Assessment of liver function in thioacetamide-induced rat acute liver injury using an empirical mathematical model and dynamic contrast-enhanced MRI with Gd-EOB-DTPA.

PURPOSE: To evaluate thioacetamide (TAA)-induced acute liver injury in rats using an empirical mathematical model (EMM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). MATERIALS AND METHODS: Eighteen rats were divided into three groups (normal control [n = 6], TAA [140] [n = 6], and TAA [280] groups [n = 6]). The rats of the TAA (140) and TAA (280) groups were intravenously injected with 140 and 280 mg/kg body weight (BW) of TAA, respectively, while those of the normal control group were intravenously injected with the same volume of saline. DCE-MRI studies were performed using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 48 hours after TAA or saline injection. After the DCE-MRI study, blood was sampled and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. We calculated the rate of contrast uptake (α), the rate of contrast washout (ß), the elimination half-life of relative enhancement (RE) (T(1/2)), the maximum RE (RE(max)), and the time to (RE(max)) (T(max)) from time-signal intensity curves using EMM. RESULTS: The RE(max) values in the TAA (140) groups and TAA (280) groups were significantly smaller than that in the normal control group. The T(max) value in the TAA (280) group was significantly greater than that in the normal control group. The ß value in the TAA (280) group was significantly smaller than those in the normal control and TAA (140) groups, whereas there were no significant differences in ß among groups. The T(1/2) value in the TAA (280) group was significantly greater than those in the normal control and TAA (140) groups. The RE(max), T(max), ß, and T(1/2) values significantly correlated with AST and ALT. CONCLUSION: The EMM is useful for evaluating TAA-induced acute liver injury using DCE-MRI with Gd-EOB-DTPA.

Electrocardiography-triggered high-resolution CT for reducing cardiac motion artifact: evaluation of the extent of ground-glass attenuation in patients with idiopathic pulmonary fibrosis.

PURPOSE: The aim of this study was to evaluate the decreasing of cardiac motion artifact and whether the extent of ground-glass attenuation of idiopathic pulmonary fibrosis (IPF) was accurately assessed by electrocardiography (ECG)-triggered high-resolution computed tomography (HRCT) by 0.5-s/rotation multidetector-row CT (MDCT). MATERIALS AND METHODS: ECG-triggered HRCT were scanned at the end-diastolic phase by a MDCT scanner with the following scan parameters; axial four-slice mode, 0.5 mm collimation, 0.5-s/rotation, 120 kVp, 200 mA/rotation, high-frequency algorithm, and half reconstruction. In 42 patients with IPF, both conventional HRCT (ECG gating(-), full reconstruction) and ECG-triggered HRCT were performed at the same levels (10-mm intervals) with the above scan parameters. The correlation between percent diffusion of carbon monoxide of the lung (%DLCO) and the mean extent of ground-glass attenuation on both conventional HRCT and ECG-triggered HRCT was evaluated with the Spearman rank correlation coefficient test. RESULTS: The correlation between %DLCO and the mean extent of ground-glass attenuation on ECG-triggered HRCT (observer A: r = -0.790, P < 0.0001; observer B: r = -0.710, P < 0.0001) was superior to that on conventional HRCT (observer A: r = -0.395, P < 0.05; observer B: r = -0.577, P = 0.002) for both observers. CONCLUSION: ECG-triggered HRCT by 0.5 s/rotation MDCT can reduce the cardiac motion artifact and is useful for evaluating the extent of ground-glass attenuation of IPF.

Kinetic analysis of superparamagnetic iron oxide nanoparticles in the liver of body-temperature-controlled mice using dynamic susceptibility contrast magnetic resonance imaging and an empirical mathematical model.

The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM). First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Second, we investigated the kinetic behavior of SPIONs in the liver when mice were injected with various doses of GdCl3, while keeping the body temperature at 36°C. Finally, we investigated it when mice were injected with various doses of zymosan, while keeping the body temperature at 36°C. We also investigated the effect of these substances on the number of Kupffer cells by immunohistochemical analysis using the specific surface antigen of Kupffer cells (CD68). To quantify the kinetic behavior of SPIONs in the liver, we calculated the upper limit of the relative enhancement (A), the rates of early contrast uptake (α) and washout or late contrast uptake (ß), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum change of transverse relaxation rate (ΔR2) (ΔR2(max)), the time to ΔR2(max) (Tmax), and ΔR2 at the last time point (ΔR2(last)) from the time courses of ΔR2 using the EMM. The ß and Tmax values significantly decreased and increased, respectively, with decreasing body temperature, suggesting that the phagocytic activity of Kupffer cells is significantly affected by body temperature. The AUC, ΔR2(max), and ΔR2(last) values decreased significantly with increasing dose of GdCl3, which was consistent with the change in the number of CD68-positive cells. They increased with increasing dose of zymosan, which was also consistent with the change in the number of CD68-positive cells. These results suggest that AUC, ΔR2(max), and ΔR2(last) reflect the number of Kupffer cells. In conclusion, we presented a method for analyzing the kinetic behavior of SPIONs in the liver using DSC-MRI and EMM, and investigated the influence of body temperature, GdCl3, and zymosan using body-temperature-controlled mice. The present study suggests that control of body temperature is essential for investigating the kinetic behavior of SPIONs in the liver and that our method will be applicable and useful for quantifying the responses of Kupffer cells to various drugs under control of body temperature.

