{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:25:44Z","timestamp":1790105144559,"version":"4.0.1"},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971684"],"award-info":[{"award-number":["81971684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271958"],"award-info":[{"award-number":["82271958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:label\/><jats:p>This review aimed to perform a scoping review of promising MRI methods in assessing tumor hypoxia in hepatocellular carcinoma (HCC). The hypoxic microenvironment and upregulated hypoxic metabolism in HCC are determining factors of poor prognosis, increased metastatic potential, and resistance to chemotherapy and radiotherapy. Assessing hypoxia in HCC is essential for personalized therapy and predicting prognoses. Oxygen electrodes, protein markers, optical imaging, and positron emission tomography can evaluate tumor hypoxia. These methods lack clinical applicability because of invasiveness, tissue depth, and radiation exposure. MRI methods, including blood oxygenation level\u2010dependent, dynamic contrast\u2010enhanced MRI, diffusion\u2010weighted imaging, MRI spectroscopy, chemical exchange saturation transfer MRI, and multinuclear MRI, are promising noninvasive methods that evaluate the hypoxic microenvironment by observing biochemical processes in vivo, which may inform on therapeutic options. This review summarizes the recent challenges and advances in MRI techniques for assessing hypoxia in HCC and highlights the potential of MRI methods for examining the hypoxic microenvironment via specific metabolic substrates and pathways. Although the utilization of MRI methods for evaluating hypoxia in patients with HCC is increasing, rigorous validation is needed in order to translate these MRI methods into clinical use. Due to the limited sensitivity and specificity of current quantitative MRI methods, their acquisition and analysis protocols require further improvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Level<\/jats:title><jats:p>3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Technical Efficacy<\/jats:title><jats:p>Stage 4.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmri.28694","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T13:00:39Z","timestamp":1679922039000},"page":"12-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of Hypoxia in Hepatocellular Carcinoma Using Quantitative<scp>MRI<\/scp>: Significances, Challenges, and Advances"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7604-0776","authenticated-orcid":false,"given":"Meicheng","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huasong","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasonics, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayu","family":"You","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenpeng","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-7290","authenticated-orcid":false,"given":"Shi\u2010Ting","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Radiology, The First Affiliated Hospital Sun Yat\u2010sen University Guangzhou Province Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/409272"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071715"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1628"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-0074"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.5"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26224"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.26838"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108676"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-177"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11040686"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MNM.0000000000000010"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02706-z"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.18.20517"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2018.11.012"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-011-1570-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2015.09.013"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-011-0724-8"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0229-5"},{"issue":"12","key":"e_1_2_7_21_1","article-title":"Targeting hypoxia at the forefront of anticancer immune responses","volume":"3","author":"Noman MZ","year":"2014","journal-title":"Onco Targets Ther"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065753"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31846"},{"issue":"1093","key":"e_1_2_7_25_1","doi-asserted-by":"crossref","DOI":"10.1259\/bjr.20180036","article-title":"Hypoxia gene expression signatures as predictive biomarkers for personalising radiotherapy","volume":"92","author":"Yang L","year":"2019","journal-title":"Br J Radiol"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.112.114355"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.09.045"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121487"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.9868"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2007.01.018"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25051"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27661"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-019-09670-4"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.213256"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2014.05.011"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-015-0602-x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.12120686"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-3806"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26604"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24538"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-020-01531-7"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.23014"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2018.05.006"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-2610"},{"issue":"7","key":"e_1_2_7_45_1","first-page":"506","article-title":"Expression characteristics of hypoxia inducible factor\u20101a and its clinical values in hepatocellular carcinoma","volume":"18","author":"Dong ZZ","year":"2010","journal-title":"Zhonghua Gan Zang Bing Za Zhi"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i11.1705"},{"issue":"12","key":"e_1_2_7_47_1","first-page":"3930","article-title":"Targeting lactate\u2010fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux P","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-005-0398-1"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26144"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3587"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2020.109171"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3861"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21756"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.11.091"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-015-3972-0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-015-0887-8"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.578985"},{"issue":"9","key":"e_1_2_7_58_1","first-page":"1184","article-title":"Metabolic characterization of human IDH mutant and wild type gliomas using simultaneous pH\u2010 and oxygen\u2010sensitive molecular MRI","volume":"21","author":"Yao J","year":"2019","journal-title":"Neuro Oncol"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3943"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26131"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.24284"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00723-021-01401-7"},{"issue":"19","key":"e_1_2_7_63_1","first-page":"5440","article-title":"31P nuclear magnetic resonance spectroscopy studies of tumor energy metabolism and its relationship to intracapillary oxyhemoglobin saturation status and tumor hypoxia","volume":"48","author":"Rofstad EK","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910220253"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1558"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600421"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2010.02.056"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10334-014-0441-8"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26952"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.01.008"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aat7314"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0499-8"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3310"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1733835100"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2011.04.012"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-80952-4"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28901"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.28196"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.07.017"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2021.3101149"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2020.06.021"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.28694","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T03:26:40Z","timestamp":1729135600000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.28694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/jmri.28694"],"URL":"https:\/\/doi.org\/10.1002\/jmri.28694","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,27]]},"assertion":[{"value":"2022-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}