DOI:10.2214/AJR.07.3452
AJR 2008; 191:772-777
© American Roentgen Ray Society
Optimal Arterial Phase Imaging for Detection of Hypervascular Hepatocellular Carcinoma Determined by Continuous Image Capture on 16-MDCT
Xiaozhou Ma1,
Anthony E. Samir,
Nagaraj-Setty Holalkere and
Dushyant V. Sahani
1 All authors: Department of Abdominal Imaging and Interventional Radiology,
Massachusetts General Hospital and Harvard Medical School, WHT 2-270, 55 Fruit
St., Boston, MA 02114.
Received November 20, 2007;
accepted after revision March 6, 2008.
D. V. Sahani has a research agreement with GE Healthcare, is a member of
the speaker bureau of Bracco Diagnostics, and is on the advisory board of
E-Z-EM Company.
Address correspondence to D. V. Sahani
(dsahani{at}partners.org).
Abstract
OBJECTIVE. The purpose of this study is to estimate the optimal time
delay before the initiation of arterial phase scanning for detection of
hypervascular hepatocellular carcinoma (HCC) on 16-MDCT when a rapid bolus
injection of contrast medium is administered.
SUBJECTS AND METHODS. In this prospective study, 25 patients (19 men
and six women; mean age, 63.5 years; age range, 50–81 years) with
pathologically confirmed HCC were included. Dynamic 16-MDCT imaging was
performed in cine mode using 70 mL of nonionic iodinated contrast medium (300
mg I/mL) at an injection rate of 7 mL/s. Four consecutive 5-mm-thick slices at
the maximum diameter of the HCC were selected as the region of interest.
Time–attenuation curves were generated by region of interest drawn on
the aorta, tumor, and liver. Qualitative assessments of conspicuity for
contrast medium wash-in, peak, and wash-out of aorta and tumor were
performed.
RESULTS. There were 108 arterial phase enhancing lesions (mean
[±SD], 4.9 ± 2.4 cm; range, 0.7–12.9 cm) in the 25
patients. The maximum Hounsfield value of aorta, tumor, and background liver
parenchyma were 463.8 ± 98 HU, 106.5 ± 19 HU, and 98.3 ±
14 HU, respectively. At the time of onset of peak tumor enhancement, the
difference between tumor density and background liver density was 38.2
± 19 HU. The time–attenuation curve showed that the mean times of
contrast enhancement start, peak, and end were 9.2 ± 2.7 seconds, 19.4
± 2.1 seconds, and 38 ± 13.5 seconds, respectively, for the
aorta, and 15.5 ± 2.6 seconds, 26.3 ± 2.9 seconds, and 57.7
± 14.4 seconds, respectively, for 25 pathologically confirmed
hepatocellular carcinomas. Qualitatively, the mean times of contrast
enhancement wash-in, peak, and washout were 10.2 ± 2.8 seconds, 19.9
± 3 seconds, and 39.9 ± 9.2 seconds, respectively for the aorta,
and 18 ± 4.2 seconds, 27 ± 3 seconds, and 55.7 ± 21
seconds, respectively, for tumor. There were no differences between
quantitative and qualitative measurements of wash-in and peak time for the
aorta (p = 0.00017, p = 0.00016) and tumor (p =
0.00163, p = 0.00040).
CONCLUSION. When using 70 mL of 300 mg I/mL of contrast medium with
an injection rate of 7 mL/s in 16-MDCT scanning, the optimal time to initiate
scanning for HCC is 26.3 ± 2.9 seconds (range, 24.0–34.5 seconds)
after contrast medium administration.
Keywords: hepatocellular carcinoma • liver • MDCT • MRI • peak enhancement • rapid bolus injection
Introduction
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and
the eighth most common cancer in women. Currently, it is one of the most
common causes of cancer related death worldwide
[1]. HCCs derive their blood
supply predominantly from the hepatic arterial system, whereas normal liver
parenchyma receives 70–80% of its blood supply from the portal vein
[2]. Dynamic contrast-enhanced
imaging studies exploit this physiologic difference by imaging the hepatic
parenchyma and HCC during the arterial phase of contrast enhancement, when
differential enhancement is maximized
[2,
3].
The technique of dual phase arterial scanning is a well-established imaging
technique that improves the detection of hypervascular HCC
[3,
4]. However, dual phase
arterial scanning does present technical challenges. Because of the highly
angiogenic tumor biology of HCCs, arteriovenous shunts are often present.
These shunts alter hepatic CT contrast kinetics, creating a narrow contrast
wash-in and wash-out imaging time window
[5]. Consequently, the optimal
execution of arterial phase imaging for the diagnosis of HCC
[3,
6–8]
is dependent on precise timing of image acquisition after administration of
the contrast bolus.
