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Original Research |
1 Departments of Radiology, Gifu University School of Medicine, 1-1 Yanagido,
Gifu 501-1194, Japan.
2 Departments of Radiology Services, Gifu University School of Medicine, Gifu
501-1194, Japan.
3 Center of Brain and Oral Science, Kanawaga Dental College, Yokosuka 238-8580,
Japan.
4 Department of Medical Informatics, Gifu University School of Medicine, Gifu
501-1193, Japan.
5 Department of Physiology and Neuroscience, Kanagawa Dental College, Yokosuka
238-8580, Japan.
6 Research Center for Cancer Prevention and Screening, National Cancer Center
Hospital, Tsukiji, Japan.
7 Radiology and Biomedical Engineering University of Pittsburgh, Pittsburgh, PA
15261.
Received March 14, 2006;
accepted after revision July 31, 2006.
Address correspondence to H. Kondo
(hkondo{at}gifu-u.ac.jp).
Abstract
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SUBJECTS AND METHODS. Three-phase 8-MDCT of the pancreas was performed on 170 patients after administration of 2 mL/kg of 300 mg I/mL contrast medium injected at 4 mL/s to a total dose of 150 mL. Patients were prospectively randomized into three groups with different scanning delays for the three phases (arterial, pancreatic, and venous) after bolus tracking was triggered at 50 H of aortic contrast enhancement: group 1 (5, 20, 45 seconds); group 2 (10, 25, 50 seconds); and group 3 (15, 30, 55 seconds). Mean attenuation values of the abdominal aorta, superior mesenteric artery, pancreatic parenchyma, splenic vein, superior mesenteric vein, portal vein, and hepatic parenchyma were measured. Increases in attenuation values after contrast administration were assessed as change in attenuation value. Qualitative analysis also was performed.
RESULTS. Mean contrast enhancement in the aorta (change in attenuation, 321-327 H) and the superior mesenteric artery (change in attenuation, 304-307 H) approached peak enhancement 5-10 seconds after bolus tracking was triggered. Pancreatic parenchyma became most intensely enhanced (change in attenuation, 84-85 H) 15-20 seconds after triggering, and then the enhancement gradually decreased. Enhancement of the splenic vein and portal vein peaked 25 seconds and that of the superior mesenteric vein peaked 30 seconds after triggering. Liver parenchyma reached 52 H 30 seconds after triggering and reached a plateau (change in attenuation, 58-61 H) at a further scanning delay of 45-55 seconds. Qualitative results were in good agreement with quantitative results.
CONCLUSION. For the injection protocol used in this study, optimal scanning delay after triggering of bolus tracking at 50 H of aortic contrast enhancement was 5-10 seconds for the peripancreatic arterial phase, 15-20 seconds for the pancreatic parenchymal phase, and 45-55 seconds for the hepatic parenchymal phase.
Keywords: contrast media • CT technique • liver • MDCT • pancreas
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With MDCT, a scan can be acquired at each phase within a few seconds, allowing completion of the entire scan while a substantial amount of contrast medium circulates and remains in the blood vessels and visceral parenchyma [4, 7]. Thus MDCT is well suited for multiphasic imaging of the pancreas. The fast-scanning capability of MDCT, however, presents a new challenge for contrast enhancement. McNulty et al. [4] reported that the multiphase imaging capability, increased speed of acquisition, and greater anatomic coverage achieved with MDCT have resulted in the need to redesign imaging protocols and pay more attention to bolus timing. Appropriate timing to achieve adequate contrast enhancement at each phase of scanning is more difficult and critical in MDCT than in single-detector CT. Inappropriate timing reduces tumor conspicuity.
Various helical CT protocols with injection rates ranging from 2 to 6 mL/s have been described for pancreatic imaging [8-10]. Scanning delays used in these dual-phase protocols were 18-35 seconds for early or arterial phase imaging to maximize enhancement of the pancreas and mesenteric arteries and 60-70 seconds for late or portal venous phase imaging to maximize enhancement of the mesenteric and portal veins and hepatic parenchyma. These scanning delays were determined as fixed values without consideration of individual variations in cardiovascular circulation time. To acquire images at precisely determined individualized enhancement phases, however, it is essential to use a test bolus or bolus-tracking technique to measure contrast arrival time. To our knowledge, no study has been conducted to systematically investigate individualized scanning delay for multiphase MDCT of the pancreas and surrounding structures. The purpose of this study was to determine optimal scanning delay for MDCT imaging with a bolus-tracking technique for peripancreatic arterial, pancreatic parenchymal, peripancreatic venous, and hepatic parenchymal contrast enhancement.
