{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:11:26Z","timestamp":1791573086050,"version":"4.3.4"},"reference-count":96,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["5UL1\u2010TR000130\u201005"],"award-info":[{"award-number":["5UL1\u2010TR000130\u201005"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R01\u2010HL136484\u201001A1"],"award-info":[{"award-number":["1R01\u2010HL136484\u201001A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1U01\u2010HL\u2010117718\u201001"],"award-info":[{"award-number":["1U01\u2010HL\u2010117718\u201001"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1F31NS106828\u201001A1"],"award-info":[{"award-number":["1F31NS106828\u201001A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010ES024936"],"award-info":[{"award-number":["R01\u2010ES024936"]}],"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":["R01\u2010NS074980"],"award-info":[{"award-number":["R01\u2010NS074980"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO<jats:sub>2<\/jats:sub>) are less well understood. In this study, we examined 47 sickle\u2010cell anemia subjects (age 21.7\u00a0\u00b1\u20097.1, female 45%), 27 non\u2010sickle anemic subjects (age 25.0\u00a0\u00b1\u200910.4, female 52%) and 44 healthy controls (age 26.4\u00a0\u00b1\u200910.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T<jats:sub>2<\/jats:sub>\u2010relaxation\u2010under\u2010spin\u2010tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO<jats:sub>2<\/jats:sub>. We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO<jats:sub>2<\/jats:sub> (respectively 27.4\u00a0\u00b1\u20094.1% and 3.39\u2009\u00b1\u20090.71\u2009ml O<jats:sub>2<\/jats:sub>\/100\u2009g\/min in sickle cell disease, 30.8\u00a0\u00b1\u20095.2% and 3.53\u2009\u00b1\u20090.64\u2009ml O<jats:sub>2<\/jats:sub>\/100\u2009g\/min in other anemias) compared to controls (36.7\u00a0\u00b1\u20096.0% and 4.00\u2009\u00b1\u20090.65\u2009ml O<jats:sub>2<\/jats:sub>\/100\u2009g\/min). Impaired CMRO<jats:sub>2<\/jats:sub> was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non\u2010nutritive flow, or physiological shunting, in sickle cell disease patients.<\/jats:p>","DOI":"10.1002\/ajh.26203","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T18:24:33Z","timestamp":1619202273000},"page":"901-913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1773-4388","authenticated-orcid":false,"given":"Chau","family":"Vu","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7787-596X","authenticated-orcid":false,"given":"Adam","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"},{"name":"Department of Radiology Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7165-4691","authenticated-orcid":false,"given":"Soyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Program University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7010-2318","authenticated-orcid":false,"given":"Matthew","family":"Borzage","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Fetal and Neonatal Institute Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Department of Pediatrics, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7812-5423","authenticated-orcid":false,"given":"Xin","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aart J.","family":"Nederveen","sequence":"additional","affiliation":[{"name":"University of Amsterdam, Amsterdam UMC, Radiology and Nuclear Medicine  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-6029","authenticated-orcid":false,"given":"Thomas D.","family":"Coates","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Pediatrics Children's Hospital Los Angeles  Los Angeles California USA"},{"name":"Departments of Pediatrics and Pathology, Keck School of Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0996-3439","authenticated-orcid":false,"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"},{"name":"Division of Cardiology, Departments of Pediatrics and Radiology Children's Hospital Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172399499"},{"key":"e_1_2_9_3_1","volume-title":"Physiology, Oxyhemoglobin Dissociation Curve","author":"Kaufman DP","year":"2019"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2005.07.014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.13"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.17"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23846"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00994.2015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24441"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.04.023"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.12810"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2008.01950.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-129544"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25570"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.21627"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv397"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16682509"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17746808"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27972"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28757"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.22970"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27015"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.26311"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI101995"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.27210"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-545186"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401731"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2014.02.031"},{"issue":"1","key":"e_1_2_9_29_1","first-page":"123","article-title":"Blood flow in major cerebral arteries measured by phase\u2010contrast cine MR","volume":"15","author":"Enzmann DR","year":"1994","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28422"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.17.4.692"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004728-198012000-00001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI102668"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V6.3.213.213"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(54)90371-X"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI100868"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1961.00450080014002"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI103158"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI101680"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25423"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-08-868075"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anclin.2016.04.007"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408367909105855"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2018.01.005"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.107.044008"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.15.4.635"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-04-841247"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.103.3.640"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.23.3.423"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf047"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410290302"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-017-0125-6"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105148"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.16.4.675"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.6.1584"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.2004.00549.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916641117"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00068-4"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(01)00567-6"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198806000-00019"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/108.1.81"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10576"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.929199"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6734"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0b013e3181a800e5"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1009940031063"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199910000-00018"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24467"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-04-901124"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000561252.50212.c6"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28668"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2019.01.008"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-09-618579"},{"issue":"6","key":"e_1_2_9_74_1","first-page":"889","article-title":"Clinical silent cerebral infarct (SCI) in patients with thalassemia diseases assessed by magnetic resonance imaging (MRI)","volume":"91","author":"Metarugcheep P","year":"2008","journal-title":"J Med Assoc Thai"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184860"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157090"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22879"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1345.036"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1978"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-599852"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00668"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2014.1098"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1994.84"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.280.280"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3681"},{"issue":"5","key":"e_1_2_9_86_1","first-page":"320","article-title":"Arterialization of peripheral venous blood in sickle cell disease","volume":"94","author":"Nahavandi M","year":"2002","journal-title":"J Natl Med Assoc"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199701000-00009"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.254"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.11.3999"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000243584.45145.3f"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.ndt.a027970"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.153"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.13594"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.09.030"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-06-789842"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005194"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.24750"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26203","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajh.26203","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.26203","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T12:33:54Z","timestamp":1693139634000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.26203"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":96,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/ajh.26203"],"URL":"https:\/\/doi.org\/10.1002\/ajh.26203","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"2021-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}