Michael R. Violante

Hepatic CT contrast enhancement: effect of dose, duration of infusion, and time elapsed following infusion.

Contrast enhancement of the liver of anesthetized, paralyzed, and artificially ventilated rabbits was measured during suspended respiration prior to, during, and after the intravenous infusion of meglumine diatrizoate at doses of 208, 416, and 624 mg I/kg. Infusion time was 30 seconds, and, at the highest dose, infusion times of 1, 2, and 4 minutes were also used. Highest contrast enhancement values were obtained at the conclusion of each infusion, with contrast enhancement increasing proportionately with increase in dose. Highest enhancement was obtained at all times studied from the most rapid infusion. Unlike cranial CT, optimum hepatic contrast enhancement in body CT requires rapid contrast medium injection with immediate CT scanning with a very fast scanner.

Particulate Suspensions as Ultrasonic Contrast Agents for Liver and Spleen

Violante MR, Parker KJ, Fischer HW. Particulate suspensions as ultrasonic contrast agents for liver and spleen. Invest Radiol 1988;23(Suppl 1):S294‐S297. Ultrasonic backscatter and attenuation coefficients of a medium can be increased by the addition of solid, micron‐size inhomogeneities. A potentially useful agent for ultrasonic contrast of liver images has been identified. Iodipamide ethyl ester (IDE) particles can be produced in the form of dense, relatively incompressible solids with high impedance mismatch to water. The chemical, biochemical, andpharmacologic properties of the small, uniform diameter IDE particles permit safe intravenous injection followed by rapid accumulation of reticuloendothelial (RE) cells of the liver and spleen, and later elimination from these organs. Since the particles are phagocytized by RE cells, present in normal liver but not in tumors and many lesions, the selective enhancement of ultrasonic backscatter should improve detectability of lesions that are hypoechoic or isoechoic compared with surrounding tissue. The mechanisms of particle‐ultrasound interaction may be described by relative motion attenuation, and scattering from a cloud of dense, incompressible spheres for the case of IDE particles in agar. Thus, values of attenuation and backscatter can be controlled by choice of ultrasound frequency and particle concentration and size. When the particles are accumulated in rat and rabbit livers, additional mechanisms induce attenuation and backscatter in excess of that predicted by IDE in agar. This preliminary work demonstrates that solid, biocompatible particles may be useful as an ultrasonic contrast agent.

A particulate contrast agent with potential for ultrasound imaging of liver

Ultrasonic backscatter and attenuation coefficients of a medium can be increased by the addition of solid, micron sized inhomogeneities. A potentially useful agent for ultrasonic contrast of liver images has been identified. Iodipamide ethyl ester (IDE) particles can be produced in the form of dense, relatively incompressible solids with high impedance mismatch to water. The chemical, biomechanical, and pharmacological properties of the small, uniform diameter IDE particles permit safe intravenous injection followed by rapid accumulation by reticuloendothelial (RE) cells of the liver and spleen, and later elimination from these organs. Since the particles are phagocytized by RE cells, present in normal liver but not in tumors and many lesions, the selective enhancement of ultrasonic backscatter should improve detectability of lesions which are hypo- or iso-echoic compared to surrounding tissue. The mechanisms of particle-ultrasound interaction may be described by relative motion attenuation, and scattering from a cloud of dense, incompressible spheres for the case of IDE particles in agar. Thus, values of attenuation and backscatter can be controlled by choice of ultrasound frequency and particle concentration and size. When the particles are accumulated in rat livers, additional mechanisms induce attenuation and backscatter in excess of that predicted by IDE in agar. This preliminary work demonstrates that solid, biocompatible particles may be useful as an ultrasonic contrast agent.

Reduction in Ventricular Fibrillation Using Calcium-Enriched Renografin 76

Renografin 76 has been shown to have significant calcium-binding properties in vivo and in vitro. Two contrast media solutions were compared by selective injection into the right coronary artery of dogs. One set of injections was made with commercially available Renografin 76 (referred to as stock Renografin) and another set of injections was made with Renografin 76 to which had been added 24 mMols/liter of calcium chloride dihydrate. Ventricular fibrillation occurred significantly more often with the stock Renografin 76. The nature of the calcium binding and its effects are discussed.