With the advent of MDCT, image acquisition time has been tremendously
reduced [9]. With current
16-MDCT scanners, arterial phase imaging of the entire liver can be
accomplished within 8–10 seconds and within 5 seconds with 64-MDCT
scanners. Previously published protocols for arterial phase imaging of the
liver have recommended that imaging commence 30–40 sec onds after the
initiation of IV contrast medium injection at a rate between 3 and 5 mL/s
[3,
9,
10]. The faster image
acquisition times of modern MDCT scanners raises the possibility that rapid
contrast administration followed by high speed MDCT image acquisition may
better differentiate HCC from liver parenchyma.
This study is aimed at estimating the optimal scanning delay before the
initiation of arterial phase scanning for the detection of HCC on 16-MDCT and
continuous data capture after the bolus injection of 300 mg I/mL of contrast
medium at a rate of 7 mL/s.
Subjects and Methods
Study Design
This prospective study was approved by the insti tutional review board and
conformed to HIPAA regu lations. All patients were required to provide written
informed consent before participation in the study. This project was part of a
phase 3 clinical trial of neoadjuvant chemotherapy for locally advanced HCC,
and patients were enrolled before the initiation of chemotherapy. A baseline
CT examination was used for our study. The subject inclusion criteria were
histo pathologically (biopsy) confirmed primary HCC and having undergone an IV
gadolinium-enhanced liver MRI within 4 days of CT image acquisition as part of
a study protocol to stage HCC. Any patient with a history of transarterial
chemoembolization or tumor ablation was excluded.
Patients
From July 2004 to January 2005, 25 patients (19 men and six women; mean
age, 63.5 years; age range, 50–81 years), including 10 patients without
a diagnosis of liver cirrhosis and 15 patients with liver cirrhosis, met our
selection criteria and agreed to participate in the study.
CT Technique
All imaging was performed on a 16-MDCT scanner (LightSpeed, GE Healthcare).
For initial localization of the HCC, an unenhanced CT scan of the abdomen was
obtained during an end-expiratory breath-hold and then compared with the most
recent contrast-enhanced CT study of the same patient. Four consecutive
5-mm-thick slices in the region of the known HCC were selected for cine image
acquisition. A dynamic contrast-enhanced study of the selected four slices was
performed in a single breath-hold at the end of expiration with a static table
position.
Contrast Media Protocol
A total of 70 mL of nonionic iodinated contrast medium (300 mg I/mL) was
injected in the antecubital vein at the rate of 7 mL/s through an 18-gauge IV
cannula using a power injector (EMPOWERCTA, E-Z-EM). The following
CT parameters were used to acquire dynamic data: gantry rotation time, 1
second; 100 kVp; 240 mA; acquisition in 4i axial mode (four images per gantry
rotation); and a reconstructed slice thickness of 5 mm. Six seconds after the
start of contrast medium injec tion an initial scan was obtained, followed by
continuous image acqui sition for a total duration of 25 or 30 seconds,
depending on the patient's maximum breath-hold capacity. Intermittent imaging
of the four 5-mm slices once every 12 seconds for a total scan duration of 148
or 153 seconds was then performed.
Data Analysis
The data were analyzed on a workstation (Advantage Windows 4.0, GE
Healthcare) using CT perfusion software (Perfusion 3.0, GE Healthcare) by two
abdominal radiologists in consensus. The time–attenuation curves were
generated on the basis of regions of interest (ROIs) drawn within the HCC, the
adjacent normal liver parenchyma, and the aorta in all four selected image
slices. HCC ROIs were placed on the enhancing portion of the hypervascular
HCC, taking care to avoid adjacent normal vasculature, large tumoral blood
vessels, and necrotic tumor components. Care was taken to ensure that aortic
ROIs did not include any aortic mural calcification
(Fig. 1). First, the cine
sequences were displayed at an appropriate window (width, 400 HU; level, 40
HU) to maximally display the HCCs; second, ROIs of at least 1 cm2
were placed within the HCC, aorta, and adjacent liver parenchyma on all four
images; and third, the highest Hounsfield value of the tumor in one of the
four slices was chosen for analysis and the time–attenuation curves were
generated for the tumor, aorta, and liver
(Fig. 1).
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Fig. 1 —Graph shows time–attenuation curve of hepatocellular
carcinoma (HCC) (green curve marked 1), aorta (pink curve marked 2), and
background liver (pink curve marked 3). Inset shows drawings for ROIs (green
circle labeled as 1 is ROI for tumor; pink circles labeled as 2 and 3 show
aorta and liver parenchyma, respectively, in 75-year-old woman with known HCC
in right hepatic lobe. As = aorta enhancement start; Ap = aorta enhancement
peak; Ts = HCC enhancement start; Tp = HCC enhancement peak.
