title: Value of transverse relaxometry difference methods for iron in human brain.
abstract: OBJECTIVE
  To investigate the brain iron dependence of transverse relaxation rate difference methods derived from spin echo and gradient echo measurements from two field strengths.
  
  
  METHODS
  Transverse relaxation rates R2 and R2(⁎) were measured in human brain in 17 healthy subjects at 1.5T and 4.7T using multi-slice, multiecho spin echo and gradient echo sequences. R2 quantification used stimulated echo compensation and R2(⁎) quantification used linear background gradient correction at 4.7T only. Subtraction of R2 from R2(⁎) within each field strength yielded R2('), and R2 subtraction across fields yielded Field Dependent R2 Increase (FDRI). All transverse relaxation measures were then correlated with published post-mortem iron concentrations using linear regression analysis. Regional differences were tested using paired t-tests. Phantom measurements of FDRI were also performed.
  
  
  RESULTS
  In deep grey matter, all transverse relaxation rates (R2, R2(⁎), R2(')) at both 1.5T and 4.7T, and FDRI had moderate to strong correlations (r>0.71, p<0.0001) with estimated non-heme iron. The 4.7T methods and FDRI had higher correlations (r>0.9) than 1.5T measures. R2, R2(⁎), R2' at 4.7T and FDRI had slopes 0.49, 1.96, 1.48 and 0.33 [s(-1)/mg Fe/100g wt. tissue] and intercepts 14.40, 16.87, 2.47 and 3.21 [s(-1)] respectively. Even though FDRI yielded a zero intercept in phantom, in vivo FDRI was found to be ineffective at fully removing non-iron contributions and yielded a large intercept. The slope for R2(') was 3.4 times greater at 4.7T than 1.5T. For white matter fiber tracts oriented predominantly perpendicular versus parallel to B0, R2(') increased by ~50% at 4.7T and ~30% at 1.5T, while R2 and FDRI in white matter was insensitive to its orientation with respect to B0.
  
  
  CONCLUSIONS
  The transverse relaxation difference methods FDRI and R2(') at 4.7T had high correlations to predicted iron content similar to R2 and R2(⁎) at 4.7T. Although R2(') had smaller y-intercept with estimated iron concentration than FDRI, in white matter R2(') demonstrated strongest dependence on fiber orientation with respect to B0. These results suggest that for brain iron correlation, there is minimal value of transverse difference methods over a single R2(⁎) measurement at highest available field, which was 4.7T.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
authors.forename: Md Nasir
authors.initials: MN
authors.lastname: Uddin
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Canada.
authors.forename: R Marc
authors.initials: RM
authors.lastname: Lebel
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Canada. Electronic address: wilman@ualberta.ca.
authors.forename: Alan H
authors.initials: AH
authors.lastname: Wilman
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D007501:Iron
keywords: FDRI; Iron; R(2)(’); Stimulated echo compensation; Transverse relaxometry