A simple and inexpensive system for controlling body temperature in small animal experiments using MRI and the effect of body temperature on the hepatic kinetics of Gd-EOB-DTPA.

The purpose of this study was to develop a simple and inexpensive system for controlling body temperature in small animal experiments using magnetic resonance imaging (MRI) and to investigate the effect of body temperature on the kinetic behavior of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) in the liver. In our temperature-control system, body temperature was controlled using a feedback-regulated heated or cooled air flow generated by two Futon dryers. The switches of the two Futon dryers were controlled using a digital temperature controller, in which the rectal temperature of a mouse measured by an optical fiber thermometer was used as the input. In experimental studies, male ICR mice aged 8weeks old were used and allocated into 5 groups (39-, 36-, 33-, 30-, and 27-degree groups, n=10), in which the body temperature was maintained at 39 °C, 36 °C, 33 °C, 30 °C, and 27 °C, respectively, using our system. The dynamic contrast-enhanced MRI (DCE-MRI) data were acquired with an MRI system for animal experiments equipped with a 1.5-Tesla permanent magnet, for approximately 43min, after the injection of Gd-EOB-DTPA into the tail vein. After correction of the image shift due to the temperature-dependent drift of the Larmor frequency using the gradient-based image registration method with robust estimation of displacement parameters, the kinetic behavior of Gd-EOB-DTPA was analyzed using an empirical mathematical model. With the use of this approach, the upper limit of the relative enhancement (A), the rates of contrast uptake (α) and washout (ß), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum relative enhancement (REmax), the time to REmax (Tmax), and the elimination half-life of the contrast agent (T1/2) were calculated. The body temperature of mice could be controlled well by use of our system. Although there were no significant differences in α, AUC, and q among groups, there were significant differences in A, REmax, ß, Tmax, and T1/2, indicating that body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver. In conclusion, our system will be useful for controlling body temperature in small animal experiments using MRI. Because body temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the liver, the control of body temperature is essential and should be carefully considered when performing DCE-MRI studies in small animal experiments.

An empirical mathematical model applied to quantitative evaluation of thioacetamide-induced acute liver injury in rats by use of dynamic contrast-enhanced computed tomography.

Our purpose in this study was to apply an empirical mathematical model (EMM) to the quantitative evaluation of thioacetamide (TAA)-induced acute liver injury in rats by use of dynamic contrast-enhanced computed tomography (DCE-CT), and to investigate its usefulness in comparison with a dual-input, single-compartment model. The rats in the TAA-treated group were injected intravenously with 140 mg/kg body weight (n = 10) or 280 mg/kg body weight (n = 10) of TAA, whereas those in the control group (n = 10) were injected with saline instead of TAA. The DCE-CT studies were performed 2 days after injection of TAA or saline by use of a 4-detector row CT. The upper limit of the time-density curve (A), the rates of contrast uptake (α) and washout (ß), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the time to the maximum enhancement (T (max)), the maximum enhancement (C (Lmax)), and the elimination half-life of the contrast agent (T (1/2)) were calculated by use of the EMM. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Both α and q decreased significantly in the rats of the TAA-treated group compared to those in the control group, whereas T (max) and T (1/2) increased significantly. The values of α, q, AUC, and T (max) were significantly correlated with both AST and ALT. Our results suggest that the EMM is useful for quantitative evaluation of TAA-induced acute liver injury and can be used as an alternative to the dual-input single-compartment model, especially when the vascular input functions cannot be obtained.

Usefulness of a dual-input single-compartment model for quantitative evaluation of thioacetamide-induced acute liver injury in rats using dynamic contrast-enhanced computed tomography.

We undertook this study to investigate the usefulness of a dual-input single-compartment model for evaluating thioacetamide (TAA)-induced acute liver injury in rats by use of dynamic contrast-enhanced computed tomography (DCE-CT). The rats in the TAA-treated group were injected intravenously with 140 mg/kg (n = 10) or 280 mg/kg (n = 10) of TAA, whereas those in the control group (n = 10) were injected with saline. The rate constants for the transfer of the contrast agent from the hepatic artery to the liver (K(1a)), from the portal vein to the liver (K(1p)), and from the liver to the blood (k2), as well as liver perfusion (LP), the arterial fraction of LP (AFLP), distribution volume (DV), and mean transmit time (MTT) were estimated with use of the dual-input single-compartment model. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. K(1p), k2, and LP decreased significantly in the TAA-treated group compared to those in the control group, whereas K(1a), AFLP, DV, and MTT increased significantly. The above parameters except for K (1a) were significantly correlated with both AST and ALT. We concluded that DCE-CT using the dual-input single-compartment model is useful for quantitative evaluation of TAA-induced acute liver injury.