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Quantitative Measurements
The maximum Hounsfield value and its time of onset were recorded for aorta,
HCC, and background liver. HCC conspicuity was assessed by subtracting the
Hounsfield value of background liver from the Hounsfield value of the known
HCC at the time of onset of peak HCC enhancement. The parameters of start
time, peak time, and end time for both aorta and the HCCs were measured and
recorded.
The contrast enhancement start time in the aorta was defined as the time
when the aortic Hounsfield value showed an increase of 100 HU or greater,
whereas the contrast enhancement end time was defined as the time when aortic
Hounsfield decreased to below 100 HU. The peak time was defined as the time
when the maximum aortic Hounsfield value was recorded. The HCC contrast
enhancement start time was defined as the time when an increase of 10 HU or
greater occurred compared with the baseline HCC Hounsfield value, whereas the
HCC contrast enhancement end time was defined as the time when the HCC
Hounsfield value decreased to below the background liver contrast enhancement
Hounsfield measurement. Similarly, the peak time was defined as the time when
the maximum HCC Hounsfield measurement was obtained
(Fig. 1).
Qualitative Measurements
Image sets were subjectively assessed for wash-in, peak, and wash-out time
of contrast medium in the aorta and the proven HCC. In addition, wash-in and
wash-out times were qualitatively assessed for lesions that were 2 cm or
smaller in diameter, that showed MR characteristics compatible with a
diagnosis of HCC (increased T2 signal and arterial phase enhancement), and
that had not been biopsied.
Aortic wash-in time was defined as the time when contrast medium had first
arrived in the aorta in the consensus opinion of the two readers. HCC wash-in
time was similarly defined as the time when contrast enhancement was first
subjective ly visible in the HCC. Similarly wash-out times for the aorta and
HCC were defined as the times when the contrast medium density was less than
the background liver in the aorta and HCC.
Statistical Analysis
Data were compiled in a database using Microsoft Access 2000 software, and
statistical analysis was performed using Microsoft Excel 2000 software. The
paired Student's t test was used to assess the correlation between
quantitative and qualitative measurements. A p value was cal culated
for each comparison and a value of 
0.05 was considered statistically
significant.
Results
A total of 25 patients were enrolled in this study, including 15 (60%) with
cirrhosis and 10 (40%) without cirrhosis. None of our patients experienced
adverse events related to the 7 mL/s bolus injection of contrast medium. The
HCCs included well-differentiated (n = 8), moderately differentiated
(n = 11), and poorly differentiated HCC (n = 6) sub-types.
There were 108 T2 hyperintense arterial phase enhancing lesions that ranged in
number from one to 10 per patient with a mean of four. Three lesions per
patient within 2 cm thickness as imaged corresponded to dynamic CT images. Of
these, 81 lesions were 2 cm or smaller in diameter. Quantitative and
qualitative analyses were performed on the 25 histopathologically confirmed
HCCs (size [± SD], 7.1 ± 2.3 cm), whereas the 81 lesions that
were less than 2 cm in diameter (average, 1.34 ± 0.34 cm; range,
0.7–2 cm) and exhibited MRI findings of arterial phase enhancement and
T2 hyperintensity underwent qualitative analysis alone. The maximal Hounsfield
values obtained in the aorta, biopsy-proven HCC, and background liver were
463.8 ± 98, 106.5 ± 19, and 98.3 ± 14, respectively. At
the average peak enhancement of HCC (106.5 HU), the average liver Hounsfield
value was 68.3 ± 11, yielding a density difference of 38.2 ± 19
HU between the HCC and background liver
(Table 1).
The quantitative analysis of aortic time–attenuation curves yielded a
contrast medium enhancement start time (an increase of 100 HU), peak
enhancement time, and end time of 9.2 ± 2.7 seconds, 19.4 ± 2.1
seconds, and 38 ± 13.5 seconds, respectively. Quantitative analysis of
HCC contrast enhancement yielded a start time (an increase of 10 HU), peak
enhancement time, and end time of 15.5 ± 2.6 seconds, 26.3 ± 2.9
seconds, and 57.7 ± 14.4 seconds, respectively
(Table 2 and Fig.
2A,
2B,
2C,
2D).
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TABLE 2: Comparison of Qualitative and Quantitative Analysis on Aorta and
Hepatocellular Carcinoma in 25 Pathology-Confirmed Subjects
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Fig. 2A —53-year-old man with hepatitis C virus cirrhosis.
Contrast-enhanced MDCT images in transverse planes at level of largest
hepatocellular carcinoma (HCC) (arrows) in right lobe show start of
biopsy-proven HCC enhancement (17 seconds) (A), peak enhancement of HCC
(26 seconds) (B), and contrast medium end time of HCC (85 seconds)
(C). Also note, additional mass (asterisks) that invades
portal vein and results in segmental biliary ductal dilatation
(arrowheads) in left lobe. Corresponding contrast-enhanced
T1-weighted MR image (D) shows right and left lobe HCCs.
