Abstract
The authors developed a method to quantitatively evaluate renal function using dynamic contrast-enhanced computed tomography (DCE-CT) and a compartment model. They applied this method to evaluation of drug-induced nephrotoxicity in rats. They performed the DCE-CT studies using a total of 36 male Sprague-Dawley rats (n=9 for control and n=27 for treatment). The rats in the drug-treated groups were given 1.8 mg/kg/day of cis-dichlorodiammineplatinum (cisplatin) intraperitoneally every other day twice (n=9), four times (n=9), or six times (n=9). The rate constants for the transfer of the contrast agent (CA) from the intravascular space to the renal corpuscle and tubular space via glomerular filtration (K1), outflow of the CA from the renal tubules (k2), and the fraction of blood volume (f) were estimated from the DCE-CT data, and their functional images were generated using the linear least squares method. When estimating the above parameters, the partial volume effect (PVE) on the arterial input function was corrected using a calibration curve obtained by phantom experiments. The endogenous creatinine clearance (Ccr) was also measured for comparison. The K1 images became lower and more heterogeneous and the K1 values decreased significantly with increasing cisplatin injection number (3.20+/-0.73, 2.49+/-0.75, 1.80+/-0.36, and 1.27+/-0.47 ml/ml/min for control, two-, four-, and six-times treated groups, respectively). When the PVE was not corrected, the K1 values were overestimated by 15+/-3% as compared with the case when the PVE was corrected. There was a good correlation between K1 and Ccr (r=0.903 and 0.901 for cases with and without correction of PVE, respectively). In conclusion, the authors' method using DCE-CT appears to be useful for quantitatively evaluating the extent of renal dysfunction such as renal damage due to drug-induced nephrotoxicity.
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