DOI:10.2214/AJR.07.3047
AJR 2008; 190:W323-W326
© American Roentgen Ray Society
Comparison Between One-Route and Two-Route Injection for Liver and Aortic Enhancement Using MDCT
Masahiro Okada1,
Takamichi Murakami1,
Seishi Kumano1,
Izumi Imaoka1,
Taro Shimono1,
Ryuichiro Ashikaga1 and
Makoto Hosono1
1 Department of Radiology, Kinki University School of Medicine, 377-2
Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Received August 21, 2007;
accepted after revision December 6, 2007.
Address correspondence to M. Okada
(mokada{at}gaia.eonet.ne.jp).
WEB This is a Web exclusive article.
Abstract
OBJECTIVE. The purpose of our study was to evaluate whether
simultaneous injection into cubital veins bilaterally at one half of the
standard injection rate achieves similar hepatic and aortic enhancement on
MDCT as the conventional injection rate into a single cubital vein.
MATERIALS AND METHODS. Thirty-two patients underwent multiphase MDCT
because they were suspected of having a hepatic tumor. Patients were assigned
to one of the following two groups: group A, 100 mL of 370 mg I/mL of contrast
medium injected into a unilateral cubital vein (one-route) via a 20-gauge
cannula at a rate of 4 mL/s; or group B, 50 mL of contrast medium injected
into the cubital veins bilaterally (two-route) via 24-gauge cannulas at 2
mL/s. Peak contrast enhancement of the liver and abdominal aorta for groups A
and B was measured using regions of interest and compared; arrival time of the
contrast media was also compared using a bolus-tracking system. Analysis was
performed using Wilcoxon's signed rank test.
RESULTS. Peak aortic enhancement of groups A and B was 367 ±
67 H and 361 ± 113 H (p = 0.61, not significant),
respectively, and peak hepatic enhancement of groups A and B was 56 ±
11 H and 56 ± 16 H (p = 0.88, not significant), respectively.
Mean arrival time to the aorta of group B (19.4 ± 3.4 seconds) was
significantly later compared with that of group A (15.5 ± 3.5 seconds)
(p = 0.005).
CONCLUSION. The slower two-route injection produced the same aortic
and hepatic enhancement as the faster one-route method with faster injection,
but the arrival time of the contrast medium was later using the two-route
method.
Keywords: contrast medium injection protocol liver MDCT two-route injection
Introduction
Recent technologic advances in MDCT allow high temporal and spatial
resolution. The latest achievements in MDCT enable multi phase data to be
acquired rapidly during maximum vascular and liver parenchymal enhancement. An
optimal dynamic MDCT study is required to detect hypervascular hepatocellular
carcinoma (HCC), which is shown as a hyperattenuated lesion in the arterial
dominant phase [1]. This
hepatic artery phase is especially important for detecting tumor vascularity
[2,
3]. Double arterial phase
imaging is sometimes performed and is recommended to improve the detection of
hypervascular HCCs and reduce the incidence of false-positive lesions
[4].
The two-route injection method is performed by injecting contrast media
into the bilateral cubital veins of patients using a slower injection rate
than the conventional one-route injection. This method is unpopular because
the procedure is cumbersome; however, a slower injection rate is sometimes
used in daily routine CT because a large-size cannula cannot be kept in the
cubital vein of patients with thin blood vessels (e.g., elderly patients or
underweight patients). In these cases, it is almost impossible to obtain an
effective dynamic aortic and hepatic study using the conventional one-route
injection.
Although the effect of the injection rate
[5,
6] and iodine concentration
[7] of contrast media on liver
enhancement has been studied, to the best of our knowledge, no clinical data
have been published regarding aortic and liver enhancement obtained using a
method with two injection routes. We therefore designed the present study as a
retrospective review of acquired MDCT data to compare the effect of the
one-route and two-route contrast media injection methods for hepatic
enhancement in abdominal MDCT imaging. We also compared the arrival time of
contrast medium at the abdominal aorta between the two injection techniques to
assess the optimal scan timing for arterial phase imaging.
