{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:19:35Z","timestamp":1791908375752,"version":"4.3.4"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"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":["Eur Radiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>To assess whether extended delayed phase imaging, performed after gadoxetic acid administration for 60\u2013120\u2009min (termed as super delayed phase [SDP]), improves liver contrast and nodule visibility in patients with chronic liver disease and to identify predictors for contrast enhancement.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this retrospective study, 116 patients with chronic liver disease were selected from 6933 gadoxetic acid-enhanced MRI examinations, which included SDP images. The liver-to-spleen contrast (LSC) was quantitatively evaluated, and factors influencing the improvement of LSC were analyzed. By comparing the standard hepatobiliary phase images at 20\u2009min post-contrast (HBP20) with SDP images, nodule visibility was evaluated by two readers who were blinded to the study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>SDP significantly enhanced LSC (SDP: 1.81\u2009\u00b1\u20090.48 vs HBP20: 1.50\u2009\u00b1\u20090.34, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and improved nodule visibility in patients with initially poor LSC. Total bilirubin levels and visible biliary excretion during HBP20 are predictors of LSC enhancement. Furthermore, nodule visibility scores significantly increased in the group with poor initial contrast (Reader 1: from 2.92\u2009\u00b1\u20091.57 to 3.79\u2009\u00b1\u20091.44; Reader 2: from 2.34\u2009\u00b1\u20091.42 to 3.36\u2009\u00b1\u20091.57, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>SDP enhanced liver contrast and nodule detection in patients with chronic liver disease, particularly in those with impaired liver function. Total bilirubin levels and visible biliary excretion during HBP20 are useful predictors of improvement. This technique may improve the diagnostic utility of MRI for hepatocarcinogenesis in cirrhotic nodules, specifically for detecting precursors of hepatocellular carcinoma, in cirrhotic patients with compromised liver function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key Points<\/jats:title>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Question<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>In gadoxetic acid-enhanced MRI, inadequate liver contrast can occur in patients with impaired liver function, potentially limiting the diagnostic value of the examination<\/jats:italic>.<\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Findings<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>SDP images improved liver parenchymal signal intensity and visibility of hepatocellular carcinoma, even in cases with impaired liver function<\/jats:italic>.<\/jats:p>\n            <jats:p>\n              <jats:bold>\n                <jats:italic>Clinical relevance<\/jats:italic>\n              <\/jats:bold>\n              <jats:italic>The addition of SDP imaging in gadoxetic acid-enhanced MRI improves liver contrast and early detection of hepatocellular carcinoma, especially in patients with impaired liver function, such as Child\u2013Pugh B or C, aiding in making appropriate treatment decisions<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00330-024-11227-z","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T18:08:03Z","timestamp":1732903683000},"page":"3195-3205","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Super delayed phase imaging in gadoxetic acid-enhanced MRI: investigating factors contributing to improved liver contrast"],"prefix":"10.1007","volume":"35","author":[{"given":"Tomohiro","family":"Kobayashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-7623","authenticated-orcid":false,"given":"Kazuto","family":"Kozaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Yokka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saya","family":"Igarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Kitao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihide","family":"Yoneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Okuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Gabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"11227_CR1","unstructured":"International