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The contrast enhancement of six contrast media (CM) was compared in 13 tissues of the rat after rapid intravenous bolus injection. The rats were sacrificed at 0 and 40 seconds and 2, 5, and 15 minutes after contrast injection. 125I labeled diatrizoate, metrizamide, ioxaglate, iohexol, iopamidol, and a nonionic dimer, iodecol, were each injected at a dose of 612 mg iodine per kg body weight, and iodine concentration (IC) and contrast enhancement were calculated from radioactivity measurements. Higher blood IC values were obtained with the nonionic CM; similar enhancement patterns were seen in the spleen, heart, lungs, and brain. Renal IC was directly related to the number of iodine atoms per ion or molecule of CM. In consequence, renal IC was inversely related to the CM osmolality, but no such correlation was seen with the blood IC. Metrizamide produced the greatest IC in the organs of the gastrointestinal tract. There was no apparent correlation of IC with molecular structure of physicochemical parameters of the CM in any of the other tissues studied.

In order to assess their potential usefulness in conjunction with dynamic CT scans of the liver, functional images of several variables related to blood flow were created from dynamic CT scans of 15 patients with a variety of liver diseases. Seven of the patients received intra-arterial and intravenous boluses of contrast; the other eight received intravenous boluses alone. Intra-arterial contrast injections yielded superior functional images, but useful functional images could also be created from studies with intravenous boluses. Although respiratory motion artifacts caused some problems, images that can be interpreted in terms of effective distribution volume, transit time, and blood flow were successfully created. Functional imaging of the liver can provide a useful display of regional physiologic differences.

The aim of contrast enhancement is to increase the difference in attenuation coefficients between pathological lesions and the surrounding normal tissues. Unlike cranial CT, in body CT the contrast-enhanced scans should be taken when the blood and normal tissue levels of contrast enhancement are at their maximum possible levels. This has not been feasible in most currently available scanners, and most reports in the literature on contrast enhancement in CT have used suboptimal enhancement. In most cases, maximal enhancement will occur immediately at the end of a rapid intravenous injection using a high dose of contrast media. Repeat scans of certain slice levels at fixed time intervals may further improve diagnostic accuracy. Computers are only beginning to be used to analyze the reconstructed CT image, and recent increases in scanning rapidity make optimum contrast enhancement much more feasible. Renal toxicity from high doses of contrast media places a rather indefinite upper limit to contrast enhancement, which can be partially overcome with intra-arterial contrast media injection at CT. Nonenhanced scans should always precede contrast enhancement in body CT. In this article the experimental and theoretical background to CT contrast enhancement is reviewed and suggestions for optimum application are made in the light of present limitations of the technique. Improvement in both detection and differentiation of pathological lesions should result from minimizing the overlap of CT attenuation measurements of normal and pathological tissue by increasing the difference between their means and decreasing the range of variability of individual attenuation measurements.

The effect of contrast media (CM) dilution on contrast enhancement was studied using CM representing four structurally different molecular types at osmolalities ranging from 135 to 1340 mosm/kg. Diatrizoate (ionic monomer), iopamidol (nonionic monomer), ioxaglate (ionic dimer), and iodecol (nonionic dimer) were each given at a dose of 500 mgI/kg and at concentrations of both 300 and 150 mgI/mL. Contrast media concentrations were measured using iodine 125I. Tissue blood volumes were determined using human serum albumin labeled with 131I. For each of the four CM at each of the two concentrations and after each of five time intervals following injection (0, 15, 40, 120, and 300 seconds), five rats were killed (total = 200 rats). Blood and 14 other tissues were studied. Dilution of the CM did not lead to any lower iodine tissue concentrations, iodine distribution volumes, plasma volumes, or hematocrit. The authors conclude that lowering CM osmolality by dilution with water should improve tolerance without affecting CT contrast enhancement.

