To determine whether gadoxetic acid-enhanced B1 corrected volumetric T1 map of the liver is able to demonstrate global liver function and functional heterogeneity in patients with liver cirrhosis, and to contribute to estimate the risk of with development of hepatic insufficiency or decompensation.

In this Institutional Review Board approved retrospective study, 234 consecutive patients (M:F=179:55) who underwent gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) including B1 corrected volumetric T1 map at 3T were included. The requirement of informed consent was waived. Patients were chronic liver disease (n=9), Child-Pugh classification A (n=198) and B (n=28) based on typical cross-sectional or ultrasound features and clinical findings.

Image acquisition— Volumetric B1 and T1 maps were obtained ten minutes after standard dose of gadoxetic acid (0.025mmol/kg) was injected intravenously. For obtaining B1 field map, double-angle method using two-dimensional (2D) turbo spin echo imaging (1) was acquired by applying following parameters: TR/TE, 771/40msec; and FA, 130º and 260 º. For T1 map, multi-slice, three-dimensional (3D) T1-weighted fast field echo with variable flip angle method (2), using following scan parameter: T1 map: TR, 9msec; FA, 5º and 29º; and slice thickness 8-10mm with inter slice gap of 8mm. FAs were determined by reported T1 relxation time of the liver (T1liver) at 3T (3, 4) and our preliminary phantom study. In both maps, field of view (300~350), number of excitation (1.0), matrix (128x98~128x128) and slice thickness were identical in a patient. A total of 10 slices were obtained in a breath-hold for each map.

Data analysis—T1 relaxation time of the liver (T1liver) and liver volume was measured at MR. T1liver with and without B1 correction were compared by using paired t-test. In addition, diagnostic performance to differentiate Child-Pugh class B from class A was compared between B1 corrected T1liver and uncorrected T1liver. B1 corrected T1liver, functional liver volume-to-weight ratio, which is liver volume divided by B1 corrected T1liver and patient’s weight, were compared between Child-Pugh A and B patients. The associations with serum markers (albumin, total bilirubin, prothrombin time), B1 corrected T1liver, functional liver volume-to-weight ratio, hepatic insufficiency and hepatic decompensation were investigated by using Cox proportional hazards analysis. In addition, we classified the patients into two groups based on criterion of albumin level of <3.5g/dL according to Child-Pugh classification, <4g/dL (5) and ≥462msec of T1liver, which was average value in patients with portal hypertension in previous study results using modified look-locker method (6). Heterogeneity of regional liver function was assessed by using kurtosis of T1liver.

Effect of B1 correction—Median, kurtosis and skewness of T1liver were significantly different before and after B1 correction (Table 1, Fig. 1, P <0.0001). Median T1liver was significantly higher after B1 correction and showed higher kurtosis in the whole liver as well as in each lobe (Table 1, P <0.0001).

Performance of B1 corrected T1 map in comparison with categorical liver function —Compared with patients with Child-Pugh A, patients with Child-Pugh B showed significantly higher T1liver (Table 2, 372.2 ± 77.5 vs. 548.2 ± 257.7, P<0.0001) and lower kurtosis of T1liver (29.1 ± 39.6 vs. 43.9 ± 64.9, P= 0.016). According to ROC analysis, B1 corrected T1liver showed significantly better diagnostic performance for distinguishing patients with Child B from Child A than uncorrected T1liver (Fig. 2, area under the curve [AUC], 0.78 [95% CI: 0.72-0.83] vs. AUC, 0.66 [95% CI: 0.60-0.72], P= 0.001).

Long-term clinical outcome and B1 corrected T1liver — After a median follow-up of 16.2 months (range: 4.1months, 27.8 months), 10.7% of patients (25/234; M:F = 19:6, mean age 64.7 ± 8.8 years) developed hepatic insufficiency: hepatic encephalopathy (n=9); death due to hepatic insufficiency (n=8); intractable ascites (n=6); and intractable itching sense due to hyperbilirubinemia, which was treated by transplantation (n=1). According to multivariate analyses, albumin <3.5g/dL (HR, 20.71 [3.9, 221.9]) and B1 corrected T1liver ≥462msec (HR, 5.9 [1.1, 62.8]) were significantly associated with development of hepatic insufficiency. In addition, six out of 207 patients with Child A class (2.9%) developed hepatic decompensation. Functional liver volume-to weight ratio was associated with development of hepatic decompensation in patients with Child-Pugh A (Table 3, HR, 0.03 [95% CI: 0.004, 0.23]), after the amendment of albumin and B1 corrected T1liver.

B1 inhomogeneity corrected volumetric T1 mapping was able to provide global liver function and demonstrate heterogeneity of regional liver function. B1 corrected T1liver ≥462msec was independently associated with the development of hepatic insufficiency. Functional liver volume-to-weight ratio may be related with development of decompensation in compensated liver cirrhosis patients.