Magnetic resonance imaging of hereditary spontaneous hepatitis in Long-Evans cinnamon rats.

RATIONALE AND OBJECTIVES: Long-Evans Cinnamon (LEC) rats have abnormal metal metabolism and spontaneously develop hereditary hepatitis. The influence of in-vivo metals on magnetic resonance imaging (MRI) was studied using LEC rats. METHODS: Short spin-echo images of the livers of LEC rats were obtained using a 7.05-T small-bore MR unit. Effectively, these images were proton-density images because of T2-shortening mechanism in high magnetic field. The LEC rats were imaged during pre-, acute, and chronic hepatitis phases. The accumulation of copper and iron in the livers of LEC rats was evaluated. RESULTS: Signal intensities, which were homogeneous throughout the liver in every phase, decreased in the acute hepatitis phase and recovered in the chronic hepatitis phase. Copper was accumulated in all phases. Iron was observed grossly in the hepatocytes in the acute phase, but decreased in the chronic phase. CONCLUSIONS: Signal intensities of proton-density images of the livers of LEC rats in phases of pre-, acute, and chronic hepatitis were influenced by iron.

Elevation of plasma lipid peroxides in non-insulin dependent diabetics with multiple lacunar infarcts.

Our purpose was to determine whether lipid peroxides are elevated in the plasma of patients with non-insulin dependent diabetes with multiple lacunar infarcts as detected by magnetic resonance imaging (MRI), and to confirm whether peroxide levels correlate with glycemic controls and blood lipid levels. The level of lipid peroxide (measured as thiobarbituric acid reactive substances (TBARS)) was measured in 23 healthy controls and 28 diabetics showing normal MRI findings and 22 diabetics with multiple lacunar infarcts. These groups were age-matched. In patients with multiple lacunar infarcts, systolic blood pressure, diastolic blood pressure and TBARS levels were significantly higher than in diabetics without such infarcts (p < 0.05). When the diabetic patients were divided into two groups according to the presence or absence of hypertriglyceridemia or hyperglycemia, in both groups plasma TBARS levels in patients with multiple lacunar infarcts were significantly higher than in patients without such infarcts. Multivariate analysis showed systolic blood pressure and plasma TBARS levels to be independent predictors of multiple lacunar infarcts. Among diabetics, total plasma TBARS levels were positively correlated with fasting blood glucose, HbA1c and triglyceride levels, but not with total cholesterol levels and age. In conclusion plasma lipid peroxides were elevated in diabetics with multiple lacunar lesions, and are related to the metabolic imbalance of plasma glucose and lipids.

Copper concentration in hyperintense hepatocellular carcinomas of Long-Evans cinnamon rats on T1-weighted images.

The Long-Evans Cinnamon (LEC) rat has abnormal intrahepatic copper accumulation and spontaneously develops hepatocellular carcinomas following hereditary hepatitis. The hepatocellular carcinomas are very similar to human well-differentiated hepatocellular carcinoma in histopathological features and on MR images. Copper is believed to be one of the causes of hyperintensity of hepatocellular carcinomas compared to surrounding non-cancerous tissues on T1-weighted MR image. Eight LEC rats were studied by MR imaging. We measured copper concentrations from the hepatocellular carcinomas and surrounding non-cancerous liver tissues. Signal intensity of hepatocellular carcinomas without cystic areas was iso- to slightly hyperintense relative to surrounding non-cancerous tissues on T1-weighted images. Histopathologically, most of the tumors resembled human highly or well-differentiated hepatocellular carcinomas. Copper concentrations of the hepatocellular carcinomas were lower than the surrounding non-cancerous liver tissues. Copper may not be the cause of increased signal intensity typically observed on T1-weighted images of hepatocellular carcinomas.

Quantitative analyses of correlations of signal intensity on T1-weighted images and T1 relaxation time with copper concentration in the rat liver.

RATIONALE AND OBJECTIVES: To evaluate the effects of intrahepatic copper on magnetic resonance (MR) images, we studied the signal intensity (SI) of T1-weighted images and the T1 relaxation time of Long-Evans Cinnamon (LEC) rats, which have abnormal copper metabolism, and compared them with those of Sprague-Dawley (SD) rats. METHODS: We imaged the livers of four LEC rats before they developed hepatitis and four SD rats. The SI ratio of the liver to a phantom of polyvinyl alcohol gel was measured on T1-weighted images, and the T1 relaxation time was obtained from calculated T1 images. Copper concentration was measured by atomic absorption spectrophotometry. RESULTS: The mean copper concentrations in the liver of LEC rats were approximately 20-fold and statistically higher than in SD rats. There was no significant difference in the SI ratio and the T1 relaxation time between the LEC and SD rats. CONCLUSION: Intrahepatic copper does not significantly influence either the SI of T1-weighted MR images or the T1 relaxation time of the rat liver.

Magnetic resonance imaging of Long-Evans cinnamon rats as a new model of hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: Following hereditary hepatitis, Long-Evans Cinnamon (LEC) rats spontaneously develop hepatocellular carcinomas (HCC) histopathologically similar to human well-differentiated HCC. We demonstrated that LEC rats are an appropriate model of evaluating magnetic resonance (MR) imaging of well-differentiated liver tumors. METHODS: Six 23-25-month-old LEC rats were studied using liver MR imaging and histologic observation. RESULTS: Signal intensity of HCCs without cystic areas was normal or slightly high on T1-weighted images and slightly high on T2-weighted images. Histopathologically, most tumors resembled human highly or well-differentiated HCCs. CONCLUSION: The LEC rat is a good model of investigating MR imaging of well-differentiated HCC.

