ª Springer Science+Business Media, LLC 2009
Abdominal Published online: 9 July 2009
Imaging
Pancreatic adenocarcinoma: a comparison
of automatic bolus tracking and empirical scan
delay
Yoshihiko Fukukura, Koji Takumi, Takuro Kamiyama, Toshikazu Shindo,
Ryutaro Higashi, Masayuki Nakajo
Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka,
Kagoshima City 890-8544, Japan
Abstract
Background: To evaluate the efficacy of automatic bolus
tracking in multidetector row CT (MDCT) for pancre-
atic adenocarcinoma as compared with standard scan
delay using the fixed duration contrast injection tech-
nique.
Materials and methods: Seventy-nine patients with
pancreatic adenocarcinomas underwent three-phase
enhanced CT with an individualized scan delay as deter-
mined by automatic bolus tracking (protocol 1) or an
empiric scan delay (protocol 2). We evaluated enhance-
ment of the aorta, portal vein, hepatic parenchyma,
pancreatic parenchyma, and pancreatic adenocarcinoma
during each phase. Two radiologists graded the conspicu-
ity of pancreatic adenocarcinoma in the pancreatic
parenchymal phase. The results for the different groups
were statistically compared.
Results: Pancreatic parenchymal enhancement (mean ±
standard deviation, 100.2 HU ± 17.6 vs. 88.5 HU ± 22.1;
P < 0.05) and tumor-to-pancreas contrast (mean ± stan-
dard deviation, 75.3 HU ± 25.0 vs. 63.1HU ± 24.1;
P < 0.05) were significantly greater in protocol 1 than
in protocol 2 during pancreatic parenchymal phase.
Qualitative results correlated well with quantitative results
(reviewer 1: Rs = 0.78, P < 0.001; reviewer 2: Rs = 0.66,
P < 0.001)
Conclusion: The use of automatic bolus tracking with
MDCT can significantly improve the degree of contrast
enhancement in the pancreatic parenchyma and tumor-
to-pancreas conspicuity.
Correspondence to: Yoshihiko Fukukura; email: yoshihiko2002jp@
yahoo.co.jp
Abdom Imaging (2010) 35:548–555
DOI: 10.1007/s00261-009-9560-5
Key words: MDCT—Pancreatic
adenocarcinoma—Contrast media—CT
technique—Bolus tracking
CT of the pancreas has been widely accepted for depic-
tion and preoperative staging of pancreas cancer [1, 2],
and recent advances in this field have allowed imaging of
the abdomen during the optimal phase after intravenous
injection of a bolus of contrast material [3]. Pancreatic
phase imaging plays an especially important role in the
detection of pancreatic adenocarcinoma [4–7]. Inappro-
priately timed imaging will result in suboptimal timing of
the CT images, a reduction of tumor conspicuity, and
missed diagnosis. With the advent of multidetector row
CT (MDCT), the acquisition time for upper abdominal
imaging is less than 5–10 s, which may be short enough
to capture peak enhancement in visceral organs by
optimizing contrast medium injection and scan proto-
cols. Appropriate scan timing with MDCT, however, is
more difficult and critical than with single-detector row
CT because of such extremely rapid scan speed with
MDCT scanners [5, 8, 9]. The time to peak contrast
enhancement would certainly be affected by circulation
time and injection duration [10]. A bolus-tracking tech-
nique has become widely available for the optimization
of scan timing in individual patients to compensate for
the variation of circulation time between patients,
although the technique requires additional patient
imaging. The usefulness of a bolus tracking in aortic or
hepatic dynamic CT has been analyzed in several previ-
ous studies [11–15]. However, there have been few
reports about the usefulness of automatic bolus tracking
with MDCT for pancreatic adenocarcinoma as com-
pared with the use of standard scan delay. On the other
Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma
hand, several researchers recently have proposed con-
trast injection protocol with dose tailored to patient
weight and fixed injection duration to minimize indi-
vidualizations of contrast enhancements in aortic,
hepatic, or pancreatic CT [16–19]. Nevertheless, it is
unclear whether or not bolus-tracking technique results
in actual advantages as compared with standard scan
delay with dose tailored to patient weight and fixed
injection duration. Therefore, the purpose of our study
was to evaluate the efficacy of automatic bolus tracking
in MDCT for pancreatic adenocarcinoma compared
with standard scan delay using the fixed duration con-
trast injection technique.
Materials and methods
Patients and contrast material injection
This study was approved by our institutional review
board and informed consent was obtained from all pa-
tients.
Between January 2006 and June 2007, we enrolled 250
patients (147 men and 103 women; age range, 16–
91 years; mean age, 65 years) in this prospective study.
Inclusion criteria were suspicion of pancreaticobiliary
