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Gastrointestinal Imaging |
1 From the Department of Radiology, Charité Medical University Center, Campus Virchow Clinic, Humboldt University, D-13344 Berlin, Germany (E.L.H., T.J.V., W.P., J.B., R. Felix); the Department of Radiology, St.-Hedwig-Hospitals of Berlin, Germany (R. Felfe); and Schering, Berlin, Germany (W.C.). Received August 4; revision requested September 24; revision received November 24; accepted December 7. Address correspondence to E.L.H. (e-mail: elh@charite.de).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: One hundred two patients (64 men, 38 women) with neoplastic (n = 85) and nonneoplastic focal lesions (n = 17) were prospectively assigned to biphasic injection group A or B and received 180 mL of iopromide containing 370 or 300 mg of iodine per milliliter, respectively, during spiral CT. Comparison included assessment of quantitative and qualitative parameters.
RESULTS: Hepatic time-attenuation curves and mean hepatic enhancement in the portal venous phase and aortic time-attenuation curves in both arterial and portal venous phases were statistically superior in group A compared with group B. There was no significant difference in the mean enhancement in all lesions in either group. In contrast, among patients with hepatocellular carcinoma, mean contrast enhancement in lesions in the arterial phase was significantly superior in group A compared with group B. Blinded readers classified hepatic attenuation and lesion visibility as very good and as improved significantly more often in group A than in group B.
CONCLUSION: A decrease in iodine concentration significantly affects aortic and hepatic contrast enhancement and may impair the detectability of focal liver lesions during biphasic spiral CT.
Index terms: Aorta, CT, 981.12911, 981.12912, 981.12914, 981.12915 • Computed tomography (CT), contrast media, 761.12112, 761.12114 • Computed tomography (CT), helical, 761.12115 • Contrast media, comparative studies • Iodine and iodine compounds • Liver, CT, 761.12111, 761.12112, 761.12114, 761.12115 • Liver neoplasms, 761.312, 761.319, 761.321, 761.323 • Liver neoplasms, secondary, 761.332
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Previously, it has been hypothesized that abdominal spiral CT with a rapid scanning time and with volume acquisition during a single breath hold may allow for a reduction in the volume of contrast material and in the iodine concentration used (11). Thus, the use of this method may lead to a substantial cost reduction without a compromise in diagnostic sensitivity or specificity.
Since the majority of hepatic tumors are hypoattenuating compared with hepatic parenchyma, image acquisition during the portal venous phase has usually been considered sufficient. However, hypervascularized hepatic tumors, including hepatocellular carcinoma (HCC) or metastatic lesions from some solid tumors (eg, melanoma, breast cancer, neuroendocrine tumors, adrenal carcinoma, or renal cell carcinoma), may be isoattenuating and might not be depicted on portal venous phase images. Therefore, a more recent development in spiral CT with the use of a so-called biphasic or dual-phase technique (ie, arterial and portal venous phases) exploits the short "temporal window" that allows scanning during arterial and portal venous phases with improved sensitivity for hypervascular hepatic lesions (12–16).
The aim of this study was to assess the influence of iodine concentration on hepatic enhancement and lesion detectability at biphasic spiral CT.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Excluded patients were those with known or suspected hypersensitivity to iodinated contrast material, known severe renal impairment or serum creatinine levels of greater than 2.0 mg/dL (176.8 µmol/L), known history of asthma, evidence of hyperthyroidism, or severe hypertension or congestive heart failure. Also excluded were pregnant or lactating women and patients who were clinically unstable and whose clinical course during the observational period was unpredictable. In addition, patients who had decompensated heart failure or severe cardiac rhythm disturbances, severe cirrhosis or diffuse hepatic metastases (more than three lesions), or Wilson disease and hemochromatosis were excluded. Also excluded were patients who had received any investigational drug during the 30 days prior to this study, those who were unable to complete the examination for various reasons, those with mental retardation, those for whom a clear medical history was not available, and those who had already been examined in this study.
The study received institutional review board approval, and written informed consent was obtained from all patients before their entry into this study.
