| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Contrast Media |
1 From the Department of Radiology, Kinki University School of Medicine, 2–23 Ono-higashi, Osaka-Sayama, Osaka 589-8511, Japan (K.A., M.I., Y. Yagyu, M.W., T.S., S.N., R.K., Y.N.); and Department of Radiology, Kumamoto University Graduate School of Medical Science, Kumamoto, Japan (Y. Yamashita). Received October 10, 2003; revision requested December 30; revision received February 12, 2004; accepted March 26. Address correspondence to K.A.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. One hundred eighty-six patients were studied, and 67 patients with hypervascular HCC were identified. Ninety-four patients were assigned to receive iohexol 350 (mg iodine per milliliter) with protocol A; 92, iohexol 300 with protocol B. In both protocols, iohexol with same iodine load per weight (518 mg/kg) was administered with same injection duration (25 seconds). Multiphase CT scanning was started 10, 20, 50, and 180 seconds after the trigger (threshold level set at increase of 100 HU over baseline CT number of aorta). Enhancement of aorta and liver was measured in 186 patients. Tumor-to-liver contrast was measured in 67 patients with hypervascular HCC. Statistical analysis was performed with Mann-Whitney U test.
RESULTS: Medians of aortic enhancement during four phases were 325, 185, 112, and 69 HU with protocol A. Corresponding values were 344, 266, 121, and 73 HU with protocol B. During all phases, aortic enhancement was significantly higher with protocol B (P = .046, P < .001, P < .001, and P = .002). Hepatic enhancement during four phases was 6, 21, 48, and 34 HU with protocol A. Corresponding values were 3, 17, 47, and 35 HU with protocol B. Hepatic enhancement was significantly higher with protocol A during first and second phases (P < .001 for both), although there was no significant difference between protocols during third and fourth phases (P = .778 and P = .178, respectively). Medians of tumor-to-liver contrast during four phases were 22, 34, 0.5, and –1.1 HU with protocol A. Corresponding values were 23, 45, 0, and –8.6 HU with protocol B. Tumor-to-liver contrast was significantly higher with protocol B during second phase (P = .049), although there was no difference between protocols during other phases.
CONCLUSION: When total iodine dose was adjusted to body weight and injection duration was fixed, rapid administration of moderate concentration of contrast material was more effective for depiction of hypervascular HCC than was high concentration of contrast material.
© RSNA, 2004
Index terms: Aorta, CT, 56.12112, 56.12114, 56.12115 • Computed tomography (CT), contrast media • Liver, CT, 761.12112, 761.12114, 761.12115 • Liver, diseases, 761.323 • Liver neoplasms, CT, 761.12112, 761.12114, 761.12115
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
The purpose of this study was therefore to prospectively evaluate aortic and hepatic enhancement and depiction of hypervascular HCC between two nonionic contrast materials with moderate (300 mg I/mL) and high (350 mg I/mL) iodine concentrations when administered with the same iodine dose per body weight and the same injection duration at multi–detector row helical CT.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
-fetoprotein or des-gamma-carboxy prothrombin); and (c) absence of renal failure (serum creatinine level of more than 1.5 mg/dL [114 mol/L]) or presence of a contraindication for iodinated contrast material. All patients who were enrolled in this study satisfied all of these three criteria. Two patients were excluded from the study because of extravasation of contrast material. One patient was excluded because the scan timing deviated from the scanning protocol. Two patients with extensive arterioportal shunts, four patients with numerous tumors throughout the whole liver, and five patients with tumor thrombi in the central portal vein or central hepatic vein were excluded because hemodynamics of the liver might be altered in these patients. A total of 186 patients were included for assessment, which consisted of 135 men and 51 women aged 40–94 years (mean, 67.1 years). The age range was 43–94 years (mean, 66.3 years) for male patients and 40–83 years (mean, 67.1 years) for female patients. There was no significant difference in age between male and female patients according to results of the Student t test (P = .57). This study received approval from the review board of the Kinki University School of Medicine. Informed consent to participate in the study was obtained from all patients.
