{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:47:54Z","timestamp":1792259274624,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"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":["Jpn J Radiol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the CT imaging features including extracellular volume (ECV) fraction measured by dual-layer spectral detector CT for differentiating G1 from G2 tumors in pancreatic neuroendocrine neoplasms (pNENs), as compared with single-energy CT (SECT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included 45 patients with histologically confirmed pNENs (G1,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200928; G2,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917) who underwent dynamic contrast-enhanced CT using a dual-layer spectral detector system. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for tumor and the aorta, and SECT-ECV fraction was calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and dual-energy CT (DECT)-ECV fraction of the tumor was calculated. Histological tumor cell density and Ki-67 index were also assessed to evaluate the correlations with ECV fractions. Statistical analysis was performed to identify independent predictors of tumor grade and evaluate diagnostic performance using receiver operating characteristic (ROC) analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DECT-ECV fractions were significantly lower in G2 tumors than in G1 tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0045). G2 tumors tended to be larger than G1 tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0591), while no other CT features were significantly different between G1 and G2 tumors. The multivariable analysis showed that only DECT-ECV fraction was significantly associated with tumor grade (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0115). ROC analysis for the DECT-ECV fraction showed an area under the curve of 0.756. DECT-ECV fraction demonstrated significant inverse correlations with tumor cell density (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u2212\u20090.434,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0065) and Ki-67 index (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u2009\u2212\u20090.440,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0025).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among the CT imaging findings, only DECT-ECV fraction showed a significant difference between G1 and G2 tumors. DECT-ECV fraction appears to be a useful imaging biomarker for differentiating G1 from G2 tumors in pNENs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11604-026-01976-w","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:16:07Z","timestamp":1778559367000},"page":"1394-1405","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of extracellular volume fraction determined by dual-layer spectral detector CT in predicting the tumor grade of pancreatic neuroendocrine neoplasms"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-050X","authenticated-orcid":false,"given":"Nobuhiro","family":"Fujita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Tabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Ishimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ushijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Makise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nao","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Nakata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Itoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Aishima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinao","family":"Oda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kousei","family":"Ishigami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"1976_CR1","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1136\/gutjnl-2011-300831","volume":"61","author":"JK Ramage","year":"2012","unstructured":"Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, et al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2012;61:6\u201332.","journal-title":"Gut"},{"key":"1976_CR2","first-page":"343","volume-title":"WHO classification of tumours: digestive system tumours","author":"G Kl\u00f6ppel","year":"2019","unstructured":"Kl\u00f6ppel G, Adsay NV, Couvelard A, Hruban RH, Kasajima A, Klimstra DS, et al. Pancreatic neuroendocrine neoplasms. In: WHO classification of tumours: digestive system tumours. 5th ed. Lyon, France: IARC; 2019. p. 343\u201372.","edition":"5th ed"},{"key":"1976_CR3","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s11864-019-0670-1","volume":"20","author":"MB Sonbol","year":"2019","unstructured":"Sonbol MB, Halfdanarson TR. Management of well-differentiated high-grade (G3) neuroendocrine tumors. Curr Treat Options Oncol. 2019;20:74.","journal-title":"Curr Treat Options Oncol"},{"key":"1976_CR4","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1007\/s00330-015-3941-7","volume":"26","author":"JH Kim","year":"2016","unstructured":"Kim JH, Eun HW, Kim YJ, Lee JM, Han JK, Choi BI. Pancreatic neuroendocrine tumour (PNET): Staging accuracy of MDCT and its diagnostic performance for the differentiation of PNET with uncommon CT findings from pancreatic adenocarcinoma. Eur Radiol. 