The CT protocol is presented in Table 2; examinations were performed by using a Somatom Plus unit (Siemens, Erlangen, Germany) and a biphasic spiral technique with a 1-second gantry rotation period, 120 kV, and 165 mAs. During scanning, all patients were instructed to hold their breath to avoid motion artifacts. Examinations were started at the top of the liver in a cephalocaudal direction and included nonenhanced and contrast-enhanced (arterial and portal venous phase) scanning.
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Contrast material was intravenously administered by using a power injector (XD 5500; Ulrich, Ulm, Germany) through a 20-gauge intravenous catheter placed into an antecubital vein. Arterial phase scanning was started with a 15-second delay after the beginning of the injection of contrast material (volume, 100 mL; flow, 4 mL/sec). The section thickness was 5 mm, and the table increment was 5 mm. Overlapping transverse images were reconstructed every 3 mm. Portal venous phase scanning was started with a 70-second delay after the beginning of the injection of contrast material (volume, 80 mL; flow, 1 mL/sec). The section thickness was 8 mm, and the table increment was 8 mm. Transverse images were reconstructed every 8 mm.
Histopathologic specimens were obtained in 83 patients at percutaneous hepatic biopsy or surgery (tumor resection or intraoperative biopsy), and clinical-radiologic diagnoses of unambiguous benign lesions or extensive malignant tumors were made in 19 patients. In patients with multiple lesions, a biopsy was performed in one lesion. At CT, all lesions with an appearance identical to that of the biopsy lesion were considered to have the same diagnosis as that of the biopsy lesion.
In the 102 patients, final diagnoses were malignant and nonmalignant lesions; 85 and 17 patients had a total of 136 malignant and 26 nonmalignant lesions, respectively. Malignant lesions included metastases of colorectal cancer (n = 56), metastatic lesions of other primary tumors (breast cancer, n = 6; ovarian cancer, n = 4; cholangiocarcinoma, n = 4; renal cell carcinoma, n = 2; schwannoma, n = 3; leiomyosarcoma, n = 2; thyroid cancer, n = 2; gallbladder carcinoma, n = 2; adrenal carcinoma, n = 2; pancreatic cancer, n = 2; and cancer of unknown primary tumor, n = 2), HCC (n = 46), and cholangiocarcinoma (n = 3). Benign lesions included hemangioma (n = 8), adenoma (n = 1), cyst (n = 7), abscess (n = 4), regenerative nodule (n = 3), and focal steatosis (n = 3).
Quantitative Assessment of Hepatic and Vascular Enhancement
Attenuation values were measured in the hepatic parenchyma and aorta at both nonenhanced and arterial and portal venous phase CT in each protocol group. Attenuation values were obtained by using 0.5–2.1-cm2 circular regions of interest. An attempt was made to attain a constant region of interest of at least 2 cm2 in the liver and 1 cm2 in the aorta. Enhancement values were used to generate hepatic and aortic time-attenuation curves. The attenuation values in the hepatic parenchyma were measured, excluding visible hepatic and portal vessels, bile ducts, and artifacts. The aorta was measured once in its central position. In normal hepatic parenchyma, two measurements were performed in the right and left lobes, and the results were averaged. The regions of interest were placed by one author (R. Felfe).
In addition, quantitative analyses of nonenhanced and contrast-enhanced images were performed in relevant lesions in representative solid portions of the tumor. Regions with cystic components or capsules were excluded to minimize partial volume effects.
For the evaluation of contrast-enhanced images, the change in attenuation (in Hounsfield units) was calculated by subtracting attenuation values of the contrast-enhanced images obtained during the arterial and portal venous phases from the corresponding baseline values on the nonenhanced images. Mean hepatic enhancement was measured on 19 and 12 sections, respectively, during the arterial (15–37-second) and portal venous (70–92-second) phases. To overcome small intersection variations during the arterial and portal venous phases, mean hepatic enhancement was additionally calculated with groups of two or three sections that corresponded to delay times of approximately 18–20, 26–28, 34–36, 70–72, 80–82, and 90–92 seconds after the beginning of the bolus injection.
Distribution analyses were performed in individual groups by using the Kolmogorow-Smirnow test. If the distribution of the mean change in attenuation and percent enhancement appeared normal, a one-sided t test was applied for a pairwise comparison between the two groups with the two different concentrations of contrast agent. Nonparametric, two-independent-sample tests (Mann-Whitney U test) were used to analyze values that were not normally distributed. Results were considered to be statistically significant if the P values was less than .05.