Evaluation of concanavalin A-induced acute liver injury in rats using an empirical mathematical model and dynamic contrast-enhanced MR imaging with Gd-EOB-DTPA.

PURPOSE: We evaluated concanavalin A (Con A)-induced acute hepatic injury in rats using an empirical mathematical model (EMM) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA). MATERIALS AND METHODS: We allocated 18 rats into 3 groups of six each and intravenously injected them with either 10 mg/kg body weight (BW) of Con A (Con A [10] group), 20 mg/kg BW of Con A (Con A [20] group), or a single dose of of saline (4 mL/kg BW, normal control group). We performed the DCE-MRI studies using Gd-EOB-DTPA (0.025 mmol Gd/kg; 0.1 mL/kg BW) as the contrast agent 24 hours after injection of Con A or saline. We then sampled blood, measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and calculated the rate of contrast uptake (α), rate of contrast washout (ß), area under the curve (AUC), time to maximum relative enhancement (RE) (T(max)), and elimination half-life of RE (T(1/2)) from the time-signal intensity curves using the EMM. RESULTS: ß values were significantly smaller in the Con A (10) and Con A (20) groups than the control group, but α did not differ significantly among the 3 groups. The AUC value was significantly greater in the Con A (10) group than controls, and the T(max) and T(1/2) values were significantly greater in the Con A (20) group than controls. The ß, T(max), and T(1/2) values correlated significantly with AST and ALT. CONCLUSION: In conclusion, the EMM is useful for evaluating Con A-induced acute hepatic injury using DCE-MRI with Gd-EOB-DTPA.

Evaluation of time-intensity curves in ductal carcinoma in situ (DCIS) and mastopathy obtained using dynamic contrast-enhanced magnetic resonance imaging.

PURPOSE: The aim of this study was to retrospectively evaluate the ability of dynamic, contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their signal intensities (SIs). METHODS: After the pre-contrast MRI was performed using a 1.5-T MRI system, DCE-MRI was performed four times following intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland and obtained the SIs in these VOIs. We calculated the entropy (EPY) in the pre-contrast (EPY0) and four post-contrast scans (EPY1, EPY2, EPY3, and EPY4 for the first, second, third and fourth scans, respectively) using the volume histogram method, and the wash-in (WR(in)) and washout rates (WR(out)) according to the Breast-Imaging Reporting and Data System developed by the American College of Radiology. We also calculated the early slope (Slope(early)) from the pre- and post-contrast SIs in the tumor and normal gland. We evaluated the usefulness of the above parameters for differentiating between DCIS and mastopathy using the area under the receiver operating characteristic curve (Az). RESULTS: There were significant differences in EPY2 (P=.009), EPY3 (P=.017), EPY4 (P=.034), WR(in) (P=.036), WR(out) (P=.019), and Slope(early) (P=.002) between DCIS and mastopathy. The average Az values were 0.67, 0.52, 0.64, 0.63, 0.67 and 0.70 for EPY2, EPY3, EPY4, WR(in), WR(out) and Slope(early), respectively. CONCLUSION: We evaluated the usefulness of various parameters calculated from SIs obtained by DCE-MRI for differentiating between DCIS and mastopathy. Our results suggested that Slope(early) is more useful than EPYs, WR(in) and WR(out).

Differentiation between ductal carcinoma in situ and mastopathy using dynamic contrast-enhanced magnetic resonance imaging and a model of contrast enhancement.

The purpose of this study was to retrospectively evaluate the feasibility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between ductal carcinoma in situ (DCIS) and mastopathy by analyzing their time-intensity curves (TICs) using the two-compartment pharmacokinetic model with an assumption of instantaneous injection of contrast medium (TCPM). After the pre-contrast MRI was performed using a 1.5 T MRI system, DCE-MRI was performed four times after the intravenous administration of contrast medium. We set the volumes of interest (VOIs) on the tumor and normal mammary gland, and obtained the TICs in these VOIs. We calculated the following parameters by fitting these TICs to the equation derived from TCPM; the initial slope of the TIC (Slopeini), the area under the TIC (AUC), the time to peak enhancement (TTP) and the peak enhancement (PeakE). We calculated these parameters in both the lesion and normal mammary gland and the ratios of the parameters in the lesion to those in the normal gland (rSlopeini, rAUC, rTTP and rPeakE). There were significant differences in Slopeini (P=0.009), PeakE (P=0.019), rSlopeini (P=0.010), and rTTP (P=0.005) between DCIS and mastopathy. The areas under the receiver operating characteristic curve for Slopeini, PeakE, rSlopeini, and rTTP were 0.67±0.06 (P=0.009), 0.65±0.06 (P=0.019), 0.67±0.06 (P=0.01), and 0.68±0.06 (P=0.005), respectively. In conclusion, our results suggest that analysis of TICs obtained by DCE-MRI using TCPM appears to be useful for differentiating between DCIS and mastopathy.