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Multidetector CT of Pancreas: Effects of Contrast Material Flow Rate and Individualized Scan Delay on Enhancement of Pancreas and Tumor Contrast¹

¹ From the Departments of Radiology (G.S., W.S., C.S., M.W., R.P.) and Surgery (A.S., M.G.), Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. From the 2004 RSNA Annual Meeting. Received July 1, 2005; revision requested September 1; revision received September 27; accepted October 4; final version accepted February 1, 2006. Address correspondence to W.S. (e-mail: wolfgang.schima{at}meduniwien.ac.at).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 
Purpose: To prospectively assess whether high contrast material flow rate (8 mL/sec) and individualized scan delay improve enhancement of normal pancreas with multidetector computed tomography (CT) and, as a result, tumor-to-pancreas contrast of pancreatic adenocarcinoma.

Materials and Methods: Informed consent was obtained in 40 patients (21 women, 19 men; mean age, 67.1 years); the institutional review board approved this protocol. Patients were referred for multidetector CT because they were suspected of having a pancreatic tumor and were randomized to receive 150 mL of nonionic contrast material (300 mg of iodine per milliliter) at a flow rate of 4 mL/sec (n = 21) or 8 mL/sec (n = 19). Patients underwent dynamic scanning at one level every 2 seconds for 66 seconds after intravenous administration of contrast material. Contrast enhancement of pancreas and tumors was measured with circular regions of interest (analysis of variance and Bonferroni-Holm corrected post hoc t tests).

Results: Peak contrast enhancement in pancreas was observed significantly earlier (mean ± standard deviation, 28.7 seconds ± 3.5 vs 48.2 seconds ± 5.3; P < .05) and was significantly higher (129.0 HU ± 25.7 vs 106.2 HU ± 35.4, P < .05) with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec. Tumor-to-pancreas contrast greater than 40 HU lasted significantly longer with a flow rate of 8 mL/sec than with a flow rate of 4 mL/sec (26.4 seconds ± 11.9 vs 8.6 seconds ± 8.3, P < .05). With a flow rate of 8 mL/sec, an individualized scan delay of 19 seconds after aortic transit time revealed higher tumor-to-pancreas contrast than did a fixed scan delay, and tumor conspicuity was better.

Conclusion: With 16-section CT, increased contrast material flow rate of 8 mL/sec and individualized scan delay were associated with improved pancreatic enhancement and tumor-to-pancreas contrast compared with flow rate of 4 mL/sec and fixed scan delay.

© RSNA, 2006

	INTRODUCTION

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Pancreatic cancer ranks as the fourth leading cause of death from cancer in the United States (1). In general, the prognosis is dismal, with a 5-year survival rate of 4% (1). Surgical resection represents the only potentially curative treatment (2). However, only 20% of patients with pancreatic cancer have disease that is surgically resectable at the time of diagnosis (3). In these patients, the 5-year survival rate improves to about 20% (3). Nevertheless, laparotomy in such patients carries a substantial perioperative morbidity rate of 20%–30%, and Whipple resection is associated with a mortality rate of up to 5% (4–6). Therefore, careful patient selection based on accurate computed tomographic (CT) assessment of disease extent is of major importance.

Contrast material–enhanced helical CT has been suggested as an accurate technique for the detection and staging of pancreatic ductal adenocarcinoma (7–9). One of the challenges is to determine the method for delivery of contrast material and scan delay time to optimize tumor contrast in the pancreas. Most authors recommend a dual-phase CT technique with image acquisition in the pancreatic phase and the portal venous phase. A fixed scan delay of 40 seconds for the pancreatic phase has been suggested by Lu et al (7), whose recommendation has been followed by others (2).

However, the increased acquisition speed that has accompanied the advent of multi–detector row CT can be used to increase z-axis resolution, which provides better spatial resolution. However, reports in the literature indicate that even multi–detector row CT of the pancreas may lack conspicuity for pancreatic cancer, rendering up to 11% of adenocarcinomas isoattenuating at CT (8,9).

