{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:15:59Z","timestamp":1788470159198,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL164895"],"award-info":[{"award-number":["1R01HL164895"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2R01CA154491"],"award-info":[{"award-number":["2R01CA154491"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"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 Noninvasive quantitative assessment of marrow recovery after curative therapies such as total marrow irradiation (TMI) and bone marrow transplantation (BMT) remain poorly defined, particularly in sickle cell disease (SCD).<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n To evaluate MRI\u2010derived proton density fat fraction (PDFF) as a biomarker of marrow recovery following organ\u2010sparing total marrow irradiation\u2010based transplantation (OS\u2010TMI\/BMT) in an SCD mouse model and to assess initial clinical feasibility in patients.<\/jats:p>\n <\/jats:sec>\n \n Study Type<\/jats:title>\n Exploratory preclinical study with descriptive pilot feasibility analysis in humans.<\/jats:p>\n <\/jats:sec>\n \n Subjects<\/jats:title>\n \n Townes SCD mice (\n n<\/jats:italic>\n \u2009=\u200910 controls,\n n<\/jats:italic>\n \u2009=\u20098 treated) and 2 adults (male, 24\u2009\u00b1\u20091\u2009years old) with SCD.\n <\/jats:p>\n <\/jats:sec>\n \n Field Strength\/Sequence<\/jats:title>\n Preclinical 7\u2010T small\u2010bore MRI used a spoiled gradient echo (GRE) multi\u2010echo sequence for PDFF and R2* mapping, while clinical 3\u2010T MRI employed a spoiled GRE\u2010based sequence.<\/jats:p>\n <\/jats:sec>\n \n Assessment<\/jats:title>\n Marrow recovery in an animal study was assessed using MRI\u2010derived PDFF with ROI analysis, complemented by micro\u2010CT and histologic evaluation. Translational feasibility was assessed with longitudinal PDFF MRI in 2 adults with severe SCD undergoing marrow transplantation.<\/jats:p>\n <\/jats:sec>\n \n Statistical Tests<\/jats:title>\n \n Parametric data were analyzed using\n t<\/jats:italic>\n \u2010tests and Pearson correlation, nonparametric data using Mann\u2013Whitney U and Spearman correlation, and two\u2010way ANOVA assessed group, region, and interaction effects, with significance set at\n p<\/jats:italic>\n \u2009<\u20090.05.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Right femur MRI showed partial restoration of adipose\u2010rich marrow in the OS\u2010TMI\/BMT group versus controls, higher PDFF in the proximal metaphysis (42.5\u2009\u00b1\u20092.7 vs. 34.8\u2009\u00b1\u20096.5), midshaft diaphysis (44.8\u2009\u00b1\u20093.0 vs. 26.9\u2009\u00b1\u20097.0), and distal metaphysis (45.1\u2009\u00b1\u20092.6 vs. 36.2\u2009\u00b1\u20094.9). OS\u2010TMI\/BMT also improved trabecular structure, with increased trabecular thickness, reduced bone surface\u2010to\u2010volume ratio, lower structure model index and anisotropy, and increased distal bone volume density. In 2 patients, PDFF increased post\u2010transplant, and 1\u2010year biopsy showed trilineage hematopoiesis without fibrosis.<\/jats:p>\n <\/jats:sec>\n \n Data Conclusion<\/jats:title>\n Marrow\u2010selective transplantation was associated with partial normalization of the marrow and skeletal microenvironment in SCD. PDFF may provide a practical noninvasive approach for monitoring post\u2010transplant marrow recovery.<\/jats:p>\n <\/jats:sec>\n \n Level of Evidence<\/jats:title>\n 4.<\/jats:p>\n <\/jats:sec>\n \n Technical Efficacy<\/jats:title>\n Stage 2.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jmri.70510","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:31:02Z","timestamp":1788427862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["MRI<\/scp>\n Proton Density Fat Fraction as a Biomarker of Marrow Recovery Following Organ\u2010Sparing Total Marrow Irradiation in Sickle Cell Disease"],"prefix":"10.1002","author":[{"given":"Malakeh","family":"Malekzadeh","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemendra","family":"Ghimire","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srideshikan S.","family":"Madabushi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-5262","authenticated-orcid":false,"given":"Weidong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Immunology & Theranostics City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-1900","authenticated-orcid":false,"given":"Marco Andrea","family":"Zampini","sequence":"additional","affiliation":[{"name":"MR Solutions Ltd. Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"},{"name":"Department of Medical Physics and Engineering The University of Osaka Graduate School of Medicine Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-6093","authenticated-orcid":false,"given":"Raghda","family":"Fouda","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine Stanford University School of Medicine Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-7915","authenticated-orcid":false,"given":"Guy","family":"Storme","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy Universitair Ziekenhuis (UZ) Brussels Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-2513","authenticated-orcid":false,"given":"Joo","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-0711","authenticated-orcid":false,"given":"Bihong T.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiology City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9466-6396","authenticated-orcid":false,"given":"Anna","family":"Pawlowska","sequence":"additional","affiliation":[{"name":"Pediatric Hematopoietic Cell Transplantation Program, Department of Pediatrics City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1394-3724","authenticated-orcid":false,"given":"Susanta K.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology City of Hope National Medical Center Duarte California USA"},{"name":"Beckman Research Institute City of Hope National Medical Center Duarte California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001484"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2009.12.022"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genom\u2010120122\u2010081037"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(04)17192\u20104"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012663"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2025.01.178"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.969429"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010022\u201001579\u20109"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102017\u201003\u2010772392"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.11.002"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/tomography9020038"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","unstructured":"H.Ghimire M.Malekzadeh J. E.Lim et\u00a0al. \u201cProton Density Fat Fraction Micro\u2010MRI for Non\u2010Invasive Quantification of Bone Marrow Aging and Radiation Effects in Mice \u201d12 no.4(2025):349.","DOI":"10.3390\/bioengineering12040349"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24071"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25769"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100609.2005.00587.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.21781"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e3280d2b76b"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139220"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.07.018"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010200409000\u201000027"},{"key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-1-0716-0978-1_8","volume-title":"Preclinical MRI of the Kidney: Methods and Protocols","author":"Ramos Delgado P.","year":"2021"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25193"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.23199"},{"issue":"4","key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"S512","DOI":"10.1016\/j.amepre.2009.12.022","article-title":"Population Estimates of Sickle Cell Disease in the US","volume":"38","author":"Hassell K. L.","year":"2010","journal-title":"American Journal of Preventive Medicine"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017204\u20105"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2363041425"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891\u2010023\u201006846\u20104"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crad.2022.11.014"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2011.07.004"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.295095034"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010023\u201009599\u20109"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004424\u2010199002000\u201000013"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010006\u20100504\u2010y"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22488"},{"key":"e_1_2_12_36_1","first-page":"442","volume-title":"Proceedings of the International Society of Magnetic Resonance in Medicine","author":"Storey P.","year":"2015"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmbbm.2015.04.019"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119908"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00077"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.06.003"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004424\u2010198606000\u201000005"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3570"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.29526"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.70510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmri.70510","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.70510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:31:04Z","timestamp":1788427864000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.70510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":42,"alternative-id":["10.1002\/jmri.70510"],"URL":"https:\/\/doi.org\/10.1002\/jmri.70510","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"assertion":[{"value":"2026-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jmri.70510"}}