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Twenty patients who had a major abdominal surgery (e.g., partial hepatectomy, total splenectomy) were excluded from the study population because of concern that normal hemodynamic and physiologic values were greatly disturbed in these patients. An additional eight patients were excluded because of technically inadequate scans and severe artifacts on the CT images. The 170 patients who participated in the study were 114 men and 56 women (age range, 18-92 years; mean, 63.7 years). Three of the patients had pancreatic adenocarcinoma; 14, hepatocellular carcinoma; 18, liver metastasis from colorectal (n = 9), gastric (n =4), pulmonary (n = 3), duodenal (n = 1), and uterine cervical (n = 1) cancer; nine, chronic hepatitis; three, cavernous hemangioma; and 123, extrahepatic primary neoplasms and healthy liver. The conditions in these patients were gastric (n = 29), colorectal (n = 31), lung (n = 21), uterine (n =14), esophageal (n = 5), ovarian (n = 3), breast (n = 2), and renal (n = 2) neoplasms; lymphoma (n = 4); malignant melanoma (n = 2); cholangiocarcinoma (n = 2); cholelithiasis (n = 4); urinary stone (n = 3); and fever of unknown origin (n =1).
Contrast Injection and Scan Protocols
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All patients were given nonionic iodinated contrast material (Omnipaque 300 [iohexol], Daiichi Pharmaceutical) administered with a power injector (Autoenhance A-50, Nemotokyorindo) at a rate of 4 mL/s through a 21-gauge angiocatheter placed in an antecubital vein. The volume of contrast material delivered was 2 mL/kg of body weight in patients with a weight range of 38-75 kg (n = 163) but was fixed at 150 mL/kg of body weight for patients weighing 76-86 kg (n = 7), which resulted in a total volume of contrast material of 76-150 mL (mean, 112 mL).
A bolus-tracking program (SmartPrep, GE Healthcare) was used to monitor contrast enhancement after injection of contrast medium before initiation of the diagnostic scans. The region-of-interest cursor for bolus tracking was placed in the aorta at the level of the diaphragmatic dome. This level was also used as a starting position for the diagnostic scans. Real-time low-dose (120 kVp, 50 mA) serial monitoring scanning was initiated 5 seconds after the start of the contrast injection.
Patients were prospectively randomized into three groups with different scanning delays for the three phases (arterial, pancreatic parenchymal, and venous) after bolus tracking was triggered at 50 H of aortic enhancement. Sixty-six patients were in group 1 (5, 20, 45 seconds), 60 patients in group 2 (10, 25, 50 seconds), and 44 patients in group 3 (15, 30, 55 seconds). Scanning duration was 4.3 seconds for the first and second phases and 9.1 seconds for the third phase. First- and second-phase scanning was completed during a single breath-hold, and third-phase scanning was begun after a 20-second breathing interval.
Quantitative Image Analysis
Mean attenuation values in the abdominal aorta, superior mesenteric artery,
pancreatic parenchyma, splenic vein, superior mesenteric vein, right and left
main portal veins, and liver parenchyma were measured for all patients on a CT
console monitor with a circular region-of-interest cursor. The size range of
the cursor was 5-30 mm in diameter for the unenhanced and first, second, and
third phases of the enhanced images. Attenuation values of the abdominal aorta
were measured at the level of the diaphragmatic dome. Pancreatic parenchymal
values were measured in three areas (pancreatic head, body, and tail) and then
averaged. Portal venous values were measured in two areas (right and left main
branches) and then averaged. All of the vessels were measured at the largest
cross-section on image sections, and the measurement locations were kept the
same in the image sections acquired at different enhancement phases. Hepatic
parenchymal values were measured in three areas (right anterior segment, right
posterior segment, and left lobe) and averaged. Focal lesions, blood vessels,
bile and pancreatic ducts, calcification, and artifacts were carefully
excluded from all measurement areas. Quantitative degrees of contrast
enhancement were expressed as change in attenuation, which was calculated by
subtraction of CT values on unenhanced images from those on contrast-enhanced
images.
Qualitative Image Analysis
Two independent gastrointestinal radiologists with 7 and 18 years 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 and subjectively by
these two reviewers, who were blinded to clinical information and results of
quantitative image analysis. The degree of contrast enhancement in the
superior mesenteric artery, pancreatic parenchyma, superior mesenteric artery,
portal vein, and hepatic parenchyma was graded on a four-point scale: 0,
almost no enhancement; 1, minimal to mild enhancement; 2, moderate
enhancement; 3, intense enhancement.