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Fig. 2B —53-year-old man with hepatitis C virus cirrhosis.
Contrast-enhanced MDCT images in transverse planes at level of largest
hepatocellular carcinoma (HCC) (arrows) in right lobe show start of
biopsy-proven HCC enhancement (17 seconds) (A), peak enhancement of HCC
(26 seconds) (B), and contrast medium end time of HCC (85 seconds)
(C). Also note, additional mass (asterisks) that invades
portal vein and results in segmental biliary ductal dilatation
(arrowheads) in left lobe. Corresponding contrast-enhanced
T1-weighted MR image (D) shows right and left lobe HCCs.
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Fig. 2C —53-year-old man with hepatitis C virus cirrhosis.
Contrast-enhanced MDCT images in transverse planes at level of largest
hepatocellular carcinoma (HCC) (arrows) in right lobe show start of
biopsy-proven HCC enhancement (17 seconds) (A), peak enhancement of HCC
(26 seconds) (B), and contrast medium end time of HCC (85 seconds)
(C). Also note, additional mass (asterisks) that invades
portal vein and results in segmental biliary ductal dilatation
(arrowheads) in left lobe. Corresponding contrast-enhanced
T1-weighted MR image (D) shows right and left lobe HCCs.
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Fig. 2D —53-year-old man with hepatitis C virus cirrhosis.
Contrast-enhanced MDCT images in transverse planes at level of largest
hepatocellular carcinoma (HCC) (arrows) in right lobe show start of
biopsy-proven HCC enhancement (17 seconds) (A), peak enhancement of HCC
(26 seconds) (B), and contrast medium end time of HCC (85 seconds)
(C). Also note, additional mass (asterisks) that invades
portal vein and results in segmental biliary ductal dilatation
(arrowheads) in left lobe. Corresponding contrast-enhanced
T1-weighted MR image (D) shows right and left lobe HCCs.
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The qualitative analysis of aortic contrast medium enhancement yielded
wash-in time, peak time, and wash-out time of 10.2 ± 2.6 seconds, 19.9
± 3.0 seconds, and 40.5 ± 9.4 seconds, respectively. Qualitative
analysis of HCC contrast medium enhancement yielded wash-in time, peak time,
and wash-out time of 18.1 ± 4.3 seconds, 27 ± 3 seconds, and
53.2 ± 20.6 seconds, respectively
(Table 2 and Fig.
3A,
3B,
3C,
3D).
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Fig. 3A —57-year-old woman without cirrhosis. Contrast-enhanced MDCT
images in transverse planes at level of largest hepatocellular carcinoma (HCC)
(arrows) with care taken that regions of interest did not include
necrotic areas show start of HCC enhancement (14 seconds) (A), peak
enhancement (26 seconds) (B), and contrast medium end time of HCC (73
seconds) (C). Corresponding contrast-enhanced T1-weighted MR image
(D) shows left lobe HCC.
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Fig. 3B —57-year-old woman without cirrhosis. Contrast-enhanced MDCT
images in transverse planes at level of largest hepatocellular carcinoma (HCC)
(arrows) with care taken that regions of interest did not include
necrotic areas show start of HCC enhancement (14 seconds) (A), peak
enhancement (26 seconds) (B), and contrast medium end time of HCC (73
seconds) (C). Corresponding contrast-enhanced T1-weighted MR image
(D) shows left lobe HCC.
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Fig. 3C —57-year-old woman without cirrhosis. Contrast-enhanced MDCT
images in transverse planes at level of largest hepatocellular carcinoma (HCC)
(arrows) with care taken that regions of interest did not include
necrotic areas show start of HCC enhancement (14 seconds) (A), peak
enhancement (26 seconds) (B), and contrast medium end time of HCC (73
seconds) (C). Corresponding contrast-enhanced T1-weighted MR image
(D) shows left lobe HCC.
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Fig. 3D —57-year-old woman without cirrhosis. Contrast-enhanced MDCT
images in transverse planes at level of largest hepatocellular carcinoma (HCC)
(arrows) with care taken that regions of interest did not include
necrotic areas show start of HCC enhancement (14 seconds) (A), peak
enhancement (26 seconds) (B), and contrast medium end time of HCC (73
seconds) (C). Corresponding contrast-enhanced T1-weighted MR image
(D) shows left lobe HCC.
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The contrast enhancement start time and wash-in time for the aorta and HCC
on the quantitative and qualitative analyses showed strong concordance with
one another (p = 0.00017 and 0.00163, respectively). However, end
time for lesion enhancement or for washout time of contrast medium showed no
statistically significant correlation (p = 0.153 and 0.341)
(Table 2).