2016;26:1338\u201347.","journal-title":"Eur Radiol"},{"key":"1976_CR5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1148\/radiol.2016160586","volume":"284","author":"SK Jeon","year":"2017","unstructured":"Jeon SK, Lee JM, Joo I, Lee ES, Park HJ, Jang JY, et al. Nonhypervascular pancreatic neuroendocrine tumors: differential diagnosis from pancreatic ductal adenocarcinomas at MR imaging-retrospective cross-sectional study. Radiology. 2017;284:77\u201387.","journal-title":"Radiology"},{"key":"1976_CR6","doi-asserted-by":"publisher","first-page":"390","DOI":"10.2214\/AJR.19.21921","volume":"215","author":"HY Chen","year":"2020","unstructured":"Chen HY, Zhang XY, Deng XY, Ge YL, Tang YQ, Cui H, et al. Grade 3 pancreatic neuroendocrine tumors on MDCT: Establishing a diagnostic model and comparing survival against pancreatic ductal adenocarcinoma. AJR Am J Roentgenol. 2020;215:390\u20137.","journal-title":"AJR Am J Roentgenol"},{"key":"1976_CR7","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1159\/000494355","volume":"107","author":"G Rindi","year":"2018","unstructured":"Rindi G, Klersy C, Albarello L, Baudin E, Bianchi A, Buchler MW, et al. Competitive testing of the WHO 2010 versus the WHO 2017 grading of pancreatic neuroendocrine neoplasms: Data from a large international cohort study. Neuroendocrinology. 2018;107:375\u201386.","journal-title":"Neuroendocrinology"},{"key":"1976_CR8","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.3390\/cancers15072006","volume":"15","author":"ML Sulciner","year":"2023","unstructured":"Sulciner ML, Clancy TE. Surgical management of pancreatic neuroendocrine tumors. Cancers (Basel). 2023;15:2006.","journal-title":"Cancers (Basel)"},{"key":"1976_CR9","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1016\/j.ejrad.2015.05.005","volume":"84","author":"K Takumi","year":"2015","unstructured":"Takumi K, Fukukura Y, Higashi M, Ideue J, Umanodan T, Hakamada H, et al. Pancreatic neuroendocrine tumors: Correlation between the contrast-enhanced computed tomography features and the pathological tumor grade. Eur J Radiol. 2015;84:1436\u201343.","journal-title":"Eur J Radiol"},{"key":"1976_CR10","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/s11604-017-0627-x","volume":"35","author":"F Toshima","year":"2017","unstructured":"Toshima F, Inoue D, Komori T, Yoshida K, Yoneda N, Minami T, et al. Is the combination of MR and CT findings useful in determining the tumor grade of pancreatic neuroendocrine tumors? Jpn J Radiol. 2017;35:242\u201353.","journal-title":"Jpn J Radiol"},{"key":"1976_CR11","doi-asserted-by":"publisher","first-page":"e180003","DOI":"10.1148\/ryct.2019180003","volume":"1","author":"S Oda","year":"2019","unstructured":"Oda S, Emoto T, Nakaura T, Kidoh M, Utsunomiya D, Funama Y, et al. Myocardial late iodine enhancement and extracellular volume quantification with dual-layer spectral detector dual-energy cardiac CT. Radiol Cardiothorac Imaging. 2019;1:e180003.","journal-title":"Radiol Cardiothorac Imaging"},{"key":"1976_CR12","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1148\/rg.2016150220","volume":"36","author":"M Patino","year":"2016","unstructured":"Patino M, Prochowski A, Agrawal MD, Simeone FJ, Gupta R, Hahn PF, et al. Material separation using dual-energy CT: current and emerging applications. Radiographics. 2016;36:1087\u2013105.","journal-title":"Radiographics"},{"key":"1976_CR13","doi-asserted-by":"publisher","first-page":"5779","DOI":"10.1007\/s00330-021-07706-2","volume":"31","author":"Y Nagayama","year":"2021","unstructured":"Nagayama Y, Kato Y, Inoue T, Nakaura T, Oda S, Kidoh M, et al. Liver fibrosis assessment with multiphasic dual-energy CT: diagnostic performance of iodine uptake parameters. Eur Radiol. 2021;31:5779\u201390.","journal-title":"Eur Radiol"},{"key":"1976_CR14","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.2214\/AJR.12.10039","volume":"201","author":"MH Zissen","year":"2013","unstructured":"Zissen MH, Wang ZJ, Yee J, Aslam R, Monto A, Yeh BM. Contrast-enhanced CT quantification of the hepatic fractional extracellular space: correlation with diffuse liver disease severity. AJR Am J Roentgenol. 2013;201:1204\u201310.","journal-title":"AJR Am J Roentgenol"},{"key":"1976_CR15","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s40291-014-0091-6","volume":"18","author":"JC Dudley","year":"2014","unstructured":"Dudley JC, Gurda GT, Tseng LH, Anderson DA, Chen G, Taube JM, et al. Tumor cellularity as a quality assurance measure for accurate clinical detection of BRAF mutations in melanoma. Mol Diagn Ther. 2014;18:409\u201318.","journal-title":"Mol Diagn Ther"},{"key":"1976_CR16","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1186\/s12916-023-03048-6","volume":"21","author":"N White","year":"2023","unstructured":"White N, Parsons R, Collins G, Barnett A. Evidence of questionable research practices in clinical prediction models. BMC Med. 2023;21:339.","journal-title":"BMC Med"},{"key":"1976_CR17","doi-asserted-by":"publisher","first-page":"195","DOI":"10.4103\/tjem.tjem_182_23","volume":"23","author":"\u015eK \u00c7orbac\u0131o\u011flu","year":"2023","unstructured":"\u00c7orbac\u0131o\u011flu \u015eK, Aksel G. Receiver operating characteristic curve analysis in diagnostic accuracy studies: a guide to interpreting the area under the curve value. Turk J Emerg Med. 2023;23:195\u20138.","journal-title":"Turk J Emerg Med"},{"key":"1976_CR18","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1016\/j.ejrad.2015.12.029","volume":"85","author":"M Kim","year":"2016","unstructured":"Kim M, Kang TW, Kim YK, Kim SH, Kwon W, Ha SY, et al. Pancreatic neuroendocrine tumour: correlation of apparent diffusion coefficient or WHO classification with recurrence-free survival. Eur J Radiol. 