Among the 186 patients, 147 had solitary or multiple HCC nodules. A definite diagnosis of HCC was assigned by means of surgery (n = 3) or percutaneous liver biopsy (n = 15) or by means of substantially increased levels of -fetoprotein or des-gamma-carboxy prothrombin at follow-up CT that showed the progression of hepatic tumors (n = 129). Among 147 patients with HCC, 128 had received treatment for hepatic cancer more than 3 months before CT examination: 61 received radiofrequency ablation therapy, 46 received transarterial chemoembolization, two received partial segmentectomy of the liver, 16 received radiofrequency ablation and transarterial chemoembolization, one received transarterial chemoembolization and percutaneous microwave coagulation therapy, one received transarterial chemoembolization and percutaneous ethanol infusion therapy, and one received transarterial chemoembolization and partial segmentectomy of the liver.
Among 147 patients with HCC, 67 had hypervascular tumors. We defined hypervascular tumors as tumors that showed an enhancement of 10 HU higher than that of the hepatic parenchyma in the first or second phase of contrast material–enhanced scanning. The 67 patients consisted of 51 men and 16 women aged 40–94 years (mean, 68.7 years). The mean body weight of patients with hypervascular HCC was 59.2 kg ± 8.5 (standard deviation) (range, 38–88 kg).
Contrast Material Infusion and CT Protocols
Iohexol (Omnipaque; Daiichi Pharmaceutical, Tokyo, Japan) was administered with two different iodine concentrations (350 mg I/mL for protocol A and 300 mg I/mL for protocol B) via insertion of 18-gauge IV catheters into an antecubital vein and use of a power injector (Autoenhance A-250; Nemoto Kyorindo, Tokyo, Japan). Heiken et al (2) and Brink et al (3) reported that a maximum hepatic enhancement of at least 50 HU is needed to perform high-diagnostic-quality hepatic CT and that 521 mg of iodine per kilogram of body weight is necessary to achieve this level of hepatic enhancement. Therefore, a contrast material dose of 518 mg of iodine per patient body weight was administered in all patients. This dose corresponds to about 1.7 mL/kg contrast material with an iodine concentration of 300 mg I/mL and 1.5 mL/kg contrast material with an iodine concentration of 350 mg I/mL. Consequently, the volume of the contrast material per body weight used for protocol B was 1.17 times larger than that for protocol A.
The injection duration of the contrast material was 25 seconds with both protocols. The reason we adopted 25 seconds as an injection duration was that enough aortic enhancement (about 300 HU) was achieved in most patients by using an injection protocol with an iodine dose of 518 mg/kg and injection duration of 25 seconds (16). The mean injection rate was 3.6 mL/sec (range, 2.3–5.3 mL/sec) in group A and 4.0 mL/sec (range, 2.8–5.4 mL/sec) in group B. Injection of contrast material was not followed by a flush with saline solution.
Among 186 patients, the first 94 were assigned to protocol A, and the subsequent 92 were assigned to protocol B. The age range of patients that received protocol A was 40–94 years (mean, 67.6 years), and the age range of patients that received protocol B was 44–82 years (mean, 66.6 years). There was no significant difference in age between patients that received the two protocols according to results of the Student t test (P = .73). The mean body weight of patients that received protocol A was 59.6 kg ± 9.7 (range, 39–89 kg), and the mean body weight of patients that received protocol B was 58.2 kg ± 8.0 (range, 41–79 kg). There was no significant difference in body weight between patients that received protocols A or B according to results of the Student t test (P = .27). The 94 patients that received protocol A consisted of 68 men and 26 women, and the 92 patients that received protocol B consisted of 67 men and 25 women. There was no significant difference in sex distribution between patients that received protocols A or B according to results of the 
2 test (P = .73).
Among 67 patients with hypervascular HCC, 33 received iohexol 350 with protocol A, and 34 received Iohexol 300 with protocol B. There was no significant difference in the distribution of patients with hypervascular HCC between protocols A and B according to results of the 2 test (P = .72).
All patients were scanned by using a four–detector row CT scanner (Aquilion; Toshiba Medical Systems, Tokyo, Japan) with the following parameters: 0.5-second rotation time; 5.0-mm detector row width; 7.0-mm section thickness and image interval; 0.86 helical pitch (beam pitch); 40-cm field of view; and 120 kV and 300 mAs. Image reconstruction was performed in a 25–35-cm display field of view, depending on the patient’s physique. These scanning parameters were the same as those used in routine clinical practice in our hospitals. All helical scans were started at the top of the liver in a cephalocaudal direction. Unenhanced and four-phase contrast-enhanced helical scans of the whole liver were obtained. Patients were instructed to hold their breath, with tidal inspiration during scanning.