An intravenous injection of 153Gd-labeled gadolinium-DTPA or gadolinium chloride was given to 60 rats, which were killed either 15, 40, 120, 300, 900, or 3600 seconds later. Tissue concentrations of gadolinium in the blood, liver, spleen, stomach, pancreas, renal cortex, renal medulla, lungs, heart, adrenals, gluteal muscle, fat, skin, thymus, brain, thyroid, and parathyroids were measured. Five animals were killed at each time interval with gadolinium-DTPA, and at each of the latter four time intervals (15 and 40 seconds excluded) with gadolinium chloride. The pharmacokinetics of gadolinium-DTPA and chloride differ markedly in terms of tissue concentration, distribution volumes, and the time course of these parameters. Gadolinium, when injected as a chloride, evidently forms insoluble carbonate and phosphate precipitates in the blood, which are taken up by the reticuloendothelial system. The distribution of gadolinium-DTPA on dynamic MRI should closely parallel the distribution of iodinated contrast media on dynamic computed tomography.

Contrast media injected into the circulation produce a variety of cardiovascular effects. Agents with low osmolality and low concentrations of cations cause considerably less hemodynamic effects. This study compared the effects of a nonionic dimer, iotrol, which has an osmolality (340 mosm/kg) close to that of serum (290 mosm/kg), with a standard ionic monomer, meglumine diatrizoate, and a nonionic monomer, iosimide. The effects of intravenous bolus injection of these three contrast agents on coronary and systemic hemodynamics were studied in eight anesthetized dogs. The influence of the contrast media on subendocardial and subepicardial perfusion was assessed by injecting radioactive microspheres into the left atrium 30 seconds after injection of the media. Alterations in coronary hemodynamics occurred with both iosimide and meglumine diatrizoate. Iotrol produced minimal changes in coronary hemodynamics. Thus, iotrol is the least perturbing contrast indicator and seems the best for use in quantitative digital subtraction and dynamic computed tomography studies designed to measure myocardial perfusion.

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.

The contrast enhancement of low-osmolality (iohexol) and high-osmolality (diatrizoate) contrast media was compared in 18 pigs following intravenous bolus administration. Liver and blood attenuation and blood sample iodine concentration were measured during the first 3 minutes after injection. Iohexol produced a significantly higher contrast enhancement in the blood during the period from 0.5 to 3 minutes after injection. Diatrizoate produced a significantly higher contrast enhancement in the liver during the period from 9 to 30 minutes after injection. The greater contrast enhancement of iohexol during the acute phase should be advantageous in dynamic CT.

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.

Diastizoate concentrations in the blood and twelve tissues and organs of 20 rats were measured at 40 seconds, and 2, 5, 15 and 60 minutes after bolus intravenous administration of 125 I-labeled diatrizoate and 131 I-labeled albumin. Contrast enhancement (HU) and distribution volumes(%) were calculated from this data, and the results are presented graphically. The tissues can be separated into two groups according to the rapidity of extravascular contrast medium uptake. The liver appeared to concentrate the contrast medium. Curves of local contrast enhancement with time could be constructed by a CT scanner from the data of several consecutive scans and are of potential importance in the differential diagnosis of lesions detected on CT. Repeat postcontrast CT scans could be used to detect and characterize lesions which raise a diagnostic problem. The potential diagnostic advantages of calculating percent distribution volumes from CT scans are demonstrated and discussed.

Iohexol and meglumine-sodium diatrizoate were injected intravenously into 18 pigs as either a 99:1 or 1:99 mixture. Blood samples were taken for 30 minutes and the concentration of each of the two contrast media was measured by means of a double labeling technique with 125I and 131I. Relative concentrations of iohexol were significantly higher during the first 3 minutes when it was injected as a moderately hyperosmolar (99% iohexol) solution than when it was injected as a very hyperosomolar (99% diatrizoate) solution. The greater intravascular dilution of the 99% diatrizoate solution by extravascular water may explain this finding as well as the significantly longer rapid disposition phase and the slightly lower distribution volume of iohexol.