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Biomedical subjects

M R Violante

Publications and source records attributed to M R Violante.

At least 19 recordsLinked to original sources

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 particle's biodistribution in the liver.

Absorption↗

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.

Animals↗

Potential of microparticles for diagnostic tracer imaging.

The development of tracer imaging agents with sufficiently high label activity can lead to problems of poor aqueous solubility of the labeled tracer, causing formulation difficulty, inadvertent accumulation by phagocytic cells, or inadequate signal to noise. Our approach to solving these problems is to administer the tracer in the form of monodispersed nanoparticles which can safely be administered intravenously. Since the phagocytosis of these particles can be controlled or avoided in a predictable manner by altering particle size and surface characteristics, imaging tracers can be designed for a variety of intended applications. This paper summarizes the results and ideas for several applications involving computed tomography, ultrasound, magnetic resonance imaging, and radioisotope imaging modalities.

Animals↗

Particulate suspensions as ultrasonic contrast agents for liver and spleen.

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, and pharmacologic 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.

Animals↗

Accumulation and elimination of particulate iodipamide ethyl ester in the lungs and kidneys of the rat. A morphological study.

Particulate iodipamide ethyl ester, a new hepatolienographic x-ray contrast agent, was intravenously injected into rats. Lung and kidney biopsies taken at various intervals after the injection were examined by light and electron microscopy. IDE particles could be found in the lung capillaries phagocytized by polymorphonuclear neutrophils (PMNs). There were also free particles in the alveolar capillaries in the samples taken 5 min to 4 hours after the injection. No aggregates or emboli were seen. Two days or more after the injection no intra- and extracellular particles were present. The PMNs underwent transient local hydropic degeneration; the lung cells were morphologically intact. In the kidneys, the particles first appeared in both cortical and medullary capillaries. No emboli were observed. The kidney cells did not ingest IDE, but polymorphonuclear neutrophils (PMNs) with ingested IDE were often seen loosely attached to the glomerular capillary walls. In addition, free particles were evident in the capillaries in the samples taken up to 1 hour after injection. All particles in subsequent kidney samples were located in PMNs in the glomeruli. After three or more days the renal tissue was totally devoid of particulate IDE. No morphological evidence of kidney cell injury was observed.

Animals↗

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.

Animals↗

Computed tomographic enhancement of liver and spleen in the dog with iodipamide ethyl ester particulate suspensions.

Particulate suspensions have been developed for use as contrast agents to aid in the detection of hepatic lesions by CT. In several previous rodent studies, the toxicity and tissue concentrations of iodipamide ethyl ester (IDE) particles have been evaluated. The purpose of this study was to determine the pharmacokinetics of IDE in three dogs by evaluation of CT enhancement. Serum chemistry and hematologic parameters after intravenous administration were also followed. A dose of 75 mgI/kg IDE caused an increase of 40-60 Hounsfield units (HU) in liver attenuation, which persisted from 5 minutes to ten hours postinfusion. No enhancement of tissues other than liver and spleen was observed. IDE was completely eliminated from the liver within seven days. A mild transient elevation of liver enzymes may be attributable to the use of barbiturates rather than IDE. A transient depression of the white blood count was the only biochemical or hematologic change that was clearly in response to the infusion of IDE particulates.

Animals↗

Uptake and dissolution of particulate iodipamide ethyl ester in the spleen. A morphologic study.

Iodipamide ethyl ester (IDE) is an experimental particulate contrast agent being developed for CT image enhancement of the liver and spleen. IDE particles are phagocytized by the reticuloendothelial cells after an intravenous injection. The uptake and dissolution of IDE particles were studied in the spleen with light and electron microscopy. Two minutes after injection, intra- and extracellular IDE particles were found in the red pulp of the spleen. Highest concentration of IDE was seen in the marginal zone surrounding the white pulp. Particles also were seen elsewhere in the red pulp but only occasionally between the outermost cells of the white pulp. The extracellular particles disappeared within 4 hours postinjection. At one day postinjection, the amount of intracellular IDE particles had begun to decrease. Electron micrographs showed that the intracellular particles dissolved gradually in the phagocytes and caused transient degenerative morphologic changes. At three days postinjection, practically all IDE particles had disappeared from the spleen. Polystyrene latex particles were used as controls. They were phagocytized like the IDE particles, but they did not disappear from the phagocytes. IDE particles caused no morphologic injuries in nonphagocytic cells of the spleen.

