{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:40:39Z","timestamp":1788864039519,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Beijing Hope Run Special Fund of Cancer Foundation of China","award":["LC2022A14"],"award-info":[{"award-number":["LC2022A14"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-066 and 2022-I2M-C&T-B-062"],"award-info":[{"award-number":["2021-I2M-1-066 and 2022-I2M-C&T-B-062"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Insights Imaging"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objectives<\/jats:title>\n            <jats:p>To explore the role of apparent diffusion coefficient (ADC) changes in predicting pathological response to preoperative radiotherapy (RT) in hepatocellular carcinoma (HCC) compared to existing evaluation criteria, using histopathology as the reference standard.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Materials and methods<\/jats:title>\n            <jats:p>Building on the prospective clinical trial, we included 35 patients with 38 HCCs who underwent preoperative RT followed by hepatectomy between December 2014 and January 2019. Pre- and post-RT ADC parameters (ADC<jats:sub>roi<\/jats:sub> and ADC<jats:sub>slice<\/jats:sub> measured from representative areas and histogram parameters derived from whole-tumor volume) were compared, and the percentage change of parameters (\u0394-parameters%) was calculated to correlate with major pathological response (MPR). The modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Liver Imaging Reporting and Data System Treatment Response (LR-TR) categories were evaluated. ROC analysis was performed to assess discrimination performance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>ADC values, interquartile range, range, variance, mean absolute deviation, robust mean absolute deviation, and root mean squared increased; energy and total energy decreased; and skewness developed into negative skewness after RT. Higher \u0394-ADC<jats:sub>roi<\/jats:sub>%, \u0394-ADC<jats:sub>slice<\/jats:sub>%, \u0394-ADC<jats:sub>mean<\/jats:sub>%, and \u0394-ADC<jats:sub>median<\/jats:sub>% and lower \u0394-energy% and \u0394-total energy% were associated with MPR. LR-ADC<jats:sub>slice<\/jats:sub> showed the best performance, with significantly higher AUC than mRECIST\/LR-TR, \u0394-ADC<jats:sub>mean<\/jats:sub>%, and \u0394-ADC<jats:sub>median<\/jats:sub>% (0.917 vs 0.708, 0.732, and 0.705, respectively; <jats:italic>p<\/jats:italic>\u2009=\u20090.005, 0.029, and 0.023). Responders had significantly better RFS than non-responders according to \u0394-ADC<jats:sub>roi<\/jats:sub>% (<jats:italic>p<\/jats:italic>\u2009=\u20090.024).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>ADC changes have the potential to predict the pathological response of HCC to preoperative RT, thereby enhancing current evaluation criteria. Integration of \u0394-ADC<jats:sub>slice<\/jats:sub>% and LR-TR yielded the best results.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Critical relevance statement<\/jats:title>\n            <jats:p>\u0394-ADC<jats:sub>slice<\/jats:sub>%, with high performance in predicting pathological response, excellent inter-observer agreement, and the potential to supplement existing evaluation criteria, is a promising method for determining therapeutic response to preoperative radiotherapy and may facilitate the early indication for further surgery.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Key Points<\/jats:title>\n            <jats:p>\n              <jats:list list-type=\"bullet\">\n                <jats:list-item>\n                  <jats:p>Precise assessment of hepatocellular carcinoma response is required for patients undergoing preoperative radiotherapy.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>Radiotherapy induced an increase in ADC values and heightened intratumoral heterogeneity.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>As the delineated region of interest expanded, AUC decreased and inter-observer agreement increased.<\/jats:p>\n                <\/jats:list-item>\n                <jats:list-item>\n                  <jats:p>\u0394-ADC<jats:sub>slice<\/jats:sub>% exhibited excellent performance in predicting pathological response and the potential to supplement existing evaluation criteria.