Materials and Methods
Subjects
This study followed the Declaration of Helsinki principles. Informed
consent was obtained from all patients who underwent the contrast-enhanced
MDCT examination. Because we studied the hepatic and aortic enhancement of
patients undergoing routine abdominal MDCT for clinical reasons, approval by
the institutional ethics committee was not required for this retrospective
study.

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Fig. 1 —Graph shows time-density curve using bolus-tracking system
(arrival time to abdominal aorta). Time taken (from initiation of injection of
contrast medium) for abdominal aorta to show enhancement greater than 100 H
from baseline attenuation was 18 seconds (arrival time) in this group B
(two-route technique) patient.
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Fig. 2 —Graph shows time-density curve using bolus-tracking system
(gradient of curves of first increase). Enhancement of 150 H from baseline
with rise time of 6 seconds was seen in this group B (two-route technique)
patient. Thus gradient of curve was 150/6 = 25 H/s.
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Between May 2003 and October 2003, 32 consecutive patients with chronic
liver diseases were scheduled to undergo four-phase hepatic CT (early arterial
phase, late arterial phase, portal venous phase, and equilibrium phase) using
MDCT. The patients consisted of 18 men and 14 women (age range, 24-89 years;
mean age, 68 years). Patients were referred to one of the following two
groups: group A, 100 mL of contrast medium injected into one antecubital vein
via a 20-gauge cannula at a rate of 4 mL/s (one-route injection method); or
group B, 50 mL of contrast medium injected into the cubital veins bilaterally
via two 24-gauge cannulas at a rate of 2 mL/s (two-route injection method).
Patients were placed in group B when a 20-gauge cannula could not be placed in
their cubital veins because of thin blood vessels. Neither group had
biopsy-proven HCC or definite HCC depicted on CT and MRI. None of the patients
had heart disease.
Imaging
A commercially available 8-MDCT scanner (LightSpeed Ultra QX/i, GE
Healthcare) was used for all patients, with the following protocol: tube
voltage, 120 kV; tube current, 400 mA; reconstruction section and interval
thickness, 5 mm; detector configuration, 8 x 1.25 mm; pitch, 1.35; and
0.5 second per rotation. All scanner settings remained unchanged throughout
the study. Initially, unenhanced phase images were obtained from the liver to
the kidneys. Single-level serial CT was performed at the level of the celiac
artery, and the arrival time of contrast medium to the abdominal aorta was
then measured using an automatic bolus-tracking program (Smart Prep, GE
Healthcare). The arrival time was defined as the time from the initial
injection of contrast medium until the abdominal aorta showed enhancement of
100 H greater than the baseline attenuation value
(Fig. 1).
We then obtained abdominal helical scans from the top of the liver to the
bottom of the kidneys with four-phase imaging (early arterial phase at 10
seconds after the arrival time, late arterial phase at 25 seconds after the
arrival time, portal venous phase at a fixed delay 80 seconds after the start
of contrast medium injection, and equilibrium phase at a fixed delay 180
seconds after the start of injection). The parameters for the automatic
bolus-tracking program were as follows: tube voltage, 120 kV; and tube
current, 40 mAs; 7 seconds was required after the contrast medium had arrived
in the abdominal aorta for the table to move to the start position. All
patients received 370 mg I/mL of nonionic contrast medium ([iopamidol]
Iopamiron 370, Bayer HealthCare). Two automatic injectors (Auto Enhance A50
and A250, Nemotokyorindo) were used without a saline flush for the two-route
injection in group B. One injector (Auto Enhance A250) was used without a
saline flush in group A. In our CT room, an A250 injector hanging from the
ceiling and an A50 injector moving across the floor were simultaneously used
for the procedure in group B. These injectors were manually operated from the
control room. Because we did not follow the injection with a saline bolus
after either the unilateral or bilateral injections, there was a
"loss" of a fixed amount of contrast medium (approximately 5-10
mL) in the tubing and veins. The acquired images were all saved as DICOM data
on a workstation (Virtual Place, AZE) for quantitative analysis.