diseases at ultrasonography or elevated tumor marker
levels (CA19-9 or DUPAN-2) and absence of renal fail-
ure (serum creatinine level >1.5 mg/dL) or absence of a
contraindication to iodinated contrast material. All pa-
tients satisfied both criteria. In 81 of these patients, the
final diagnosis of pancreatic adenocarcinoma ranging in
size from 11 to 135 mm (mean, 38.3 mm) was confirmed
histopathologically in 50 patients by either surgery (n =
38) or biopsy (n = 12). Remaining 31 patients were
diagnosed with a combination of elevated tumor marker
levels, and imaging findings, including ultrasonography,
18
F-fluorodeoxyglucose positron emission tomography,
and follow-up enhanced CT for over 1 year. However, 2
patients were excluded from this study because of inad-
equate scan timing or injection rate. This study group
therefore comprised 79 patients with pancreatic
adenocarcinomas (43 men and 36 women; age range, 46–
86 years; mean age, 69 years; body weight range, 38–
74 kg; mean body weight, 53 kg). In this study, cardiac
function was assessed based on interviews and medical
charts. Physicians interviewed the patients before the CT
examination in order to examine whether they were
receiving or had previously received medical treatment
for cardiovascular disease. We also reviewed the medical
charts in all patients and cardiac ultrasound results in 58
patients. Seventy-six patients were considered to have
normal cardiac function.
The patients were randomly assigned to one of two
protocols. In protocol 1, an individual scan delay was
determined by automatic bolus-tracking methods, and in
protocol 2, fixed scan delay from the beginning of contrast
material injection was used. Forty of the 79 patients were
549
assigned to protocol 1, and 39 were assigned to protocol 2.
The protocol 1 group comprised 21 men and 19 women
aged 52–86 years (mean, 68.1 years) and weighing 38–
71 kg (mean, 52.0 kg). The protocol 2 group comprised 22
men and 17 women aged 46–86 years (mean, 69.9 years)
and weighing 39–74 kg (mean, 53.8 kg). No statistically
significant difference in the distribution of sex (P = 0.73,
v2 test), age (P = 0.40, two-tailed Student t test), body
weight (P = 0.36, two-tailed Student t test), height
(P = 0.50, two-tailed Student t test), body mass index
(BMI), which is defined as the weight in kilograms divided
by the square of the height in meters (P = 0.50, two-tailed
Student t test), or body surface area (BSA [m2] = square
root of product of weight [kg] 9 height [cm]/60)
(P = 0.50, two-tailed Student t test) was observed
between the two protocols. Furthermore, there were no
significant differences between the two protocols in size
(P = 0.74, two-tailed Student t test) or location (P =
0.93, v2 test) of pancreatic adenocarcinoma (Table 1).
Thirty-nine patients in protocol 1 and 37 patients in pro-
tocol 2 were considered to have normal cardiac function
(P = 0.98, v2 test). In patients with normal cardiac func-
tion, there was no statistically significant difference in the
distribution of sex (P = 0.63, v2 test), age (P = 0.56, two-
tailed Student t test), body weight(P = 0.22, two-tailed
Student t test), height (P = 0.41, two-tailed Student
t test), BMI (P = 0.37, two-tailed Student t test), BSA
(P = 0.21, two-tailed Student t test), tumor size (P =
0.89, two-tailed Student t test), or tumor location
(P = 0.76, v2 test) between the two protocols.
CT acquisition
CT was performed on a 16-MDCT scanner (Aquilion,
Toshiba Medical Systems). All scans began at the top of
the liver and went through to the end of the pancreas
with tube voltage of 120 kVp and gantry rotation speed
of 0.5 s. Unenhanced images were acquired using fol-
lowing parameters: tube current of 350 mA, detector row
configuration of 16 9 2 mm, and table increment of
30 mm/rotation. Imaging parameters for three-phase
enhanced images were as follows: tube current of
440 mA, detector row configuration of 16 9 1 mm, and
table increment of 15 mm/rotation in the cephalocaudal
direction. In all patients, 2 mL per kilogram of body
weight of nonionic contrast material with an iodine
concentration of 300 mg I/mL was injected over a fixed
duration of 30 s, and 20 mL of saline was injected at the
same rate immediately after the end of contrast material
injection through a 20-gauge plastic intravenous catheter
sited in an upper extremity vein, typically an antecubital
vein. In protocol 1, the automatic bolus-tracking method
was employed using Sure Start software (Toshiba,
Tokyo) in order to determine individual scan delays from
administration of contrast material to commencement of
the first pass. For bolus tracking, a series of nonhelical
550 Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma

Table 1. All patients in protocol 1 and 2

Patient or protocol characteristics Protocol 1 (n = 40) Protocol 2 (n = 39) Difference between
protocol 1 and 2

Gender (male:female) 21:19 22:17 P = 0.73

Age (year) P = 0.40
Range 52–86 46–86
Mean ± SD 68.1 ± 8.8 69.9 ± 10.5
Body weight (kg) P = 0.36
Range 38–71 39–74
Mean ± SD 52.0 ± 9.2 53.8 ± 8.4
Height (cm) P = 0.50
Range 138–177 140–174
Mean ± SD 156.0 ± 9.9 157.4 ± 9.3
Body mass index P = 0.50
Range 16.3–27.4 17.3–29.0
Mean ± SD 21.3 ± 3.1 21.7 ± 2.7
Body surface area (m2) P = 0.36
Range 1.20–1.80 1.25–1.87
Mean ± SD 1.49 ± 0.16 1.53 ± 0.15
Attenuation in unenhanced CT (HU)
Pancreatic parenchyma 36.6 ± 11.9 35.2 ± 7.8 P = 0.56
Adenocarcinoma 35.2 ± 7.2 34.1 ± 5.1 P = 0.42
Size of adenocarcinoma (mm) 39.1 ± 16.8 37.6 ± 21.9 P = 0.74
Location of adenocarcinoma P = 0.93
(head:body:tail) 22:12:6 23:11:5
Normal cardiac function 39/40 37/39 P = 0.98