<\/jats:p>\n                <\/jats:list-item>\n              <\/jats:list>\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s13244-025-02090-7","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:18:28Z","timestamp":1760635108000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Can ADC changes help mRECIST or LI-RADS treatment response algorithm better diagnose pathological response of HCC after preoperative radiotherapy? Secondary analysis of a prospective phase 2 trial"],"prefix":"10.1186","volume":"16","author":[{"given":"Rong","family":"Cong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirui","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjian","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9048-8374","authenticated-orcid":false,"given":"Xiaohong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"2090_CR1","first-page":"394","volume":"68","author":"F Bray","year":"2018","unstructured":"Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394\u2013424","journal-title":"CA Cancer J Clin"},{"key":"2090_CR2","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","volume":"391","author":"A Forner","year":"2018","unstructured":"Forner A, Reig M, Bruix J (2018) Hepatocellular carcinoma. Lancet 391:1301\u20131314","journal-title":"Lancet"},{"key":"2090_CR3","doi-asserted-by":"publisher","first-page":"8069","DOI":"10.3748\/wjg.v27.i47.8069","volume":"27","author":"HT Zhao","year":"2021","unstructured":"Zhao HT, Cai JQ (2021) Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma. World J Gastroenterol 27:8069\u20138080","journal-title":"World J Gastroenterol"},{"key":"2090_CR4","doi-asserted-by":"publisher","first-page":"7462","DOI":"10.3748\/wjg.v27.i43.7462","volume":"27","author":"MS Makary","year":"2021","unstructured":"Makary MS, Ramsell S, Miller E, Beal EW, Dowell JD (2021) Hepatocellular carcinoma locoregional therapies: outcomes and future horizons. World J Gastroenterol 27:7462\u20137479","journal-title":"World J Gastroenterol"},{"key":"2090_CR5","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41575-020-00395-0","volume":"18","author":"JM Llovet","year":"2021","unstructured":"Llovet JM, De Baere T, Kulik L et al (2021) Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 18:293\u2013313","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2090_CR6","doi-asserted-by":"crossref","unstructured":"Ohri N, Dawson LA, Krishnan S et al (2016) Radiotherapy for hepatocellular carcinoma: new indications and directions for future study. J Natl Cancer Inst 108:djw133","DOI":"10.1093\/jnci\/djw133"},{"key":"2090_CR7","doi-asserted-by":"publisher","first-page":"7311","DOI":"10.3748\/wjg.v22.i32.7311","volume":"22","author":"SH Park","year":"2016","unstructured":"Park SH, Kim JC, Kang MK (2016) Technical advances in external radiotherapy for hepatocellular carcinoma. World J Gastroenterol 22:7311\u20137321","journal-title":"World J Gastroenterol"},{"key":"2090_CR8","doi-asserted-by":"publisher","first-page":"E718","DOI":"10.1111\/ans.14387","volume":"88","author":"H Lin","year":"2018","unstructured":"Lin H, Li X, Liu Y, Hu Y (2018) Neoadjuvant radiotherapy provided survival benefit compared to adjuvant radiotherapy for hepatocellular carcinoma. ANZ J Surg 88:E718\u2013E724","journal-title":"ANZ J Surg"},{"key":"2090_CR9","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1200\/JCO.18.02184","volume":"37","author":"X Wei","year":"2019","unstructured":"Wei X, Jiang Y, Zhang X et al (2019) Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol 37:2141\u20132151","journal-title":"J Clin Oncol"},{"key":"2090_CR10","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1001\/jamasurg.2022.4702","volume":"157","author":"F Wu","year":"2022","unstructured":"Wu F, Chen B, Dong D et al (2022) Phase 2 evaluation of neoadjuvant intensity-modulated radiotherapy in centrally located hepatocellular carcinoma: a nonrandomized controlled trial. JAMA Surg 157:1089\u20131096","journal-title":"JAMA Surg"},{"key":"2090_CR11","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1097\/JS9.0000000000000574","volume":"109","author":"X Wei","year":"2023","unstructured":"Wei X, Jiang Y, Feng S et al (2023) Neoadjuvant intensity modulated radiotherapy for a single and small (\u22645 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial. Int J Surg 109:3052\u20133060","journal-title":"Int J Surg"},{"key":"2090_CR12","doi-asserted-by":"publisher","first-page":"e190024","DOI":"10.1148\/rycan.2020190024","volume":"2","author":"M Mendiratta-Lala","year":"2020","unstructured":"Mendiratta-Lala M, Masch WR, Shampain K et al (2020) MRI assessment of hepatocellular carcinoma after local-regional therapy: a comprehensive review. Radiol Imaging Cancer 