Application of Pharmacokinetics to Computed Tomography

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Abstract
OBJECTIVE The objective of the current study was to test whether optimization of dose regimens for detecting focal liver lesions by computed tomography is possible by using the available time-density data of former studies published in the literature and a computer program so that the number of further clinical tests with the exclusive objective of optimizing injection schemes could be reduced. METHODS Computed tomography enhancement data of the aorta and/or the liver obtained after injecting a conventional ionic and a nonionic contrast agent were used to calculate pharmacokinetic parameters and to simulate the time course of enhancement for a variety of different infusion regimens modifying contrast medium strength, dose, and injection rate. The study consisted of two parts. In the first part, mean relative enhancement curves of the aorta and of liver parenchyma (0 to 300 sec) using meglumine diatrizoate (306 mg iodine per mL, 300 mg iodine per kg) were taken from the literature and their values were approximated using the computer program TOPFIT. In the second part, equivalent data for iohexol including a total of three strengths (240, 300, and 350 mg iodine per kg) and doses from 30 to 45 grams of iodine were used. “Validation” of the simulation method was obtained, first by comparing measured and calculated maximum intensities and times to reach maximum and, second, by using one injection scheme for the simulation of a second and comparing the results with actually measured data. RESULTS The computer program TOPFIT allowed for excellent curve fitting of the measured density values. The data obtained in the first part of the study of showed that after a dose of 300 mg I/kg and a rate of 2 mL/sec maximal enhancement is achieved in the aorta after 30 seconds (approximately 100 HU) and in the liver after 50 seconds (approximately 30 HU). The higher the dose and the rate of infusion were, the higher was the enhancement. The difference in density between aorta and liver was proportional to the infusion rate approaching asymptotically approximately 90 HU at 8 mL/sec for a dose of 300 mg I/kg. Bi- or triphasic infusion schemes did not improve differences in enhancement. The curve fitting obtained in the second part of the study also confirmed the results reported in the literature. A “crossover” prediction of data was possible within the range of interindividual variations of pharmacokinetic parameters and thus validated the chosen approach of computer simulation. Furthermore, data sets selected randomly out of the simulation results could be used—within the limits of interindividual variability—to predict data determined in other clinical trials. CONCLUSION The computer program TOPFIT appears useful for the optimization of time-density profiles in computed tomography. The number of further clinical studies with the objective of optimization could therefore possibly be reduced.