sequential images were obtained 8 s after administering
the contrast material. These images were acquired with a
gantry rotation speed of 0.5 s and a low-dose radiation
technique (120 kVp, 50 mA). A circular region of inter-
est (ROI) with an area of 50 pixels was placed in the
aorta at the level of the celiac axis. The arterial phase
scan was initiated automatically 8 s after the bolus-
tracking program detected the threshold enhancement of
50 HU in the aorta. The pancreatic parenchymal phase
scan was commenced after a 10-s breathing interval. The
time interval between pancreatic parenchymal and portal
venous phase scanning was fixed at 27 s (Fig. 1). In
Fig. 1. Diagram shows the CT scanning protocol 1. Arterial
phase was started at 8 s after the trigger, pancreatic paren-
chymal phase was stared 10 s after completion of the scan-
ning of the arterial phase, and portal venous phase was
started 27 s after initiation of the scanning of the pancreatic
parenchymal phase.
protocol 2, based on our experience between January
through December 2005 of 113 three-phase enhanced
MDCTs using the bolus-tracking program which was the
same scan protocol as protocol 1 in this study, the scan
delay from the administration of contrast material to the
start of arterial, pancreatic parenchymal, and portal
venous phase were fixed at 25, 43, and 70 s, respectively.
Quantitative assessment
In all 79 patients, the attenuation values of the aorta,
portal vein, hepatic parenchyma, pancreatic paren-
chyma, and pancreatic adenocarcinoma during each
phase were measured at a workstation (SYNAPS;
Fujifilm, Tokyo, Japan) by a board-certified radiologist
(K.T) who had no knowledge of the scanning protocol.
Circular ROIs were set over each region on the unen-
hanced scans and on the contrast-enhanced scans in both
groups. An attempt was made to place the ROIs at
approximately the same site on each scan from the same
patient. In the aorta, portal vein, and liver parenchyma,
attenuation values were measured at the level of the
porta hepatis. However, six patients with pancreatic
adenocarcinomas obstructing both the superior mesen-
teric and splenic veins were excluded from measurement
of portal vein and liver parenchyma because it was dif-
ficult to evaluate the degree of contrast enhancement
accurately. An attempt was made to maintain a constant
ROI area of approximately 100 mm2 for the aorta and
25 mm2 for the portal vein. Hepatic parenchymal atten-
uation values were measured on the image at the level of
the porta hepatis, while attempting to maintain a con-
stant ROI area of approximately 200 mm2. Visible blood
Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma
vessels, bile ducts, and artifacts were carefully excluded
from the ROIs for the hepatic parenchyma. For the
pancreatic parenchyma, measurements were obtained in
the head, body, and tail of the pancreas and were aver-
aged for each patient, while attempting to maintain a
constant ROI area of at least 25 mm2. Visible blood
vessels, pancreatic ducts, calcifications, and artifacts
were carefully excluded from the ROIs for the pancreatic
parenchyma. Moreover, 70 of 237 portions of the pan-
creas were excluded from the ROI analysis because of
atrophic change or tumor involvement. The ROI for the
pancreatic adenocarcinoma was carefully placed within
the confines of the entire lesion. As a rule, for heterog-
enous lesions, ROIs were placed to include the entire
lesion without excluding the various components with
different CT attenuation values. However, calcified
regions of the adenocarcinoma were avoided in the ROI
analysis.
The contrast enhancement value was calculated from
the difference in CT values between the unenhanced
image and each of the enhanced images. In addition,
tumor-to-pancreas contrast defined was calculated as the
difference in attenuation between the adenocarcinoma
and the pancreatic parenchyma.
Qualitative assessment
Two board-certified radiologists (T.K. and Y.F., with 7
and 15 years of experience, respectively) who were blin-
ded to the scanning protocol, independently performed
visual assessments of the conspicuity of pancreatic ade-
nocarcinoma in the pancreatic parenchymal phase. We
prepared the following four-point visual scale to grade
image quality: grade 1 indicated poor conspicuity (tumor
is barely shown); grade 2 indicated fair conspicuity
(tumor is shown but not clear); grade 3 indicated good
conspicuity (tumor is clearly shown but the border is not
clear); and grade 4 indicated excellent conspicuity (tumor
is clearly shown with a definite border) (Fig. 2). All
images were reviewed in random order on the worksta-
tion with the standard window settings used at our
institution (window width, 350 HU; window level, 70
HU). However, the radiologists were allowed to change
the window level and window width.
Statistical analysis
Statistical analyses were performed with a software
package (SPSS, version 14.0; SPSS, Chicago, III). Nor-
mally distributed continuous data were presented as
mean ± standard deviation. We used the two-tailed
Student’s t test to assess differences in enhancement of
the aorta, portal vein, hepatic parenchyma, pancreatic
parenchyma, pancreatic adenocarcinoma, and tumor-to-
pancreas contrast values in protocols 1 and 2. The
Mann–Whitney U test was used to compare the
551
conspicuity of pancreatic adenocarcinoma during pan-
creatic parenchymal phase in the two protocols. To as-
sess the interobserver variability in the visual analysis of
tumor conspicuity, we applied the j test of concordance
to measure the degree of agreement between the two
radiologists. We applied t statistics to estimate the 95%
CI of the population mean for tumor-to-pancreas con-
trast in the pancreatic parenchymal phase for each visual
grade. The relationship between tumor-to-pancreas
contrast in the pancreatic parenchymal phase and the
visual grades of tumor conspicuity was analyzed by using
the Spearman rank correlation coefficient (Rs). For all
statistical analysis, a P value of less than 0.05 was con-
sidered statistically significant.
Results
The aortic enhancement threshold of 50 HU was reached
between 11.4 and 24.7 s (mean ± standard deviation,
16.4 ± 2.8 in all patients and 16.3 ± 2.9 in patients with
normal cardiac function) in protocol 1. Mean time to
arterial phase acquisition as determined by bolus track-
ing was 24.4 s (range: 19.4–32.7 s; 95% confidence
interval: 23.5, 25.3). Because the duration of each scan,
depending on the individual size of the hepatic and
pancreatic region, ranged from 6.8 to 9.8 s (mean,
8.1 ± 0.7 s), scan delays for pancreatic parenchymal and
portal venous phases after the administration of contrast
material were 38.3–50.2 s (mean: 42.5 s; 95% confidence
interval: 41.6, 43.4), and 65.3–77.2 s (mean: 69.5 s; 95%
confidence interval: 68.6, 70.4), respectively.
Aortic enhancement was significantly greater in pro-
tocol 1 than in protocol 2 during arterial phase (300.4
HU ± 51.5 vs. 268.8 HU ± 64.4, P < 0.05). Contrast
enhancement of the portal vein, hepatic parenchyma,
and pancreatic adenocarcinoma in all phases of protocol
1 was equivalent to that in protocol 2. Enhancement of
the pancreatic parenchyma (100.2 HU ± 17.6 vs. 88.5
HU ± 22.1, P < 0.05) and tumor-to-pancreas contrast
(75.3 HU ± 25.0 vs. 63.1HU ± 24.1, P < 0.05) in the
pancreatic parenchymal phase were significantly greater
in protocol 1 than in protocol 2 (Table 2). Significant
differences were observed between the two protocols in
the visual grades of tumor conspicuity assigned by both
reviewers, with images obtained by protocol 1 graded
better conspicuity than those obtained using protocol 2
(reviewer 1: p < 0.01, reviewer 2: P < 0.05) (Table 3).
There was good interobserver agreement for the grade of
tumor conspicuity (j = 0.69). There was a significant
correlation between qualitative and quantitative results
(reviewer 1: Rs = 0.78, P < 0.001; reviewer 2: Rs =
0.66, p < 0.001) (Table 4).
In the 76 patients with normal cardiac function,
enhancement of the portal vein, hepatic parenchyma,
and pancreatic adenocarcinoma in all phases of protocol
1 was equivalent to that in protocol 2. Contrast
552 Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma

