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

Abstract

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- 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-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 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-T₁ to assess fibrosis.

Level of evidence: 1 J. Magn. Reson. Imaging 2017;45:450-462.

Keywords: T1 mapping; liver MRI; liver disease.