Quantitative Evaluation Of Liver Function Research Articles

Multiparametric MRI combined with liver volume for quantitative evaluation of liver function in patients with cirrhosis.

PURPOSE We aimed to establish a liver function evaluation model by combining multiparametric magnetic resonance imaging (MRI) with liver volume (LV) and further verify the effectiveness of the model to evaluate liver function. METHODS This retrospective study included 101 consecutive cirrhosis patients (69 cases for modeling group and 32 cases for validation group) who underwent gadoxetic acid-enhanced MRI. Five signal intensity parameters were obtained by measuring the signal intensities of the liver, spleen, and erector spinae before and 20 minutes after gadoxetic acid disodium enhancement. The dif fusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were obtained from intravoxel incoherent motion diffusion-weighted imaging. The LV parameters (Vliver, Vspleen, and Vliver/Vspleen) were obtained using 3-dimensional image generation software. The most effec tive parameter was selected from each of the 3 methods, and a multivariate regression model for liver function evaluation was established and validated. RESULTS In the modeling group, relative enhancement (RE), D*, and Vliver/Vspleen showed significant dif ferences among the different liver function groups (P < .001). Receiver operating characteristic analysis showed that these parameters had the highest area under the curve (AUC) values for dis tinguishing Child-Pugh A from Child-Pugh B and C groups (0.917, 0.929, and 0.885, respectively). The following liver function model was obtained by multivariate regression analysis: F(x)=3.96 - 1.243 (RE) - 0.034 (D*) - 0.080 (Vliver/Vspleen) (R2=0.811, P < .001). In the patients with cirrhosis, the F(x) of Child-Pugh A, B, and C were 1.16 ± 0.44, 1.95 ± 0.29, and 2.79 ± 0.38, respectively. In the validation group, the AUC for F(x) to distinguish Child-Pugh A from Child-Pugh B and C was 0.973. CONCLUSION Combining multiparametric MRI with LV effectively distinguished patients with different Child Pugh grades. This model could hence be useful as a novel radiological marker to estimate the liver function.

Quantitative evaluation of liver function with gadoxetic acid enhanced MRI: Comparison among signal intensity-, T1-relaxometry-, and dynamic-hepatocyte-specific-contrast-enhanced MRI- derived parameters

Aims Three types of gadoxetic acid enhanced MRI parameters have been proposed to quantify liver function. However, until now there is no consensus on which one that has the greatest potential for use in clinical practice. This study was conducted to compare the efficacy of three types of gadoxetic acid enhanced MR parameters for quantitative assessment of liver function. Methods Imaging data of 10 patients with chronic liver disease and 20 healthy volunteers were analyzed. Parameters based on signal intensity(SI), T1 changes or dynamic-hepatocyte-specific-contrast-enhancement MR were calculated. Their mutual correlations, discriminatory capacity between cirrhotic and healthy liver and correlations with Child-Pugh score and Model for end-stage liver-disease (MELD) were estimated. Results The strongest correlations were observed between relative enhancement of the liver and T1 time at 20 min after contrast agent injection, and between liver-spleen contrast ratio at 20 min after contrast agent injection and hepatic uptake rate (|r|> 0.90, p < .05, both). All parameters but input-relative blood flow (p = 0.17) were significantly different between patient and control group (p < .05), with AUROCs of liver-to-muscle ratio (LMR), increase of LMR and hepatic extraction fraction greater than 0.90 (p < .05). Liver-to-spleen ratio, LMR and hepatic uptake index presented a strong correlation with Child-Pugh score and MELD (|r|> 0.8, p < .05). Conclusion Simple SI-based parameters were as good as more complex parameters in evaluating liver function at gadoxetic acid enhanced MR. In clinical routine LMR seems to be the easiest-to-use parameter for quantitative evaluation of liver function.

