DOI: 10.1148/radiol.2411051338
(Radiology 2006;241:167-174.)
© RSNA, 2006
Pancreas: Optimal Scan Delay for Contrast-enhanced Multi–Detector Row CT1
Satoshi Goshima, MD, PhD,
Masayuki Kanematsu, MD,
Hiroshi Kondo, MD,
Ryujiro Yokoyama, MS, RT,
Toshiharu Miyoshi, RT,
Hiroki Kato, MD,
Yusuke Tsuge, MD,
Yoshimune Shiratori, MD,
Hiroaki Hoshi, MD,
Minoru Onozuka, PhD,
Noriyuki Moriyama, MD and
Kyongtae T. Bae, MD, PhD
1 From the Departments of Radiology (S.G., M.K., H. Kondo, H. Kato, Y.T., H.H.), Radiology Services (M.K., R.Y., T.M.), and Medical Informatics (Y.S.), Gifu University School of Medicine, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka, Japan (M.O.); Research Center for Cancer Prevention and Screening, National Cancer Center Hospital, Tsukiji, Japan (N.M.); and Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Mo (K.T.B.). Received August 11, 2005; revision requested October 17; revision received November 3; accepted December 1; final version accepted January 10, 2006. Supported in part by the Health and Labour Sciences Research Grants for Third Term Comprehensive Control Research for Cancer.
Address correspondence to S.G.
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ABSTRACT
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Purpose: To prospectively determine optimal scan delays for multiphasic contrast medium–enhanced imaging of the pancreas with multi–detector row computed tomography (CT).
Materials and Methods: This study was approved by an institutional review committee, and patients gave written informed consent. One hundred ninety-one patients underwent three-phase CT of the pancreas after receiving intravenous contrast medium with a fixed duration injection of 30 seconds. Patients were prospectively assigned among four groups with scan delays of 25, 45, and 65 seconds (group 1); 30, 50, and 70 seconds (group 2); 35, 55, and 75 seconds (group 3); and 40, 60, and 80 seconds (group 4). Mean CT numbers of abdominal aorta, spleen, pancreatic parenchyma, superior mesenteric artery and vein, splenic vein, and hepatic parenchyma were measured, and increases in contrast enhancement on enhanced images were assessed. Qualitative analysis was performed with a four-point scale.
Results: Abdominal aorta and superior mesenteric artery enhanced at a mean of 35 seconds from the start of injection (both P < .001). Pancreatic parenchyma enhanced most intensely at 35–45 seconds (P < .001) with a peak enhancement at the mean of 40 seconds. Liver parenchyma enhanced most intensely at 55–65 seconds with a peak at 60 seconds (P < .001). The mean time to peak enhancement was 45 seconds for the splenic vein and 55 seconds for the superior mesenteric vein. Qualitative results were in good agreement with quantitative results (both P < .001).
Conclusion: With the injection protocol used in this study, optimal scan delays for imaging the pancreas were 30–35 seconds for the abdominal aorta and the superior mesenteric artery, 35–45 seconds for the pancreas, 45 seconds for the splenic vein, and 55 seconds or later for the liver.
© RSNA, 2006
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INTRODUCTION
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Contrast medium–enhanced dynamic computed tomography (CT) of the pancreas has been widely accepted for depiction and preoperative staging of pancreatic neoplasms (1–14). Because of its capability to deliniate tumor extension to adjacent peripancreatic structures, CT imaging of the pancreas has proved to be highly specific for the determination of nonresectability of tumors (5,6). To maximize the conspicuity of pancreatic tumors, CT images of the pancreas are commonly acquired at different phases of contrast enhancement with a single bolus of intravenous contrast medium (15–17). A multiphasic CT technique allows evaluation of tumors and adjacent regions at different enhancement times and thus improves the delineation of tumors and local extent.
At multi–detector row CT, a scan at each phase can be acquired within a few seconds, which allows completion of the entire examination while a substantial amount of contrast medium circulates and remains in the vascular and visceral parenchyma. Thus, multi–detector row CT is well suited for multiphasic imaging of the pancreas. The fast scanning capability of multi–detector row CT, however, is a mixed blessing for contrast enhancement. Appropriate scan timing to achieve adequate contrast enhancement at each phase is more difficult and critical with multi–detector row CT than with single–detector row CT. Inappropriately timed imaging will result in a reduction of tumor conspicuity.
