A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T1(shMOLLI-T1) in the liver.
Tunnicliffe EM., Banerjee R., Pavlides M., Neubauer S., Robson MD.
PURPOSE: To propose a simple multicompartment model of the liver and use Bloch-McConnell simulations to demonstrate the effects of iron and fibrosis on shortened-MOLLI (shMOLLI) T1measurements. Liver T1values have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look-Locker inversion recovery (MOLLI) T1measurements are biased by the lower T2associated with high iron. MATERIALS AND METHODS: A tissue model was generated consisting of liver cells and extracellular fluid (ECF), with iron-dependent relaxation rates. Fibrosis was imitated by increasing the ECF proportion. Simulations of the shMOLLI sequence produced a look-up table (LUT) of shMOLLI-T1for a given ECF fraction and iron content. The LUT was used to calculate ECF(shMOLLI-T1), assuming normal hepatic iron content (HIC), and ECF(shMOLLI- T1,T2*), accounting for HIC determined by T2*, for 77 patients and compared to fibrosis assessed by liver biopsy. RESULTS: Simulations showed that increasing HIC decreases shMOLLI-T1, with an increase in HIC from 1.0 to 2.5 mg/g at normal ECF fraction decreasing shMOLLI-T1by 160 msec, while increasing ECF increased ShMOLLI-T1, with an increase of 20% ECF at normal iron increasing shMOLLI-T1by 200 msec. Calculated patient ECF(shMOLLI-T1) showed a strong dependence on Ishak score (3.3 ± 0.8 %ECF/Ishak stage) and 1/T2* (-0.23 ± 0.04 %ECF/Hz). However, when iron was accounted for to produce ECF(shMOLLI- T1,T2*), it was independent of HIC but retained sensitivity to Ishak score. CONCLUSION: Use of this multicompartment model of the liver with Bloch-McConnell simulation should enable compensation of iron effects when using shMOLLI-T1to assess fibrosis. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:450-462.