Agency for Research on Cancer. https:\/\/www.iarc.who.int\/"},{"key":"11227_CR2","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1148\/radiology.195.3.7754011","volume":"195","author":"B Hamm","year":"1995","unstructured":"Hamm B, Staks T, M\u00fchler A et al (1995) Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology 195:785\u2013792. https:\/\/doi.org\/10.1148\/radiology.195.3.7754011","journal-title":"Radiology"},{"key":"11227_CR3","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1148\/radiol.2342040278","volume":"234","author":"A Huppertz","year":"2005","unstructured":"Huppertz A, Haraida S, Kraus A et al (2005) Enhancement of focal liver lesions at gadoxetic acid-enhanced MR imaging: correlation with histopathologic findings and spiral CT\u2014initial observations. Radiology 234:468\u2013478. https:\/\/doi.org\/10.1148\/radiol.2342040278","journal-title":"Radiology"},{"key":"11227_CR4","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1097\/RLI.0b013e3181e943a7","volume":"45","author":"YK Kim","year":"2010","unstructured":"Kim YK, Kim CS, Han YM, Park G (2010) Detection of small hepatocellular carcinoma: Can gadoxetic acid-enhanced magnetic resonance imaging replace combining gadopentetate dimeglumine-enhanced and superparamagnetic iron oxide-enhanced magnetic resonance imaging? Invest Radiol 45:740\u2013746. https:\/\/doi.org\/10.1097\/RLI.0b013e3181e943a7","journal-title":"Invest Radiol"},{"key":"11227_CR5","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1148\/radiol.11101840","volume":"261","author":"K Sano","year":"2011","unstructured":"Sano K, Ichikawa T, Motosugi U et al (2011) Imaging study of early hepatocellular carcinoma: usefulness of gadoxetic acid-enhanced MR imaging. Radiology 261:834\u2013844. https:\/\/doi.org\/10.1148\/radiol.11101840","journal-title":"Radiology"},{"key":"11227_CR6","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1007\/s00330-020-06687-y","volume":"30","author":"A Kitao","year":"2020","unstructured":"Kitao A, Matsui O, Yoneda N et al (2020) Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background. Eur Radiol 30:3438\u20133447. https:\/\/doi.org\/10.1007\/s00330-020-06687-y","journal-title":"Eur Radiol"},{"key":"11227_CR7","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1148\/radiol.14132361","volume":"272","author":"JY Choi","year":"2014","unstructured":"Choi JY, Lee JM, Sirlin CB (2014) CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects. Radiology 272:635\u2013654. https:\/\/doi.org\/10.1148\/radiol.14132361","journal-title":"Radiology"},{"key":"11227_CR8","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1148\/radiol.10091388","volume":"255","author":"SS Ahn","year":"2010","unstructured":"Ahn SS, Kim MJ, Lim JS, Hong HS, Chung YE, Choi JY (2010) Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology 255:459\u2013466. https:\/\/doi.org\/10.1148\/radiol.10091388","journal-title":"Radiology"},{"key":"11227_CR9","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1259\/bjr\/66686028","volume":"83","author":"G Park","year":"2010","unstructured":"Park G, Kim YK, Kim CS, Yu HC, Hwang SB (2010) Diagnostic efficacy of gadoxetic acid-enhanced MRI in the detection of hepatocellular carcinomas: comparison with gadopentetate dimeglumine. Br J Radiol 83:1010\u20131016. https:\/\/doi.org\/10.1259\/bjr\/66686028","journal-title":"Br J Radiol"},{"key":"11227_CR10","unstructured":"PRIMOVIST (2010) Product monograph. https:\/\/www.bayer.com\/sites\/default\/files\/2020-11\/primovist-pm-en.pdf"},{"key":"11227_CR11","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1007\/s00330-009-1467-6","volume":"19","author":"U Motosugi","year":"2009","unstructured":"Motosugi U, Ichikawa T, Tominaga L et al (2009) Delay before the hepatocyte phase of Gd-EOB-DTPA-enhanced MR imaging: Is it possible to shorten the examination time? Eur Radiol 19:2623\u20132629. https:\/\/doi.org\/10.1007\/s00330-009-1467-6","journal-title":"Eur Radiol"},{"key":"11227_CR12","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1148\/radiol.2016151061","volume":"281","author":"M Okada","year":"2016","unstructured":"Okada