Several multiphasic CT protocols of pancreatic imaging have been described in the literature (15–17). These protocols were developed with single–detector row CT and were based on fixed injection rates that ranged from 2 to 6 mL/sec. They may not be optimal for multi–detector row CT. The use of a fixed duration of injection may simplify the determination of optimal scan delays, because the injection duration is the most important factor affecting the time to peak contrast enhancement (18). Furthermore, to achieve a consistent degree of contrast enhancement, the amount of contrast medium administered for CT imaging should be adjusted to the patient's body weight (19). We hypothesized that CT imaging protocols of the pancreas with a fixed injection duration and an amount of contrast medium adjusted to body weight would allow systematic investigation of the effect of scan delays on contrast enhancement of the pancreas, peripancreatic structures, and the liver. Thus, the purpose of our study was to prospectively determine optimal scan delays for multiphasic, contrast-enhanced imaging of the pancreas with multi–detector row CT.
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MATERIALS AND METHODS
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Patients
This study was approved by our institutional review committee (Gifu University School of Medicine), and patients gave written informed consent. During a 7-month period (May to November 2003), 219 consecutive patients suspected of having abdominal disease and who had previously undergone ultrasonography, magnetic resonance imaging, or laboratory evaluation, underwent contrast-enhanced CT of the upper abdomen in our department. Imaging examinations were performed for clinical diagnosis.
Twenty-eight patients were excluded. Six of these patients were excluded because of technical failure related to contrast material injection, breath holding, or mechanical malfunction during the CT examination. The other 22 patients (10 with total splenectomy, five undergoing transarterial chemotherapy for malignant hepatic tumors, three with a biliary stent, and four with innumerable hepatic metastases) were excluded because of a concern that the pancreatic and hepatic vascular alterations from innumerable hepatic metastases, extensive surgery, or artifacts might have adversely affected the contrast enhancement evaluation. These exclusion criteria, however, were subjective. The remaining 191 patients (124 men, 67 women; age range, 39–83 years; mean age, 65.0 years) constituted the study sample.
In these 191 patients, the clinical diagnoses were gastric cancer (n = 26), colorectal cancer (n = 25), hepatocellular carcinoma (n = 17), lung cancer (n = 12), uterine cancer (n = 9), malignant lymphoma (n = 6), esophageal cancer (n = 6), ovarian cancer (n = 3), malignant melanoma (n = 3), cholangiocarcinoma (n = 3), breast cancer (n = 2), renal cell carcinoma (n = 2), gallbladder cancer (n = 2), pancreatic cancer (n = 2), laryngeal cancer (n = l), liver cirrhosis (n = 29), chronic hepatitis (n = 13), hepatic hemangioma (n = 8), diffuse fatty liver (n = 7), acute cholecystitis (n = 5), cholelithiasis (n = 3), hepatic abscess (n = 1), acute pancreatitis (n = 1), chronic pancreatitis (n = 1), urinary stone (n = 1), and fever of an unknown cause (n = 3).
Scan Protocol and Contrast Medium Injection
A multi–detector row CT scanner (LightSpeed Ultra; GE Medical Systems, Milwaukee, Wis) with a detector configuration of 8 x 2.5 mm (ie, eight detector rows and 2.5-mm section thickness) was used. The high-speed mode used for the first- and second-phase CT examinations was equivalent to a helical pitch of 1.35, and a table speed was set at 27 mm per rotation (0.5 second). The high-quality mode used for the third-phase CT was equivalent to a pitch of 0.875, and table speed was set at 17.5 mm per rotation (0.7 second). These scanning parameters were selected to scan the upper abdomen (from the diaphragm level to the lower pole of the kidney) as rapidly as possible without impairing image quality. Transverse images were reconstructed and displayed as 40 sections of 5-mm-thick images with no intersectional gap for each phase set.