Observation of glucose metabolism in the rat liver by in vivo 13C MR spectroscopy without proton decoupling.

Glucose metabolism in rat liver was investigated by in vivo 13C-MR spectroscopy using [1-13C]glucose. Experiments were performed with a 7.05 Tesla small bore MR system using a 13C surface coil without 1H decoupling. Sprague-Dawley rat was anesthetized and kept in the spine position. [1-13C]glucose (99% enriched) was injected intravenously in a dose of 1 g per kg of body weight. The circular surface coil of 25.4 mm in diameter was placed on the surgically exposed liver in the incised abdomen. A total time of one scan was about 8 min and time course for glycogenesis was observed every 10 min, for total 90 min. The in vivo 13C-1 carbon resonances of hepatic glucose and glycogen were well resolved in spite of splitting by J-coupling, enabling the time course for the relative change in concentrations for both metabolites to be established simultaneously. The 13C resonance of glucose gradually decreased, and the 13C resonance of glycogen gradually increased to peak level at 40 min after the injection of [1-13C]glucose. We have developed a simple method of 13C-MR spectroscopy for use in rat liver.

Two cases of proton MR spectroscopy of the brain after irradiation.

Proton magnetic resonance spectroscopy (1H-MRS) is thought to be more sensitive to radiation damage of the brain than magnetic resonance imaging (MRI). We presented performed 1H-MRS using the stimulated echo acquisition method (STEAM) for non-tumor sites in 2 patients who received radiation therapy for their brain tumors. In the first case up to 45 days after radiation, we could observe a normal spectra presented three major peaks of N-acetyl aspartate (NAA), creatine and phosphocreatine (Cr), and choline (Cho). In the second case who had radiation necrosis 1 year after radiation, the spectra showed a decrease in the all peaks beneath the noise level.

[MR images of the hepatocellular carcinoma in Long-Evans cinnamon (LEC) rats].

Long-Evans Cinnamon (LEC) rats which have an abnormal copper accumulation in the liver develop hereditary hepatitis and subsequent hepatocellular carcinoma (HCC). We studied the correlation of MR images of the HCCs developed in LEC rats and histopathological features. The HCCs of LEC rats had high intensity on T 1-weighted images and iso-low intensity on T 2*-weighted images. Histopathological examination showed that the HCCs were highly differentiated. Copper concentration in the HCCs was lower than that in the surrounding non-cancerous liver tissues. From these results, we suggest that copper accumulation may not be responsible for the high intensity of HCCs on T 1-weighted images.

Myocardial high-energy phosphate metabolism in patients with stable chronic dilated cardiomyopathy under a dobutamine-induced prolonged mild workload.

BACKGROUND: The myocardial phosphocreatine (PCr) to beta-adenosine triphosphate ratio measured by phosphorus 31 nuclear magnetic resonance spectroscopy, which is analogous to energy reserve, is one of the important clinical predictors in patients with dilated cardiomyopathy (DCM). However, it may vary with the cardiac workload. METHOD: The myocardial PCr to beta-adenosine triphosphate ratio was measured before and during a 5 and 10 microgram/kg/min infusion of dobutamine in 7 patients with DCM and in 8 normal patients. Dobutamine infusion was kept constant for 50 minutes in each stage. Myocardial contractility and ventricular size were determined by echocardiography with the same protocol. RESULTS: This ratio was unchanged from 1.5 +/- 0.4 to 1.8 +/- 0.6 in the low-dose stage and stable (1.7 +/- 0.3) in the high-dose stage in patients with DCM. The heart rate and the mean rate of circumferential fiber shortening increased dose dependently both in patients with DCM and in patients without. CONCLUSION: These results demonstrate that constant loading of dobutamine for hours is tolerated without deterioration of myocardial metabolic function by patients with nonischemic DCM. We concluded that the high-energy phosphate metabolism of stable patients with cardiomyopathy is stable if the workload is temporary and weak. This implies the possibility that mild exercise can be tolerated in patients with heart failure.

Macrocyclic chelators with paramagnetic cations are internalized into mammalian cells via a HIV-tat derived membrane translocation peptide.

A major obstacle to using paramagnetic MR contrast agents for in vivo cell tracking or molecular sensing is their generally low cellular uptake. In this study, we show that a paramagnetically labeled DOTA chelator derivatized with a 13-mer HIV-tat peptide is efficiently internalized into mammalian cells. Intracellular concentrations were attained that were readily detectable by MR imaging using both gadolinium and dysprosium chelates. Using this paradigm, it should be feasible to internalize a variety of chemically different agents into mammalian cells.

Influence of in vivo copper on MR images of the liver in rats.

To investigate the effects of in vivo copper on magnetic resonance (MR) images, the authors studied Long-Evans cinnamon rats, which develop hepatitis and hepatocellular carcinoma as a result of abnormal copper metabolism. The livers of the rats were imaged before hepatitis developed; the absence of hepatic disease was confirmed histopathologically. The copper that accumulated in the liver of the rats was thought to exist in the form of divalent ions, which were suspected of reducing the T1 and T2 of neighboring protons. However, the signal intensities of the liver on T1- and T2*-weighted images did not change, suggesting that in vivo copper, even when accumulated abnormally, does not influence the signal intensity of MR images.