Along with the improvements in CT techniques, there have been several attempts to optimize the application of contrast material for pancreatic imaging protocols. In a series of prior studies (2,7,8,10–13), contrast material flow rates as high as 5 mL/sec were applied. In addition, the use of fixed scan delays, ranging from 35 to 40 seconds for pancreatic phase imaging, subsequent to the start of the administration of contrast material was proposed (12,13). With the development of 16- and 64-section CT scanners, the acquisition time for a pancreatic study does not exceed 3–4 seconds. Such a short acquisition time is not likely to fall at the peak enhancement of the pancreas in all patients if a fixed scan delay is used. Moreover, an interval for contrast material delivery of 30 seconds (given 150 mL of contrast material at a flow rate of 5 mL/sec) produces an enhancement curve with a broad peak that does not conform to a scan duration of only 3–4 seconds. Protocols for application of contrast material could potentially be optimized by an increase in the contrast material flow rate. Consequently, the question arises as to whether 16-section CT requires optimization of contrast material protocols by individualization of scan delay time and an increase of the contrast material flow rate to improve tumor-to-pancreas contrast during the pancreatic phase.

Thus, the purpose of our study was to prospectively assess whether a high contrast material flow rate (8 mL/sec) and use of an individualized scan delay improves enhancement of the normal pancreas with multi–detector row CT and, as a result, the tumor-to-pancreas contrast of pancreatic adenocarcinoma.

	MATERIALS AND METHODS

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Patients
Written informed consent was obtained in 40 patients (21 women, 19 men; mean age, 67.1 years; age range, 40–84 years) prior to CT scanning, according to a protocol approved by our institutional review board. All these patients were suspected of having pancreatic adenocarcinoma and underwent multiphase multi–detector row helical CT between January 2003 and August 2004. Inclusion criteria were as follows: suspicion of pancreatic cancer on the basis of findings at a prior imaging examination and a patient's willingness to participate. Exclusion criteria were pregnancy, age younger than 18 years, history of anaphylaxis in reaction to administration of iodine contrast agents, elevated serum creatinine level (>114.9 µmol/L [>1.3 mg/dL]), and history of chronic pancreatitis.

The patients were randomized to two groups for administration of contrast material (see following paragraph) at a flow rate of 4 mL/sec (low-flow-rate group) or 8 mL/sec (high-flow-rate group). The low-flow-rate group comprised 21 patients (12 women, nine men; mean age, 68.0 years; age range, 46–83 years), and the high-flow-rate group comprised 19 patients (nine women, 10 men; mean age, 66.1 years; age range, 40–84 years). No significant difference was seen between the two groups with regard to age (unpaired t test) or sex (Fisher exact test).

CT Technique
CT scanning was performed with a 16-section helical CT unit (Somatom Sensation 16; Siemens, Erlangen, Germany). Thirty minutes prior to scanning, the patients drank 500 mL of water to distend the stomach and duodenum. Unenhanced images of the pancreas were obtained with 1.5-mm collimation to define the craniocaudal extent of the pancreas, the area of normal parenchyma, and, if possible, the tumor for dynamic single-level scanning. An intravenous catheter with an 18-gauge diameter (Venflon; Becton Dickinson, Helsingborg, Sweden) was placed in a cubital vein. With a power injector (Injection CT2; Medtronic, Saarbrücken, Germany), 150 mL of iopromide (300 mg of iodine per milliliter; Schering, Berlin, Germany), which had been preheated to a temperature of 37°C, was injected intravenously at a rate of 4 or 8 mL/sec; this was followed by injection of 40 mL of saline. Dynamic single-level scanning with 1.5-mm collimation was started 5 seconds after the initiation of contrast material injection. During shallow breathing, the pancreas was imaged every 2 seconds for up to 66 seconds from the initiation of contrast material injection. At a fixed delay of 70 seconds, a portal venous phase study covering the upper abdomen was then obtained with 1.5-mm collimation; 120 kVp was used, and the mean tube current was 75 mAs (range, 61–95 mAs) for dynamic phase imaging and 105 mAs (range, 99–114 mAs) for portal venous phase imaging.