All patients received nonionic iodine contrast material containing 300 mg of iodine per milliliter (Omnipaque 300; Daiichi Pharmaceutical, Tokyo, Japan); a power injector (Autoenhance A-50; Nemotokyorindo, Tokyo, Japan) was used with a fixed injection duration of 30 seconds through a 21-gauge plastic intravenous catheter (Surflo; Terumo, Tokyo, Japan) placed in a vein of the upper extremity, typically in an antecubital vein. The volume of contrast material delivered was 2 mL per kilogram of body weight for 189 patients with weights ranging from 34 to 75 kg and was fixed at 150 mL for two patients with weights of 76 and 82 kg. Thus, the volume of contrast material ranged from 68 to 150 mL (mean, 104 mL).
Patients were prospectively assigned among the following four groups such that three-phase scanning (arterial, pancreatic parenchymal, and venous phases) commenced from the start of contrast medium injection at the following times: group 1: 25, 45, and 65 seconds; group 2: 30, 50, and 70 seconds; group 3: 35, 55, and 75 seconds; and group 4: 40, 60, and 80 seconds. The scan duration was 4.3 seconds for the first and second phases and 9.1 seconds for the third phase (Fig 1). First- and second-phase scans were completed during a single breath hold, and then third-phase scanning commenced after a 15-second breathing interval. Equilibrium-phase scanning commenced 150 seconds after the completion of contrast material injection in all patients; equilibrium-phase images were not evaluated in the current study.
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Figure 1: Diagram illustrates timing scheme in three-phase imaging protocols. Patients were prospectively assigned among four groups for three-phase scanning (arterial, pancreatic parenchymal, and venous phases). Scanning commenced at start of contrast medium injection. In group 1, scanning occurred at 25, 45, and 65 seconds; in group 2, at 30, 50, and 70 seconds; in group 3, at 35, 55, and 75 seconds; and in group 4, at 40, 60, and 80 seconds. Scanning duration was 4.3 seconds for first- and second-phase scanning and 9.1 seconds for third-phase scanning. First- and second-phase scanning was performed during single breath hold, and third-phase scanning was performed after 15-second breathing interval.
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Quantitative Image Analysis
Mean CT numbers (in Hounsfield units) of the abdominal aorta, spleen, pancreatic parenchyma, superior mesenteric artery and vein, splenic vein, and hepatic parenchyma were measured (S.G., who had 5 years of posttraining experience in interpreting body CT images) in all patients on a CT console monitor by using a circular region-of-interest cursor, which ranged from 5 to 30 mm in diameter, on unenhanced, first-, second-, and third-phase images. CT numbers of the abdominal aorta were measured in areas at the level of the diaphragmatic dome, CT numbers in the spleen were measured in one area covering as much of the splenic parenchyma as possible, CT numbers in the pancreatic parenchyma were measured in three areas (the pancreatic head, body, and tail) and then averaged, and CT numbers in the hepatic parenchyma were measured in three areas (right anterior segment, right posterior segment, and left lobe) and then averaged. By selecting a large region of interest encompassing most of the splenic parenchyma, we were able to measure the average representative splenic enhancement, even when splenic enhancement was heterogeneous at the early arterial phase. Focal pancreatic, hepatic, or splenic lesions, blood vessels, bile or pancreatic ducts, calcification, and artifacts were carefully excluded from all measurement areas.
Quantitative degrees of contrast enhancement were calculated by subtracting CT numbers on unenhanced images from those on contrast-enhanced images.
Qualitative Image Analysis
Two independent gastrointestinal radiologists (H. Kondo and M.K., who had 8 and 18 years, respectively, of posttraining experience in interpreting body CT images) prospectively reviewed the first-, second-, and third-phase images separately with reference to unenhanced images. Images were evaluated qualitatively by the two readers, who were blinded to patient clinical information. The degree of contrast enhancement in pancreatic parenchyma and peripancreatic arteries and veins was graded with a four-point scale: 0, when an organ had virtually no enhancement; 1, for minimal to mild enhancement; 2, for moderate enhancement; and 3, for intense enhancement.
Statistical Analysis
Analysis of variance and multiple comparisons with the Scheffé criterion (20) were used to evaluate the following factors in the four groups: patient age, body weight, and contrast enhancement values of the abdominal aorta, spleen, pancreatic parenchyma, superior mesenteric artery and vein, splenic vein, and hepatic parenchyma. The Kruskal-Wallis test and multiple comparisons with the Scheffé criterion were used to evaluate qualitative degrees, which were obtained as categorical data (21). P values less than 5.0% were considered to indicate a significant difference.