2016;85:680\u20137.","journal-title":"Eur J Radiol"},{"key":"1976_CR19","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1007\/s00330-016-4539-4","volume":"27","author":"E Lotfalizadeh","year":"2017","unstructured":"Lotfalizadeh E, Ronot M, Wagner M, Cros J, Couvelard A, Vullierme MP, et al. Prediction of pancreatic neuroendocrine tumour grade with MR imaging features: added value of diffusion-weighted imaging. Eur Radiol. 2017;27:1748\u201359.","journal-title":"Eur Radiol"},{"key":"1976_CR20","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1007\/s00261-013-0011-y","volume":"38","author":"JH Kim","year":"2013","unstructured":"Kim JH, Eun HW, Kim YJ, Han JK, Choi BI. Staging accuracy of MR for pancreatic neuroendocrine tumor and imaging findings according to the tumor grade. Abdom Imaging. 2013;38:1106\u201314.","journal-title":"Abdom Imaging"},{"key":"1976_CR21","doi-asserted-by":"publisher","first-page":"275","DOI":"10.3748\/wjg.v23.i2.275","volume":"23","author":"R De Robertis","year":"2017","unstructured":"De Robertis R, Cingarlini S, Tinazzi Martini P, Ortolani S, Butturini G, Landoni L, et al. Pancreatic neuroendocrine neoplasms: magnetic resonance imaging features according to grade and stage. World J Gastroenterol. 2017;23:275\u201385.","journal-title":"World J Gastroenterol"},{"key":"1976_CR22","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1016\/j.pan.2021.02.020","volume":"21","author":"H Iwaya","year":"2021","unstructured":"Iwaya H, Fukukura Y, Hashimoto S, Tanoue S, Kawahira M, Hinokuchi M, et al. Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms. Pancreatology. 2021;21:779\u201386.","journal-title":"Pancreatology"},{"key":"1976_CR23","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.crad.2016.10.021","volume":"72","author":"E Belousova","year":"2017","unstructured":"Belousova E, Karmazanovsky G, Kriger A, Kalinin D, Mannelli L, Glotov A, et al. Contrast-enhanced MDCT in patients with pancreatic neuroendocrine tumours: correlation with histological findings and diagnostic performance in differentiation between tumour grades. Clin Radiol. 2017;72:150\u20138.","journal-title":"Clin Radiol"},{"key":"1976_CR24","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1111\/jgh.14139","volume":"33","author":"J Kang","year":"2018","unstructured":"Kang J, Ryu JK, Son JH, Lee JW, Choi JH, Lee SH, et al. Association between pathologic grade and multiphase computed tomography enhancement in pancreatic neuroendocrine neoplasm. J Gastroenterol Hepatol. 2018;33:1677\u201382.","journal-title":"J Gastroenterol Hepatol"},{"key":"1976_CR25","doi-asserted-by":"publisher","first-page":"111090","DOI":"10.1016\/j.ejrad.2023.111090","volume":"168","author":"S Wang","year":"2023","unstructured":"Wang S, Zhang Y, Xu Y, Yang P, Liu C, Gong H, et al. Progress in the application of dual-energy CT in pancreatic diseases. Eur J Radiol. 2023;168:111090.","journal-title":"Eur J Radiol"},{"key":"1976_CR26","doi-asserted-by":"publisher","first-page":"999","DOI":"10.2214\/AJR.21.27017","volume":"218","author":"Y Wang","year":"2022","unstructured":"Wang Y, Hu X, Shi S, Song C, Wang L, Yuan J, et al. Utility of quantitative metrics from dual-layer spectral-detector CT for differentiation of pancreatic neuroendocrine tumor and neuroendocrine carcinoma. AJR Am J Roentgenol. 2022;218:999\u20131009.","journal-title":"AJR Am J Roentgenol"},{"key":"1976_CR27","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.acra.2020.01.033","volume":"28","author":"WX Li","year":"2021","unstructured":"Li WX, Miao F, Xu XQ, Zhang J, Wu ZY, Chen KM, et al. Pancreatic neuroendocrine neoplasms: CT spectral imaging in grading. Acad Radiol. 2021;28:208\u201316.","journal-title":"Acad Radiol"},{"key":"1976_CR28","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.3758\/BRM.41.4.1149","volume":"41","author":"F Faul","year":"2009","unstructured":"Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41:1149\u201360.","journal-title":"Behav Res Methods"}],"container-title":["Japanese Journal of Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11604-026-01976-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11604-026-01976-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11604-026-01976-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:08:47Z","timestamp":1784866127000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11604-026-01976-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":28,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["1976"],"URL":"https:\/\/doi.org\/10.1007\/s11604-026-01976-w","relation":{},"ISSN":["1867-1071","1867-108X"],"issn-type":[{"value":"1867-1071","type":"print"},{"value":"1867-108X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]},"assertion":[{"value":"19 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"In this article, all figures have been resized to enhance visibility.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no conflicts of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study design was approved by our institutional review board.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The requirement for informed consent was waived because of its retrospective design.","order":3,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}}]}}