b Fig. 2. Examples of visual grading of the conspicuity of

pancreatic adenocarcinoma in the pancreatic parenchymal
phase. A 57-year-old man with pancreatic adenocarcinoma in
pancreatic head (arrows). Image in A was classified as visual
grade 1 (poor tumor conspicuity). B 77-year-old woman with
pancreatic adenocarcinoma in pancreatic head (arrows). Im-
age in B was classified as visual grade 2 (fair tumor conspi-
cuity). C 62-year-old woman with pancreatic adenocarcinoma
in pancreatic head (arrows). Image in C was classified as
visual grade 3 (good tumor conspicuity). D 75-year-old man
with pancreatic adenocarcinoma in pancreatic head (arrows).
Image in D was classified as visual grade 4 (excellent tumor
conspicuity).

enhancement of the aorta during arterial phase (297.9

HU ± 49.6 vs. 271.9 HU ± 63.4, P < 0.05), contrast
enhancement of the pancreatic parenchyma during pan-
creatic parenchymal phase (100.8 HU ± 17.4 vs. 89.3
HU ± 22.5, P < 0.05), and tumor-to-pancreas contrast
during pancreatic parenchymal phase (75.1 HU ± 25.3
vs. 62.9 HU ± 24.7, P < 0.05) were significantly greater
in protocol 1 than in protocol 2. There was good inter-
observer agreement for the grade of tumor conspicuity
(j = 0.73). Qualitative results also correlated well with
quantitative results (reviewer 1: Rs = 0.78, P < 0.001;
reviewer 2: Rs = 0.69, P < 0.001).