2:e190024","journal-title":"Radiol Imaging Cancer"},{"key":"2090_CR13","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1148\/rg.220084","volume":"42","author":"PJ Navin","year":"2022","unstructured":"Navin PJ, Olson MC, Mendiratta-Lala M, Hallemeier CL, Torbenson MS, Venkatesh SK (2022) Imaging features in the liver after stereotactic body radiation therapy. Radiographics 42:2131\u20132148","journal-title":"Radiographics"},{"key":"2090_CR14","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ijrobp.2018.09.004","volume":"103","author":"M Mendiratta-Lala","year":"2019","unstructured":"Mendiratta-Lala M, Masch W, Shankar PR et al (2019) Magnetic resonance imaging evaluation of hepatocellular carcinoma treated with stereotactic body radiation therapy: long term imaging follow-up. Int J Radiat Oncol Biol Phys 103:169\u2013179","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2090_CR15","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.ejrad.2012.11.026","volume":"82","author":"L Mannelli","year":"2013","unstructured":"Mannelli L, Kim S, Hajdu CH, Babb JS, Taouli B (2013) Serial diffusion-weighted MRI in patients with hepatocellular carcinoma: prediction and assessment of response to transarterial chemoembolization. Preliminary experience. Eur J Radiol 82:577\u2013582","journal-title":"Eur J Radiol"},{"key":"2090_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.600233","volume":"10","author":"PS Sung","year":"2020","unstructured":"Sung PS, Choi MH, Yang H et al (2020) Diffusion-weighted magnetic resonance imaging in hepatocellular carcinoma as a predictor of a response to cisplatin-based hepatic arterial infusion chemotherapy. Front Oncol 10:600233","journal-title":"Front Oncol"},{"key":"2090_CR17","doi-asserted-by":"publisher","first-page":"5565","DOI":"10.1007\/s00330-020-07584-0","volume":"31","author":"L Zhao","year":"2021","unstructured":"Zhao L, Zhao M, Liu J et al (2021) Mean apparent diffusion coefficient in a single slice may predict tumor response to whole-brain radiation therapy in non-small-cell lung cancer patients with brain metastases. Eur Radiol 31:5565\u20135575","journal-title":"Eur Radiol"},{"key":"2090_CR18","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1148\/radiol.2392042202","volume":"239","author":"CY Chen","year":"2006","unstructured":"Chen CY, Li CW, Kuo YT et al (2006) Early response of hepatocellular carcinoma to transcatheter arterial chemoembolization: choline levels and MR diffusion constants-initial experience. Radiology 239:448\u2013456","journal-title":"Radiology"},{"key":"2090_CR19","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.2214\/AJR.08.1461","volume":"193","author":"L Mannelli","year":"2009","unstructured":"Mannelli L, Kim S, Hajdu CH, Babb JS, Clark TW, Taouli B (2009) Assessment of tumor necrosis of hepatocellular carcinoma after chemoembolization: diffusion-weighted and contrast-enhanced MRI with histopathologic correlation of the explanted liver. AJR Am J Roentgenol 193:1044\u20131052","journal-title":"AJR Am J Roentgenol"},{"key":"2090_CR20","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1007\/s00259-019-04318-3","volume":"46","author":"YH Chung","year":"2019","unstructured":"Chung YH, Yu CF, Chiu SC et al (2019) Diffusion-weighted MRI and 18F-FDG PET correlation with immunity in early radiotherapy response in BNL hepatocellular carcinoma mouse model: timeline validation. Eur J Nucl Med Mol Imaging 46:1733\u20131744","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"2090_CR21","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.ijrobp.2014.03.020","volume":"89","author":"JI Yu","year":"2014","unstructured":"Yu JI, Park HC, Lim DH et al (2014) The role of diffusion-weighted magnetic resonance imaging in the treatment response evaluation of hepatocellular carcinoma patients treated with radiation therapy. Int J Radiat Oncol Biol Phys 89:814\u2013821","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2090_CR22","doi-asserted-by":"publisher","first-page":"e0176118","DOI":"10.1371\/journal.pone.0176118","volume":"12","author":"G Oldrini","year":"2017","unstructured":"Oldrini G, Huertas A, Renard-Oldrini S et al (2017) Tumor response assessment by MRI following stereotactic body radiation therapy for hepatocellular carcinoma. PLoS One 12:e0176118","journal-title":"PLoS One"},{"key":"2090_CR23","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1177\/0284185118805253","volume":"60","author":"SH Song","year":"2019","unstructured":"Song SH, Jeong WK, Choi D et