Liver iron susceptometry is different in patients with transfusion dependent thalassemia and sickle cell disease compared with hemochromatosis

Biomagnetic liver susceptometry (BLS) is a non-invasive method to quantify liver iron concentration (LIC) based on a universal iron-specific paramagnetic susceptibility (χ_Fe). In a blinded prospective study validating in vivo LIC by SQUID biosusceptometry (BLS) with in vitro LIC by biopsies, unexplainable discrepancies were evident between the two methodologies. Thus, a re-analysis of relevant data was performed questioning the universal character of χ_Fe in liver tissue. The magnetic volume susceptibility difference relative to water was measured by BLS, and the LIC was assayed by ICP-MS in 40 dry weight fresh-tissue and paraffin-embedded biopsy samples in patients with transfusion dependent thalassemia (TDT) and sickle cell disease (SCD). The wet-to-dry weight ratio was confirmed as 4.1 ± 0.7. Retrospectively, χ_Fe was re-analyzed from historic wet-weight LIC in 37 patients with hereditary hemochromatosis (HFE-1). The ratio of in vivo volume susceptibility difference Δχ to wet-weight LIC resulted in significantly different iron-specific mass susceptibilities χ_Fe in patients with TDT, SCD, and HFE-1. From regression analysis of dry-weight LIC versus Δχ(BLS) in patients with TDT & SCD (r² = 0.89), we could derive a susceptibility of χ_Fe = (0.96 ± 0.03)⋅10^-6m³/kg and χ_Fe = (1.48 ± 0.03)⋅10^-6m³/kg in patients with HFE-1 (r² = 0.99). The discrepancy in former LIC by BLS can be resolved with a factor of 1.5 still using the traditional wet-to-dry weight ratio of 4. Given these findings, it is recommended that for noninvasive magnetic iron measurements, different magnetic susceptibilities be applied to patients with transfusional siderosis (TDT, SCD) compared with hereditary hemochromatosis, and presumably also for other iron loading disorders.