Magnetic resonance quantification of non-Gaussian water diffusion in hepatic fibrosis staging: a pilot study of diffusion kurtosis imaging to identify reversible hepatic fibrosis

Abstract

Background: This study aimed to evaluate the diagnostic accuracy of diffusion kurtosis imaging (DKI) in differentiating early hepatic fibrosis (HF) from normal liver and advanced HF in rabbits.

Methods: A total of 35 healthy New Zealand white rabbits were included in the study. A model of HF was established in 30 rabbits through subcutaneous injections of 50% carbon tetrachloride (CCl₄)/olive oil, while 5 rabbits received saline injections. The gradually increased doses of CCl₄ were 0.1, 0.2, and 0.3 mL/kg in weeks 1 to 3, weeks 4 to 6, and weeks 7 to 10, respectively. Two injections were given each week. Two rabbits in the experimental group died. All rabbits underwent DKI with three b values (0, 500, and 1,000 s/mm²) at week 5 (n=8), week 6 (n=9), week 7 (n=8), and week 10 (n=8). Approximately 2 liver lobes per rabbit were selected for histopathology. Mean diffusivity (MD) and mean kurtosis (MK) were calculated. Discrimination capacities of DKI parameters were analyzed and compared by receiver operating characteristic (ROC) analysis.

Results: The meta-analysis of histological data in viral hepatitis (METAVIR) scoring system was used to classify liver lobes into the control group (F0, n=0), early HF group (F1-F2, n=28), and advanced HF group (F3-F4, n=28). MD and MK values were significantly different among the three groups (all P<0.05). MD value was negatively correlated with increased fibrosis level, while MK value was positively correlated with increased fibrosis level (ρ=-0.540, 0.614; P<0.05). The area under ROC curves (AUCs) for MD and MK were 0.886 and 0.875, respectively, for characterization of F0 and F1-F2, and 0.975 and 0.957 for F0 and F3-F4. AUC for MK was 0.751 for characterization of F1-F2 and F3-F4. MD performed better than MK for characterization of F0 and F1-F2 as well as F0 and F3-F4. MK showed good differentiation performance between F1-F2 and F3-F4.

Conclusions: Our results showed that DKI contributed to discriminating reversible early HF from normal liver and advanced HF and as a result, showed promise for use in HF diagnosis.

Keywords: Hepatic fibrosis (HF); diffusion kurtosis imaging (DKI); magnetic resonance imaging (MRI); staging diagnosis.

Figure 1

The experiment flow chart. Thirty healthy, 6-to-8-month-old, male New Zealand white rabbits were randomly selected for the experimental group and 5 rabbits for the control group. A rabbit model of HF was established in the experimental group through subcutaneous injections of 50% CCl₄/olive oil. The gradually increased doses of CCl₄ were 0.1, 0.2, and 0.3 mL/kg in weeks 1 to 3, weeks 4 to 6, and weeks 7 to 10, respectively. Two injections were given each week. The control group rabbits were injected with saline for 10 consecutive weeks. A total of 33 rabbits were included in the experiment; 2 rabbits in the experimental group died (1 from hepatic failure and 1 from the anesthesia). All rabbits underwent DKI with three b values (0, 500, and 1,000 s/mm²) at 5, 6, 7, and 10 weeks. HF, hepatic fibrosis; CCl₄, carbon tetrachloride; DKI, diffusion kurtosis imaging; MRI, magnetic resonance imaging; T₂WI, T2-weighted images.

Figure 2

T₂WI, MD, and MK maps of HF at stage F3. Three ROIs were placed on the middle lobe of the right liver. (A) T₂WI. (B) ROIs ranging from 20 mm² were placed on the MD image. (C) ROIs were copied to the MK image. T₂WI, T2-weighted images; MD, mean diffusivity; MK, mean kurtosis; HF, hepatic fibrosis; ROIs, regions of interest.

Figure 3

Masson staining (original magnification ×100) based on the METAVIR scoring system. (A) F0, the normal control. (B) F1, mild fibrosis (portal fibrosis without septa). (C) F2, substantial fibrosis (periportal fibrosis and few septa). (D) F3, advanced fibrosis (septal fibrosis without cirrhosis). (E) F4, widespread fibrosis with cirrhosis. METAVIR, meta-analysis of histological data in viral hepatitis.

Figure 4

The ROC of DKI parameters (MD, MK) in discriminating F0 vs. F1–F2, F0 vs. F3–F4, and F1–F2 vs. F3–F4. ROC, receiver operating characteristic; DKI, diffusion kurtosis imaging; MD, mean diffusivity; MK, mean kurtosis; AUC, area under ROC curve.