A model for hepatic fibrosis: the competing effects of cell loss and iron on shortened modified Look-Locker inversion recovery T 1 (shMOLLI- T 1 ) in the liver

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) T1 measurements. Liver T1 values have shown sensitivity to inflammation and fibrosis, but are also affected by hepatic iron content. Modified Look-Locker inversion recovery (MOLLI) T1 measurements are biased by the lower T2 associated 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-T1 for 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- ), accounting for HIC determined by , 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-T1 by 160 msec, while increasing ECF increased ShMOLLI-T1, with an increase of 20% ECF at normal iron increasing shMOLLI-T1 by 200 msec. Calculated patient ECF(shMOLLI-T1) showed a strong dependence on Ishak score (3.3 ± 0.8 %ECF/Ishak stage) and (–0.23 ± 0.04 %ECF/Hz). However, when iron was accounted for to produce ECF(shMOLLI- ), 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-T1 to assess fibrosis. Level of Evidence: 1 J. Magn. Reson. Imaging 2017;45:450–462.