{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:01:59Z","timestamp":1790928119880,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T00:00:00Z","timestamp":1580169600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO<jats:sub>2<\/jats:sub>) directly reflects oxygen supply and consumption and may therefore be more insightful than flow\u2010based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO<jats:sub>2<\/jats:sub> at rest and that a vasodilatory challenge with acetazolamide would improve CMRO<jats:sub>2<\/jats:sub>. CMRO<jats:sub>2<\/jats:sub> was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T<jats:sub>2<\/jats:sub>\u2010prepared tissue relaxation with inversion recovery (T<jats:sub>2<\/jats:sub>\u2010TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean\u2009\u00b1\u2009SD: 74\u2009\u00b1\u200916 versus 46\u2009\u00b1\u20095\u2009mL\/100\u2009g\/min, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), resulting in similar oxygen delivery (SCD: 377\u2009\u00b1\u200967 versus controls: 368\u2009\u00b1\u200942\u2009\u03bcmol O<jats:sub>2<\/jats:sub>\/100g\/min, <jats:italic>P<\/jats:italic> = .69). OEF was lower in patients versus controls (27\u2009\u00b1\u20094 versus 35\u2009\u00b1\u20094%, <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), resulting in lower CMRO<jats:sub>2<\/jats:sub> in patients versus controls (102\u2009\u00b1\u200924 versus 127\u2009\u00b1\u200920\u2009\u03bcmol O<jats:sub>2<\/jats:sub>\/100g\/min, <jats:italic>P<\/jats:italic> = .002). After acetazolamide, CMRO<jats:sub>2<\/jats:sub> declined further in patients (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01) and did not decline significantly in controls (<jats:italic>P<\/jats:italic> = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO<jats:sub>2<\/jats:sub> could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen\u2010deprived, hence increasing the risk of localized ischemia.<\/jats:p>","DOI":"10.1002\/ajh.25727","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T07:42:16Z","timestamp":1578642136000},"page":"401-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Cerebral oxygen metabolism in adults with sickle cell disease"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8617-7752","authenticated-orcid":false,"given":"Lena","family":"V\u00e1clav\u016f","sequence":"first","affiliation":[{"name":"Radiology &amp; Nuclear Medicine, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"C.J. Gorter Center for High Field MRI, Department of Radiology Leiden University Medical Center, Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Petr","sequence":"additional","affiliation":[{"name":"Helmholtz\u2010Zentrum Dresden\u2010Rossendorf Institute of Radiopharmaceutical Cancer Research  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esben Thade","family":"Petersen","sequence":"additional","affiliation":[{"name":"Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research Copenhagen University Hospital Hvidovre  Hvidovre Denmark"},{"name":"Center for Magnetic Resonance, Department of Health Technology Technical University of Denmark  Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri J.M.M.","family":"Mutsaerts","sequence":"additional","affiliation":[{"name":"Radiology &amp; Nuclear Medicine, Amsterdam UMC Vrije Universiteit  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.L.","family":"Majoie","sequence":"additional","affiliation":[{"name":"Radiology &amp; Nuclear Medicine, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Cardiology &amp; Radiology Children's Hospital of Los Angeles  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"VanBavel","sequence":"additional","affiliation":[{"name":"Biomedical Engineering &amp; Physics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aart J.","family":"Nederveen","sequence":"additional","affiliation":[{"name":"Radiology &amp; Nuclear Medicine, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart J.","family":"Biemond","sequence":"additional","affiliation":[{"name":"Hematology, Amsterdam UMC University of Amsterdam  Amsterdam The 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