To assess interobserver variability in terms of interpreting images, 
statistics were used to measure the degree of agreement. A value of up to 0.20 was interpreted as slight agreement, 0.21–0.40 as fair agreement, 0.41–0.60 as moderate agreement, 0.61–0.80 as substantial agreement, and 0.81 or greater as almost perfect agreement.
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RESULTS
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The four patient groups contained 53, 46, 43, and 49 patients, respectively, and there was no significant difference in patient age, body weight, or injection rate (Table 1).
Mean Contrast Enhancement
The mean contrast enhancement of the abdominal aorta, spleen, pancreatic parenchyma, superior mesenteric artery and vein, splenic vein, and hepatic parenchyma in the four patient groups are summarized in Table 2. CT attenuation on unenhanced images ranged from 16 to 53 HU for the abdominal aorta, 34 to 60 HU for the spleen, 23 to 58 HU for the pancreatic parenchyma, 21 to 49 HU for the superior mesenteric artery, 28 to 55 HU for the superior mesenteric artery vein, 17 to 53 HU for the splenic vein, and 38 to 75 HU for the hepatic parenchyma.
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Table 2. Mean Contrast Enhancement of Anatomic Structures on Three-Phase CT Images of Four Patient Groups with Different Scan Delays
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The mean contrast enhancement of the abdominal aorta (314.6 HU) and superior mesenteric artery (271.2 HU) peaked at 35 seconds after the start of contrast medium injection, (both P < .001) then reduced with time (Fig 2). The mean contrast enhancement of the spleen increased constantly from 25 to 40 seconds after the start of contrast medium injection, peaked (111.0–118.5 HU) at 40–45 seconds, and then gradually decreased (87.9–65.8 HU) (Fig 3). The mean contrast enhancement of pancreatic parenchyma increased constantly from 25 to 40 seconds, peaked (82.1–85.2 HU) at 35–45 seconds, and reduced with time (74.5–49.1 HU) (Fig 3). The mean contrast enhancement of the hepatic parenchyma increased constantly, peaked (59.7–59.8 HU) at 55–60 seconds, and then plateaued (Fig 3). The mean contrast enhancement of the splenic vein increased constantly from 25 to 45 seconds, peaked (159.5–173.2 HU) at 45–55 seconds, and then gradually reduced with time. The mean contrast enhancement of the superior mesenteric vein increased constantly from 25 to 55 seconds and peaked (155.8 HU) at 55 seconds.
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Figure 2: Graph shows scan delay versus contrast enhancement (Mean  HU) curves for abdominal aorta and superior mesenteric artery. Scan delay is time from start of contrast material injection. Mean contrast enhancement of both abdominal aorta and superior mesenteric artery peaked at 35 seconds (P < .001) and then decreased with time. Error bars = standard error of the mean.
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Figure 3: Graph shows scan delay versus contrast enhancement (Mean HU) curves for spleen, pancreas (parenchyma), and liver (parenchyma). Mean contrast enhancement of spleen increased constantly from 25 to 40 seconds and peaked at 40–45 seconds. Mean contrast enhancement of spleen was significantly higher at 40 seconds than at 25–35 seconds (P < .001). Mean contrast enhancement of pancreatic parenchyma increased constantly from 25 to 40 seconds and peaked at 35–45 seconds. Mean contrast enhancement of pancreatic parenchyma was significantly higher at 35–40 seconds than at 25–30 seconds (P < .001). Mean contrast enhancement of hepatic parenchyma increased constantly, peaked (59.7–59.8 HU) at 55–60 seconds, and then plateaued. Mean contrast enhancement of hepatic parenchyma was significantly higher at 55–60 seconds than at 45–50 seconds (P < .001). Error bar = standard error of the mean.
