This prospective study was reviewed and approved by the institutional review board at Samsung Changwon Hospital (Changwon, Korea), and written informed consent was obtained from all participants. We performed 128-slice MDCT scans in 62 cirrhosis or chronic hepatitis patients (52 men and 10 women) at least twice using contrast medium with 350 mg/mL (group A) and 400 mg/mL (group B) iodine concentrations from July 2011 to June 2013 for multiple dysplastic nodules or suspicious malignant nodules on ultrasound, increased serum α-fetoprotein levels and poor sonic window due to body habitus. The patients were allocated prospectively and randomly to one of two groups using the closed envelope method (31 sealed envelopes contained a paper labeled “350 to 400 mg I/mL group” and 31 envelopes contained a paper labeled “400 to 350 mg I/mL group”). Each patient selected one sealed envelope. Patients who selected the 350 to 400 mg I/mL group received initial 128-slice scans using 350 mg I/mL contrast media and follow-up scans with 400 mg I/mL contrast media. Conversely, patients who selected the 400 to 350 mg I/mL group underwent scans using 400 mg I/mL contrast media initially and then follow-up scans with 350 mg I/mL contrast media. We then compared the effect of different iodine concentrations using the same iodine dose in the same patients on hepatic enhancement and image quality. The exclusion criteria were as follows: (1) patients who received hepatic resection or hepatic interventional procedures (transcatheter arterial chemoembolization, percutaneous alcohol injection or radiofrequency ablation) between the two MDCT examinations with possible alteration of the hepatic and portal perfusion in liver; (2) patients with a history of iodine contrast hypersensitivity, renal failure, congestive heart failure (CHF), bronchial asthma or hyperthyroidism and; and (3) patients whose weight change was more than 5% between the MDCT examinations. Four patients with renal failure and three patients with CHF were excluded from the study. Five patients were lost to follow-up. Of the remaining 50 patients, 44 were male (88.0%) and six were female (12.0%). The mean age ± standard deviation at the time of the initial MDCT examination was 64.18 ± 11 years (age range, 40 to 88). The mean weight was 64.8 ± 10.9 kg (range, 48 to 104), and the time interval between the two MDCT examinations was 111.06 ± 45.92 days (range, 57 to 271; median, 97). The patient characteristics are shown in Table 1.

For the initial and follow-up examinations, patients received 120 mL intravenous (IV) contrast medium with 350 mg/mL iomeprol (Iomeron 350, Bracco Imaging, Milan, Italy) or 105 mL IV contrast medium with 400 mg/mL iomeprol (Iomeron 400, Bracco Imaging) using the same MDCT protocol. Iomeprol is a non-ionic monomeric contrast medium. Iomeprol of 350 and 400 mg/mL has an osmolality of 620 and 730 mOsmol/kg, respectively and a viscosity of 7.5 and 12.6 mPa.s at 37°C, respectively. All examinations were performed using the same MDCT scanner (Somatom Definition AS⁺, Siemens Medical Solutions, Forchheim, Germany) with 0.6 × 64-beam collimation, 120 kVp, 210 mAs, 0.5-second gantry rotation speed, 26-mm per rotation table speed, and 5-mm section thickness and interval. Before the examinations, patients were instructed to hold their breath to avoid motion artifacts. Scans were performed from the top of the liver in the cephalocaudal direction. Contrast medium (warmed to body temperature) was administered using a dual-power injector (Medrad, Indianola, PA, USA) at a rate of 3.0 mL/sec, followed by a 20-mL saline flush at the same rate through a 20-gauge IV catheter in the antecubital vein. Total iodine loads were 42 g for the 350 mg I/mL contrast media and 42 g for the 400 mg I/mL contrast media. Acquisition of the hepatic arterial phase was bolus-triggered after the attenuation value reached 100 Hounsfield units (H) in the thoracic aorta. The scan delay for the portal venous phase was 35 seconds after the start of the arterial phase acquisition and the equilibrium phase was 105 seconds after the start of the portal phase acquisition.

After image acquisition, attenuation values for the abdominal aorta, hepatic parenchyma, and portal vein were measured by radiologists (YGS and BGJ) with 14 and 3 years of radiology experience, respectively, using a 1.0 to 2.0 cm² circular region-of-interest cursor in unenhanced scans and in the three phases of contrast-enhanced scans. Measurements from the two radiologists were averaged.

For assessment of hepatic parenchyma, region-of-interest measurements were performed in eight areas per liver, as specified in Couinaud’s segmental classification. The mean attenuation value was calculated by averaging all measurements in each phase. When comparing anatomic structures (branches of the hepatic artery, portal vein and hepatic vein and shape of the pancreas, spleen, ribs, and vertebral bodies for each patient) an attempt was made to maintain a constant region of interest between initial and follow-up examinations. Visible hepatic and portal vessels, bile ducts, calcifications, possible hepatic lesions and regions of posttreatment changes were excluded from region-of-interest areas.

In the abdominal aorta, attenuation values were measured at the porta hepatis level, lower hepatic angle and top of the diaphragm. The results were averaged for each phase.

In the portal vein, attenuation values were measured at two areas where the main portal vein was clearly visible. Results were averaged in the portal and equilibrium phase.

Changes in attenuation of these structures were calculated by subtracting attenuation values of contrast-enhanced images obtained during each phase from corresponding baseline values on unenhanced images. In the arterial, portal and equilibrium phases, liver-to-aorta contrast was also evaluated by calculating the difference in attenuation values between the liver and aorta. To compare the adequacy of contrast enhancement between the two iodine concentrations, differences in attenuation values of hepatic parenchyma during the arterial, portal and equilibrium phases, as compared with pre-contrast images, were classified into the following grades: 3, fine (mean increase > 50 H); 2, moderate (mean increase, 30 to 50 H); and 1, insufficient (mean increase < 30 H).

Two radiologists (YGS and BGJ, with 14 and 3 years of radiology experience, respectively) without prior knowledge of the injection protocol, independently assessed the image qualities of the contrast-enhanced scans. All images were analyzed on a picture archiving and communications system (PACS-Marosis, Infinitt, Seoul, Korea). The radiologists visually scored the degree of vascular and hepatic enhancement using the following 4-point scale: 4, excellent (very good contrast between the hepatic parenchyma and hepatic vessels, with clear visualization of the peripheral vascular branches and excellent overall image quality); 3, good (good contrast between the hepatic parenchyma and hepatic vessels and adequate image quality; 2, fair (insufficient contrast between the hepatic parenchyma and hepatic vessels); and 1, poor (little contrast between the hepatic parenchyma and hepatic vessels). The measurements made by the two radiologists were averaged.

Results are presented as mean ± standard deviation (range). Paired Student t test or analysis of variance was used to compare outcome variables between contrast media containing 350 or 400 mg I/mL. All statistical analyses were performed using PASW version 18.0 (SPSS Inc., Chicago, IL, USA). Statistical significance was accepted at p < 0.05. The sample size was calculated based on a 5% significance level and 80% statistical power by the GPOWER program.