Four-phase contrast-enhanced CT scanning of the liver was performed during the portal venous phase and the equilibrium phase, in addition to double arterial phase scanning as described by Foley et al (19), Murakami et al (20), and Kim et al (21). The automatic bolus tracking program (22) (SureStart; Toshiba Medical Systems) was used to decide the timing of the initiation of first-, second-, third-, and fourth-phase scanning after injection of contrast material. The CT number was monitored by the three radiologic technologists at the level of the L1 vertebral body, and the region of interest (ROI) cursor was placed in the abdominal aorta. The three technologists had 8, 18, and 22 years of experience in abdominal CT. The size of the ROI cursor in the abdominal aorta was 0.8–2.0 cm2. Real-time low-dose (120 kVp, 50 mA) serial monitoring scans were initiated at 10 seconds after the start of injection of contrast material. The trigger threshold level was set at an increase of 100 HU over the baseline CT number of the aorta. First-, second-, third-, and fourth-phase scanning was started at 10, 20, 50, and 180 seconds after the trigger, respectively (Fig 1). First- and second-phase scanning was performed during one breath hold.
|
In the aorta, attenuation values were measured on the image at the level of the main portal vein for each phase, although attenuation values in the aorta were measured at the level of the L1 vertebral body to decide the timing of CT scanning after the injection of contrast material. An attempt was made to maintain a constant ROI area of approximately 1.0 cm2. The actual ROI area ranged from 0.5 to 1.0 cm2. The contrast enhancement in the abdominal aorta for each phase was calculated as the absolute difference in the attenuation values of the aorta (in Hounsfield units) at unenhanced scanning versus each phase of contrast-enhanced scanning.
In the liver, attenuation was assessed in three areas on the image at the level of the main portal vein, and all attenuation values were averaged for each phase. The three areas were the left lobe of the liver and the anterior segment and posterior segment of the right lobe of the liver. An attempt was made to maintain a constant ROI area of approximately 2.0 cm2. The actual ROI area ranged from 0.8 to 2.0 cm2. Visible blood vessels, bile ducts, and artifacts were carefully excluded from the ROI measurements in the hepatic parenchyma. The contrast enhancement in the hepatic parenchyma for each phase was assessed as the absolute difference in the attenuation values of the liver (in Hounsfield units) at unenhanced scanning versus each phase of contrast-enhanced scanning.
In the portal vein, the attenuation values were measured in the main portal vein. An attempt was made to maintain a constant ROI area of approximately 0.5 cm2. The actual ROI area ranged from 0.3 to 0.5 cm2. The contrast enhancement in the main portal vein for each phase was assessed the same way it was in the hepatic parenchyma.
The conspicuity of hepatic tumor can be expressed by the attenuation differences between the hepatic tumor and hepatic parenchyma—that is, the tumor-to-liver contrast (23). Tumor-to-liver contrast was defined as the attenuation of hepatic tumor minus the attenuation of hepatic parenchyma. The tumor-to-liver contrast for each phase of contrast-enhanced scanning was also measured by the radiologist (Y. Yagyu) in 67 patients with hypervascular HCC. Tumor attenuation was assessed in the most enhanced portion of the tumor. An attempt was made to maintain an ROI area of approximately 0.5 cm2. The actual ROI area ranged from 0.3 to 0.5 cm2. The attenuation of the hepatic parenchyma used to calculate the tumor-to-liver contrast was assessed in the normal hepatic parenchyma adjacent to the tumor. An attempt was made to maintain a constant ROI area of approximately 2.0 cm2. The actual ROI area ranged from 0.8 to 2.0 cm2. In patients with fewer than three tumors, tumor-to-liver contrast was calculated for all tumors and averaged. In patients with three or more tumors, tumor-to-liver contrast was calculated for the largest three tumors and averaged.