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Scan Delay and Contrast Enhancement
The mean degree of pancreatic parenchymal enhancement increased constantly from 25 to 40 seconds after the start of contrast medium injection, peaked at 35–45 seconds, and reduced with time (Figs 4, 5). The mean degree of the peripancreatic artery enhancement remained constantly high at 25–40 seconds and then gradually reduced (Figs 4, 6), whereas the mean degree of the peripancreatic vein enhancement gradually increased and peaked at 55–60 seconds (Fig 4). The Kruskal-Wallis test and multiple comparisons with the Scheffé criterion were used to evaluate qualitative degrees, which were obtained as categorical data.
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Figure 4: Graph shows results of prospective qualitative image review. Mean degree of pancreatic parenchymal enhancement increased constantly from 25 to 40 seconds, peaked at 35–45 seconds, and decreased with time. Mean degree of pancreatic parenchymal enhancement was significantly higher at 35–40 seconds than at 25–30 seconds (P < .001) and at 45 seconds than at 50–60 seconds (P < .05). Mean degree of peripancreatic artery enhancement was constantly high at 25–40 seconds and then gradually reduced with time. Mean degree of peripancreatic vein enhancement gradually increased and peaked at 55–60 seconds. Mean degree of peripancreatic vein enhancement was significantly higher at 55–60 seconds than at 45–50 seconds (P < .001). Error bar = standard error of the mean.
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Figure 5: Transverse CT image of a 46-year-old woman with malignant lymphoma. Amount of contrast material administered was 100 mL. Image was obtained 40 seconds after start of contrast material injection and shows intense enhancement of abdominal aorta (*), intense enhancement of superior mesenteric artery (small arrow), intense enhancement of pancreas (large arrow), and minimal enhancement of hepatic parenchyma.
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Figure 6: Transverse CT image of a 37-year-old man with hepatic hemangioma. Amount of contrast material administered was 150 mL. Image was obtained 30 seconds after start of contrast material injection and shows intense enhancement of abdominal aorta (*), intense enhancement of celiac, splenic, and peripancreatic artery (lower left, lower right, both upper small arrows, respectively), slight enhancement with moiré pattern of spleen (arrowhead), slight enhancement of pancreas (large arrow), and minimal enhancement of hepatic parenchyma.
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Intraobserver Variability
The values for the independent rating of images by the two readers ranged from 0.81 to 0.95 (mean, 0.89), which indicated almost perfect agreement.
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DISCUSSION
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A study (22) showed that the quality of images generated by using multi–detector row CT is comparable with that of images generated by using single–detector row CT, even with a threefold increase in volume coverage. Appropriate scan timing with multi–detector row CT, however, is more difficult and critical than with single–detector row CT and requires a redesign of imaging protocols and more attention to bolus timing (23).
Bae (18) demonstrated in a pharmacokinetic study with a porcine model that time to peak aortic enhancement increases linearly with injection duration and occurs shortly after injection completion when the injection duration is longer than the time to peak test-bolus enhancement. Bae confirmed that time to peak aortic enhancement was 4.3 seconds after the completion of either a 20- or 30-second injection, which implied that this theory could be applied to pancreatic CT scanning protocols. In our study, most intense abdominal aortic enhancement was observed with a scan delay of 5 seconds after completion of a 30-second contrast material injection, which is compatible with the results of Bae.
We consider that fixed duration techniques offer two advantages. First, the time from initiation of the contrast material injection to peak aortic enhancement is highly consistent when a fixed injection duration of contrast medium is used. This finding is also supported by Awai et al (24), who reported a negligible fluctuation in time from initiation of contrast material injection to peak aortic enhancement when contrast medium was administered within a fixed time regardless of patient weight. Hypothetically, if we use a fixed injection rate scheme with a weight–adjusted volume of contrast medium of 2 mL/kg, patients of different body weights would require different volumes of contrast medium and be subject to variable injection durations. For optimal contrast enhancement at CT imaging, the scan delay has to be adjusted each time to accommodate different injection durations. Second, because radiologic technologists can set the scan delay from start of contrast material injection by using fixed injection durations, procedures are simpler than test-bolus imaging or bolus-tracking techniques and the frequencies of technical failures are likely to be decreased.