Image Interpretation
All images were reviewed on a workstation (Impax; Agfa-Gevaert, Mortsel, Belgium). For quantitative analysis, attenuation measurements were obtained by one author with 5 years of experience in abdominal imaging (G.S.) by using region-of-interest measurements in every patient. Circular regions of interest were created to be as large as possible (mean size, 115 mm²; range, 75–150 mm²). As the first step, the interval from the time of initiation of contrast material injection to the arrival of contrast material in the aorta (aortic transit time) was measured during dynamic phase imaging. Measurements of attenuation and the time to peak attenuation of the following entities were obtained: the most homogeneous region of the parenchyma; any pancreatic tumor (measurements of regions of interest with avoidance of any cystic regions within tumors), if present; and the aorta at the level of the celiac axis. In patients with histologically proved pancreatic adenocarcinoma, the difference between the attenuation values of normal pancreatic parenchyma not affected by atrophy and the tumor (ie, the tumor-to-pancreas contrast) was measured (12). In addition, the time intervals during which tumor-to-pancreas contrast exceeded 30 HU, 40 HU, and 50 HU were obtained for both groups.

In the second step, the attenuation of the normal pancreas and the tumor-to-pancreas contrast were compared by using a fixed delay of 34 or 40 seconds, as recommended in the literature (12,13), or an individualized scan delay based on pancreatic attenuation curves. From the aortic transit time, the time delays to the maximum attenuation of the pancreas and to the maximum tumor-to-pancreas contrast were measured.

For qualitative analysis, one reader with 5 years of experience in abdominal imaging (C.S.) evaluated tumor conspicuity in all patients with proved pancreatic adenocarcinoma during the dynamic phase. Tumor conspicuity was graded on a four-point scale, as follows: 0, not seen (ie, absent perceptibility of tumor mass); 1, poor (ie, faint perceptibility of the tumor, hard to detect); 2, good (ie, well-recognizable tumor, unequivocal perceptibility); and 3, excellent (ie, excellent tumor perceptibility) (12).

Histologic Analysis and Clinical Follow-up
Tumor presence was determined through histopathologic analysis for all malignant tumors. The diagnosis of tumor absence was based on the findings at clinical follow-up and on stability at repeated imaging for at least 6 months when a mass was not identified.

Of the 40 patients, 20 had a normal pancreas (low-flow-rate group, n = 11; high-flow-rate group, n = 9), and 20 had a proved pancreatic adenocarcinoma based on histologic analysis (low-flow-rate group, n = 10; high-flow-rate group, n = 10). Tumor location was as follows: pancreatic head in 14 patients (low-flow-rate group, n = 8; high-flow-rate group, n = 6), pancreatic body in five patients (low-flow-rate group, n = 1; high-flow-rate group, n = 4), and pancreatic tail in one patient (low-flow-rate group, n = 1). Mean tumor size was 2.5 cm (range, 1.3–3.7 cm).

Statistical Analysis
Data were analyzed with SPSS for Windows, release 11, software (SPSS, Chicago, Ill). Normally distributed continuous data were presented as mean ± standard deviation. For quantitative assessment (data from 40 patients), two- and three-way analysis of variance with repeated measures and Bonferroni-Holm corrected post hoc t-tests were applied (14). For qualitative evaluation (data from 20 patients with pancreatic adenocarcinoma), to assess the differences between ratings of the low- and the high-flow-rate groups, Fisher-Freeman-Halton tests were used for each time point (individualized scan delay and fixed scan delays of 34 seconds and 40 seconds) separately. Sign tests (14) were performed to calculate differences between (a) fixed scan delays of 34 seconds and 40 seconds and (b) individualized scan delay, for the whole sample as well as for the low- and the high-flow-rate groups separately. For all tests, P < .05 (two-tailed test) was considered to indicate a significant difference.