Quantitative assessment of liver function with hepatocyte fraction: Comparison with T1 relaxation‐based indices

PurposeThis study aimed to assess the use of hepatocyte fraction in gadoxetic acid-enhanced magnetic resonance imaging (MRI) for quantitatively evaluating the liver function in comparison with T1 relaxation‐based indices. MethodsThis retrospective study included 79 patients with chronic liver disease, who were divided into 2 groups based on the results of the indocyanine green retention test (ICG). All patients underwent a gadoxetic acid-enhanced MRI of the liver. Pre- and post-contrast Look-Locker sequences were used 20 min after gadoxetic acid administration to acquire T1 mapping. Two readers independently identified and measured the MRI parameters [five T1 relaxation‐based indices (T1pre, T1post, rrT1, R1post/R1pre and ΔR1) and two hepatocyte fraction indices (HeF and KHep)]. An Independent-samples t test was used to compare each parameter for the two groups. Pearson correlation analysis was used to analyze the correction in each parameter and 15-minute ICG retention rate (ICG-R15). Receiver operating characteristic analyses were performed to differentiate the diagnostic performance of each parameter in ICG-R15 ≤ 20 % and ICG-R15 > 20 % groups. ResultsT1pre and T1post were significantly lower in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). rrT1, R1post/R1pre, ΔR1, HeF, and KHep were significantly higher in the ICG-R15 ≤ 20 % group than in the ICG-R15 > 20 % group (P < 0.05). The correction coefficients between T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, KHep, and ICG-R15 were 0.343, 0.783, –0.833, –0.781, –0.803, –0.819, and –0.832, respectively. The area under the curves (AUCs) of T1pre, T1post, rrT1, R1post/R1pre, ΔR1, HeF, and KHep in assessing the ICG-R15＞20 % groups were 0.761, 0.945, 0.912, 0.912, 0.948, 0.945, and 0.950, respectively. KHep had the highest AUC, sensitivity, and specificity. ConclusionHepatocyte fraction based on gadoxetic acid-enhanced T1-mapping MRI is an efficient diagnostic tool for the quantitative evaluation of liver function.

Quantitative evaluation of liver function and pathology with hepatocyte fraction on Gadoxetic acid-enhanced MR imaging

Quantitative evaluation of liver function and pathology with hepatocyte fraction on Gadoxetic acid-enhanced MR imaging

Quantitative Evaluation of Liver Function with Gd-EOB-DTPA-enhanced MR Imaging

The quantitative evaluation of liver function is important, not only for monitoring, but also for the preoperative evaluation of the functional hepatic reserve. The indocyanine green (ICG) clearance has been used as a reliable quantitative liver function test; however, ICG clearance cannot evaluate segmental liver function. Gd-EOB-DTPA is a bolus-injectable paramagnetic contrast media taken up by hepatocytes via organic anion transporting peptide, specifically expressed on cell membrane of hepatocytes; therefore quantitative evaluation of segmental liver function with use of Gd-EOBD-TPA-enhanced MR imaging is feasible. Methods for quantitative evaluation of liver function using Gd-EOB-DTPA-enhanced MR imaging can be divided into the following two major categories : dynamic and static methods. In the dynamic method, the time-intensity curve obtained from dynamic contrast enhanced MR imaging is analyzed using various pharmacokinetic models. The compartment model analysis is a representative method, categorized as a dynamic model-dependent analysis. In the static method, post contrast enhanced images, usually during the hepatobiliary phase, are analyzed using relaxation time or signal intensity of the liver. The static methods are easy to apply in clinical practice. The hepatocellular uptake index (HUI) is a static signal intensity-based method, which is obtained from the signal intensity and volume of the liver and spleen on Gd-EOB-DTPA-enhanced MR images during the hepatobiliary phase. HUI has been accepted as the most reliable predictor of segmental liver function. In this article, pharmacokinetics of Gd-EOB-DTPA is first described using the compartment model. Subsequently, derivation of 2-in-liner-1-uptake-1-out-2-compartment model and HUI are shown as examples of quantitative evaluation of the liver function with the use of Gd-EOB-DTPA-enhanced MR imaging.