Comparison of Hepatic VX2-Carcinomas after Intra-arterial, Intraportal and Intraparenchymal Tumor Cell Injection: An Angiographic and Computed Tomographic Study in the Rabbit

Hepatic VX2-carcinomas were produced in 45 rabbits by injection of approximately 25 x 10(6) tumor cells into the proper hepatic artery, the superior mesenteric vein, or directly into the liver parenchyma. With the intra-arterial and intraportal approaches, survival times (12 +/- 4 and 13 +/- 5 days, respectively), radiographic and autopsy findings revealing a liver with diffuse tumor involvement were very similar. With intraparenchymal tumor cell injection, survival time was significantly longer (18 +/- 14 days) and the hepatic VX2-carcinoma always localized. The tumor appeared hypervascular on angiography and hypodense on computed tography (CT). After intravenous injection of diatrizoate, the attenuation in the tumor increased less than in the surrounding liver so the lesion became relatively less dense and more easily recognized on CT-scans. The apparent discrepancy between angiographic and contrast enhanced CT findings can be explained with the difference in blood supply of hepatic tumors and normal liver parenchyma.

Ultrasound Contrast for Hepatic Tumors Using IDE Particles

Iodipimide ethyl ester (IDE) can be formulated as dense spherical particles with narrow diameter distribution. When IDE particles are injected intravenously, the Kupffer cells of the hepatic sinusoids accumulate particles within 10 to 20 minutes, after which the clearance and excretion of IDE takes place. During the uptake phase, the dense particles act as scattering sites, increasing the echogenicity of normal liver tissue. In comparison, tumors and other lesions remain at pre-injection echogenicity, as they lack Kupffer cells and therefore do not retain particles. This report provides initial studies of contrast enhancement in rabbit livers with implanted VX2 tumors, scanned in vivo and evaluated ex vivo using pulse-echo techniques. The distribution of particles within hepatic lobules may explain why the observed echogenicity is greater than that predicted by single-particle backscatter theory. Directions for future improvements are discussed.

Doppler ultrasound in orifice flow. In vitro studies of the relationship between pressure difference and fluid velocity.

The validity of an orifice equation (Torricellis law) which expresses a simple relationship between the pressure difference across an orifice and the maximum fluid velocity in the orifice was tested in vitro. An aqueous suspension of barium sulfate particles with a polymer added to attain variations in viscosity, was forced through orifices which ranged in diameter from 0.4 to 4.7 mm. The pressure difference across the orifice was determined with a transducer and the maximum fluid velocity in the orifice was determined with Doppler ultrasound. Tests were performed at Reynolds numbers, fluid viscosities, and pressure differences that spanned the following ranges: 400-25,000, 1-5 cP, and 3-100 mmHg, respectively. At pressure differences larger than 3 mmHg and fluid viscosity 3 cP (approximate viscosity of in vivo blood), Torricellis law was demonstrated to be valid for orifice diameters larger than 1.6 mm. The validity of the law was found to be relatively insensitive to variations in orifice length.

Particulate Contrast Media for Computed Tomographic Scanning of the Liver

A contrast agent that is selectively accumulated in the liver should greatly improve the diagnostic value of contrast enhanced CT scanning. The advantages and disadvantages of different classes of hepatographic agents are briefly reviewed. Experimental results obtained with the particulate contrast agents, iothalamate ethyl ester and iodipamide ethyl ester, are presented in more detail. Following intravenous infusion of iodipamide ethyl ester, approximately 60% of the injected dose is accumulated in the rat liver. CT scanning experiments involving iothalamate ethyl ester infusions in New Zealand White rabbits demonstrate significantly higher liver contrast enhancement at 10-30 minutes postinfusion than is observed with diatrizoate at a sixfold greater iodine dose. The selective accumulation of a particulate contrast agent in hepatic reticuloendothelial cells compared to virtually no accumulation in implanted VX2 carcinoma demonstrates the important potential value of these agents in improving detection of liver metastases.

Ultrasound properties of liver with and without particulate contrast agents.

Basic acoustic parameters are examined in rabbit liver with and without a solid contrast agent used for tumor detection. In normal liver, backscatter, attenuation, and sound speed are found to decrease with increasing water content. The addition of micron-sized particles made from iodipamide ethyl ester (IDE) can increase backscatter and attenuation depending on size and concentration. A discrepancy of the increased backscatter from theoretical predictions based on random scatterers is attributed to the particles biodistribution in the liver.

Effect of intravenously administered iodipamide ethyl ester particles on rat liver morphology.

The effect of intravenously injected iodipamide ethyl ester (IDE) particles (150 mgI/kg) on the rat liver was studied by light and electron microscopy. IDE particles were phagocytized by Kupffer cells within a few minutes postinjection. After 4 hours particles began to dissolve in the Kupffer cells causing transient morphologic alterations resembling hydropic degeneration. The number of Kupffer cells seemed, however, to be unchanged and were ultrastructurally normal by 17 days postinjection. Hepatocytes contained large lipid droplets from one to four days after IDE injection. No changes were found in the hepatocytes from one week to one year after IDE injection. The fat-storing cells and endothelial cells remained ultrastructurally normal throughout the study.