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Title: Hepatic contrast agents for computed tomography: high atomic number particulate material

Abstract

We used a stepwise approach to identify, design, synthesize, and test new high atomic number particulate contrast agents that would be especially well suited for use with computed tomography (CT). Our goal was to produce extremely radiopaque compounds with highly selective biodistribution to the normal liver. In this way, dose requirements could be lessened and toxicity minimized. Suspensions of cerium, gadolinium, and dysprosium oxide particles and silver iodide colloid were tested and compared with standard agents. All four experimental agents were selectively concentrated in the reticuloendothelial systems of rats and rabbits. These compounds produced greater and longer opacification of normal livers and larger liver-to-tumor differences in rabbits with hepatic tumors than did equivalent amounts of standard, iodinated agents. Lesions as small as 5 mm were visible with CT. These experimental materials have favorable characteristics as hepatic contrast agents, but their toxicity and long term retention may limit clinical use.

Authors:
; ; ; ; ; ; ;
Publication Date:
OSTI Identifier:
5638896
Resource Type:
Journal Article
Resource Relation:
Journal Name: J. Comput. Assist. Tomogr.; (United States); Journal Volume: 5:3
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 59 BASIC BIOLOGICAL SCIENCES; 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; CERIUM; DIAGNOSTIC USES; DYSPROSIUM OXIDES; GADOLINIUM; LIVER; COMPUTERIZED TOMOGRAPHY; SILVER IODIDES; BIOLOGICAL LOCALIZATION; CHEMICAL PREPARATION; CONTRAST MEDIA; DESIGN; RABBITS; RADIATION DOSES; RATS; RETICULOENDOTHELIAL SYSTEM; TISSUE DISTRIBUTION; TOXICITY; ANIMAL TISSUES; ANIMALS; BODY; CHALCOGENIDES; DIAGNOSTIC TECHNIQUES; DIGESTIVE SYSTEM; DISTRIBUTION; DOSES; DYSPROSIUM COMPOUNDS; ELEMENTS; GLANDS; HALIDES; HALOGEN COMPOUNDS; IODIDES; IODINE COMPOUNDS; MAMMALS; METALS; ORGANS; OXIDES; OXYGEN COMPOUNDS; RARE EARTH COMPOUNDS; RARE EARTHS; RODENTS; SILVER COMPOUNDS; SYNTHESIS; TISSUES; TOMOGRAPHY; TRANSITION ELEMENT COMPOUNDS; USES; VERTEBRATES; 550601* - Medicine- Unsealed Radionuclides in Diagnostics; 550901 - Pathology- Tracer Techniques; 560172 - Radiation Effects- Nuclide Kinetics & Toxicology- Animals- (-1987)