Statistical Analysis
Analysis of variance and multiple comparisons with the Scheffé
criterion [11] were used to
evaluate the following determinants in the three groups: patient age, body
weight, aortic transit time (i.e., time to reach 50 H of aortic enhancement in
bolus tracking) and change in attenuation value of the abdominal aorta,
superior mesenteric artery, pancreatic parenchyma, splenic vein, superior
mesenteric vein, main portal veins, and liver parenchyma. The magnitudes of
mean contrast enhancement of these structures at different scan delays were
compared. We arbitrarily chose the scanning delays that corresponded to the
two highest mean enhancement values as clinically optimal. The Kruskal-Wallis
test and multiple comparisons with the Scheffé criterion were used to
evaluate qualitative scores as categoric data
[12]. Statistical significance
was considered p < 0.05. To assess interobserver variability in
terms of image interpretation, kappa statistics were used to measure degree of
agreement. A kappa value up to 0.20 indicated slight agreement; 0.21-0.40,
fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial
agreement; and 0.81 or greater, almost perfect agreement.
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Curves of scanning delay versus mean qualitative degree of contrast enhancement are shown in Figure 4. The mean degree of superior mesenteric arterial enhancement was constantly high 5-15 seconds after triggering and then decreased with time. The mean degree of main portal venous enhancement constantly increased from 5-25 seconds after the trigger and then reached a plateau at 25-55 seconds. The mean degree of superior mesenteric venous enhancement constantly increased from 5-25 seconds after triggering and then reached a plateau at 25-55 seconds. The mean degree of pancreatic parenchymal enhancement was high 5-30 seconds after triggering with a peak at 20 seconds. The mean degree of hepatic parenchymal enhancement constantly increased 5-45 seconds after triggering and was highest at 45-55 seconds.
The kappa values for independent rating by the two reviewers ranged from 0.63 to 0.84 (mean, 0.75), indicating substantial to almost perfect agreement.
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Bae et al. [14] studied the effect of reduced cardiac output in a porcine model and concluded that time to arrival of contrast bolus in the aorta and time to peak aortic enhancement increased as cardiac output decreased. We found that aortic transit time varied widely from 7 to 33 seconds in our series, likely reflecting differences in cardiac output and circulation time. This finding shows the importance of adjusting delay according to the time of arrival of contrast medium in the abdominal aorta rather than using a fixed delay time from the start of contrast injection. A bolus-tracking technique is a means of compensating for individual patient variation in determination of optimal delay.
If a fixed scanning delay method is used, optimal delay can be obtained as the sum of mean aortic transit time and time to peak enhancement as measured in our study. The mean aortic transit time we measured was approximately 15 seconds in all three groups. Thus fixed scanning delay is estimated to be 20-25 seconds for the peripancreatic arterial phase, 30-35 seconds for pancreatic parenchymal phase, and 60-70 seconds for the hepatic parenchymal phase.
Degree of contrast enhancement in the pancreas with different scanning delays has been investigated in several studies. Hollett et al. [8], using an injection of 150 mL of contrast material (300 mg I/mL) at a rate of 5 mL/s and single-detector helical CT, found that pancreatic enhancement on images obtained with a delay of 20 seconds after the start of contrast injection was significantly greater than enhancement on images obtained with a standard delay of 49-71 seconds. Lu et al. [15], using an injection of 150 mL of contrast material (300 mg I/mL) at 3 mL/s and dual-detector CT, found that helical CT images obtained during the pancreatic phase (40-70 seconds after the start of injection) showed significantly greater tumor-to-pancreas contrast than did images obtained during the hepatic phase (70-100 seconds). More recently, McNulty et al. [4], using an injection of 150 mL of contrast material (300 mg I/mL) at 4 mL/s and 4-MDCT, found that pancreatic enhancement on images obtained with delays of 35 and 60 seconds (122 and 109 H, respectively) after the start of contrast injection was significantly greater than enhancement on images obtained 20 seconds (70 H) after the start of injection. Because the mean aortic transit time in our study was approximately 15 seconds, the pancreatic parenchyma theoretically had peak enhancement (85 H) 35 seconds after the start of injection and leveled off (53 H) at 60 seconds, which is in accord with the results of McNulty et al. The difference in attenuation value (32 H) at 35 and 60 seconds in our study was greater than the 13 H observed by McNulty et al. This difference may be attributed to the different scan durations of 4- and 8-MDCT. The timing was approximately 10 seconds for the pancreatic phase of 4-MDCT but no more than 4.3 seconds for 8-MDCT. Increasing the number of detector rows reduced scanning time and enabled scanning of the entire pancreas during the most intense period of pancreatic enhancement.
