Abstract

BackgroundThere is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.MethodsHere, we used an optimised liver T2* sequence calibrated against 50 liver biopsy samples on 25 patients with transfusional haemosiderosis using ordinary least squares linear regression, and assessed the method reproducibility in 96 scans over an LIC range up to 42 mg/g dry weight (dw) using Bland-Altman plots. Using mixed model linear regression we compared the new T2*-LIC with R2-LIC (Ferriscan) on 92 scans in 54 patients with transfusional haemosiderosis and examined method agreement using Bland-Altman approach.ResultsStrong linear correlation between ln(T2*) and ln(LIC) led to the calibration equation LIC = 31.94(T2*)-1.014. This yielded LIC values approximately 2.2 times higher than the proof-of-concept T2* method. Comparing this new T2*-LIC with the R2-LIC (Ferriscan) technique in 92 scans, we observed a close relationship between the two methods for values up to 10 mg/g dw, however the method agreement was poor.ConclusionsNew calibration of T2* against liver biopsy estimates LIC in a reproducible way, correcting the proof-of-concept calibration by 2.2 times. Due to poor agreement, both methods should be used separately to diagnose or rule out liver iron overload in patients with increased ferritin.

Highlights

  • There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload

  • Patients For the calibration analysis we retrospectively studied 25 patients with transfusional hemosiderosis, including 20 Thalassemia Major, 2 Diamond-Blackfan Anemia, 2 Congenital Sideroblastic Anemia, 1 Pyruvate Kinase Deficiency Anemia, in whom 50 liver biopsies were undertaken at University College London Hospitals (UCLH) as part of clinical iron chelation studies on deferasirox; [2,4] patients were being monitored with annual liver and heart magnetic resonance (MR) scans according to standard clinical management

  • The early T2* method [16] estimating LIC at 6.86 mg/g dw for T2* of 2 ms should be corrected by an average factor of × 2.2 + 0.57 to obtain values comparable with present calibration

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Summary

Introduction

There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC. Non-invasive estimation of LIC is increasingly used to follow responses to chelation therapy [4] This is because of the limitations of serum management of iron overload, LIC measurement is an important tool. It is important to understand how values derived with these various approaches relate to each other, so that responses to chelation therapy in different studies can be compared and thresholds for treatment intensification can be meaningfully identified

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