Citation Formats

Seltzer, S.E., Adams, D.F., Davis, M.A., Hessel, S.J., Havron, A., Judy, P.F., Paskins-Hurlburt, A.J., and Hollenberg, N.K. Hepatic contrast agents for computed tomography: high atomic number particulate material. United States: N. p., 1981. Web. doi:10.1097/00004728-198106000-00011.
Seltzer, S.E., Adams, D.F., Davis, M.A., Hessel, S.J., Havron, A., Judy, P.F., Paskins-Hurlburt, A.J., & Hollenberg, N.K. Hepatic contrast agents for computed tomography: high atomic number particulate material. United States. doi:10.1097/00004728-198106000-00011.
Seltzer, S.E., Adams, D.F., Davis, M.A., Hessel, S.J., Havron, A., Judy, P.F., Paskins-Hurlburt, A.J., and Hollenberg, N.K. 1981. "Hepatic contrast agents for computed tomography: high atomic number particulate material". United States. doi:10.1097/00004728-198106000-00011.
@article{osti_5638896,
title = {Hepatic contrast agents for computed tomography: high atomic number particulate material},
author = {Seltzer, S.E. and Adams, D.F. and Davis, M.A. and Hessel, S.J. and Havron, A. and Judy, P.F. and Paskins-Hurlburt, A.J. and Hollenberg, N.K.},
abstractNote = {We used a stepwise approach to identify, design, synthesize, and test new high atomic number particulate contrast agents that would be especially well suited for use with computed tomography (CT). Our goal was to produce extremely radiopaque compounds with highly selective biodistribution to the normal liver. In this way, dose requirements could be lessened and toxicity minimized. Suspensions of cerium, gadolinium, and dysprosium oxide particles and silver iodide colloid were tested and compared with standard agents. All four experimental agents were selectively concentrated in the reticuloendothelial systems of rats and rabbits. These compounds produced greater and longer opacification of normal livers and larger liver-to-tumor differences in rabbits with hepatic tumors than did equivalent amounts of standard, iodinated agents. Lesions as small as 5 mm were visible with CT. These experimental materials have favorable characteristics as hepatic contrast agents, but their toxicity and long term retention may limit clinical use.},
doi = {10.1097/00004728-198106000-00011},
journal = {J. Comput. Assist. Tomogr.; (United States)},
number = ,
volume = 5:3,
place = {United States},
year = 1981,
month = 6
}
  • Purpose: Currently, only iodine- and barium-based contrast media (CM) are used in clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would produce a higher contrast at equal mass density for the x-ray spectra used in clinical CT. Using such materials might allow for significant dose reductions in CE-CT. The purpose of this study was to quantify the potential for dose reduction when using CM based on heavy metals. Methods: The contrast-to-noise ratio weighted by dose (CNRD) was determined as a function of scan protocol by means of measurements and simulations on a clinical CT scanner. For simulations, water cylinders with diametersmore » 160, 320, 480, and 640 mm were used to cover a broad range of patient sizes. Measurements were conducted with 160 and 320 mm water-equivalent plastic cylinders. A central bore of 13 mm diameter was present in all phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from 60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8, and 1.2 mm was applied in the simulation to evaluate a range of spectral hardness. The bore was filled with a mixture of water and 10 mg/ml of pure iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for the simulations and with aqueous solutions of ytterbium, tungsten, gold, and bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for the measurements. CNRDs were compared to iodine at phantom size-dependent reference voltages for all high-Z materials and the resulting dose reduction was calculated for equal contrast-to-noise ratio. Results: Dose reduction potentials strongly depended on phantom size, spectral hardness, and tube voltage. Depending on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the 320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%-86% with 140 kV for gold and the 640 mm phantom. While gadolinium might be considered at 160 mm diameter, hafnium showed the best overall performance for phantom sizes of 320 mm and above. The measurements conducted on the clinical CT scanner showed very good agreement with simulations with deviations in the order of 5 to 10%. Conclusions: The results of this study encourage the development and use of CM based on high-Z materials, especially for adipose patients, where high tube voltages are necessary to reach sufficiently short scan times. Hafnium proved to be the best compromise for average-size and for adipose patients. Even higher-Z materials such as gold and bismuth showed a good overall performance in conjunction with high tube voltage, large patients or strong added filtration and may be recommended for scans under these conditions.« less
