Definition of liver tumors in the presence of diffuse liver disease: comparison of findings at MR imaging with positive and negative contrast agents.

PURPOSE: The potential to define liver tumors at magnetic resonance (MR) imaging was compared with a positive and a negative contrast agent (gadoxetic acid disodium, or gadolinium EOB-DTPA [a hepatocyte-directed agent], and ferumoxides, or superpara-magnetic iron oxide particles [a Kupffer cell-directed agent], respectively) in normal rats and in rats with induced acute hepatitis, fatty liver, or cirrhosis. MATERIALS AND METHODS: Rats with implanted liver adenocarcinomas were divided into four groups: no diffuse liver disease ("normal" [n = 6]) and diffuse liver diseases (induced acute hepatitis [n = 6], fatty liver [n = 6], or cirrhosis [n = 6]). Rats first received gadoxetic acid disodium (50 mumol/kg) and then, 45 minutes later, ferumoxides (10 mumol/kg). Liver signal intensity enhancement and tumor-to-liver contrast-to-noise ratio (C/N) were measured in each group. RESULTS: Mean liver signal intensity enhancement values with gadoxetic acid disodium and ferumoxides were excellent in the normal liver model (176% and -62%, respectively; P < .01) but were significantly reduced in the acute hepatitis model (82% and -36%, respectively). In the fatty livers compared with the normal livers, enhancement with gadoxetic acid disodium was reduced (57%) but with ferumoxides was excellent (-55%). In the cirrhotic livers compared with the normal livers, enhancement with gadoxetic acid disodium (174%) was virtually the same but was impaired with ferumoxides (-43%). CONCLUSION: Hepatic enhancement and tumor-to-liver C/N with either positive or negative liver-enhancing agents can be impaired by the presence of underlying liver disease. Prior knowledge of the type of diffuse liver disease may influence the choice of contrast agent for tumor detection.

Early detection of acute tubular injury with diffusion-weighted magnetic resonance imaging in a rat model of myohemoglobinuric acute renal failure.

We evaluated the feasibility of magnetic resonance imaging (MRI) for early detection of tubular injury by monitoring changes in the apparent diffusion coefficient (ADC) of renal water in a rat model of myohemoglobinuric glycerol-induced acute renal failure (ARF). Diffusion-weighted MRI was performed concurrently with measurements of serum creatinine and blood urea nitrogen (BUN), evaluation of renal perfusion with dynamic contrast-enhanced MRI, and renal morphological examination. ADC values in the cortex and outer medulla significantly declined within minutes after the glycerol administration (70-75% of control at 4 min and 50-60% of control at 15 min). Contrast-enhanced MRI demonstrated renal hypoperfusion at 20 min after the onset of injury. Light microscopy showed normal glomeruli and edematous tubular epithelial cells at 10 and 30 min, with more severe swelling and protein casts at 30 min. No changes in serum creatinine or BUN levels were detected. We hypothesize that decrease in renal ADC may be attributed to renal ischemia and to subsequent intracellular accumulation of diffusion-restricted water. Similar imaging evaluation in other experimental models of ARF, and in patients, will define the diagnostic value of renal ADC changes in early detection of acute tubular injury.

Effect of varying the molecular weight of the MR contrast agent Gd-DTPA-polylysine on blood pharmacokinetics and enhancement patterns.

The effects of varying the molecular weight of gadolinium-DTPA (diethylenetriaminepentaacetic acid)-polylysine, a macromolecular magnetic resonance (MR) imaging contrast agent, on blood pharmacokinetics and dynamic tissue MR imaging signal enhancement characteristics were studied in normal rats. Blood elimination half-life, total blood clearance, volume of the central compartment (Vcc) and the steady-state distribution volume (Vssd) were calculated for four Gd-DTPA-polylysine polymers with average molecular weights of 36, 43.9, 139, and 480 kd and compared with corresponding values for Gd-DTPA (0.57 kd) and Gd-DTPA-albumin (92 kd). Blood elimination half-life increased seven-fold with an increase in molecular weight from 36 to 480 kd. The Vcc values for all polylysine polymers did not differ significantly from the Vcc value for Gd-DTPA-albumin but were significantly smaller than the Vcc value for Gd-DTPA. The Vssd value for Gd-DTPA did not differ significantly from the Vssd value for the 36- and 43.9-kd polymers but was significantly larger than the Vssd values for the 139- and 480-kd polymers and for Gd-DTPA-albumin. On T1-weighted coronal spin-echo MR images, dynamic signal enhancement profiles in liver and kidney for the 36-, 43.9-, and 480-kd Gd-DTPA-polylysine chelates corresponded to the blood pharmacokinetic data. Increasing molecular weight of Gd-DTPA-polylysine formulations substantially slows blood clearance and produces a prolonged, almost constant tissue signal enhancement for the 60-minute observation period.

MR imaging of blood oxygenation-dependent changes in focal renal ischemia and transplanted liver tumor in rat.

The potential of using fast magnetic resonance (MR) imaging in conjunction with apnea-induced blood deoxygenation for the noninvasive monitoring of relative perfusion in the rat abdomen has been studied with two experimental models: glycerol-induced focal renal ischemia and transplanted liver tumor. Gradient-echo echo-planar imaging (GRE-EPI) (TE of 20 msec at 2T) of liver and kidney was performed before, during, and after a 60-second apnea episode and then was followed in the same rat by contrast-enhanced (a) GRE-EPI and (b) T1-weighted spin-echo imaging (TR msec/TE msec = 200/6) with polylysine-(gadolinium-DTPA [diethylenetriaminepentaacetic acid]). The results indicate that a noninvasive vascular challenge due to apnea can be used for the detection of focal tissue perfusion abnormalities in rat kidney and liver tumor.

