Introduction

Hepatic sinusoidal obstruction syndrome (SOS), a toxic liver injury, is commonly caused by hematopoietic stem cell transplantation and systemic chemotherapy such as Oxaliplatin. An accurate diagnosis and serial monitoring of SOS would be needed for an effective management, and therefore, a noninvasive quantification of SOS is of great importance in clinical practice. Considering that hepatic SOS is characterized by damage to hepatocyte as well as hepatic sinusoids, it may affect the diffusion as well as perfusion features of the liver. Intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) allows separate estimation of molecular diffusion and microcirculation¹; therefore, we hypothesize that IVIM-DWI can be useful in the diagnosis of hepatic SOS. Thus, the purpose of our study was to investigate the diagnostic value of IVIM-DWI in the severity assessment of hepatic SOS using a monocrotaline (MCT)-induced rat SOS model.

Materials and methods

The institutional animal care and use committee approved this study. Twenty-four Sprague-Dawley rats (250-300g) were treated with vehicle (control group, n=6), 90 mg/kg of MCT (low-dose group, n=10), and 160 mg/kg of MCT (high-dose group, n=8). All rats underwent MRI 72 hours after treatment and were sacrificed immediately after MRI for histologic analysis. All MRI exams were performed with a 3.0-T MR imaging system, and IVIM-DWI were acquired by using a free-breathing single shot EPI with 9 b-values (0, 25, 50, 75, 100, 150, 200, 400, and 800 sec/mm²). ADC values were calculated by using all b values with a mono-exponential fit, and IVIM parameters including true diffusion coefficient (Dslow), pseudo-diffusion coefficient (Dfast), and perfusion fraction (PF) were calculated by using a nonlinear bi-exponential fit (Fig. 1). Five circular regions of interests (ROIs) were drawn for each ADC and IVIM parametric map at where it covers a large homogeneous area of liver, and the mean of five measurements for each parameter was used as a representative value. Based on the histologic features including sinusoidal hemorrhage, coagulation necrosis, and endothelial damage of the central vein^2,3, each animal was categorized into one of the SOS severity groups: none, mild, moderate, and severe. The ADC and IVIM-DWI parameters were compared according to treatment groups and SOS severity groups using a Kruskal-Wallis test. In addition, those parameters were correlated with SOS severity using the using Spearman’s rank correlation test.

Results

Among ADC and IVIM-DWI parameters, PF showed a significant difference according to treatment groups with medians of 17.2%, 12.9% and 10.8 % in control, low-dose MCT group, and high-dose MCT group, respectively (P<0.01). PF of hepatic parenchyma were significantly different according to SOS severity with medians of 17.9% in none (n=5), 11.9% in mild/moderate (n=6) and 9.9% in severe SOS (n=3) (P=0.01) (Fig. 2), and showed a strong negative correlation with SOS severity (rho=-0.84, P<0.01) (Table 1). In addition, ADC and Dslow showed a negative correlation with SOS severity with statistical significance (rho=-0.70 and -0.61, P<0.01 and 0.02, respectively) (Table 1).

Discussion

Our study found that ADC, Dslow, and PF were significantly different according to the treatment groups and severity of hepatic SOS, and showed a negative correlation with SOS severity. These changes in diffusion- and perfusion-related parameters of IVIM-DWI may be explained by the histologic features of hepatic SOS including sinusoidal dilatation and congestion, fibrosis of the sinusoids and venules, and coagulation necrosis of hepatocytes that would potentially cause alterations in diffusion and perfusion characteristics of the liver^4,5,6.

Conclusion

IVIM-DWI may serve as a noninvasive method in the quantitative assessment of hepatic SOS.

Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A2A01055423).

References

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