Quantitative evaluation of liver function by liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRI

Objective To investigate the utilization of liver enhancement in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI for liver function evaluation.Methods Fifty-five patients who received enhanced MRI with Gd-EOB-DTPA were retrospectively analyzed.Images were obtained before injection and in hepatobiliary phase (5,10,and 20 minutes after Gd-EOB-DTPA injection).The patients were assigned into two subgroups according to individual liver function (n =35 in Group 1:normal liver and Child-Pugh class A; n =20 in Group 2:Child-Pugh class B and C).The relative liver enhancement (RE) was calculated at different time point.The general data (age,sex) and relevant laboratory results were recorded.Independent sample t-test was conducted to compare the RE between two groups at different time point.ROC curve was used to determine the best time point and RE threshold that can reflect the differences between two groups.Univariate analyses was performed to analyze the relationship between RE at the best time point and laboratory results.Multivariate analyses was performed to screen the independent influencing factor for RE at the best time point.Results The differences of RE between two groups were statistically significant at all time points (P ＜ 0.0001).10 minutes was the best time point for detecting the differences of liver function between two groups.When an RE cutoff value (＞ 1.52) was applied,normal or Child-Pugh class A could be predicted with sensitivity of 74.3％ and specificity of 90％.RE at the best time point was significantly related with total serum bilirubin level (TBil),serum albumin level (Alb) and prothrombin time (PT).And TBil was an independent influencing factor.Conclusion RE can be used to evaluate the liver function,and 10 minutes is the best time point that can be used to differentiate patients with normal or mild liver damage from those with moderate or severe liver damage. Key words: Liver function; Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) ; Magnetic resonance imaging (MRI)

Quantitative evaluation of liver function with T1 relaxation time index on Gd‐EOB‐DTPA‐enhanced MRI: Comparison with signal intensity‐based indices

To evaluate whether the reduction rate of T1 relaxation time of the liver (T1 relaxation time index) before and 20 minutes after gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) injection has the potential to serve as an magnetic resonance imaging (MRI)-based liver function test in comparison with signal intensity-based indices. Ninety-nine patients with suspected liver lesions underwent Gd-EOB-DTPA-enhanced MRI. T1 maps using 3D T1-weighted gradient-echo volumetric interpolated examination with two different flip angles were also performed before and 20 minutes after Gd-EOB-DTPA administration. T1 relaxation time index was compared with four signal intensity-based indices in terms of the ability to discriminate Child-Pugh A (CPA) and Child-Pugh B (CPB) from normal liver function (NLF), and in terms of its correlation with indocyanine green (ICG) clearance. Twenty-four patients were classified as NLF, 64 patients were classified as CPA, and 11 were classified as CPB group. The T1 relaxation time index was significantly lower for CPA (0.62 ± 0.08 vs. 0.68 ± 0.07, P = 0.021) and CPB (0.55 ± 0.15 vs. 0.68 ± 0.07, P < 0.001) than for NLF. All signal intensity-based indices showed significant differences only when comparing NLF and CPB. The correlation coefficient with ICG clearance was the highest for T1 relaxation time index (r = -0.605, P < 0.001). The T1 relaxation time index has the potential to serve as an MRI-based liver function test, and is most strongly correlated with ICG clearance among the Gd-EOB-DTPA MRI-based indices investigated.

Quantitative Evaluation of Liver Function within MR Imaging

Quantitative Evaluation of Liver Function within MR Imaging

Quantitative Evaluation of Liver Function with Use of Gadoxetate Disodium–enhanced MR Imaging