Discussion
The enhancement achieved after intravenous injection of
contrast material is determined by a combination of
factors, such as delay time from the start of contrast
injection, dose of contrast material, injection rate,
injection duration, and patient characteristics including
age, sex, weight, BMI, and BSA. One of the most
important patient-related factors affecting the magnitude
of vascular and parenchymal contrast enhancement is
body weight [16–19]. In our series, the total dose of
contrast material (600 mg I/kg) and the injection rate
(20 mg I/kg/s) were tailored to patient body weight. The
design of our study also allowed us to eliminate any
statistically significant influence of the patient-related
factors (age, sex, weight, height, BMI, and BSA) on
contrast enhancement.
In the present study, mean time to arterial phase
acquisition after the initiation of contrast material
injection was 24.4 s as determined by the bolus-tracking
method (protocol 1) and 25 s as determined by fixed scan
delay (protocol 2). We believe that images obtained at a
scan delay of approximately 25 s after the initiation of
contrast material injection are suitable for 3D displays of
the peripancreatic arteries in preoperative evaluation,
because aortic enhancement was prominent enough with
negligible enhancement of the pancreatic parenchyma
and portal vein. Bae et al. [10] demonstrated in their
pharmacokinetic study in a porcine model that time to
Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma 553

Table 2. Contrast enhancement in all patients

Area measured Contrast enhancement (HU) (Mean ± SD) P

Protocol 1 (n = 40) Protocol 2 (n = 39)

Aorta
Arterial phase 300.4 ± 51.5 268.8 ± 64.4 <0.05
Pancreatic phase 319.1 ± 56.5 294.2 ± 93.0 0.15
Portal venous phase 127.1 ± 13.9 122.5 ± 20.8 0.25
Portal vein 20.2 ± 21.0 20.6 ± 18.9 0.93
Arterial phase
Pancreatic phase 143.1 ± 35.6 136.1 ± 48.9 0.49
Portal venous phase 136.7 ± 17.4 134.4 ± 21.4 0.61
Liver parenchyma 5.0 ± 5.0 6.8 ± 4.5 0.12
Arterial phase
Pancreatic phase 31.2 ± 13.2 33.7 ± 14.8 0.45
Portal venous phase 61.1 ± 10.2 59.9 ± 10.7 0.63
Pancreatic parenchyma 43.0 ± 15.0 40.4 ± 22.2 0.54
Arterial phase
Pancreatic phase 100.2 ± 17.6 88.5 ± 22.1 <0.05
Portal venous phase 73.5 ± 14.2 66.3 ± 20.5 0.07
Pancreatic adenocarcinoma 9.9 ± 8.4 10.1 ± 8.3 0.89
Arterial phase
Pancreatic phase 26.3 ± 16.6 26.6 ± 17.1 0.94
Portal venous phase 29.9 ± 20.0 32.2 ± 19.4 0.61
Tumor-to pancreas contrast 1.3 ± 12.9 1.1 ± 6.9 0.93
Unenhanced CT
Arterial phase 34.5 ± 20.6 31.4 ± 22.4 0.52
Pancreatic phase 75.3 ± 25.0 63.1 ± 24.1 <0.05
Portal venous phase 44.9 ± 23.5 35.3 ± 26.7 0.09

