Value of transverse relaxometry difference methods for iron in human brain

Purpose 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 R 2 and R 2 ⁎ were measured in human brain in 17 healthy subjects at 1.5 T and 4.7 T using multi-slice, multiecho spin echo and gradient echo sequences. R 2 quantification used stimulated echo compensation and R 2 ⁎ quantification used linear background gradient correction at 4.7 T only. Subtraction of R 2 from R 2 ⁎ within each field strength yielded R 2 ’ , and R 2 subtraction across fields yielded Field Dependent R 2 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 (R 2 , R 2 ⁎ , R 2 ’ ) at both 1.5 T and 4.7 T, and FDRI had moderate to strong correlations (r > 0.71, p 0.9) than 1.5 T measures. R 2 , R 2 ⁎ , R 2 ’ at 4.7 T and FDRI had slopes 0.49, 1.96, 1.48 and 0.33 [s − 1 /mg Fe/100 g 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 R 2 ’ was 3.4 times greater at 4.7 T than 1.5 T. For white matter fiber tracts oriented predominantly perpendicular versus parallel to B 0 , R 2 ’ increased by ~ 50% at 4.7 T and ~ 30% at 1.5 T, while R 2 and FDRI in white matter was insensitive to its orientation with respect to B 0 . Conclusion The transverse relaxation difference methods FDRI and R 2 ’ at 4.7 T had high correlations to predicted iron content similar to R 2 and R 2 ⁎ at 4.7 T. Although R 2 ’ had smaller y-intercept with estimated iron concentration than FDRI, in white matter R 2 ’ demonstrated strongest dependence on fiber orientation with respect to B 0. These results suggest that for brain iron correlation, there is minimal value of transverse difference methods over a single R 2 ⁎ measurement at highest available field, which was 4.7 T.