Quantitative Analysis
We recorded the time the trigger threshold (> 100 H) was reached for
each patient and calculated the scanning time for the entire liver at the
early arterial and late arterial phases. For each patient, we calculated the
gradient of the curves of the first increase from the time-density curves of
the abdominal aorta using a bolus-tracking system
(Fig. 2). Regions of interest
(ROIs) of the aorta, area 0.5-1.0 cm2, and ROI of the liver, area
approximately 2 cm2, were placed over the aorta and liver
parenchyma of the unenhanced, early arterial, late arterial, portal venous,
and equilibrium phase images to analyze the enhancement values. All ROIs were
placed by one investigator who had 13 years of experience in liver CT, and the
mean enhancement values (in Hounsfield units) of the abdominal aorta and
hepatic parenchyma were measured. Aortic and hepatic enhancement values were
determined on three consecutive images at the level of the main portal vein.
Visible portal veins, hepatic veins, bile ducts, and artifacts were excluded
from ROI measure ments of the hepatic parenchyma. Measured enhancement values
obtained from the three consecutive images were averaged. Mean peak aortic and
peak hepatic enhancement values were compared between groups A and B, and the
arrival time of contrast medium to the abdominal aorta was also compared
between the groups. Statistical analysis was performed using the Wilcoxon's
signed rank test. The Statistical Package for the Social Sciences program
version 11.0 (SPSS) was used for analysis. A p value less than 0.05
was considered to indicate a statistically significant difference.
Results
The patients in groups A and B were similar in weight and age: the mean
body weight was 55 ± 7 kg (range, 45-73 kg) in group A and 57 ±
10 kg (range, 34-72 kg) in group B (p = 0.59, not significant),
whereas the mean age was 67 ± 11 years (range, 24-88 years) in group A
and 68 ± 14 years (range, 49-89 years) in group B (p = 0.73,
not significant). The iodine content of the injected contrast medium was 676
± 90 mg I/kg (range, 506-822 mg I/kg) in group A and 666 ± 143
mg I/kg (range, 513-1,088 mg I/kg) in group B. No technical failures in the
use of the bolus-tracking system or the IV injection of contrast medium (e.g.,
extravasation) were observed. No side effects due to the contrast medium were
noted.

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Fig. 3 —Scattergram shows time to reach trigger threshold for group A
(one-route technique). Arrival time of contrast medium to abdominal aorta is
shown. Aortic arrival times ranged from 10 to 23 seconds in group A.
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Fig. 4 —Scattergram shows time to reach trigger threshold for group B
(two-route technique). Arrival time of contrast medium to abdominal aorta is
shown. Aortic arrival time ranged from 16 to 28 seconds in group B.
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Quantitative Assessment
There was no significant difference between group A and B in the peak
aortic (p = 0.61) or peak hepatic (p = 0.88) enhancement
(Table 1). The mean arrival
time to the aorta was significantly longer in group B compared with that in
group A (p = 0.005) (Table
1). Figures 3 and
4 show scatter diagrams of the
arrival time of contrast medium to the abdominal aorta for groups A and B. The
range in aortic arrival time was 10-23 seconds in group A and 16-28 seconds in
group B.
Time-Density Curve Using the Bolus-Tracking System
We used the bolus-tracking system to calculate the gradient of the curves
of first increase using the time-density curves for the abdominal
aorta—that is, the character of aortic enhancement as the first pass of
contrast medium. Group A recorded 52.5 ± 24.8 H/s (range, 15.6-97.2
H/s), whereas group B recorded 42.0 ± 11.4 H/s (range, 23.2-61.2
H/s).
Discussion
An enhancing HCC lesion is hyperattenuated compared with surrounding liver
[8]; therefore, optimization of
scanning timing and adequate arterial enhancement are important factors for
dynamic liver MDCT study, especially in arterial phase imaging, to enable the
detection of HCC and characterization of liver tumors. The present study
revealed no significant difference in peak aortic and peak hepatic enhancement
between the one-route injection technique with a higher injection rate and the
two-route injection with a slower injection technique, although mean arrival
time to the aorta of the two-route injection was significantly longer than
that of the one-route injection technique with a higher injection rate.