To determine whether liver function correlating with indocyanine green (ICG) clearance could be estimated quantitatively from gadoxetate disodium-enhanced magnetic resonance (MR) images. This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. Twenty-three consecutive patients who underwent an ICG clearance test and gadoxetate disodium-enhanced MR imaging with the same parameters as were used for a preoperative examination were chosen. The hepatocellular uptake index (HUI) from liver volume (V(L))and mean signal intensity of the liver on contrast-enhanced T1-weighted images with fat suppression (L(20)) and mean signal intensity of the spleen on contrast-enhanced T1-weighted images with fat suppression (S(20)) on 3D gradient-echo T1-weighted images with fat suppression obtained at 20 minutes after gadoxetate disodium (0.025 mmol per kilogram of body weight) administration was determined with the following equation: V(L)[(L(20)/S(20)) - 1]. The correlation of the plasma disappearance rate of ICG (ICG-PDR) and various factors derived from MR imaging, including HUI, iron and fat deposition in the liver and spleen, and spleen volume (V(S)), were evaluated with stepwise multiple regression analysis. The difference between the ratio of the remnant HUI to the HUI of the total liver (rHUI/HUI) and ratio of the liver remnant V(L) to the total V(L) (rV(L)/V(L)) was evaluated in four patients who had segmental heterogeneity of liver function. HUI and V(S) were the factors significantly correlated with ICG-PDR (R = 0.87). The mean value and its 95% confidence interval were 0.18 and 0.01 to 0.34, respectively, for the following calculation: (rHUI/HUI) - (rV(L)/V(L)). The liver function correlating with ICG-PDR can be estimated quantitatively from the signal intensities and the volumes of the liver and spleen on gadoxetate disodium-enhanced MR images, which may improve the estimation of segmental liver function.

Quantitative Evaluation of Liver Function with MRI Using Gd-EOB-DTPA

ObjectiveGadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection, Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreted via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis.Materials and MethodsAdult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCl4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCl4. At the end of experimental period, an observer "blinded" to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCl4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL of Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, TR/TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128×128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier transform technique to calculate the hepatic extraction fraction (HEF). The presence and type of hepatic injury were determined by the histopathologic examination and statistical analysis of the changes of the hepatic enzyme levels, the ICG R15 and Gd-EOB-DTPA HEF values between the time before and after CCl4 administration with Wicoxon signed rank test. Correlation between the Gd-EOB-DTPA HEF and the change of the ICG R15 were analyzed with Pearson's correlation coefficient.ResultsHistopathologic examination showed findings that were compatible with hepatic fibrosis caused by chronic liver injury. The initial blood biochemical studies before the administration of carbon tetrachloride showed that the mean AST and ALT levels were 39.8±5.2 IU/L and 59.1±11.7 IU/L, respectively. The AST and ALT levels increased to 138.4±50.5 IU and 172.0±71.6 IU/L, respectively, after the three week administration of CCl4. The ALT and AST levels were significantly increased after the three weeks of CCl4 administration (p = 0.018). The ICG R15 values were 4.47±2.08% and 19.43±3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 administration revealed less hepatocyte extraction efficiency with a mean value of 77.7±3.6. There was a significant correlation between the HEF and changes of the ICG R15 by the Pearson correlation coefficient assessment (correlation coefficient = -0.965, p = 0.000).ConclusionThe Gd-EOB-DTPA HEF could be calculated from deconvolution analysis of aortic and hepatic parenchymal time-intensity curves obtained by dynamic MRI. The Gd-EOB-DTPA HEF was well correlated with changes of the ICG R15, which is the most common parameter used in the quantitative estimation of the hepatic function. The Gd-EOB-DTPA HEF is a direct, noninvasive technique for the quantitative evaluation of liver function. It could be a promising alternative for the determination of noninvasive hepatic function in those patients with liver disease.

Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation

Objective The early phase after liver transplant is considered the period of greatest risk for graft failure. In recent years breath tests have been proposed as a noninvasive method to assess liver function. In particular, the aminopyrine breath test is useful for evaluating the liver viable mass, and the methionine breath test could be used to evaluate oxidative capacity of liver mitochondria. We aimed to perform these tests in the early phase following liver transplant in order to correlate the time course of these tests to the outcome of transplantation. Methods Twenty-three patients undergoing liver transplant were enrolled. The methionine and aminopyrine breath tests were performed on the days 1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were expressed as the percentage of administered 13C recovered per hour and as the cumulative percentage of the 13C dose recovered over the test period. Results All but two transplants were successful in the short term and the cumulative percentage of the dose of 13C progressively increased after transplantation, reaching values not significantly different from controls (methionine at day 5). In two patients, primary non-function occurred: in these patients the cumulative percentage of the 13C dose did not increase after orthotopic liver transplant and the results of both breath tests indicated that it always remained significantly lower compared to that of other patients. Conclusions A combination of breath tests, exploring both mitochondrial and microsomal function, could be useful in the early phase after liver transplant in order to evaluate the graft outcome. Eur J Gastroenterol Hepatol 15: 727-732 © 2003 Lippincott Williams & Wilkins

1 P Quantitative evaluation of liver function by methionine and aminopyrine breath tests in the early stages of liver transplantation

1 P Quantitative evaluation of liver function by methionine and aminopyrine breath tests in the early stages of liver transplantation

A simplified method for the quantitative analysis of 99Tc(m)-GSA liver scintigraphy using spectral analysis.