Comparison of Gd-EOB-DTPA and Gd-DTPA for contrast-enhanced MR imaging of liver tumors.

A new hepatobiliary contrast agent for magnetic resonance (MR) imaging, gadolinium-ethoxybenzyl (EOB)-diethylemetriaminepentaacetic acid (DTPA), was compared with Gd-DTPA to define the potential for improving tumor-liver contrast in a rodent liver adenocarcinoma model. With a T1-weighted spin-echo sequence, the contrast-to-noise ratio (C/N) for tumor before contrast agent administration was 5 (arbitrary units), the tumor appearing slightly hypo-intense with respect to liver parenchyma. After Gd-DTPA injection (0.1 mmol/kg), tumor enhanced more strongly than liver, resulting in an equalization of tumor and liver signal intensities and a decline in C/N to zero at 3 minutes after injection. After Gd-EOB-DTPA injection (0.1 mmol/kg), liver enhanced more strongly than tumor. Five minutes after injection, C/N increased from 5 to 25 and remained above 17 for 50 minutes. The data indicate that Gd-EOB-DTPA yields higher and more prolonged tumor-liver contrast than Gd-DTPA on T1-weighted spin-echo images. The high liver-tumor contrast after Gd-EOB-DTPA administration should prove clinically advantageous for MR imaging detection of focal hepatic masses.

Magnetic resonance imaging demonstration of pharmacologic-induced myocardial vasodilatation using a macromolecular gadolinium contrast agent.

RATIONALE AND OBJECTIVES: Adenosine is a potent vasodilator used clinically in nuclear scintigraphy to assess coronary artery reserves. The potential to identify this vasodilating effect of adenosine using magnetic resonance imaging (MRI), which is superior in spatial resolution to nuclear scintigraphy, combined with a blood-pool MRI contrast agent, was investigated in normal rats. METHODS: Groups of Sprague-Dawley rats received successive infusions of either adenosine (3 mg/kg/minute; n = 7) or dipyridamole (negative control; up to 1.0 mg/kg/minute; n = 9), both before and after contrast enhancement, with a macromolecular blood-pool MRI contrast agent, albumin-gadolinium-DTPA35 (Gd-DTPA35) (4.0 mumol Gd per kilogram). Electrocardiographically (ECG) gated MRIs (2.0 Tesla), acquired serially before and after contrast enhancement, and with and without either adenosine or dipyridamole infusions, to monitor potential pharmacologic responses. RESULTS: During repeated infusions of adenosine, the postcontrast myocardial enhancement, reflecting blood volume, increased significantly (P < .05), up to 150%, compared with pre-adenosine enhancement. Infusions of dipyridamole, pharmacologically inactive in rats, produced no change in myocardial enhancement. CONCLUSIONS: The increased myocardial signal intensity observed during adenosine infusions after enhancement of the blood pool can be attributed to increased blood volume accompanying coronary vasodilatation. The method, which does not require a continuous infusion of contrast agent, has potential for the clinical evaluations of coronary artery reserves.

Evaluation of radiation-induced liver injury with MR imaging: comparison of hepatocellular and reticuloendothelial contrast agents.

Gadolinium (4s)-4-(4-ethoxybenzyl-3,6,9-tris(carboxylato-methyl)-3,6,9- triazaudecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocellular-directed magnetic resonance (MR) contrast agent, and coated superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared for uptake and enhancement in a rodent model of radiation-induced liver injury. A single x-irradiation exposure (50-70 Gy) was delivered to one side of the liver in 18 rats. MR imaging was performed 3 days after x irradiation with sequential injections of the two contrast agents in the same rats. Additionally, biliary excretion of Gd-EOB-DTPA was quantified after whole-liver irradiation in five rats. Electron microscopy of the irradiated liver demonstrated mitochondrial injury in both hepatocyte and Kupffer cell populations. With Gd-EOB-DTPA, however, liver enhancement and biliary excretion were not affected by irradiation. Uptake of SPIO was decreased in the irradiated portion of the liver, with a precise demarcation between irradiated and nonirradiated zones at MR imaging.

Detection of zonal renal ischemia with contrast-enhanced MR imaging with a macromolecular blood pool contrast agent.

The potential of magnetic resonance (MR) imaging enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid [DTPA])35, a macromolecular blood pool marker, for detection of focal changes in renal perfusion was studied in a myoglobinuric acute renal failure (ARF) model in the rat. T1-weighted spin-echo postcontrast images of injured kidneys at 3 hours after glycerol injection showed three distinct zones: a strongly enhanced outer cortex, a low-intensity inner cortex, and a strongly enhanced medulla. The distinct band of low intensity in the inner cortex indicated zonal decreased blood volume, corresponding to published microsphere data showing zonal low perfusion in the inner cortex. Contrast differences between parenchymal zones were significant for at least 30 minutes. No focal ischemic changes could be delineated on nonenhanced images. Enhanced and nonenhanced images of injured kidneys obtained at 24 hours after glycerol injection revealed no zonal differentiation. Contrast-enhanced MR imaging data in this ARF model correlated well with pathologic data and microsphere perfusion results. Contrast-enhanced characterization of the ischemic phase of renal injury with MR imaging may improve specificity for the diagnosis of ARF and may serve as a marker for therapeutic intervention.