	RESULTS

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Quantitative Assessment of Pancreatic Enhancement and Tumor-to-Pancreas Contrast
At dynamic contrast-enhanced multi–detector row CT, the aortic transit time was significantly shorter in the high-flow-rate group than in the low-flow-rate group (8.2 seconds ± 2.2 vs 12.6 seconds ± 2.5, P < .05). The mean peak pancreatic parenchymal attenuation value was significantly higher in the high-flow-rate group than in the low-flow-rate group (129.0 HU ± 25.7 vs 106.2 HU ± 35.4, P < .05), as was the mean peak attenuation value of the abdominal aorta (479.7 HU ± 108.5 vs 328.4 HU ± 74.7, P < .05; Fig 1).

View larger version (24K): [in this window] [in a new window] [Download PPT slide]   Figure 1: Mean enhancement over time of pancreas and tumor in the low-flow-rate (4 mL/sec) and high-flow-rate (8 mL/sec) groups.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 2: Representative transverse CT images of a patient in the low-flow-rate group (4 mL/sec) show attenuation of the normal pancreas (arrows) at 20, 30, 40, and 50 seconds after initiation of contrast material injection. Pancreatic enhancement is highest at 50 seconds (91 HU).

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 3: Representative transverse CT images of a patient in the high-flow-rate group (8 mL/sec) show attenuation of the normal pancreas (arrows) at 20, 30, 40, and 50 seconds after initiation of contrast material injection. Pancreatic enhancement is highest at 30 seconds (129 HU).

Tumor delineation is mainly based on the presence of tumor-to-pancreas contrast during contrast-enhanced CT (15). The maximum tumor-to-pancreas contrast was higher in the high-flow-rate group than in the low-flow-rate group (81.1 HU ± 13.3 vs 47.8 HU ± 17.1, P < .05). The time intervals of tumor-to-pancreas contrast that exceeded 30 HU, 40 HU, and 50 HU were significantly (P < .05) longer in the high-flow-rate group (Figs 4, 5; Table 1).

View larger version (98K): [in this window] [in a new window] [Download PPT slide]   Figure 4: Representative transverse CT images of a patient in the low-flow-rate group (4 mL/sec) show attenuation of pancreatic tumor and tumor-to-pancreas contrast at 20, 30, 40, and 50 seconds after initiation of contrast material injection. Adenocarcinoma (arrows) in the head is moderately hypoattenuating, with a tumor-to-parenchyma attenuation difference of 35 HU at 50 seconds.

View larger version (107K): [in this window] [in a new window] [Download PPT slide]   Figure 5: Representative transverse CT images of a patient in the high-flow-rate group (8 mL/sec) show attenuation of pancreatic tumor and tumor-to-pancreas contrast at 20, 30, 40, and 50 seconds after initiation of contrast material injection. Adenocarcinoma (arrows) in the pancreatic tail shows an excellent tumor-to-pancreas attenuation difference of 65 HU at 30 seconds.

In the low-flow-rate group, the maximum attenuation of the pancreas was significantly higher (P < .05) with an individualized scan delay (individualized aortic transit time plus time to maximum tumor-to-pancreas contrast) of 29 seconds than with a fixed delay of 34 seconds; however, it was not significantly different when compared with a fixed delay of 40 seconds. In the high-flow-rate group, the maximum attenuation of the pancreas was significantly higher (P < .05) with an individualized delay (individualized aortic transit time plus time to maximum tumor-to-pancreas contrast) of 19 seconds than with fixed delays of 34 and 40 seconds (Table 2).

