title: Liver MRI is more precise than liver biopsy for assessing total body iron balance: a comparison of MRI relaxometry with simulated liver biopsy results.
abstract: OBJECTIVE
  Liver biopsy was long considered the reference standard for measuring liver iron concentration. However, its high sampling variability and invasive nature make it poorly suited for serial analyses. To demonstrate the fallibility of liver biopsy, we use serial estimates of iron chelation efficiency (ICE) calculated by R2 and R2* MRI liver iron concentration (LIC) estimates as well as by simulated liver biopsy (over all physically reasonable sampling variability) to compare the robustness of these three techniques.
  
  
  METHODS
  R2, R2*, transfusional volume, and chelator compliance were obtained from 49 participants in a phase II clinical trial of deferitazole over two years. Liver biopsy LIC results were simulated using sampling errors of 0%, 10%, 20%, 30%, 40% and iron assay variability of 12%. LIC estimates by R2, R2*, and simulated biopsy were used to calculate ICE over time. Bland-Altman limits of agreement were compared across observation intervals of 12, 24, and 48 weeks.
  
  
  RESULTS
  At 48 week intervals, LIC estimates by R2, R2* and "perfect" liver biopsy had comparable accuracy in predicting ICE; both MRI methods were superior to any physically realizable liver biopsy (sampling error 10% or higher). LIC by R2* demonstrated the most robust ICE estimates at monitoring intervals of 24 and 12 weeks, but this difference did not remain significant at 48 week intervals.
  
  
  CONCLUSIONS
  MRI relaxometry is superior to liver biopsy for serial LIC observations, such as used in the care of tranfusional siderosis patients, and should also be considered the new standard of LIC determination for regulatory purposes. Among relaxometry techniques, LIC estimates by R2* are more robust for tracking changes in iron balance over intermediate time scales (<=24 weeks).
authors.affiliation: Department of Pediatrics and Radiology, Children's Hospital Los Angeles.
authors.forename: John C
authors.initials: JC
authors.lastname: Wood
authors.affiliation: Shire Pharmaceuticals, Chesterbrook, PA.
authors.forename: Pinggao
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Ferrokin Biosciences Inc., San Carlo, CA.
authors.forename: Hugh
authors.initials: H
authors.lastname: Rienhoff
authors.affiliation: Shire, Global Development, Eysins, Switzerland.
authors.forename: Walid
authors.initials: W
authors.lastname: Abi-Saab
authors.affiliation: Boston Children's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007501:Iron / Q000032:analysis*; D019190:Iron Overload / Q000175:diagnosis* / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D007501:Iron
keywords: Iron overload; Liver; Monte-Carlo Simulation; Relaxometry; Sickle cell disease; Thalassemia