Mean change in the attenuation of the aorta was classified as very good (mean increase, >80 HU), moderate (mean increase, 40–80 HU), or insufficient (mean increase, <40 HU). Mean change in the attenuation of hepatic parenchyma was classified as very good (mean increase, >40 HU), moderate (mean increase, 20–40 HU), or insufficient (mean increase, <20 HU).
Qualitative Assessment of Focal Liver Lesions
At retrospective review, findings at CT examination were analyzed by two radiologists (R. Felfe, E.L.H.) in consensus. The size, location, and maximum number of lesions were documented on nonenhanced and contrast-enhanced (arterial and portal venous phase) images. In addition, the contrast pattern of the lesions (ie, hyperattenuating, hypoattenuating, or isoattenuating compared with adjacent hepatic parenchyma) on nonenhanced and contrast-enhanced images was categorized. In addition, two blinded readers (J.B., W.P.) separately compared the enhanced arterial and portal venous phase images with the nonenhanced images, in a newly randomized order, regarding the visualization of liver lesions. Diagnostic visualization was defined as improved, unchanged, or worsened.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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Qualitative Assessment of Focal Liver Lesions
Evaluation of all lesions (n = 162) revealed hyperattenuating (n = 51), hypoattenuating (n = 98), and isoattenuating (n = 13) contrast patterns during the arterial phase. During venous-phase scanning, 26, 125, and 11 lesions were hyperattenuating, hypoattenuating, and isoattenuating, respectively. Qualitative evaluation of lesion visualization by the two blinded readers revealed improved visualization in 65 (84%) of 77 lesions in group A (370 mg/mL) when images obtained in the arterial phase were compared with those obtained before contrast enhancement. In contrast, visualization of only 58 (68%) of 85 lesions improved in group B (300 mg/mL). Evaluation of images obtained in the portal venous phase revealed improved visualization in 72 (94%) of 77 lesions in group A versus 67 (79%) of 85 lesions in group B.
Quantitative Assessment of HCC Focal Liver Lesions
Arterial phase assessment demonstrated a mean increase in lesion attenuation of 34 HU in group A (n = 18; 25 lesions) and 21 HU in group B (n = 15; 21 lesions), with a significantly superior (P < .05) increase in attenuation in group A. In contrast, no significant difference in lesion enhancement was documented during portal venous phase evaluation.
Qualitative Assessment of HCC Focal Liver Lesions
During the arterial phase, evaluation of HCCs demonstrated 32 lesions with hyperattenuating contrast patterns, 11 lesions with hypoattenuating contrast patterns, and three lesions with isoattenuating contrast patterns. Detectability of HCC by two blinded readers was assessed as improved on arterial phase images versus precontrast images in 22 (88%) of 25 and 14 (67%) of 21 of HCC lesions in groups A (iodine concentration, 370 mg/mL) and B (iodine concentration, 300 mg/mL), respectively. Lesion visualization on portal venous phase images versus precontrast images was classified as improved in 21 (84%) of 25 lesions in group A and in 14 (67%) of 21 lesions in group B (Table 5).
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Qualitative Assessment of Metastatic Focal Liver Lesions
Evaluations conducted during the arterial and portal venous phases, respectively, revealed six and six hyperattenuating lesions, 72 and 78 hypoattenuating lesions, and nine and 11 isoattenuating lesions. Assessment of lesion visualization during the portal venous phase was classified as improved in 43 (96%) of 45 and 34 (81%) of 42 metastatic lesions in groups A and B, respectively (Table 5).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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As demonstrated herein, our results indicate that the injection of contrast material with a higher iodine concentration results in a significantly superior enhancement. Thus, both aortic time-attenuation curves and hepatic enhancement attained during the portal venous phase revealed a significantly higher enhancement in the group A (higher iodine concentration) compared with group B (lower iodine concentration) (Figs 1, 2; Tables 3, 4). Analyses of aortic enhancement during the arterial phase revealed that the maximum aortic attenuation occurred, on average, in the middle of our acquisition of data in the arterial phase in all patients. However, the mean maximum aortic enhancement during the arterial phase was significantly (P < .05) lowered when the iodine concentration was decreased from 370 to 300 mg/mL. It must be noted that all attenuation measurements were obtained in a blinded fashion.