Fletcher et al. [7] reported that mean pancreatic attenuation was significantly greater in the pancreatic phase (107 ± 30 H) than in the arterial (65 ± 23 H) or hepatic (98 ± 29 H) phases. In their report, pancreatic enhancement was greatest in the pancreatic phase in 27 (71%) of 38 patients, whereas pancreatic enhancement was greatest in the hepatic phase in 11 (29%) of the patients. It is known that pancreatic parenchyma in chronic pancreatitis or parenchyma distal to pancreatic carcinoma causing a stricture and dilatation of the main pancreatic duct may be insufficiently enhanced in the pancreatic phase [16]. This phenomenon may be attributable to edema, atrophy, or fibrosis of varying degrees or to a combination of these pathologic changes in the pancreatic parenchyma. Parenchyma in such cases may be slightly more enhanced than in the late phase. However, because pancreatic carcinoma often becomes enhanced in the late phase [17], probably owing to internal desmoplastic reaction, late phase imaging may not maximize tumor-to-pancreas contrast.
In our study, the abdominal aorta showed peak enhancement 10 seconds after bolus tracking was triggered and the superior mesenteric artery 5 seconds after triggering, whereas the proximal portal, splenic, and superior mesenteric veins became moderately to intensely enhanced at 10-15 seconds. Thus, instead of choosing a single time point, we suggest 5-10 seconds after bolus-tracking triggering as optimal scanning delays for peripancreatic arteries (i.e., combining aorta and superior mesenteric artery). For 3D display of peripancreatic arteries in preoperative evaluations, an imaging delay of 5 seconds after triggering may be optimal because the changes in attenuation of the aorta and the superior mesenteric artery were exceptionally high with negligible enhancement of peripancreatic veins at this time. This finding indicates this time may be optimal for CT angiographic source images of the peripancreatic arteries. Our qualitative evaluation results support this deduction.
Splenic and superior mesenteric veins had peak enhancement 25 and 30 seconds, respectively, after bolus-tracking triggering. These delays, however, may not be optimal for evaluating venous invasion because of the frequent presence of heterogeneous enhancement [7] caused by incompletely mixed contrast material returning from organs through the splenic, superior mesenteric, and main portal veins. As a result, flattening or narrowing of vessels may not be easily discernible, particularly when a vessel abuts a pancreatic tumor [7]. On the other hand, images obtained with a delay of 45 seconds or more after triggering showed relatively intense enhancement in the splenic, superior mesenteric, and portal veins. The liver parenchyma was also most intensely enhanced (58-61 H) 45-55 seconds after triggering. These observations suggest that scanning the liver and peripancreatic veins at one time with a delay of 45 seconds or more after triggering may be desirable in view of the requirement for optimal liver evaluation, and venous involvement and the need to minimize X-ray exposure from multiple-phase scanning.
We used a relatively high injection rate of 4 mL/s. This rate was found to be clinically acceptable in all patients despite debate about contrast material injection rates. For example, Tublin et al. [18] reported that peak enhancement of the pancreas and liver were significantly different for two contrast injection rates (2.5 vs 5.0 mL/s), and Kim et al. [13] reported that contrast material volume and injection rate are directly related to pancreatic parenchymal enhancement; that is, pancreatic parenchymal enhancement increased as injection rate and volume were increased.
Our study had limitations. First, we did not directly evaluate tumor-to-pancreas contrast with pancreatic tumors because of the small number of patients with pancreatic tumors. We assume that improvement in enhancement of the pancreatic parenchyma will help in diagnosis and staging of pancreatic tumors. Second, we recognize that the time-to-peak contrast enhancement would certainly be affected by individual patients' cardiac outputs and circulation times. We measured group means in our study because we assumed individual patient variations would average out and become less critical in group comparison.
In conclusion, for the injection protocol used in this study, optimal scanning delays after bolus tracking triggered at 50 H of aortic contrast enhancement were 5-10 seconds for the peripancreatic arterial phase, 15-20 seconds for the pancreatic parenchymal phase, and 45-55 seconds for the hepatic parenchymal phase. Individualized scanning delays based on the bolus-tracking technique appear useful for improvement of contrast enhancement in multiphase MDCT of the pancreas, peripancreatic vessels, and liver.
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