Qualitative analysis of the 81 HCCs that measured 2 cm or smaller in
diameter yielded earliest and average wash-in times of 18.5 ± 2.8 and
19.4 ± 2.6 seconds, respectively, which was highly concordant with the
contrast enhancement kinetics of the pathologically confirmed HCCs (p
= 0.003) (Fig. 4A,
4B,
4C,
4D). The average wash-out time
of these smaller lesions was 59.3 ± 18.4 seconds, which had no
correlation with the pathologically confirmed larger HCCs
(Table 3).
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Fig. 4A —64-year-old man with liver cirrhosis. Transverse plane
contrast-enhanced MDCT images from level of largest hepatocellular carcinoma
(HCC) (arrows) in right lobe show start of HCC enhancement (15
seconds) (A) and peak enhancement (23.5 seconds) (B). At 68
seconds (C), multiple additional lesions are now obvious in liver, and
most HCCs have washed out. Ascites (asterisks) is also noted in
parahepatic region. Corresponding contrast-enhanced T1-weighted MR image
(D) shows scattered HCCs.
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Fig. 4B —64-year-old man with liver cirrhosis. Transverse plane
contrast-enhanced MDCT images from level of largest hepatocellular carcinoma
(HCC) (arrows) in right lobe show start of HCC enhancement (15
seconds) (A) and peak enhancement (23.5 seconds) (B). At 68
seconds (C), multiple additional lesions are now obvious in liver, and
most HCCs have washed out. Ascites (asterisks) is also noted in
parahepatic region. Corresponding contrast-enhanced T1-weighted MR image
(D) shows scattered HCCs.
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Fig. 4C —64-year-old man with liver cirrhosis. Transverse plane
contrast-enhanced MDCT images from level of largest hepatocellular carcinoma
(HCC) (arrows) in right lobe show start of HCC enhancement (15
seconds) (A) and peak enhancement (23.5 seconds) (B). At 68
seconds (C), multiple additional lesions are now obvious in liver, and
most HCCs have washed out. Ascites (asterisks) is also noted in
parahepatic region. Corresponding contrast-enhanced T1-weighted MR image
(D) shows scattered HCCs.
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Fig. 4D —64-year-old man with liver cirrhosis. Transverse plane
contrast-enhanced MDCT images from level of largest hepatocellular carcinoma
(HCC) (arrows) in right lobe show start of HCC enhancement (15
seconds) (A) and peak enhancement (23.5 seconds) (B). At 68
seconds (C), multiple additional lesions are now obvious in liver, and
most HCCs have washed out. Ascites (asterisks) is also noted in
parahepatic region. Corresponding contrast-enhanced T1-weighted MR image
(D) shows scattered HCCs.
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Discussion
We have observed that when 70 mL of 300 mg I/mL contrast medium was rapidly
injected (7 mL/s), both biopsy-proven HCC and background liver show
enhancement (peak HCC = 106.5 ± 19 HU and peak liver = 98.3 ± 14
HU), with a difference in density of 38.2 ± 19 HU between background
liver and the known HCC at the time of peak HCC enhancement. The contrast
medium arrival/peak enhancement time in the aorta (9.2 ± 2.7/19.8
± 3 seconds) and HCC (15.2 ± 2.6/26.3 ± 2.9 seconds) was
early and consistent in all patients. However, the contrast medium wash-out
time in the aorta and HCC was variable. The quantitative and qualitative
analyses of contrast medium arrival and peak enhancement time for both the
aorta and biopsy-proven HCCs were highly concordant (p < 0.001).
In addition, lesions that lacked histopathologic confirmation but had MRI
features consistent with HCC showed qualitative contrast medium wash-in time
highly concordant with the qualitative washin time of pathologically confirmed
HCC. This study lays out an optimal window for image acquisition during the
arterial phase for the detection of both small and large hypervascular liver
tumors after rapid bolus contrast medium injection.
The optimal arterial phase scanning window for liver study has been
investigated in the past using different contrast media concentrations and
injection rates with single-detector and MDCT helical scanners. Using a
single-detector CT, Hwang et al.
[9] reported that the peak
aortic and hepatic enhancement occurs at 50–60 seconds and 80–90
seconds, respectively, when a 50 g iodine load is injected at 3 mL/s.
Likewise, Tublin et al. [11]
reported the peak hepatic enhancement time at 87 seconds and 63 seconds using
300 mg I/mL of contrast medium injected at 2.5 mL/s and 5 mL/s, respectively.
Using 8-MDCT scanners, two investigators used a similar contrast medium
injection protocol of 300 mg I/mL concentration injected at 4 mL/s. The peak
enhancement of the aorta was found 5–10 seconds after a 50 HU threshold
was achieved in the aorta
[12], and the optimal window
for HCC detection was observed 10–15 seconds after the achievement of
the 50-HU threshold [13].