Statistical Analysis
Contrast enhancement in the hepatic parenchyma, aorta, and portal vein and tumor-to-liver contrast were reported as medians and ranges. Comparison between attenuation values in the aorta, liver, and portal vein and tumor-to-liver contrast values between protocols A and B was performed by using the Mann-Whitney U test. This test was used because the following data sets did not show normal distribution: protocol B for the abdominal aorta in the second phase, protocol A for the liver in the first and second phases, protocol A for the main portal vein in the second phase, protocol A for tumor-to-liver contrast in the first and second phases, and protocol B for tumor-to-liver contrast in the fourth phase.
P < .05 was considered to indicate a statistically significant difference. Statistical analysis was performed with a statistical software package (StatView 5.0; SAS Institute, Cary, NC).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
We reported previously that aortic peak enhancement is higher with contrast material with high iodine concentration (370 mg I/mL) than with moderate concentration (300 mg I/mL) when administrated at the same total iodine dose with an injection duration of 25 seconds for the high-concentration contrast material and 30 seconds for the moderate-concentration contrast material (9). The result of the current study seemed to be contradictory to results of our previous study. Injection duration can be an important factor in the determination of aortic enhancement in the arterial phases, especially when the contrast medium is not injected completely before the start of scanning. In our previous study, the injection duration of 30 seconds for moderate-concentration contrast material may be too long and may justify a lower enhancement in some patients with fast circulation time.
The conspicuity of hypervascular HCC is better with iohexol 300 during the second phase than with iohexol 350. This may be related to the fact that the difference in aortic enhancement between iohexol 300 and iohexol 350 in the second phase was much higher than that during the first phase, though aortic enhancement was higher with iohexol 300 than with iohexol 350 during both the first and second phases.
The best depiction of hypervascular HCC is achieved during the second phase, the so-called late arterial phase (19–21,28–30). Therefore, iohexol 300 may have advantages in the depiction of hypervascular HCC over iohexol 350 when both contrast materials are administered with the same injection duration.
In the liver, enhancement achieved with iohexol 350 was higher than that with iohexol 300 during the first and second phases. However, the difference in enhancement between iohexol 300 and iohexol 350 was only several Hounsfield units and could be considered practically negligible, though statistically significant. There was no statistically significant difference in enhancement during the third and fourth phases. Since sufficient time had passed for contrast material retained in the "dead space" to be pushed out to the blood flow, there was no difference in the amount of contrast material delivered to the liver between iohexol 300 and iohexol 350.
In a uniphasic injection protocol for contrast material, if the injection duration is fixed, the time to the peak of the density-time curve after arrival of contrast material in the aorta and the aortic peak enhancement tend to become constant in any patient (31). In patients with hypervascular HCC, blood is usually supplied to tumors from the hepatic artery, which is a branch of the aorta. Therefore, with the protocol in which contrast material is administered with a fixed injection duration, CT scanning can be performed with the same scan timing in all patients. Thus, if CT examination of HCC is performed according to the injection protocol with a fixed injection duration, the contrast material with moderate iodine concentration will be effective for depiction of HCC, rather than the high-concentration contrast material. Nevertheless, it remains unclear whether contrast materials with iodine concentration of less than 300 mg I/mL further improve depiction of HCC. Further investigation is required.
Low osmotic pressure is one of the advantages of the contrast material with moderate iodine concentration over that with high concentration, with the exclusion of depiction of hypervascular HCC. Generally, it is indicated that toxic side effects of contrast material are attributable to hyperosmolarity (32). Accordingly, the contrast material with moderate iodine concentration is expected to be associated with toxic side effects less frequently than with high-concentration contrast material.
The moderate-concentration contrast material has a disadvantage in that it has to be administered at a more rapid injection rate. The faster injection rate increases the risk of extravasation of contrast material, though previous reports suggest that there is no correlation between the injection rate and the incidence of extravasation (33,34).
This study has some potential limitations. First, assignment of patients to protocol A or B was not performed in a randomized manner, though there were no statistically significant differences in the age, sex distribution, body weight, or number of patients with HCC between protocols A and B. Second, this study included patients who underwent transarterial chemoembolization. It cannot be ruled out completely that hepatic blood flow might be affected in such patients, though patients who received any treatment within 3 months before CT examination were excluded. Finally, the results from this study cannot be applied directly to patients without liver damage because this study was performed in patients who had type B or C hepatitis or alcoholic hepatitis.
