{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:03:21Z","timestamp":1792512201455,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["19PRE34380371"],"award-info":[{"award-number":["19PRE34380371"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23 HL133455\u201001A1"],"award-info":[{"award-number":["K23 HL133455\u201001A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41 EB015909"],"award-info":[{"award-number":["P41 EB015909"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"National Institute of Biomedical Imaging and Bioengineering","doi-asserted-by":"publisher","award":["P41 EB031771"],"award-info":[{"award-number":["P41 EB031771"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54 HD079123"],"award-info":[{"award-number":["U54 HD079123"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS106702"],"award-info":[{"award-number":["R01 NS106702"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS106711"],"award-info":[{"award-number":["R01 NS106711"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG064792"],"award-info":[{"award-number":["R01 AG064792"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["RF1 AG071515"],"award-info":[{"award-number":["RF1 AG071515"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006085","name":"Office of Disease Prevention","doi-asserted-by":"publisher","award":["S10 OD021648"],"award-info":[{"award-number":["S10 OD021648"]}],"id":[{"id":"10.13039\/100006085","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":[[2022,5]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Blood\u2013brain barrier (BBB) disruption may lead to endothelium dysfunction and inflammation in sickle cell disease (SCD). However, abnormalities of BBB in SCD, especially in pediatric patients for whom contrast agent administration less than optimal, have not been fully characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To examine BBB permeability to water in a group of pediatric SCD participants using a non\u2010invasive magnetic resonance imaging technique. We hypothesized that SCD participants will have increased BBB permeability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Type<\/jats:title><jats:p>Prospective cross\u2010sectional.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>Twenty\u2010six pediatric participants (10\u2009\u00b1\u20091\u2009years, 15F\/11M) were enrolled, including 21 SCD participants and 5 sickle cell trait (SCT) participants, who were siblings of SCD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Field Strength\/Sequence<\/jats:title><jats:p>3\u2009T. Water extraction with phase\u2010contrast arterial spin tagging with echo\u2010planer imaging, phase\u2010contrast and T<jats:sub>1<\/jats:sub>\u2010weighted magnetization\u2010prepared rapid acquisition of gradient echo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Assessment<\/jats:title><jats:p>Water extraction fraction (<jats:italic>E<\/jats:italic>), BBB permeability\u2010surface area product (PS), cerebral blood flow, hematological measures (hemoglobin, hematocrit, hemoglobin S), neuropsychological scores (including domains of intellectual ability, attention and executive function, academic achievement and adaptive function, and a composite score). Regions of interest were drawn by Z.L. (6\u2009years of experience).<\/jats:p><\/jats:sec><jats:sec><jats:title>Statistical Tests<\/jats:title><jats:p>Wilcoxon rank sum test and chi\u2010square test for group comparison of demographics. Multiple linear regression analysis of PS with diagnostic category (SCD or SCT), hematological measures, and neuropsychological scores. A two\u2010tailed <jats:italic>P<\/jats:italic> value of 0.05 or less was considered statistically significant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with SCT participants, SCD participants had a significantly higher BBB permeability to water (SCD: 207.0\u2009\u00b1\u200933.3\u2009mL\/100\u2009g\/minute, SCT: 171.2\u2009\u00b1\u200927.2\u2009mL\/100\u2009g\/minute). SCD participants with typically more severe phenotypes also had a significantly leakier BBB than those with typically milder phenotypes (severe: 217.3\u2009\u00b1\u200931.7\u2009mL\/100\u2009g\/minute, mild: 193.3\u2009\u00b1\u200931.8\u2009mL\/100\u2009g\/minute). Furthermore, more severe BBB disruption was associated with worse hematological symptoms, including lower hemoglobin concentrations (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0\u22128.84, 95% confidence interval [CI] [\u221214.69, \u22123.00]), lower hematocrits (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a0\u22122.96, 95% CI [\u22124.84, \u22121.08]), and higher hemoglobin S fraction (<jats:italic>\u03b2<\/jats:italic>\u00a0=\u00a00.77, 95% CI [0.014, 1.53]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Conclusion<\/jats:title><jats:p>These findings support a potential role for BBB dysfunction in SCD pathogenesis of ischemic injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>2<\/jats:p><\/jats:sec><jats:sec><jats:title>Technical Efficacy<\/jats:title><jats:p>Stage 2<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmri.27965","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T12:31:23Z","timestamp":1634905883000},"page":"1551-1558","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Imaging Blood\u2013Brain Barrier Permeability Through <scp>MRI<\/scp> in Pediatric Sickle Cell Disease: A Feasibility Study"],"prefix":"10.1002","volume":"55","author":[{"given":"Zixuan","family":"Lin","sequence":"first","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eboni","family":"Lance","sequence":"additional","affiliation":[{"name":"Department of Neurology and Developmental Medicine Kennedy Krieger Institute  Baltimore Maryland USA"},{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Department of Neurology and Developmental Medicine Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiying","family":"Liu","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantelle","family":"Lim","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Fan","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aylin","family":"Tekes","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Neuropsychology Kennedy Krieger Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Casella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Hematology Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3871-1564","authenticated-orcid":false,"given":"Hanzhang","family":"Lu","sequence":"additional","affiliation":[{"name":"The Russell H. Morgan Department of Radiology and Radiological Science Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"F. M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Research Institute  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-120611-143127"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70469-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv397"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27015"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20913123"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2017.12.011"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27972"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005194"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0009922815594356"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/DBP.0000000000000914"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.10.3924.422k07_3924_3935"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/582018"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2839"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.22666"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.1171"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.09.030"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27141"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.12.026"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27632"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28613"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.01.035"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2020.04.017"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27058"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28687"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26134"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4793"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1109\/MCSE.2016.93"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24866"},{"key":"e_1_2_7_30_1","volume-title":"Wechsler Intelligence Scale for Children","author":"Wechsler D","year":"1949"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-79948-3_1535"},{"key":"e_1_2_7_32_1","volume-title":"BRIEF2: Behavior Rating Inventory of Executive Function","author":"Gioia GA","year":"2015"},{"key":"e_1_2_7_33_1","first-page":"269","volume-title":"Contemporary intellectual assessment: Theories, tests, and issues","author":"Singer JK","year":"2012"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01543465"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-79948-3_1602"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.030"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.1.314.013k39_314_320"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/10739680490278402"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.10145"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400178111"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20178"}],"container-title":["Journal of Magnetic Resonance Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.27965","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmri.27965","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmri.27965","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T17:30:21Z","timestamp":1692984621000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmri.27965"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.1002\/jmri.27965"],"URL":"https:\/\/doi.org\/10.1002\/jmri.27965","archive":["Portico"],"relation":{},"ISSN":["1053-1807","1522-2586"],"issn-type":[{"value":"1053-1807","type":"print"},{"value":"1522-2586","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"assertion":[{"value":"2021-08-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}