Dynamic contrast-enhanced magnetic resonance imaging with hepatocyte -selective contrast agent in the evaluation of the extent and severity of liver fibrosis in patients with chronic liver disease
Date Issued
2008
Date
2008
Author(s)
Chen, Bang-Bin
Abstract
Chronic liver disease is an important disease in Taiwan. A large percentage of these patients will develop chronic hepatitis, liver fibrosis and cirrhosis and then hepatic tumors. The evaluation of liver fibrosis currently needs pathological grading from the invasive biopsy procedure. Noninvasive imaging of liver fibrosis would reduce biopsy-related risks and costs and thus potentially eliminate sampling errors and enable global liver assessment. Although the presence of cirrhosis can be confirmed by using ultrasonography, computed tomography, and magnetic resonance imaging, these findings are insensitive in the detection of early cirrhosis and milder fibrosis. he possibility of noninvasively diagnosing cirrhosis on the basis of the hepatic texture alterations seen on contrast material–enhanced MR images has been suggested. After injection of superparamagnetic iron oxides or gadolinium chelates, hyperintense reticulations can be observed against the hypointense liver background. Besides, the delayed distribution of extracellular gadolinium chelates in fibrotic tissue is well documented. For these reasons, it may be possible to diagnose cirrhosis and grade liver fibrosis on gadolinium-chelated agent on the basis of hepatic texture alterations.he current image modalities such MRI with extra-cellular contrast agents could only detect the liver with abnormal vascularity or tumor formation. Gd-EOB-DTPA is hepatocyte-specific contrast agent, which distributed through the blood vessel to the intravascular, extra-vascular interstitial space and intracellular space of hepatocyte. Thus, the effectiveness and enhancement pattern will be influenced by the degree of liver fibrosis. Because Gd-EOB-DTPA is taken up selectively into normal hepatocytes and subsequently excreted into the bile, this agent is particularly advantageous for differentiating between normal tissue and abnormal liver tissue such as chronic liver disease. he purpose of our study is to develop a non-invasive method for evaluation of liver fibrosis by using comprehensive dynamic contrast-enhanced MR imaging (DCE-MRI) using Gd-EOB-DTPA, with histologic analysis as reference standard. CE-MRI with Gd-EOB-DTPA was performed in 79 subjects (healthy group, 21 subjects, 14 male, 7 female, mean age, 39.1 years；hepatitis group, 41male, 17 female, mean age, 42.4 years). The following estimated perfusion parameters were measured with a dual-input single-compartment (Van Beers) model: absolute arterial blood flow (Fa), absolute portal venous blood flow (Fp), absolute total liver blood flow (Ft) (Ft = Fa + Fp), arterial fraction (ART), distribution volume (DV), and mean transit time (MTT) of Gd-EOB-DTPA. The curve analysis model uses parameters including Peak, slope, area under curve(AUC), full width at half maximum (FWHM), and mean time (MT) to evaluate the signal-intensity curve of liver after injection of Gd-EOB-DTPA.hese 79 subjects were assigned into three groups according to fibrotic stage. The AVONA and the nonparametric Kruskal-Wallis test were used to compare perfusion and curve parameters between groups. There was an increase in Fa, ART, and a decrease in DV, AUC, FWHM and MT in hepatitis group compared with healthy group. The slope and AUC were lower in advanced fibrosis group compared with those without fibrosis. n hepatic equilibrium phase (2~50 minutes after injection of Gd-EOB-DTPA), the signal of liver and common hepatic ducts were measured. We use parameters including average signal (Ave), maximal enhanced signal (Max), maximal enhanced ratio (Max %) and summed signal (Sum) to evaluate the signal-intensity curve of liver and common hepatic duct. There was an increase in Max %, and a decrease in Sum in hepatitis group compared with healthy group. The Ave was lower in advanced fibrosis group compared with those without fibrosis. he perfusion parameters of DCE-MRI with Gd-EOB-DTPA and Gd-DTPA were compared in 10 healthy subjects. At 60 seconds after injection, there was no significant difference of perfusion parameters between these two contrast agents. At 100 seconds after injection, there was a decrease in Ft, and an increase in DV and MT in Gd-EOB-DTPA compared with those using Gd-DTPA. These findings implied that Gd-EOB-DTPA entered hepatocytes in a large mount at 100 seconds after injection.ollagen deposition in the space of Disse is associated with restricted diffusion of Gd-EOB-DTPA in the extravascular space and its transportation into the liver in fibrotic and cirrhotic livers; thus, there is an expected decrease in signal enhancement throughout the liver. The distribution volume, reflects hepatocyte volume, is also decreased in liver with hepatitis and fibrosis. n conclusion, we found that DCE-MRI with Gd-EOB-DTPA is a feasible and noninvasive imaging modality in which multiple perfusion and curve parameters can be measured and potentially used as biomarkers of liver fibrosis. The development of noninvasive imaging methods to detect and grade fibrosis throughout the entire liver would represent a major advance in the understanding of liver disease. These capabilities would enable serial follow-up of patients and assessment of therapy response; and serve as a powerful research tool for therapy development.
Subjects
DCE-MRI
Gd-EOB-DTPA
Liver fibrosis
SDGs
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