Table 3. Visual assessment for detecting pancreatic adenocarcinoma empirical delay (protocol 2) during arterial phase. This is
during pancreatic parenchymal phase in all patients
supported by previous study that showed that the indi-
Grade Mean % of cases (no. of cases assigned by Reviewer vidual variations of aortic enhancement can be reduced
1 and 2)
using a fixed-duration injection technique, but there are
Protocol 1 (n = 40) Protocol 2 (n = 39) still substantial variations [17].
In general, enhancement of the pancreatic paren-
4 20.0 (8, 8) 5.1 (2, 2)
3 61.3 (25, 24) 56.4 (21, 23) chyma parallels that of the aorta, and peak pancreatic
2 18.8 (7, 8) 29.5 (13, 10) parenchymal enhancement might occur several seconds
1 0.0 (0, 0) 9.0 (3, 4) behind peak aortic enhancement because the pancreatic
parenchyma are supplied arterial flow from the abdom-
inal aorta. In our study, mean time to pancreatic phase
Table 4. Tumor-to pancreas contrast values during pancreatic paren-
chymal phase by visual grade in all patients acquisition was 42.5 s as determined by the bolus-
tracking technique (protocol 1) and 43 s as determined
Grade Mean tumor-to pancreas 95% Confidence interval
contrast (HU) (HU) by fixed scan delay (protocol 2). Based on the results of
previous studies, the time to peak pancreatic enhance-
Reviewer 1 Reviewer 2 Reviewer 1 Reviewer 2 ment is 43 s when contrast material is injected over 30 s
4 105.7 ± 15.0 101.1 ± 18.0 94.9, 116.4 88.2, 114.0 without saline pushing [20]. Goshima et al. [18] reported
3 74.3 ± 15.8 73.0 ± 18.8 69.6, 79.0 67.5, 78.6 that optimal scan delay for imaging the pancreas was 35–
2 46.8 ± 15.2 51.3 ± 18.4 39.7, 53.9 42.1, 60.4 45 s using a combination of a body-weight-tailored dose
1 23.6 ± 14.1 28.6 ± 15.2 -11.5, 58.7 4.4, 52.8
of contrast material and fixed 30-s injection duration
without saline pushing. We injected 20 mL of saline
peak aortic enhancement is determined by the relative during approximately 6 s to push out contrast material
contributions of injection duration and contrast medium remaining in the injector tubing, peripheral veins, supe-
traveling time. In the present study, contrast material rior vena cava, and right heart after the end of contrast
was injected for a fixed 30-s period regardless of patient material injection. Theoretically, aortic peak time is
weight. Therefore, time to peak aortic enhancement was consistent with the sum of aortic arrival time and the
affected by aortic arrival time of contrast medium. duration of the injection [10, 21]. The saline pushing
Considering the wide range of aortic transit time (11.4– technique saves contrast medium and prolongs the time
24.7 s) among patients, it is not surprising that aortic to the peak aortic enhancement [22]. With the present
enhancement was significantly greater in scanning with a both injection protocols with saline pushing, optimal
bolus-tracking technique (protocol 1) than with an scan delay might be somewhat later than in their studies.
554 Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma
We believe that time to pancreatic phase acquisition in
the present both protocol is optimal for imaging the
pancreas.
Pancreatic adenocarcinoma tends to be most
conspicuous when the pancreatic parenchyma is
well-enhanced because most pancreatic adenocarcino-
mas show hypovascularity and delayed enhancement [3,
4]. Therefore, considerable enhancement of the pancre-
atic parenchyma is essential to ensure high tumor-to-
pancreas contrast. Tumor delineation is mainly based
on the presence of tumor-to-pancreas contrast during
contrast-enhanced CT. The timing of optimal scanning
delay for the pancreatic parenchymal phase is crucial in
the detection of pancreatic adenocarcinoma [4–7, 18,
23]. However, most prior investigators have relied on
fixed delays when evaluating pancreatic adenocarcino-
mas without incorporating circulation time differences
in individual patients, which significantly influence peak
enhancement [4–7]. To our knowledge, there have been
no reports evaluating the usefulness of automatic bolus
tracking in MDCT for pancreatic adenocarcinoma as
compared with standard scan delay using the fixed
duration contrast injection technique, although bolus
tracking can adjust the scan delay individually by
compensating for the variation of circulation time. In
the present quantitative analysis, enhancement of the
pancreatic parenchyma was significantly greater in
scanning with the bolus-tracking technique (protocol 1)
than with an empirical delay (protocol 2) during
the pancreatic parenchymal phase. Tumor-to-pancreas
contrast in the pancreatic phase was significantly