al (2019) Evaluation of early treatment response to radiotherapy for HCC using pre- and post-treatment MRI. Acta Radiol 60:826\u2013835","journal-title":"Acta Radiol"},{"key":"2090_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-50503-7","volume":"9","author":"CH Lo","year":"2019","unstructured":"Lo CH, Huang WY, Hsiang CW et al (2019) Prognostic significance of apparent diffusion coefficient in hepatocellular carcinoma patients treated with stereotactic ablative radiotherapy. Sci Rep 9:14157","journal-title":"Sci Rep"},{"key":"2090_CR25","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.jhep.2017.07.030","volume":"67","author":"S Gordic","year":"2017","unstructured":"Gordic S, Corcuera-Solano I, Stueck A et al (2017) Evaluation of HCC response to locoregional therapy: validation of MRI-based response criteria versus explant pathology. J Hepatol 67:1213\u20131221","journal-title":"J Hepatol"},{"key":"2090_CR26","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1055\/s-0030-1247132","volume":"30","author":"R Lencioni","year":"2010","unstructured":"Lencioni R, Llovet JM (2010) Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 30:52\u201360","journal-title":"Semin Liver Dis"},{"key":"2090_CR27","doi-asserted-by":"publisher","first-page":"92","DOI":"10.2214\/AJR.12.10212","volume":"202","author":"HJ Park","year":"2014","unstructured":"Park HJ, Kim SH, Jang KM et al (2014) Added value of diffusion-weighted MRI for evaluating viable tumor of hepatocellular carcinomas treated with radiotherapy in patients with chronic liver disease. AJR Am J Roentgenol 202:92\u2013101","journal-title":"AJR Am J Roentgenol"},{"key":"2090_CR28","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1080\/02841860903099972","volume":"48","author":"CL Eccles","year":"2009","unstructured":"Eccles CL, Haider EA, Haider MA et al (2009) Change in diffusion weighted MRI during liver cancer radiotherapy: preliminary observations. Acta Oncol 48:1034\u20131043","journal-title":"Acta Oncol"},{"key":"2090_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s40644-019-0216-6","volume":"19","author":"S Gordic","year":"2019","unstructured":"Gordic S, Wagner M, Zanato R et al (2019) Prediction of hepatocellular carcinoma response to 90Yttrium radioembolization using volumetric ADC histogram quantification: preliminary results. Cancer Imaging 19:29","journal-title":"Cancer Imaging"},{"key":"2090_CR30","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1148\/radiol.2017164040","volume":"282","author":"IM Blazic","year":"2017","unstructured":"Blazic IM, Lilic GB, Gajic MM (2017) Quantitative assessment of rectal cancer response to neoadjuvant combined chemotherapy and radiation therapy: comparison of three methods of positioning region of interest for ADC measurements at diffusion-weighted MR imaging. Radiology 282:615","journal-title":"Radiology"},{"key":"2090_CR31","doi-asserted-by":"publisher","first-page":"e104","DOI":"10.1158\/0008-5472.CAN-17-0339","volume":"77","author":"JJM van Griethuysen","year":"2017","unstructured":"van Griethuysen JJM, Fedorov A, Parmar C et al (2017) Computational radiomics system to decode the radiographic phenotype. Cancer Res 77:e104\u2013e107","journal-title":"Cancer Res"}],"container-title":["Insights into Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13244-025-02090-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13244-025-02090-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13244-025-02090-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:18:38Z","timestamp":1760635118000},"score":1,"resource":{"primary":{"URL":"https:\/\/insightsimaging.springeropen.com\/articles\/10.1186\/s13244-025-02090-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2090"],"URL":"https:\/\/doi.org\/10.1186\/s13244-025-02090-7","relation":{},"ISSN":["1869-4101"],"issn-type":[{"value":"1869-4101","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]},"assertion":[{"value":"9 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted under a prospective phase 2 nonrandomized controlled trial (ClinicalTrials.gov identifier: NCT02580929) approved by the ethical committee of the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences (Number: NCC2014 YP-22).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from all of the patients before participating in the clinical trial.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"S.C.W. is affiliated with GE Healthcare. The remaining authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"220"}}