Using 16-MDCT, Kim et al. [14]
reported that when 370 mg I/mL was injected at 3–4 mL/s, the optimal
window for HCC detection ranged between 14 and 30 seconds after a 100 HU
threshold was achieved in the abdominal aorta.
Optimal MDCT multiphase liver imaging technique is crucial for improving
the sensitivity of HCC detection
[15]. Using transplanted liver
as the reference standard, the reported accuracy for HCC detection using
single-detector helical CT and MDCT has ranged from 44% to 88%
[15–19].
Despite advances in CT technology, part of the reported variability in HCC
detection rates may be attributed to suboptimal contrast media injection and
scanning protocols. A number of contrast media injection protocols have been
proposed to improve tumor conspicuity and vascular enhancement
[20–22].
Achieving a higher IV iodine flux is considered an important determinant in
improving the conspicuity of hypervascular tumors, such as HCC
[20].
Several authors have investigated this approach and their results have
supported that higher iodine flux achieved by increasing contrast media volume
[23,
24], by increasing contrast
media concentration
[25–27],
or by increasing the rate of contrast medium injection improves tumor
conspicuity and vascular enhancement
[28]. Injection rates of 5
mL/s have been considered to provide superior tumor and vascular enhancement
than injection rates of 3 mL/s
[20,
29]. Injection rates exceeding
5 mL/s have not been investigated in HCC studies. Schueller et al.
[30] reported improved
pancreatic enhancement and tumor conspicuity with a 16-MDCT scanner using an
injection rate of 8 mL/s in comparison with a 4 mL/s injection protocol. They
also did not report any adverse events such as contrast medium extravasation
in their high-contrast-medium injection rate protocol group
[30]. Similarly, Bader et al.
[31] investigated contrast
medium injection at 10 mL/s to study liver perfusion and reported no adverse
events. In our study, by using a bolus injection rate of 7 mL/s, we achieved
an HCC-to-liver enhancement of 38.2 ± 19 HU (range, 12.6–78.3 HU)
at the time of peak HCC, which showed an adequate enhancement for HCC
conspicuity [32].
In a study by Kim et al.
[14] to define the optimal
imaging time window for biphasic arterial phase imaging for the detection of
HCC, 33 ± 3.4 seconds was considered the optimal scanning time for
early arterial phase imaging and 46 ± 3.4 seconds for late arterial
phase imaging when contrast medium of 370 mg I/mL was injected at 3–4
mL/s. In our study protocol, although a lower iodine dose (21 g) was used, a
higher IV iodine flux was achieved by using a contrast bolus injection rate of
7 mL/s. Our image acquisition protocol was designed as a continuous capture,
permitting accurate assessment of contrast enhancement kinetics. As a
consequence, our data permit accurate analysis of the optimal time window for
maximal aortic and HCC enhancement at a bolus injection rate of 7 mL/s. We
believe that our study is the first study to investigate HCC contrast
enhancement kinetics using continuous data capture in 16-MDCT. This
investigation supports the concepts proposed in prior studies
[6,
20,
28,
33] but also adds to our
understanding of the contrast enhancement kinetics of HCC and the abdominal
aorta. Moreover, our data may be used as a reference for imaging protocol
designs for faster MDCT scanners in which contrast media injection rates
exceeding 5 mL/s can be used because of shorter scanning times.
In addition, on the basis of our data, we can design a CT angiography
protocol specifically for the faster image acquisition times possible with 16-
and 64-MDCT scanners, where-by a faster injection bolus could potentially be
used to decrease the administered contrast medium volume and iodine dose but
still achieve optimal vascular enhancement.
Limitations
There were several limitations in this study. First, the image acquisition
was limited to a 2-cm-thick slice of liver and tumor tissue, and therefore, we
did not study the entire liver. Second, a lower iodine dose (21 g) was used
for the dynamic imaging; however, adequate hypervascular HCC conspicuity was
achieved because of the faster injection rate, and we believe that this is a
reasonable injection protocol for hypervascular lesion evaluation. In
addition, pathologic proof for lesions less than 2 cm in size was not
obtained, with a presumptive diagnosis of HCC based on MRI features alone.
Finally, tumors of different grades and disease status (such as angioinvasion
or background cirrhosis) were included in the study, with uncertain impact on
the data obtained. The characterization of subcentimeter HCCs on arterial
phase CT could be limited because of imaging overlap with arterial portal
shunts, particularly if no corresponding washout to suggest an HCC is detected
on delayed contrast-enhanced imaging. Because we have not specifically
compared the efficacy of our fast-contrast-medium administration protocol with
a relatively slower-contrast-medium injection protocol in the same patient, we
are unsure of the clinical benefits of this protocol for HCC detection over
the currently used scanning technique. However, our protocol can be used as a
reference if a shorter-contrast-medium injection time is desired with faster
MDCT scanners.