greater in scanning with the bolus-tracking technique.
In visual evaluation of tumor conspicuity, the lower
limits of the 95% CI for tumor-to-pancreas contrast in
the pancreatic phase were 69.6 HU in reviewer 1 and
67.5 HU in reviewer 2 for grade 3. Given these results,
we regarded 67.5 HU as the lower limit for a good
tumor conspicuity which provides adequate information
for making a radiologic diagnosis. The mean tumor-to-
pancreas contrast in the pancreatic phase exceeded 67.5
HU in scanning with the bolus-tracking technique
(protocol 1), but it was lower in scanning with an
empirical delay (protocol 2).
The portal venous phase is suitable for delineating the
portal venous branches by achieving intense and
homogenous enhancement of portal venous system and
for detecting liver metastases by achieving adequate
enhancement of the hepatic parenchyma [23]. In this
study, the use of a bolus-tracking technique did not im-
prove the contrast enhancement of the portal vein and
hepatic parenchyma during the portal venous phase. This
can be attributed to the enhancement curve of the portal
vein and hepatic parenchyma which shows a relatively
gentle and prolonged slope in the portal venous phase
[18, 22–24]. Accordingly, the variation of circulation time
between patients might not have markedly affect contrast
enhancement of the portal vein and hepatic parenchyma
during this prolonged slope.
In our patients who lacked clinical evidence of car-
diac dysfunction, enhancement of the aorta during
arterial phase, enhancement of the pancreatic paren-
chyma during pancreatic parenchymal phase, and tu-
mor-to-pancreas contrast during pancreatic paren-
chymal phase were significantly greater in scanning with
the bolus-tracking technique (protocol 1) than with an
empirical delay (protocol 2). Our results suggested that
the time to the aortic and pancreatic peak enhancement
can vary significantly even in patients without cardiac
dysfunction. However, the results of previous studies
demonstrated that the use of bolus-tracking did not
improve the aortic enhancement [25] or attenuation
conspicuity of hepatocellular carcinoma in patients
considered to have normal cardiac function [15]. The
reason for the discrepancy between their results and our
results might be differences in the study populations.
Forty-one (51.9%) of 79 patients in the present study
was 70 years of age or over, and mean patient age was
larger in this study than in their studies. As patient age
increases, aortic transit time increases [13]. Itoh et al.
[15] reported that automatic bolus tracking is preferable
in patients over 70 years of age. However, half the
number of patients with pancreatic adenocarcinomas
are over the age of 70 years [26]. Moreover, it may be
difficult to always adjust scan delay to patient age in
routine clinical work.
The present study has several potential limitations.
First, the study population with histopathologically
proven pancreatic adenocarcinoma was small. However,
all patients had confirmatory imaging examinations,
including ultrasonography and 18F-fluorodeoxyglucose
positron emission tomography followed by several fol-
low-up enhanced CTs. Second, because the ranges and
mean values of body weight in this study were smaller
than those of people in North America and Europe, the
applicability of our results to populations of greater body
weight must be confirmed in the future. A third criticism
could be that our timing for the pancreatic phase as
determined by the bolus-tracking method was affected by
the scan duration, which in turn depended on the indi-
vidual size of the hepatic and pancreatic regions. How-
ever, the range of scanning duration was narrow at 6.8–
9.8 s compared with the range of aortic transit time
(11.4–24.7 s). In addition, the accuracy of detecting
pancreatic adenocarcinoma and staging of this tumor
were not evaluated in the present study owing to small
number of patients with surgically proven pancreatic
adenocarcinoma and should be investigated in a future
study.
In conclusion, the results of the present study suggest
that a bolus-tracking technique can improve contrast
enhancement in the aorta and pancreatic parenchyma,
and give greater tumor-to-pancreas conspicuity as
Y. Fukukura et al.: Bolus tracking for pancreatic adenocarcinoma
compared with a standard scan delay using a fixed
injection duration technique even in patients with normal
cardiac function. Therefore, the bolus-tracking technique
is recommended for determining the optimal timing of
arterial and pancreatic parenchymal phase scanning.
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