp":1769648264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.70100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,13]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/jor.70100"],"URL":"https:\/\/doi.org\/10.1002\/jor.70100","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,13]]},"assertion":[{"value":"2025-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70100"}}