In conclusion, rapid contrast medium bolus injection at a rate of 7 mL/s
produces predictable arterial phase enhancement in biopsy-proven HCC. With our
contrast medium injection protocol, the optimal time for HCC detection was
26.3 ± 2.9 seconds from the start of contrast medium injection in the
arterial phase. In addition, lesions measuring 2 cm or smaller in diameter
with MRI characteristics compatible with HCC showed contrast enhancement
kinetics similar to pathologically proven HCC, suggesting that the optimal
timing for the detection of smaller lesions after rapid contrast medium bolus
injection is similar to the optimal timing for the detection of larger
biopsy-proven HCCs.
References
- Bosch FX, Ribes J, Díaz M, Clíries R. Primary liver
cancer: worldwide incidence and trends.
Gastroenterology 2004;127
[5 suppl 1]:S5
–S16[CrossRef][Medline]
- Matsui O, Kadoya M, Kameyama T, et al. Benign and malignant nodules
in cirrhotic livers: distinction based on blood supply.
Radiology 1991;178
: 493–497[Abstract/Free Full Text]
- Murakami T, Kim T, Takamura M, et al. Hypervascular hepatocellular
carcinoma: detection with double arterial phase multi-detector row helical CT.
Radiology 2001;218
: 763–767[Abstract/Free Full Text]
- Kim T, Murakami T, Hori M, et al. Small hypervascular
hepatocellular carcinoma revealed by double arterial phase CT performed with
single breath-hold scanning and automatic bolus tracking.
AJR 2002; 178:899
–904[Abstract/Free Full Text]
- Kanematsu M, Oliver JH 3rd, Carr B, Baron RL. Hepatocellular
carcinoma: the role of helical biphasic contrast-enhanced CT versus CT during
arterial portography. Radiology 1997;205
: 75–80[Abstract/Free Full Text]
- Baron RL, Oliver JH 3rd, Dodd GD 3rd, Nalesnik M, Holbert BL, Carr
B. Hepatocellular carcinoma: evaluation with biphasic, contrast-enhanced,
helical CT. Radiology 1996;199
: 505–511[Abstract/Free Full Text]
- Mitsuzaki K, Yamashita Y, Ogata I, Nishiharu T, Urata J, Takahashi
M. Multiple-phase helical CT of the liver for detecting small hepatomas in
patients with liver cirrhosis: contrast-injection protocol and optimal timing.
AJR 1996; 167:753
–757[Abstract/Free Full Text]
- Oliver JH 3rd, Baron RL, Federle MP, Rockette HE Jr. Detecting
hepatocellular carcinoma: value of unenhanced or arterial phase CT imaging or
both used in conjunction with conventional portal venous phase
contrast-enhanced CT imaging. AJR 1996;167
: 71–77[Abstract/Free Full Text]
- Hwang GJ, Kim MJ, Yoo HS, Lee JT. Nodular hepatocellular
carcinomas: detection with arterial-, portal-, and delayed-phase images at
spiral CT. Radiology 1997;202
: 383–388[Abstract/Free Full Text]
- Kawata S, Murakami T, Kim T, et al. Multidetector CT: diagnostic
impact of slice thickness on detection of hypervascular hepatocellular
carcinoma. AJR 2002;179
: 61–66[Abstract/Free Full Text]
- Tublin ME, Tessler FN, Cheng SL, Peters TL, McGovern PC. Effect of
injection rate of contrast medium on pancreatic and hepatic helical CT.
Radiology 1999;210
: 97–101[Abstract/Free Full Text]
- Kondo H, Kanematsu M, Goshima S, et al. MDCT of the pancreas:
optimizing scanning delay with a bolus-tracking technique for pancreatic,
peripancreatic vascular, and hepatic contrast enhancement.
AJR 2007; 188:751
–756[Abstract/Free Full Text]
- Goshima S, Kanematsu M, Kondo H, et al. MDCT of the liver and
hypervascular hepatocellular carcinomas: optimizing scan delays for
bolus-tracking techniques of hepatic arterial and portal venous phases.
AJR 2006; 187:207
[web]W25–W32
- Kim MJ, Choi JY, Lim JS, et al. Optimal scan window for detection
of hypervascular hepatocellular carcinomas during MDCT
examination.AJR 2006;187
: 198–206[Abstract/Free Full Text]
- Kim HC, Kim TK, Sung KB, et al. Preoperative evaluation of
hepatocellular carcinoma: combined use of CT with arterial portography and
hepatic arteriography. AJR 2003;180
:1593
–1599[Abstract/Free Full Text]
- Chalasani N, Horlander JC Sr, Said A, et al. Screening for
hepatocellular carcinoma in patients with advanced cirrhosis. Am J
Gastroenterol 1999; 94:2988
–2993[CrossRef][Medline]
- Gambarin-Gelwan M, Wolf DC, Shapiro R, Schwartz ME, Min AD.