Animals↗

Response of white blood cells to iodipamide ethyl ester particles.

The effect of intravenously injected iodipamide ethyl ester (IDE) particles (150 mgl/kg) on white blood cells was studied by light and electron microscopy. The clearance of IDE from rat plasma also was determined by analyzing free IDE particles in a counting chamber. The total white blood cell count remained essentially unchanged up to 40 minutes after the IDE injection, but the polymorphonuclear (PMN) neutrophil count decreased significantly. At 5 minutes postinjection, occasional PMNs contained ingested IDE particles, but by 40 minutes no intracellular particles could be found in the peripheral circulation. In vitro incubation experiments confirmed that human PMNs ingest IDE particles. In electron microscopy, the cells and particles seemed to be morphologically intact. Of the IDE particles counted at 5 minutes postinjection, only 4% remained in plasma at 30 minutes and none at 40 minutes. The decrease in PMN count apparently reflects sequestration of phagocytic cells from the circulation.

Animals↗

Improved detectability of VX2 carcinoma in the rabbit liver with contrast enhancement in computed tomography.

Detection of liver metastases by CT scanning depends on both size and difference in attenuation between the metastasis and the surrounding liver parenchyma. VX2 carcinoma cells were injected into the liver parenchyma of rabbits which were subsequently scanned under suspended respiration before, during and after infusion of iothalamate ethyl ester, a particulate contrast agent. The results demonstrate the greater attenuation difference between tumor and parenchyma required for the detection of smaller lesions. Contrast enhancement was most beneficial in the detection of tumors having diameters less than the scan section width.

Animals↗

Ventricular fibrillation from diatrizoate with and without chelating agents.

The toxicity of Renografin 76% was compared with that of Hypaque 76% by selective injection of each into the right coronary artery of dogs. Renografin contains the chelating agents sodium citrate and disodium edetate, while Hypaque contains calcium disodium edetate and no sodium citrate. Ventricular fibrillation occurred significantly more often with Renografin, suggesting that chelating agents contribute to toxicity in coronary angiography.

Angiography↗

The effect of barium on blood in the gastrointestinal tract.

The effect of various commercial barium sulfate preparations on blood coagulation, flocculation, and hemolysis was studied. There was considerable variation not only among different barium products but also among different concentrations of the same product. There is no good experimental evidence that barium enemas do stop bleeding. It is probably best to avoid the use of any enema in attempting to control major colonic bleeding; but if an enema is given for this purpose, a tap-water enema is better, as it contains no anticoagulants and is more effective in producing clot formation than most barium suspensions.

Barium Sulfate↗

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

The validity of an orifice equation (Torricelli's 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), Torricelli's 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.

Carotid Artery Diseases↗

Iothalamate ethyl ester as hepatolienographic agent.

In search of a hepatolienographic agent, the iothalamate ethyl ester particulate suspension was prepared with the average particle size of 1.5 mu in diameter. When mixed with plasma of different animal species, the physical properties of the particular suspension changed significantly. The nature of this difference is not understood but is probably related to protein-particle interaction in the different species. Doses of 550 mg iodine per kg body weight as a single intravenous infusion of the particulate suspension resulted in satisfactory opacification of liver and spleen in rats, followed by complete loss of radiopacity within three days. Larger doses resulted in the death of the rats within 12-14 hours. In general, the mice tolerated larger doses than rats, but there was very poor opacification of the liver, despite good opacification of spleen. Further work is being carried out to improve the suspension and to better understand the difference in behavior of the particulate suspension in different animal species.

Animals↗