title: Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.
abstract: Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems.
  
  
  
  Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues.
  
  
  
  Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T).
  
  
  
  Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement.
  
  
  
  ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. colin.stirrat@ed.ac.uk.
authors.forename: Colin G
authors.initials: CG
authors.lastname: Stirrat
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Shirjel R
authors.initials: SR
authors.lastname: Alam
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.|Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacGillivray
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.|Edinburgh Clinical Research Facility, University of Edinburgh, Edinburgh, UK.
authors.forename: Calum D
authors.initials: CD
authors.lastname: Gray
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: Forsythe
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Dweck
authors.affiliation: Department of Cardiology, Golden Jubilee National Hospital, Clydebank, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Payne
authors.affiliation: Department of Cardiology, Royal Brompton Hospital, London, UK.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Prasad
authors.affiliation: Department of Cardiology, Golden Jubilee National Hospital, Clydebank, UK.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Petrie
authors.affiliation: Department of Cardiology, Golden Jubilee National Hospital, Clydebank, UK.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Gardner
authors.affiliation: Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Saeed
authors.initials: S
authors.lastname: Mirsadraee
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Henriksen
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.|Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.affiliation: British Heart Foundation/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.|Clinical Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
authors.forename: Scott I K
authors.initials: SI
authors.lastname: Semple
mesh_terms: D016477:Artifacts; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005240:Feasibility Studies; D005260:Female; D052203:Ferrosoferric Oxide / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006321:Heart / Q000000981:diagnostic imaging*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007262:Infusions, Intravenous; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D009942:Organometallic Compounds; C097921:ferumoxtran-10; C090600:gadobutrol; D052203:Ferrosoferric Oxide
keywords: Cardiac; Inflammation; MRI; USPIO