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This study was designed to compare the effects of dietary supplementation with nondigestible carbohydrates, differing in fermentability by colonic bacteria, on hepatic steatosis in growing obese Zucker rats. Male Zucker fa/fa rats were divided into three groups: a control group that received the basal diet, a fructan group that received 10 g highly fermented Synergy 1/100 g diet and a cellulose group that received 10 g poorly fermented Vivapur Microcrystalline cellulose/100 g diet. Rats consuming fructan had a lower energy intake, a lower body weight and less triacylglycerol accumulation in the liver as assessed in vivo by nuclear magnetic resonance (NMR) spectroscopy, and ex vivo by biochemical and histochemical analysis compared with the control and/or cellulose groups. The high fermentation of fructans compared with cellulose was reflected by greater cecal contents and by a twofold greater propionate concentration in the portal vein of rats fed fructan compared with those fed cellulose. By measuring the capacity of hepatocytes isolated from liver of Zucker rats to synthesize triglycerides or total lipids from different precursors, we showed that propionate, at the concentrations measured in the portal vein of rats treated with fructan, selectively decreased the incorporation of acetate into total lipids, a phenomenon that could contribute, along with the lower energy intake, to less triglyceride accumulation in the liver of obese Zucker rats fed dietary fructans.

Rationale and Objectives: The authors compare the potential value of unenhanced and gadoxetate disodium-enhanced spin-echo images for the detection of hepatocellular carcinoma in a rat model., Methods: Eleven rats with chemically induced hepatocellular carcinoma underwent unenhanced T2-weighted fast spin-echo imaging followed by T1-weighted spin-echo imaging before and at 5 minutes, 30 minutes, 3 hours, 1 day, and 3 days after intravenous administration of 60 micromol/kg gadoxetate disodium at 4.7 tesla. Tumor and liver enhancement, and tumor-to-liver contrast-to-noise (C/N) ratio were calculated., Results: After gadoxetate disodium administration, the tumors showed less enhancement than the liver. Tumor-to-liver C/N ratio increased from 5.5 +/- 0.8% on unenhanced T1-weighted images to 12.9 +/- 2.4% on gadoxetate-enhanced T1-weighted images (P = 0.02). However, the C/N ratio on unenhanced T2-weighted images (23.5 +/- 3.6%) remained higher than that on gadoxetate-enhanced T1-weighted images, a difference that is statistically significant (P < 0.01)., Conclusions: In the experimental setting of our study, the higher tumor-to-liver C/N ratio on unenhanced T2-weighted spin-echo images suggests that unenhanced T2-weighted spin-echo images are superior to gadoxetate disodium-enhanced T1-weighted spin-echo images for the detection of hepatocellular carcinoma.

Objective: The aim of our prospective study was to compare the values of ferumoxides-enhanced gradient-echo and T2-weighted spin-echo MR imaging for the detection and segmental location of malignant hepatic tumors., Subjects and Methods: Eighteen patients underwent ferumoxides-enhanced T2 weighted spin-echo and steady-state gradient-echo imaging before surgery. Intraoperative sonography was used as the reference examination and showed 28 malignant tumors involving 39 of the 144 hepatic segments. The MR images were reviewed independently by two observers who recorded the number of tumors and their segmental location. The results of the segmental location were subjected to receiver-operating-characteristic analysis. Tumor-liver, vessel-liver, and tumor-vessel contrast-to-noise ratios were calculated., Results: Detection on the gradient-echo images did not differ significantly from that on the T2-weighted spin-echo MR images (observers A and B detected 23 and 24 tumors, respectively, on the gradient-echo images; the two observers each detected 22 tumors on the T2-weighted spin-echo images). Segmental localization was significantly better on the gradient-echo images than on the T2-weighted spin-echo images (mean area under the receiver-operating-characteristic curve: 0.974 versus 0.895 for observer A and 0.962 versus 0.906 for observer B, p = .024). The highest contrast-to-noise ratios for vessel to liver and tumor to vessel were obtained on the gradient-echo images and the highest tumor-liver contrast-to-noise ratio was obtained on the T2-weighted spin-echo images., Conclusion: In our study, ferumoxides-enhanced gradient-echo imaging was as accurate as T2-weighted spin-echo imaging for revealing malignant hepatic tumors and was superior for showing their segmental location.

The tumor-to-liver uptake of two reticuloendothelial agents, namely ferumoxides and technetium-99m (Tc-99m) sulfur colloid, was compared in focal nodular hyperplasia (FNH). Twelve patients with FNH who had undergone ferumoxides-enhanced MR imaging and planar Tc-99m sulfur colloid scintigraphy within 1 year were included from the study. Fourteen patients with FNH with a diameter larger than 3 cm were selected for the comparison. The tumor-to-liver ferumoxides uptake was calculated and the Tc-99m sulfur colloid uptake was assessed visually. Fermuoxides uptake was observed in all but one patient with FNH (mean tumor-to-liver ratio = .36). The six tumors showing normal (n = 5) or increased (n = 1) radiocolloid uptake when compared to the liver accumulated more ferumoxides than the eight tumors showing decreased radiocolloid uptake (P < .01). However, in some tumors, no direct relation was observed between ferumoxides and Tc-99m sulfur colloid uptake. Our observations suggest that ferumoxides uptake might not exactly mimic Tc-99m sulfur colloid uptake in FNH.

The enhancement pattern of chemically induced hepatocellular carcinomas (HCCs) after intravenous administration of the hepatobiliary magnetic resonance (MR) contrast agent gadolinium-EOB-DTPA (ethoxybenzyl-diethylenetriaminepentaacetic acid) was compared with the uptake pattern of technetium-99m-labeled iminodiacetic acid (IDA), a hepatobiliary radioactive tracer. The hepatocyte uptake of both the contrast agent and the scintigraphic agent has been shown to be driven by the organic anion transporter. The tumors enhanced less than the liver after Gd-EOB-DTPA administration, whereas the Tc-99m-IDA uptake of differentiated HCCs exceeded that of the liver at 30 minutes and 3 hours after administration. The enhancement pattern of a differentiated HCC with Gd-EOB-DTPA does not mirror that seen with Tc-99m-IDA.

In this study, we report the synthesis and the evaluation as MRI contrast agent of a new compound (nitroxyl fatty acid, NFA), where a pyrrolidinoxyl radical (3-carboxy-proxyl, PCA) is linked to a fatty acid moiety. Fatty acids were selected as vector because they present a high affinity for the liver, their efficient cellular uptake being the result of a specific interaction with a transmembrane transporter (liver plasma membrane-fatty acid binding protein). The uptake of 3H-oleic acid is inhibited after the injection of 1 mmol/kg of NFA, suggesting that NFA recognizes the same transmembrane transporter as the natural fatty acids. The higher relaxivity R1 of NFA in albumin solutions, compared with PCA, was explained by the immobilization of the nitroxyl radical in the protein. MR imaging was performed using T1-weighted images on mice in order to compare the contrast effect obtained after the injection of 1 mmol/kg of radical. The % signal enhancement in the liver 5 min after intravenous injection was 49 +/- 4 and 14 +/- 5 for NFA and PCA, respectively. NFA allowed a better delimitation of some necrotic tumors (Novikoff hepatocarcinoma) due to its preferential uptake by the nontumorous tissue.