Our results show that the mean contrast enhancement of the abdominal aorta peaked (314.6 HU) at 5 seconds after completion of contrast medium injection (ie, 35 seconds after the start of injection) and that images obtained at this time can be used for CT angiography reconstruction or for the evaluation of peripancreatic arteries. Furthermore, we found that the mean contrast enhancement of pancreatic parenchyma peaked (82.1–85.2 HU) at 5–15 seconds after completion of a 30-second contrast material injection (ie, 35–45 seconds after the start of injection). Images obtained at this time were close to optimal pancreatic parenchymal phase images and offered the greatest likelihood of pancreatic tumor depiction (14–16,25). The mean contrast enhancement of peripancreatic veins and hepatic parenchyma peaked at 25–30 seconds after completion of a 30-second contrast material injection (ie, 55–60 seconds after the start of injection), and images obtained at this time probably represent optimal peripancreatic or portal venous phase images.
The injection rate varied from 2.1 to 5.0 mL/sec because of the fixed injection duration (30 seconds) in our study. Prior studies (26,27) on injection rate and volume of contrast medium administered at pancreatic CT have found that both the rate and volume affect the degree of pancreatic enhancement. Tublin et al (26) found that the higher the injection rate, the greater the peak enhancement and the shorter the time to peak pancreatic enhancement. As they administered a fixed amount (150 mL) of contrast medium, the injection duration at an injection rate of 2.5 mL/sec was 60 seconds and that of 5.0 mL/sec was 30 seconds. They found that peak pancreatic enhancement occurred at 69 seconds at the rate of 2.5 mL/sec and at 43 seconds at the rate of 5 mL/sec, which resulted in peak pancreatic enhancement at 9 and 13 seconds after the completion of injection, respectively, which corresponds well to our present results.
Tublin et al (26) indicated that peak pancreatic enhancement was lower at a low injection rate: 65 HU at 2.5 mL/sec and 84 HU at 5.0 mL/sec. Thus, although we can determine when abdominal aortic peak enhancement occurs after completion of injection and optimize scan timing for peak enhancement of the pancreas and peripancreatic vessels by using a fixed duration technique, we may need to optimize injection duration further to maximize peak contrast enhancement in the pancreas. Moreover, the injection duration may need to be determined to maintain the injection rate at 3.0–5.0 mL/sec to produce maximal pancreatic peak enhancement.
Our study is not without its limitations. First, we did not directly evaluate patients with pancreatic tumors because the number of such patients was not large enough. Moreover, chronic pancreatitis and pancreatic atrophy distal to pancreatic carcinoma are known to show insufficient or delayed pancreatic enhancement (28). Second, we used fixed scan delays for all patients within each group without individualizing scan delays for each patient by means of a test bolus or bolus-tracking techniques (17). We recognize that the time to peak contrast enhancement would be certainly affected by an individual patient's cardiac output and circulation times. By measuring group means in our study of individual patients, however, we assumed that the variations of individual patients would be averaged and become less critical in group comparison.
With the injection protocol used in our study, optimal scan delays for imaging the pancreas with a fixed injection duration (30 seconds) were, from the start of contrast medium injection, 30–35 seconds for the abdominal aorta and the superior mesenteric artery, 35–45 seconds for the pancreas, 45 seconds for the splenic vein, and 55 seconds or later for the hepatic parenchyma. We believe that these findings may be of potential use in designing multiphase scan protocols for the depiction and staging of pancreatic carcinoma.
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ADVANCE IN KNOWLEDGE
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- For the injection protocol used in our study, optimal scan delays for imaging the pancreas were from the administration of contrast medium injection, 30–35 seconds for the abdominal aorta and the superior mesenteric artery, 35–45 seconds for the pancreas, and 55 seconds or later for the splenic vein and the liver.
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FOOTNOTES
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Authors stated no financial relationship to disclose.
Author contributions: Guarantor of integrity of entire study, S.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, S.G., M.K., H. Kato, Y.T., Y.S., H.H., M.O., N.M., K.T.B.; clinical studies, S.G., M.K., H. Kondo, R.Y., T.M., H. Kato, Y.T.; statistical analysis, S.G., M.K., H. Kondo, R.Y., T.M., H. Kato, Y.T., Y.S., H.H., M.O., K.T.B.; and manuscript editing, S.G., M.K., Y.S., H.H., M.O., N.M., K.T.B.
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ABSTRACT
INTRODUCTION