M, Murakami T, Kuwatsuru R et al (2016) Biochemical and clinical predictive approach and time point analysis of hepatobiliary phase liver enhancement on Gd-EOB-DTPA-enhanced MR images: a multicenter study. Radiology 281:474\u2013483. https:\/\/doi.org\/10.1148\/radiol.2016151061","journal-title":"Radiology"},{"key":"11227_CR13","doi-asserted-by":"publisher","first-page":"152","DOI":"10.2463\/mrms.mp.2020-0050","volume":"20","author":"Y Takatsu","year":"2021","unstructured":"Takatsu Y, Nakamura M, Kobayashi S, Miyati T (2021) Prediction of sufficient liver enhancement on the gadoxetate disodium-enhanced hepatobiliary phase imaging using transitional phase images and albumin\u2013bilirubin grade. Magn Reson Med Sci 20:152\u2013159. https:\/\/doi.org\/10.2463\/mrms.mp.2020-0050","journal-title":"Magn Reson Med Sci"},{"key":"11227_CR14","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1097\/RLI.0b013e318200f67d","volume":"46","author":"T Katsube","year":"2011","unstructured":"Katsube T, Okada M, Kumano S et al (2011) Estimation of liver function using T1 mapping on Gd-EOB-DTPA-enhanced magnetic resonance imaging. Invest Radiol 46:277\u2013283. https:\/\/doi.org\/10.1097\/RLI.0b013e318200f67d","journal-title":"Invest Radiol"},{"key":"11227_CR15","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7630671","volume":"2019","author":"Y Inoue","year":"2019","unstructured":"Inoue Y, Hata H, Nakajima A et al (2019) Quantitative evaluation of display contrast of Gd-EOB-DTPA-enhanced magnetic resonance images: effects of the flip angle and grayscale gamma value Radiol Res Pract 2019:7630671. https:\/\/doi.org\/10.1155\/2019\/7630671","journal-title":"Radiol Res Pract"},{"key":"11227_CR16","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2214\/AJR.13.11903","volume":"204","author":"ES Cho","year":"2015","unstructured":"Cho ES, Yu JS, Park AY, Woo S, Kim JH, Chung JJ (2015) Feasibility of 5-minute delayed transition phase imaging with 30 degrees flip angle in gadoxetic acid-enhanced 3D gradient-echo MRI of liver, compared with 20-minute delayed hepatocyte phase MRI with standard 10 degrees flip angle. AJR Am J Roentgenol 204:69\u201375. https:\/\/doi.org\/10.2214\/AJR.13.11903","journal-title":"AJR Am J Roentgenol"},{"key":"11227_CR17","doi-asserted-by":"publisher","first-page":"e0139863","DOI":"10.1371\/journal.pone.0139863","volume":"10","author":"D Lee","year":"2015","unstructured":"Lee D, Cho ES, Kim DJ, Kim JH, Yu JS, Chung JJ (2015) Validation of 10-minute delayed hepatocyte phase imaging with 30\u00b0 flip angle in gadoxetic acid-enhanced MRI for the detection of liver metastasis. PLoS One 10:e0139863. https:\/\/doi.org\/10.1371\/journal.pone.0139863","journal-title":"PLoS One"},{"key":"11227_CR18","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/j.crad.2015.03.005","volume":"70","author":"YB Esterson","year":"2015","unstructured":"Esterson YB, Flusberg M, Oh S, Mazzariol F, Rozenblit AM, Chernyak V (2015) Improved parenchymal liver enhancement with extended delay on Gd-EOB-DTPA-enhanced MRI in patients with parenchymal liver disease: associated clinical and imaging factors. Clin Radiol 70:723\u2013729. https:\/\/doi.org\/10.1016\/j.crad.2015.03.005","journal-title":"Clin Radiol"},{"key":"11227_CR19","doi-asserted-by":"publisher","first-page":"626","DOI":"10.6009\/jjrt.65.626","volume":"65","author":"S Akimoto","year":"2009","unstructured":"Akimoto S, Mori H, Fujii T, Furuya K (2009) [Optimal scan timing for Gd-EOB-DTPA enhanced liver dynamic MR imaging]. Nihon Hoshasen Gijutsu Gakkai Zasshi 65:626\u2013630","journal-title":"Nihon Hoshasen Gijutsu Gakkai Zasshi"},{"key":"11227_CR20","unstructured":"American College of Radiology. \u201cTechnique.