  • Purpose: To evaluate the sensitivity of dual-phase cone-beam computed tomography during hepatic arteriography (CBCTHA) for the detection of hepatocellular carcinoma (HCC) by comparing it with the diagnostic imaging 'gold standard': contrast-enhanced magnetic resonance imaging (CE-MRI) of the liver. Materials and Methods: Eighty-eight HCC lesions (mean diameter 3.9 {+-} 3.3 cm) in 20 patients (13 men, mean age 61.4 years [range 50 to 80]), who sequentially underwent baseline diagnostic liver CE-MRI and then underwent early arterial- and delayed portal venous-phase CBCTHA during drug eluting-bead transarterial chemoembolization, were evaluated. Dual-phase CBCTHA findings of each tumor in terms of conspicuity were compared withmore » standard CE-MR images and classified into three grades: optimal, suboptimal, and nondiagnostic. Results: Seventy-seven (mean diameter 4.2 {+-} 3.4 cm [range 0.9 to 15.9]) (93.9%) of 82 tumors were detected. Sensitivity of arterial-phase (71.9%) was lower than that of venous-phase CBCTHA (86.6%) for the detection of HCC lesions. Of the 82 tumors, 33 (40.2%) and 52 (63.4%), 26 (31.7%) and 19 (23.2%), and 23 (28%) and 11 (13.4%) nodules were classed as optimal, suboptimal, and nondiagnostic on arterial- and venous-phase CBCTHA images, respectively. Seventeen (73.9%) of the 23 tumors that were not visible on arterial phase were detected on venous phase. Six (54.5%) of the 11 tumors that were not visible on venous phase were detected on arterial phase. Conclusions: Dual-phase CBCTHA has sufficient image quality to detect the majority of HCC lesions compared with the imaging 'gold standard': CE-MRI of the liver. Moreover, dual-phase CBCTHA is more useful and reliable than single-phasic imaging to depict HCC nodules.« less
  • Purpose: Absorbable IVC filters are shown to be safe and efficacious in preventing pulmonary embolism. These absorbable filters disappear from the body after their required duration, alleviating costly removal procedures and downstream complications. Monitoring the positioning and integrity of absorbable devices using dual-energy computed tomography (DECT) would improve treatment efficacy. The purpose of this study is to determine the limit of detection and the energy dependence of DECT for various contrast agents that may be infused within the IVC filters including gold nanoparticles (AuNP) having diameters of 2 and 4 nm. Methods: All imaging studies were performed on a GEmore » Discovery CT750 system in Gemstone Spectral Imaging (GSI) mode. Plastic vials containing the contrast agent solutions of water and blood were placed in a water bath, and images were acquired with the GSI-5 preset. The images were reformatted into the coronal plane and 5mm diameter ROIs were placed within each solution on a GE Advantage Workstation. Monoenergetic reconstructions were generated from 40 – 140 keV. Results: Mass attenuation (contrast per unit density) for AuNPs was greater than iron, but less than barium and iodine. Contrast was 10.2 (± 3.6) HU for 4 nm AuNP at 0.72 mg/ml and 12.1 (± 4.2) for 2 nm AuNP at 0.31 mg/ml at 70 keV suggesting reasonable chance of visualization at these concentrations for 70 keV reconstruction. The contrast as a function of CT energy is similar in both water and blood. Iodine is most dependent, followed closely by barium and iron, and trailed by a large margin by the AuNP. This was unexpected given Au’s large atomic number and the predominance of photoelectric effect at low energy. Conclusion: Infusion of IVC filters with AuNP is feasible. Discrimination of AuNP-infused IVC filters from surrounding anatomy warrants further investigation.« less
  • An iodinated starch suspension was used as a model particulate hepatic contrast agent for computed tomography (CT). The material, synthesized from starch and triiodobenzoic acid, formed a stable concentrated suspension, containing particles smaller than 4 micrometer. Following intravenous administration of 0.16 gI/kg to rabbits, approximately 85% of the injected dose was present in the liver, resulting in a 180 to 200 Hounsfield unit (1,000 scale) increase in liver CT value. The material produced marked and sustained normal liver opacification but no hepatic tumor enhancement. Lesions as small as 2 mm in diameter were detected. The approximate LD50 of the suspensionmore » in mice was 0.9 g I/kg. There were no signs of toxicity at sublethal doses. This suspension produces greater, more sustained, and more selective liver opacification than conventional biliary and urographic contrast materials.« less
  • Large unilamellar phospholipid vesicles were prepared and loaded with various radiographic contrast media. Body CT following in vivo adminstration of these vesicles in the rat demonstrated opacification of organs associated with the reticuloendothelial system. Image enhancement in the spleen and liver was dose dependent and was linearly related within the dose range investigated. Clearance of the radiographic contrast material was complete within 24 hours. Diffuse splenic lymphoma following intraperitoneal or intrasplenic injection of lymphoma cells, and solitary lymphoma nodules following intrahepatic injection were readily detected as nonenhanced areas following injection of liposomes.