Previously, the time to peak hepatic enhancement was demonstrated to depend on the injection rate, and a shorter time to peak enhancement was observed when faster injections rates were used. In addition, faster injection rates have been demonstrated to increase maximum aortic enhancement without a decrease in the time of the arterial phase itself (10). In their study, Kim et al (10) defined the start of the arterial phase as the time when aortic enhancement reached 100 HU and defined the end of the arterial phase as the time when hepatic enhancement reached 20 HU. On the other hand, in the study described herein in which identical injection rates and overall contrast material volumes were used, the iodine concentration appeared to have no substantial effect on the duration of the arterial phase in both protocol groups.
Primary hepatic tumors and hypervascular metastases receive most of their blood supply from the hepatic arteries; this knowledge led to the design of spiral CT with biphasic technique (16–20). The biphasic approach exploits the fact that, during arterial scanning, no substantial hepatic enhancement occurs, whereas the arterial blood supply of hypervascularized hepatic neoplasms demonstrate an early enhancement that results in increased lesion-to-liver contrast. Therefore, it has more recently been suggested that hypervascular hepatic tumors such as hypervascular HCC or hypervascular metastases are best depicted during hepatic arterial peak enhancement (10,16–20).
In the randomized study described herein, we found superior aortic enhancement during the arterial phase with the higher iodine concentration, which potentially increased the maximum enhancement of hypervascularized hepatic lesion fed by the hepatic artery. Here, arterial phase evaluation in groups A and B demonstrated 15 and nine patients with 21 and 11 hypervascular HCC lesions, respectively; a total of 11 hypervascular lesions were seen during only the arterial phase. In addition, although we observed significantly superior lesion enhancement in the hypervascular HCCs in the subgroups with the higher iodine concentration, direct quantitative comparison of lesion enhancement is subject to interindividual variability and, thus, is less meaningful in the determination of contrast material parameters.
With the subsequently increased supply of contrast material from the portal vein, higher hepatic contrast enhancement can be observed. As was demonstrated here, after a delay of 70–92 seconds, the mean hepatic enhancement curves became parallel. However, while the portal venous phase was characterized by a significant increase in hepatic enhancement in both protocol groups, which had identical volume and flow parameters, the hepatic parenchyma showed an iodine concentration–dependent, significantly superior increase in hepatic enhancement in the 370 mg/mL group versus the 300 mg/mL group. Thus, hypodense liver lesions are potentially better depicted with the higher concentration.
When qualitative data were compared with quantitative results, it appeared that the higher iodine concentration was rated as being superior to the lower concentration. We are aware that subjective assessment is often not reliable; however, in this study, the higher concentration was better than the lower concentration in most categories.
In summary, the results of the spiral CT protocol described in this trial indicate that a higher iodine concentration of contrast material increases hepatic arterial enhancement during the arterial phase and increases hepatic enhancement during the portal venous phase; thus, we conclude that a higher iodine concentration yields a higher diagnostic output at hepatic spiral CT in both hyper- and hypovascularized hepatic lesions. Undoubtedly, a reduction in both iodine concentration and contrast material volume may result in cost savings. However, the potential economic benefits may be compromised by impaired diagnostic efficacy and the costs of subsequent use of further diagnostic modalities or of wrong therapeutic strategies. Further studies are warranted to substantiate the cost-benefit ratios of applicable spiral CT protocols.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, E.L.H., T.J.V., R. Felix; study concepts and design, E.L.H., T.J.V.; definition of intellectual content, E.L.H., T.J.V.; literature research, R. Felfe; clinical studies, E.L.H., T.J.V., R. Felfe; data acquisition, E.L.H., R. Felfe; data analysis, J.B., W.P., R. Felfe; statistical analysis, R. Felfe; manuscript preparation, E.L.H., R. Felfe; manuscript editing, E.L.H., T.J.V., R. Felfe; manuscript review, E.L.H., T.J.V., W.P., W.C., R. Felix.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
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; iodine concentration, 370 mg/mL) and B (•; iodine concentration, 300 mg/mL). Note the significantly superior mean maximum aortic attenuation in group A.
