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Published on: November 27, 2019
Noninvasive Assessment of APAP (N-acetyl-p-aminophenol)-Induced Hepatotoxicity Using Multiple MRI Parameters in an
Dan Chen1,2, Xinyan Zhao3, Hui Xu1
1Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Yongan Road 95, West District, Beijing, 100050, China.
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.
Insights
Early detection of N-acetyl-p-aminophenol (APAP)-induced liver injury is crucial. MRI parameters, specifically precontrast T1 and ΔT1-T2/3, show promise in assessing the severity of APAP-induced hepatotoxicity in rats.
Area of Science:
- Radiology and Medical Imaging
- Hepatology
- Toxicology
Background:
- Early detection of N-acetyl-p-aminophenol (APAP)-induced hepatotoxicity is vital for preventing liver failure.
- Accurate assessment of liver injury severity aids in timely intervention.
Purpose of the Study:
- To evaluate the utility of multiple magnetic resonance imaging (MRI) parameters for assessing APAP-induced hepatotoxicity.
- To correlate MRI findings with histological severity in a rat model.
Main Methods:
- Utilized a 3T MRI scanner with T1 mapping and intravoxel incoherent motion (IVIM) sequences.
- Administered APAP to rats, classifying livers into normal, mild, and moderate necrosis groups based on histology.
- Measured T1 relaxation times and diffusion parameters, calculating various T1 reduction metrics.
Main Results:
- Precontrast T1 and ΔT1-T2/3 strongly correlated with necrosis severity (r=0.9094, r=0.7978).
- Lower apparent diffusion coefficient (ADC) and diffusivity (D) values were observed in moderate necrosis.
- Reduced organic anion-transporting polypeptide 1 (oatp1) activity was noted in necrotic groups.
Conclusions:
- Precontrast T1 and ΔT1-T2/3 are promising MRI parameters for assessing early-stage APAP-induced hepatotoxicity.
- MRI can potentially differentiate and quantify the severity of liver injury.
- Further research can explore these MRI parameters for clinical application.
