title: Liver iron concentration measurements by MRI in chronically transfused children with sickle cell anemia: baseline results from the TWiTCH trial.
abstract: Noninvasive, quantitative, and accurate assessment of liver iron concentration (LIC) by MRI is useful for patients receiving transfusions, but R2 and R2* MRI techniques have not been systematically compared in sickle cell anemia (SCA). We report baseline LIC results from the TWiTCH trial, which compares hydroxyurea with blood transfusion treatment for primary stroke prophylaxis assessed by transcranial Doppler sonography in pediatric SCA patients. Liver R2 was collected and processed using a FDA-approved commercial process (FerriScan®), while liver R2* quality control and processing were performed by a Core Laboratory blinded to clinical site and patient data. Baseline LIC studies using both MRI techniques were available for 120 participants. LICR2* and LICR2 results were highly correlated (r(2)  = 0.93). A proportional bias of LIC(R2*)/LIC(R2), decreasing with average LIC, was observed. Systematic differences between LICR2* and LICR2 were also observed by MRI manufacturer. Importantly, LICR2* and LICR2 estimates had broad 95% limits of agreement with respect to each other. We recommend LICR2 and LICR2* not be used interchangeably in SCA patients to follow individual patient trends in iron burden.
authors.affiliation: Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.affiliation: The University of Texas Health Science Center, Houston, Texas.
authors.forename: Sara
authors.initials: S
authors.lastname: Pressel
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Zora R
authors.initials: ZR
authors.lastname: Rogers
authors.affiliation: Division of Haematology/Oncology, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Isaac
authors.initials: I
authors.lastname: Odame
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Penninsylvania.
authors.forename: Janet L
authors.initials: JL
authors.lastname: Kwiatkowski
authors.affiliation: Columbia University, New York, New York.
authors.forename: Margaret T
authors.initials: MT
authors.lastname: Lee
authors.affiliation: Children's Hospital of the King's Daughters, Norfolk, Virginia.
authors.forename: William C
authors.initials: WC
authors.lastname: Owen
authors.affiliation: School of Physics, University of Western Australia, Crawley, Australia.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Cohen
authors.affiliation: School of Physics, University of Western Australia, Crawley, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: St Pierre
authors.affiliation: Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Heeney
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: William H
authors.initials: WH
authors.lastname: Schultz
authors.affiliation: The University of Texas Health Science Center, Houston, Texas.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000473:pathology / Q000628:therapy*; D000986:Antisickling Agents / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001681:Biological Assay / Q000592:standards*; D002648:Child; D002675:Child, Preschool; D000077588:Deferasirox; D003676:Deferoxamine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D020521:Stroke / Q000517:prevention & control; D065227:Transfusion Reaction; D014230:Triazoles / Q000627:therapeutic use; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000986:Antisickling Agents; D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D007501:Iron; D003676:Deferoxamine; D000077588:Deferasirox; D006918:Hydroxyurea