Therefore the scanning delay time for the arterial phase was longer for the
two-route injection technique relative to the one-route injection technique
because of the delay in the mean arrival time of the contrast medium. Our
results indicated that we could produce sufficient arterial and liver
enhancement using the two-route injection technique even when only a
small-gauge cannula could be placed in the cubital vein because of the
patient's thin blood vessels.
Early and late arterial phase imaging with optimal timing can detect
hypervascular HCC. Kim et al.
[9] showed that an automated
bolus-tracking program can be used to time, optimally and individually, the
acquisition of hepatic artery phase CT images and stated that double arterial
phase images enabled the detection of small HCCs with greater sensitivity than
acquiring images with either of the single arterial phase scan timings. In the
present study, optimal scan timing of the arterial phase regarding detection
of HCC could not be evaluated in the two-route injection technique because
hypervascular HCC was not included in our data. Therefore further study is
required regarding the detection of HCC using the two-route injection
method.
In our clinical experience, dynamic CT can generally be performed
successfully using a higher injection rate of contrast medium to improve tumor
and vascular enhancement. Slower injection is sometimes used if a largersize
cannula cannot be kept in the cubital vein; however, the arrival time of the
contrast medium, and therefore optimal timing of the arterial phase of the
liver, is later using the two-route method. On the basis of pharmacokinetic
results, Bae et al. [10]
reported that the time to peak aortic enhancement is the sum of the injection
duration and bolus transfer time of the contrast medium from the injection
site to the aorta. In the present study, we used a fixed injection duration
(25 seconds) for both the one-route and two-route injection methods. Therefore
the bolus transfer time was different for the one-route and two-route
injections. Thus the possibility that there was a "delayed" mean
arrival time to the aorta for the slower two-route injection (19.4 ±
3.4 seconds) compared with the faster one-route injection (15.5 ± 3.5
seconds) is based on injection speed because faster injection rates lead to a
reduction in the time from injection to the beginning of the arterial phase.
We also believe that the cause may be partly related to venous dilution.
Several articles [11,
12] have already reported that
bolus-tracking with dynamic CT is useful in determining the optimal time,
whereas others have reported that it is not
[13,
14]. Mehnert et al.
[12] stated that the timing
using automatic bolus tracking is more accurate than in time-delay scanning.
They used a time delay of 25 seconds for the arterial phase and 55 seconds for
the portal venous phase or an automatic scan start triggered by contrast
enhancement of the aorta with a flow rate of 4.0 mL/s. On the basis of the
results of the present study, which showed the arrival time of contrast medium
to the abdominal aorta with the two-route injection technique different from
that with the one-route injection technique, we consider the use of a
bolus-tracking system effective in determining the optimal scan timing during
early and later arterial phase imaging—not only for the conventional
faster one-route method with a faster injection but also for the slower
two-route method with a slower injection.
Our study has some limitations. First, the study was designed and reviewed
as a daily routine study to test the feasibility of optimal dynamic
enhancement for liver imaging on a limited number of patients. Because the
patient groups were divided on the basis of vein size, it is possible that our
study includes selection bias. Thus further study is necessary to determine
the efficacy of two-route slower injection by conducting a randomized study.
Second, we did not assess the effect of the different injection rates and did
not use a method to determine the dose of contrast material based on patient
weight. According to previous reports, 1.7-2.0 mL/kg of contrast medium is the
recommended dose to obtain optimal enhancement of the liver
[15,
16]. On the basis of the
results of a previous study
[17], aortic peak time and
aortic peak enhancement are closely related to injection duration for a
protocol in which the dose of contrast material is determined according to
patient weight. Kim et al.
[18] stated that faster
injection rates can provide better results in revealing hypervascular liver
tumors. Different injection speeds and volumes of contrast material may cause
varying enhancement of the abdominal aorta and liver. Thus further study is
required to evaluate simultaneous injection into the bilateral cubital veins
in various clinical settings.
In conclusion, our results indicate no difference in the peak of hepatic
and aortic enhancement using the bilateral injection technique, but there is a
delay in aortic enhancement. It will be important in a future study to clarify
the effectiveness and efficiency of implementing the two-route injection
technique for aortic and hepatic peak enhancement for various injection
protocols.
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