\u201d RADS - Reporting and Data Systems Support. Last modified March 6, 2020. Accessed November 24, 2024. https:\/\/radssupport.acr.org\/support\/solutions\/articles\/11000079466-technique"},{"key":"11227_CR21","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.jhep.2012.01.031","volume":"57","author":"BE Van Beers","year":"2012","unstructured":"Van Beers BE, Pastor CM, Hussain HK (2012) Primovist, eovist: What to expect? J Hepatol 57:421\u2013429. https:\/\/doi.org\/10.1016\/j.jhep.2012.01.031","journal-title":"J Hepatol"},{"key":"11227_CR22","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s00330-022-08984-0","volume":"33","author":"S Poetter-Lang","year":"2023","unstructured":"Poetter-Lang S, Dovjak GO, Messner A et al (2023) Influence of dilution on arterial-phase artifacts and signal intensity on gadoxetic acid-enhanced liver MRI. Eur Radiol 33:523\u2013534. https:\/\/doi.org\/10.1007\/s00330-022-08984-0","journal-title":"Eur Radiol"},{"key":"11227_CR23","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1080\/08941939.2016.1238983","volume":"30","author":"J Kim","year":"2017","unstructured":"Kim J, Kim T, Hong KS et al (2017) Pre-hepatectomy assessment of bile transporter expression by gadoxetic acid-enhanced MRI in a rat model of liver cirrhosis. J Invest Surg 30:265\u2013271. https:\/\/doi.org\/10.1080\/08941939.2016.1238983","journal-title":"J Invest Surg"},{"key":"11227_CR24","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1002\/jmri.25288","volume":"44","author":"S Lee","year":"2016","unstructured":"Lee S, Choi D, Jeong WK (2016) Hepatic enhancement of Gd-EOB-DTPA-enhanced 3 Tesla MR imaging: assessing severity of liver cirrhosis. J Magn Reson Imaging 44:1339\u20131345. https:\/\/doi.org\/10.1002\/jmri.25288","journal-title":"J Magn Reson Imaging"},{"key":"11227_CR25","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3348\/kjr.2021.0407","volume":"23","author":"JA Hwang","year":"2022","unstructured":"Hwang JA, Min JH, Kim SH, Choi SY, Lee JE, Moon JY (2022) Total bilirubin level as a predictor of suboptimal image quality of the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with extrahepatic bile duct cancer. Korean J Radiol 23:389\u2013401. https:\/\/doi.org\/10.3348\/kjr.2021.0407","journal-title":"Korean J Radiol"},{"key":"11227_CR26","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/S0022-3565(24)34879-7","volume":"290","author":"JE van Montfoort","year":"1999","unstructured":"van Montfoort JE, Stieger B, Meijer DK, Weinmann HJ, Meier PJ, Fattinger KE (1999) Hepatic uptake of the magnetic resonance imaging contrast agent gadoxetate by the organic anion transporting polypeptide Oatp1. J Pharmacol Exp Ther 290:153\u2013157","journal-title":"J Pharmacol Exp Ther"},{"key":"11227_CR27","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/jmri.22805","volume":"35","author":"H Haradome","year":"2012","unstructured":"Haradome H, Grazioli L, Al manea K et al (2012) Gadoxetic acid disodium-enhanced hepatocyte phase MRI: Can increasing the flip angle improve focal liver lesion detection? J Magn Reson Imaging 35:132\u2013139. https:\/\/doi.org\/10.1002\/jmri.22805","journal-title":"J Magn Reson Imaging"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-024-11227-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-024-11227-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-024-11227-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T11:07:54Z","timestamp":1747307274000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-024-11227-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,29]]},"references-count":27,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["11227"],"URL":"https:\/\/doi.org\/10.1007\/s00330-024-11227-z","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,29]]},"assertion":[{"value":"14 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 November 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The scientific guarantor of this publication is Satoshi Kobayashi.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guarantor"}},{"value":"The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"No complex statistical methods were necessary for this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statistics and biometry"}},{"value":"Written informed consent was waived by the Institutional Review Board.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Institutional Review Board approval was obtained (approval number: 2389-6).","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"There is no overlap of study subjects or cohorts.","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Study subjects or cohorts overlap"}},{"order":8,"name":"Ethics","group":{"name":"EthicsHeading","label":"Methodology"}}]}}