	DISCUSSION

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Investigators have stated that both the volume and the rate of contrast material administration are of major importance for enhancement of the pancreatic parenchyma (16,17). The peak enhancement and the time to peak enhancement of the pancreas are related to the rate of contrast material injection (16). Kim et al (17) found both the contrast material volume and the rate of injection were directly related to pancreatic enhancement: The larger the contrast material volume and the faster the rate of injection, the better the pancreatic parenchymal enhancement. Our data are in accordance with these findings. In our patients, we applied a volume of 150 mL of contrast material. When we sought to reduce the volume to 120 mL, we observed inappropriate enhancement of the normal pancreas, even at a flow rate of 8 mL/sec.

Several studies have optimized the application protocols for contrast material with helical CT (7,10,18–20). Although the results of these studies differed because different flow rates and volumes of contrast material and different scan delays were used, widely accepted standard protocols for helical CT of the pancreas could be established: a volume of contrast material of 140–160 mL, a flow rate of 3–4 mL/sec, a scan delay of 40 seconds for the pancreatic phase, and a fixed total scan delay of 60–70 seconds for the portal venous phase (7,20).

Multi–detector row CT of the pancreas provides substantial improvement in scanning speed, anatomic volume coverage, and the separation of different image acquisition phases (12). These improvements have resulted in the redesign of imaging protocols, especially in the timing of the traditional vascular phases. Several authors indicated that superior enhancement of normal pancreatic tissue was achieved during the arterial phase (7,11,18–21). McNulty et al (12) used 150 mL of nonionic contrast material at a flow rate of 4 mL/sec and a fixed scan delay of 35 seconds for pancreatic phase imaging. They showed that the tumor-to-pancreas contrast was slightly higher in the pancreatic phase than in the portal venous phase, with maximal enhancement of the arterial vasculature obtained in the pancreatic phase. They found that the routine acquisition of arterial phase images is not necessary and should be reserved for patients in whom CT angiography is required (12).

Fletcher et al (13) used a sliding scale for the timing of the arterial, pancreatic, and hepatic phases, depending on the rate of contrast material injection that was possible with venous access. For the pancreatic phase, they used scan delays of 40 seconds for a flow rate of 5 mL/sec, 45 seconds for a flow rate of 4 mL/sec, and 50 seconds for a flow rate of 3 mL/sec. In their experience, the pancreatic phase was rated best for tumor detection, but the hepatic phase was superior for detection of vascular invasion because fewer flow artifacts were present in the superior mesenteric vein (13). They confirmed the findings of McNulty et al (12) that routine acquisition of arterial phase images was unnecessary. Our results show that a flow rate of 4 mL/sec with an individualized scan delay of aortic transit time plus 29 seconds is superior to a fixed scan delay of 35 or 40 seconds.

Our study findings indicate that use of a flow rate of 8 mL/sec (referred to as the high flow rate) for multi–detector row CT improves tumor-to-pancreas contrast when compared with a standard flow rate of 4 mL/sec. To fully exploit the advantage of this effect, an individualized scan delay should be used rather than a fixed scan delay of 35 or 40 seconds, as suggested in the literature (12,13). The administration of the same volume of contrast material (ie, 150 mL) with a high flow rate of 8 mL/sec provides substantially superior results in the attenuation of the pancreas and a substantially superior tumor-to-pancreas contrast at a scan delay that could be defined as an early pancreatic phase: The mean pancreatic enhancement and the tumor-to-pancreas contrast were greatest during the pancreatic phase with a scan delay of aortic transit time plus 20.2 seconds and 18.9 seconds, respectively. Considering that with the development of 16- and 64-section CT scanners the acquisition time of a pancreatic study does not exceed 3–4 seconds, the optimal time window for first-phase pancreatic imaging may be defined as aortic transit time plus 19 seconds. As a consequence, we feel that multi–detector row CT protocols for imaging of the pancreas should be adapted: The timing of pancreatic phase imaging should be individualized for optimal congruence of the ultra-short image acquisition of current multi–detector row CT scanners and maximal pancreatic enhancement and tumor contrast.