Sensitivity of commonly available screening tests in detecting hepatocellular
carcinoma in cirrhotic patients undergoing liver transplantation.
Am J Gastroenterol 2000;95
:1535
–1538[CrossRef][Medline]
- Lim JH, Kim CK, Lee WJ, et al. Detection of hepatocellular
carcinomas and dysplastic nodules in cirrhotic livers: accuracy of helical CT
in transplant patients. AJR 2000;175
: 693–698[Abstract/Free Full Text]
- Peterson MS, Baron RL, Marsh JW Jr, Oliver JH 3rd, Confer SR, Hunt
LE. Pretransplantation surveillance for possible hepatocellular carcinoma in
patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430
cases with surgical pathologic correlation. Radiology2000; 217:743
–749[Abstract/Free Full Text]
- Laghi A, Iannaccone R, Rossi P, et al. Hepatocellular carcinoma:
detection with triple-phase multi-detector row helical CT in patients with
chronic hepatitis. Radiology 2003;226
: 543–549[Abstract/Free Full Text]
- Awai K, Inoue M, Yagyu Y, et al. Moderate versus high concentration
of contrast media for aortic and hepatic enhancement and tumor-to-liver
contrast at multi-detector row CT. Radiology2004; 233:682
–688[Abstract/Free Full Text]
- Awai K, Takada K, Onishi H, Hori S. Aortic and hepatic enhancement
and tumor-to-liver contrast: analysis of the effect of different
concentrations of contrast media at multi-detector row helical CT.
Radiology 2002;224
: 757–763[Abstract/Free Full Text]
- Heiken JP, Brink JA, McClennan BL, Sagel SS, Crowe TM, Gaines MV.
Dynamic incremental CT: effect of volume and concentration of contrast
material and patient weight on hepatic enhancement.
Radiology 1995;195
: 353–357[Abstract/Free Full Text]
- Kopka L, Rodenwaldt J, Fischer U, Mueller DW, Oestmann JW, Grabbe
E. Dual-phase helical CT of the liver: effects of bolus tracking and different
volumes of contrast material. Radiology1996; 201:321
–326[Abstract/Free Full Text]
- Hanninen EL, Vogl TJ, Felfe R, et al. Detection of focal liver
lesions at biphasic spiral CT: randomized double-blind study of the effect of
iodine concentration in contrast materials. Radiology2000; 216:403
–409[Abstract/Free Full Text]
- Yagyu Y, Awai K, Inoue M, et al. MDCT of hypervascular
hepatocellular carcinomas: a prospective study using contrast materials with
different iodine concentrations. AJR2005; 184:1535
–1540[Abstract/Free Full Text]
- Furuta A, Ito K, Fujita T, Koike S, Shimizu A, Matsunaga N. Hepatic
enhancement in multiphasic contrast-enhanced MDCT: comparison of high- and
low-iodine-concentration contrast medium in same patients with chronic liver
disease. AJR 2004;183
: 157–162[Abstract/Free Full Text]
- Bae KT, Heiken JP, Brink JA. Aortic and hepatic peak enhancement at
CT: effect of contrast medium injection rate—pharmacokinetic analysis
and experimental porcine model. Radiology1998; 206:455
–464[Abstract/Free Full Text]
- Ianora AA, Memeo M, Sabba C, Cirulli A, Rotondo A, Angelelli G.
Hereditary hemorrhagic telangiectasia: multi-detector row helical CT
assessment of hepatic involvement. Radiology2004; 230:250
–259[Abstract/Free Full Text]
- Schueller G, Schima W, Schueller-Weidekamm C, et al. Multidetector
CT of pancreas: effects of contrast material flow rate and individualized scan
delay on enhancement of pancreas and tumor contrast.
Radiology 2006;241
: 441–448[Abstract/Free Full Text]
- Bader TR, Herneth AM, Blaicher W, et al. Hepatic perfusion after
liver transplantation: noninvasive measurement with dynamic single-section CT.
Radiology 1998;209
: 129–134[Abstract/Free Full Text]
- Baron RL. Understanding and optimizing use of contrast material for
CT of the liver. AJR 1994;163
: 323–331[Abstract/Free Full Text]
- Schoellnast H, Brader P, Oberdabernig B, et al. High-concentration
contrast media in multiphasic abdominal multidetector-row computed tomography:
effect of increased iodine flow rate on parenchymal and vascular enhancement.
J Comput Assist Tomogr 2005;29
: 582–587[CrossRef][Medline]
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Abstract
Introduction