In conclusion, when total iodine dose was adjusted for body weight, and injection duration was fixed, administration of a moderate concentration of contrast material was more effective for depiction of hypervascular HCC than was administration of a high concentration of contrast material.
|
FOOTNOTES |
|---|
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, K.A., Y.N.; study concepts, K.A.; study design, K.A., M.I.; literature research, K.A., Y. Yamashita; clinical studies, K.A., M.W., T.S., S.N., R.K.; data acquisition, Y. Yagyu; data analysis/interpretation, K.A., Y.N.; statistical analysis, K.A.; manuscript preparation and definition of intellectual content, K.A.; manuscript editing, K.A., Y.N.; manuscript revision/review, K.A.; manuscript final version approval, all authors
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  X. Ma, A. E. Samir, N.-S. Holalkere, and D. V. Sahani Optimal Arterial Phase Imaging for Detection of Hypervascular Hepatocellular Carcinoma Determined by Continuous Image Capture on 16-MDCT Am. J. Roentgenol., September 1, 2008; 191(3): 772 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Fei, X. Du, Q. Yang, Y. Shen, P. Li, J. Liao, and K. Li 64-MDCT Coronary Angiography: Phantom Study of Effects of Vascular Attenuation on Detection of Coronary Stenosis Am. J. Roentgenol., July 1, 2008; 191(1): 43 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. F. Behrendt, A. H. Mahnken, S. Stanzel, P. Seidensticker, E. Jost, R. W. Gunther, and G. Muhlenbruch Intraindividual Comparison of Contrast Media Concentrations for Combined Abdominal and Thoracic MDCT Am. J. Roentgenol., July 1, 2008; 191(1): 145 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yanaga, K. Awai, T. Nakaura, T. Namimoto, S. Oda, Y. Funama, and Y. Yamashita Optimal Contrast Dose for Depiction of Hypervascular Hepatocellular Carcinoma at Dynamic CT Using 64-MDCT Am. J. Roentgenol., April 1, 2008; 190(4): 1003 - 1009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Schindera, R. C. Nelson, S. Mukundan Jr, E. K. Paulson, T. A. Jaffe, C. M. Miller, D. M. DeLong, K. Kawaji, T. T. Yoshizumi, and E. Samei Hypervascular Liver Tumors: Low Tube Voltage, High Tube Current Multi Detector Row CT for Enhanced Detection Phantom Study Radiology, December 1, 2007; 246(1): 125 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.M. Silvennoinen, L.M. Hamberg, L. Valanne, and G.J. Hunter Increasing Contrast Agent Concentration Improves Enhancement in First-Pass CT Perfusion AJNR Am. J. Neuroradiol., August 1, 2007; 28(7): 1299 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Cademartiri, N. R. Mollet, P. A. Lemos, F. Saia, M. Midiri, P. J. de Feyter, and G. P. Krestin Higher Intracoronary Attenuation Improves Diagnostic Accuracy in MDCT Coronary Angiography Am. J. Roentgenol., October 1, 2006; 187(4): W430 - W433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kubo, E. Tadamura, M. Yamamuro, R. Hosokawa, T. Kimura, T. Kita, M. Komeda, and K. Togashi Thoracoabdominal-aortoiliac MDCT angiography using reduced dose of contrast material. Am. J. Roentgenol., August 1, 2006; 187(2): 548 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Schima, R. Hammerstingl, C. Catalano, L. Marti-Bonmati, E. J. Rummeny, F. T. Montero, A. Dirisamer, B. Westermayer, M. Bellomi, D. Brisbois, et al. Quadruple-phase MDCT of the liver in patients with suspected hepatocellular carcinoma: effect of contrast material flow rate. Am. J. Roentgenol., June 1, 2006; 186(6): 1571 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Johnson and E. K. Fishman IV Contrast Selection for MDCT: Current Thoughts and Practice Am. J. Roentgenol., February 1, 2006; 186(2): 406 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. T. Bae, K. Awai, and Y. Yamashita Comparison of Moderate versus High Concentration of Contrast Media Injected at the Same Total Iodine Dose and Fixed Injection Duration * Drs Awai and Yamashita respond: Radiology, August 1, 2005; 236(2): 740 - 741. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