The results of qualitative tumor assessment demonstrated the high flow rate was superior to the low flow rate: Tumor conspicuity was rated as excellent in 80% versus 60% of the cases and as excellent or good in 100% versus 80% of the cases. However, these results were not significant, most likely because of a comparably low number of tumors in the study population. However, lesion conspicuity was superior when an individualized scan delay was used. In general, qualitative tumor assessment in our study yielded excellent results. This may, in part, be caused by fewer volume motion artifacts (13) with 16-section CT than with four-section CT (12,13).

The contrast material flow rate of 8 mL/sec is assumed to be comparatively high. To our knowledge, this high flow rate for CT of the pancreas has not been reported in the literature before. However, there are several considerations that justify this high flow rate. First, for other contrast material applications into forearm veins, the flow rate has been reported to be as high as 10 mL/sec (eg, in CT perfusion imaging of the liver) (22). Second, in our series, we have not observed any side effects associated with the high flow rate: There was no extravasation of contrast material or any systemic disorder in 20 patients.

Our study had several limitations. First, we did not perform a dedicated detection study for pancreatic adenocarcinoma. Dynamic single-level scanning was performed, but it did not cover the pancreas in each phase. Thus, we cannot predict whether a quantitatively higher tumor-to-pancreas contrast would translate into better detection of pancreatic tumors. Furthermore, we did not determine sensitivity and specificity of vascular invasion of pancreatic adenocarcinoma.

Second, in our study, dynamic scanning was performed every 2 seconds from the beginning of contrast material administration. As a result, we were able to obtain attenuation values only at 34 seconds and 40 seconds after initiation of contrast material administration, not at 35 seconds (12). Therefore, a direct comparison of our data to data obtained with a 35-second delay reported in the literature (12) was impossible. However, the differences in attenuation values at 34 seconds and 36 seconds were so minute that a substantially different result at 35 seconds seems unlikely. Third, no intraindividual comparisons in the attenuation patterns at different contrast material flow rates were obtained because of ethical reasons.

Several conclusions from our evaluation of a dynamic phase 16-section CT investigation of the pancreas can be drawn. First, with 16-section CT scanners, the use of a high contrast material flow rate (8 mL/sec) and an individualized scan delay substantially improve the attenuation of the normal pancreas compared to established acquisition protocols with a flow rate of 4 mL/sec and the use of fixed scan delays of 35 or 40 seconds. Second, tumor contrast is substantially increased by using a flow rate of 8 mL/sec during pancreatic phase imaging with an individualized scan delay. Thus, most important, as a consequence of the faster scanning speed of multi–detector row CT, acquisition protocols for the pancreas could be redesigned and include a high contrast material flow rate of 8 mL/sec during the pancreatic phase, with an individualized scan delay of aortic transit time plus 19 seconds. This optimized protocol for administration of contrast material may improve 16-section CT scanning of pancreatic cancer. However, large detection studies in patients suspected of having pancreatic cancer are necessary to confirm whether this protocol translates into better detection of small pancreatic tumors.

	ADVANCES IN KNOWLEDGE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE References

 

• The use of high contrast material flow rates (8 mL/sec) and the use of an individualized scan delay substantially improve the attenuation of the normal pancreas compared to established acquisition protocols with a flow rate of 4 mL/sec and the use of fixed scan delays of 35 or 40 seconds.
  
• Tumor contrast is substantially increased by providing a flow rate of 8 mL/sec during pancreatic phase imaging with an individualized scan delay.
  

	ACKNOWLEDGMENTS

 
We are grateful to Mary McAllister, Johns Hopkins University Hospital, Baltimore, Md, for editorial assistance.

	FOOTNOTES

 
Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, G.S., W.S.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, G.S., C.S.; clinical studies, G.S., W.S., C.S., A.S., M.G., R.P.; statistical analysis, G.S., M.W.; and manuscript editing, all authors

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