{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:21Z","timestamp":1790717121624,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"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":["Magnetic Resonance Imaging"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Orally administered Ascelia\u2010manganese\u2010based contrast agent (ACE\u2010MBCA) is used for liver MRI, but its feasibility in patients with hepatic dysfunction remains unknown.<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of ACE\u2010MBCA in subjects without\/with hepatic impairment.<\/jats:p>\n <\/jats:sec>\n \n Study Type<\/jats:title>\n Prospective, open\u2010label, sequential\u2010cohort study.<\/jats:p>\n <\/jats:sec>\n \n Population<\/jats:title>\n \n Thirty\u2010five participants (mean age 56.5\u2009years): 13 with normal hepatic function and 22 with liver disease, consisting of Child\u2010Pugh class A (\n n<\/jats:italic>\n \u2009=\u20099), B (\n n<\/jats:italic>\n \u2009=\u20096), and C (\n n<\/jats:italic>\n \u2009=\u20097).\n <\/jats:p>\n <\/jats:sec>\n \n Field Strength\/Sequence<\/jats:title>\n 1.5\u2009T, pre\u2010 and post\u2010contrast T1\u2010weighted gradient recalled\u2010echo.<\/jats:p>\n <\/jats:sec>\n \n Assessment<\/jats:title>\n \n Liver signal intensity (SI) was measured on pre\u2010 and post\u2010contrast T1\u2010weighted images acquired 1, 4, 8, and 24\u2009h after ACE\u2010MBCA administration. PK assessments included measured manganese concentrations in blood, plasma, urine, and feces over 72\u2009h. PK parameters included AUC,\n C<\/jats:italic>\n max<\/jats:sub>\n , and\n T<\/jats:italic>\n max<\/jats:sub>\n . Adverse events were reported.\n <\/jats:p>\n <\/jats:sec>\n \n Statistical Tests<\/jats:title>\n \n Non\u2010compartmental analysis was performed for PK parameters. Log\u2010transformed AUC and\n C<\/jats:italic>\n max<\/jats:sub>\n were compared using ANOVA. Changes in liver SI enhancement were analyzed using a mixed model. Significance was set at\n p<\/jats:italic>\n \u2009\u2264\u20090.05.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n T<\/jats:italic>\n max<\/jats:sub>\n of manganese in blood ranged from 0.625 to 3.50\u2009h.\n C<\/jats:italic>\n max<\/jats:sub>\n was 44.4\u2009ng\/mL in Child\u2010Pugh class C compared to 5.77\u2009ng\/mL in the normal group.\n C<\/jats:italic>\n max<\/jats:sub>\n increased by 25%\u201329% in normal\/class A and 58%\u201361% in class B\/C. AUC\n 0\u201324.<\/jats:sub>\n It increased progressively with hepatic impairment, ranging from 38.4\u2009h\u2009\u00d7\u2009ng\/mL (normal) to 320\u2009h\u2009\u00d7\u2009ng\/mL (severe impairment). Liver SI peaked at 4\u2009h and was significantly different among normal, mild, moderate, and severe hepatic impairment (45.8%, 35.1%, 18.9%, and 18.4%, respectively), while no difference was observed at 24\u2009h (\n p<\/jats:italic>\n \u2009=\u20090.343). Mild to moderate gastrointestinal disorders were reported.\n <\/jats:p>\n <\/jats:sec>\n \n Data Conclusion<\/jats:title>\n Peak liver enhancement occurred 4\u2009h after a single oral dose of ACE\u2010MBCA in all groups, but its magnitude decreased and circulating manganese exposure increased with worsening hepatic function. The single dose of ACE\u2010MBCA was well tolerated.<\/jats:p>\n <\/jats:sec>\n \n Evidence Level<\/jats:title>\n 2.<\/jats:p>\n <\/jats:sec>\n \n Technical Efficacy<\/jats:title>\n 1.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jmri.70548","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:45:12Z","timestamp":1790131512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of Ascelia\u2010Manganese\u2010Based MRI Contrast Agent (ACE\u2010MBCA) in Adult Subjects With and Without Hepatic Impairment"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-3971","authenticated-orcid":false,"given":"Amit G.","family":"Singal","sequence":"first","affiliation":[{"name":"Department of Internal Medicine UT Southwestern Medical Center Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4234-224X","authenticated-orcid":false,"given":"Eric","family":"Lawitz","sequence":"additional","affiliation":[{"name":"Texas Liver Institute University of Texas Health San Antonio San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1875-8292","authenticated-orcid":false,"given":"Andreas","family":"Norlin","sequence":"additional","affiliation":[{"name":"Ascelia Pharma AB Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1410-6477","authenticated-orcid":false,"given":"Nadilka","family":"Hettiarachchige","sequence":"additional","affiliation":[{"name":"Ascelia Pharma AB Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"StatMind AB Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6409-1333","authenticated-orcid":false,"given":"Bachir","family":"Taouli","sequence":"additional","affiliation":[{"name":"BioMedical Engineering and Imaging Institute and Department of Diagnostic, Molecular, and Interventional Radiology Icahn School of Medicine at Mount Sinai New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jhep.2022.01.023","article-title":"HCC Surveillance Improves Early Detection, Curative Treatment Receipt, and Survival in Patients With Cirrhosis: A Meta\u2010Analysis","volume":"77","author":"Singal A. 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