The aim of this study was to develop a simplified method for quantitative analysis of liver scintigraphy with 99Tc(m)-diethylenetriamine pentaacetic acid-galactosyl-human serum albumin (GSA) using spectral analysis. Dynamic liver scintigraphy using GSA was performed in three normal volunteers and 19 patients with chronic liver disease. Dynamic data were obtained with a gamma camera for 30 min after the injection of approximately 185 MBq GSA. The rate constant for the liver uptake of GSA from the blood (Ku, min(-1)), total excretion rate (Ke, min(-1)) and non-specific volume of distribution (Vh) were obtained by spectral analysis. Vh was defined as the volume in the liver region of interest (ROI) occupied by GSA which was in equilibrium with that in the blood. It should be noted that Vh had no units, since the counts in both the liver and heart ROIs were normalized by scan length to obtain counts pixel(-1) min(-). For comparison, compartmental analysis was also performed. A receptor index (LHL15) was calculated by dividing the radioactivity of the liver ROI by that of the liver plus heart ROIs 15 min post-injection. The Ku values obtained by spectral analysis (y) agreed well with those obtained by compartmental analysis (x) (y = 0.953x - 0.013, r = 0.992, S.E.E. = 0.016 min(-1)). The Ke and Vh values obtained by spectral analysis (y) correlated significantly with those obtained by compartmental analysis (x) (y = 1.149x - 0.016, r = 0.826, S.E.E. = 0.017 min(-1) for Ke; y = 1.191x + 0.044, r = 0.975, S.E.E. = 0.021 for Vh). The Ku values obtained by spectral analysis decreased as the severity of liver disease progressed, and were non-linearly related to the LHL15 values, suggesting that Ku is more sensitive to liver damage than LHL15, especially in the early stages of liver damage. These results suggest that spectral analysis applied to dynamic liver scintigraphy with GSA provides a simple, non-invasive and useful tool for the quantitative evaluation of liver function.

Measuring lidocaine metabolite — monoethylglycinexylidide as a quantitative index of hepatic function in adults with chronic hepatitis and cirrhosis

Lidocaine is metabolized to form monoethylglycinexylidide (MEGX) via oxidative N-deethylation in the liver. To assess the clinical value of this lidocaine metabolite as a quantitative liver function test, we measured the serum MEGX concentration 15 min after intravenous administration of a single dose of lidocaine (1 mg/kg) in 24 adults with chronic hepatitis, 47 patients with cirrhosis and 26 normal controls. A fluorescence polarization immunoassay was used to obtain the MEGX value. The MEGX concentration in controls was 67 (54-95) ng/ml (median with 16th-84th percentile in parentheses), which was higher than 43 (23-61) ng/ml in patients with chronic hepatitis and 24 (7-52) ng/ml in those with cirrhosis (P < 0.05). In addition, the serum MEGX levels are proportional to the galactose elimination capacity, and inversely proportional to Pugh's score, the prothrombin time and indocyanine green retention ratio. If a MEGX concentration of below 54 ng/ml is taken as an indicator of hepatic dysfunction, its diagnostic sensitivity for hepatic disorder is 84.5%, specificity 88.5% and accuracy 85.6%. Furthermore, after a 10-month follow-up, patients with MEGX formation above 30 ng/ml had a higher survival rate than those with a MEGX concentration below this level (P = 0.004). In conclusion, the MEGX formation test reflects the severity of hepatic dysfunction quite well, making it valuable both in the quantitative evaluation of liver function and in the prognostic prediction of adults with liver diseases.