title: Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.
abstract: Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.
authors.affiliation: 1 Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN, USA lori.jordan@vanderbilt.edu.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Jordan
authors.affiliation: 1 Department of Pediatrics, Division of Pediatric Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Gindville
authors.affiliation: 2 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Allison O
authors.initials: AO
authors.lastname: Scott
authors.affiliation: 2 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Meher R
authors.initials: MR
authors.lastname: Juttukonda
authors.affiliation: 2 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Megan K
authors.initials: MK
authors.lastname: Strother
authors.affiliation: 3 Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Adetola A
authors.initials: AA
authors.lastname: Kassim
authors.affiliation: 4 Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sheau-Chiann
authors.initials: SC
authors.lastname: Chen
authors.affiliation: 5 Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Lu
authors.affiliation: 2 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Pruthi
authors.affiliation: 4 Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.affiliation: 2 Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA 6 Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA 7 Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010092:Oximetry / Q000379:methods; D010100:Oxygen / Q000378:metabolism*; D013113:Spin Labels; D055815:Young Adult
chemical_list: D013113:Spin Labels; D010100:Oxygen
keywords: arterial spin labelling; brain ischaemia; cerebral haemodynamics; oxygen extraction fraction; sickle cell anaemia
references.citation: Am J Physiol. 1989 Sep;257(3 Pt 2):H912-7
references.pmid: 2782448
references.citation: Magn Reson Med. 2015 Apr;73(4):1579-92
references.pmid: 24757044
references.citation: Expert Rev Hematol. 2011 Dec;4(6):597-606
references.pmid: 22077524
references.citation: J Cereb Blood Flow Metab. 2014 Jul;34(7):1243-52
references.pmid: 24780904
references.citation: J Nucl Med. 2001 Aug;42(8):1195-7
references.pmid: 11483680
references.citation: Neurology. 1999 Jul 22;53(2):251-9
references.pmid: 10430410
references.citation: Neurology. 2006 Aug 22;67(4):572-4
references.pmid: 16924006
references.citation: Proc Natl Acad Sci U S A. 1986 Feb;83(4):1140-4
references.pmid: 3485282
references.citation: Magn Reson Med. 2004 Sep;52(3):679-82
references.pmid: 15334591
references.citation: J Cereb Blood Flow Metab. 2009 Apr;29(4):803-10
references.pmid: 19209182
references.citation: Blood. 2002 Apr 15;99(8):3014-8
references.pmid: 11929794
references.citation: Ment Retard Dev Disabil Res Rev. 2006;12(3):192-9
references.pmid: 17061288
references.citation: Brain. 2002 Mar;125(Pt 3):595-607
references.pmid: 11872616
references.citation: Blood. 2011 Jan 20;117(3):772-9
references.pmid: 20940417
references.citation: NMR Biomed. 2014 Mar;27(3):332-40
references.pmid: 24399806
references.citation: Magn Reson Med. 2006 Sep;56(3):546-52
references.pmid: 16894581
references.citation: Magn Reson Med. 2008 Aug;60(2):357-63
references.pmid: 18666116
references.citation: Magn Reson Med. 2012 Jan;67(1):42-9
references.pmid: 21590721
references.citation: Neuroimage. 2014 Jul 15;95:185-92
references.pmid: 24685437
references.citation: Blood. 1998 Jan 1;91(1):288-94
references.pmid: 9414296
references.citation: Stroke. 2007 Mar;38(3):1091-6
references.pmid: 17272767
references.citation: Am J Respir Crit Care Med. 1999 Feb;159(2):447-51
references.pmid: 9927356
references.citation: Stroke. 1986 Jul-Aug;17 (4):692-8
references.pmid: 3488606
references.citation: Cereb Cortex. 2011 Jun;21(6):1426-34
references.pmid: 21051551
references.citation: J Cereb Blood Flow Metab. 2012 Oct;32(10 ):1909-18
references.pmid: 22739621
references.citation: Med Image Anal. 2001 Jun;5(2):143-56
references.pmid: 11516708
references.citation: IEEE Trans Med Imaging. 2001 Jan;20(1):45-57
references.pmid: 11293691
references.citation: Magn Reson Med. 2012 Nov;68(5):1458-71
references.pmid: 22294414
references.citation: Magn Reson Med. 2011 Dec;66(6):1550-62
references.pmid: 21674615
references.citation: Blood. 2014 Aug 7;124(6):830-1
references.pmid: 25104860
references.citation: J Pediatr. 1992 Mar;120(3):360-6
references.pmid: 1538280
references.citation: Stroke. 2009 Sep;40(9):3039-44
references.pmid: 19628806
references.citation: Stroke. 2009 Jul;40(7):2408-12
references.pmid: 19443807
references.citation: Magn Reson Med. 2015 Jan;73(1):102-16
references.pmid: 24715426
references.citation: Neuroimage. 2014 Nov 1;101:458-65
references.pmid: 25091128
references.citation: Stroke. 2015 Apr;46(4):982-8
references.pmid: 25721017
references.citation: Ann Neurol. 1991 Mar;29(3):231-40
references.pmid: 2042939
references.citation: Neurology. 1998 Jul;51(1):169-76
references.pmid: 9674798
references.citation: Lancet Neurol. 2013 Aug;12(8):822-38
references.pmid: 23867200
references.citation: Magn Reson Med. 2014 Jun;71(6):2035-42
references.pmid: 23843129
references.citation: J Cereb Blood Flow Metab. 2012 Mar;32(3):403-12
references.pmid: 22252237
references.citation: Blood. 1993 Jun 15;81(12):3422-7
references.pmid: 7685205
references.citation: Magn Reson Med. 2007 Sep;58(3):592-7
references.pmid: 17763354
references.citation: J Cereb Blood Flow Metab. 1992 Sep;12(5):745-9
references.pmid: 1506442
references.citation: Control Clin Trials. 1998 Feb;19(1):110-29
references.pmid: 9492971
references.citation: Magn Reson Med. 2009 Jul;62(1):141-8
references.pmid: 19353674
references.citation: Pediatr Hematol Oncol. 2010 Mar;27(2):69-89
references.pmid: 20201689
references.citation: N Engl J Med. 1998 Jul 2;339(1):5-11
references.pmid: 9647873