Noninvasive Assessment of APAP (N-acetyl-p-aminophenol)-Induced Hepatotoxicity Using Multiple MRI Parameters in an Experimental Rat Model

Abstract

Background: Early detection and accurate assessment of N-acetyl-p-aminophenol (APAP)-induced hepatotoxicity can prevent further aggravation of liver injury and reduce the incidence of liver failure.

Purpose: To evaluate the potential of multiple MRI parameters for assessing APAP-induced hepatotoxicity in an experimental rat model.

Study type: Prospective.

Animal model: Twenty-one APAP-treated rats and 12 control rats.

Field strength/sequence: A 3 T, T1 mapping, Gd-EOB-DTPA-enhanced MRI, and intravoxel incoherent motion (IVIM).

Assessment: The severity of histological changes was assessed by a liver pathologist. Rat livers were pathologically classified into three groups: normal (n = 12), mild necrosis (n = 13), and moderate necrosis (n = 8). T1 relaxation time (T1) and diffusion parameters were measured. The reduction rate of T1 (ΔT1%) at different time points, the maximum value of ΔT1%, time period to the maximum value of ΔT1%, and time period from ΔT1max (%) to 2/3 value of ΔT1max (%) (ΔT1-T2/3) were calculated. Transporters activities like organic anion-transporting polypeptide 1 (oatp1) and multidrug resistance-associated protein 2 (mrp2) were compared among different necrotic groups.

Statistical tests: ANOVA/Kruskal-Wallis. Pearson/Spearman correlation. P < 0.05 was considered statistical significance.

Results: T1 Precontrast and ΔT1-T2/3 were strongly correlated with the severity of necrosis (r = 0.9094; r = 0.7978, respectively) and showed significant differences between the two groups. The apparent diffusion coefficient (ADC) and tissue diffusivity (D) values were significantly lower in the moderate necrosis group than in the normal and mild necrosis groups. The oatp1 activity of the necrosis groups was significantly reduced compared to that of the normal group, but the differences between normal and mild (P = 0.21), normal and moderate group (P = 0.56) were not significant. Meanwhile, enlargement of bile canaliculi and sparse microvilli was observed in the necrotic groups.

Conclusion: MRI parameters such as precontrast T1 and ΔT1-T2/3 had promising potential in assessing the severity of early-stage hepatotoxicity in an APAP overdose rat model.

Evidence level: 1 TECHNICAL EFFICACY: Stage 1.

Keywords: APAP; Gd-EOB-DTPA-enhanced MRI; T1 mapping; drug-induced liver injury; hepatotoxicity; intravoxel incoherent motion.