Received: 19 October 2021 Revised: 22 February 2022 Accepted: 12 March 2022

DOI: 10.1002/jcu.23197

REVIEW

The clinical value of dual-energy computed tomography

and diffusion-weighted imaging in the context of liver
cancer: A narrative review

Pei-Lin Fan MB | Jun Chu MB | Qing Wang MB | Chen Wang MB

Discipline of Diagnostic Radiography,

University of Sydney, Sydney, Australia
Correspondence
Pei-Lin Fan, Discipline of Diagnostic
Radiography, University of Sydney, Sydney,
NSW 2006, Australia.
Email: fampeilim@21cn.com
Abstract
The dual-energy computed tomography (DECT) and diffusion-weighted magnetic
resonance imaging (DWI-MRI) are used to diagnose liver cancer. The clinical value of
these two examination methods needs to be further summarized. We collected and
summarized relevant literature published from 2011 to 2021. The diagnostic perfor-
mance of DECT was assessed between conventional computed tomography and
DWI-MRI. DWI-MRI had a 69% sensitivity for detecting small hepatocellular carci-
noma (HCC) lesions and a 60% diagnostic specificity for differentiating between
types of HCC lesions. DECT had a sensitivity to small liver lesions (<1 cm) of 69%,
and the diagnostic specificity for HCC and metastasis was about 60%. DWI was more
sensitive (90.3% vs. 74.9%) and accurate (91.9% vs. 76.9%) in diagnosing HCC com-
pared with conventional MRI sequencing. With the aid of contrast media, DWI-MRI
had 90.0% specificity for detecting small HCCs (smaller than 1 cm). Furthermore,
DWI-MRI not only provided physicians with valuable diagnostic information but also
delivered histological grading information, with 78% accuracy for all benign lesions
and 71% for solid lesions. DECT had relatively high sensitivity and required a lower
contrast medium dose. With standardized quantitative parameters, it can be an
extremely useful tool for HCC surveillance. DWI-MRI is the preferred imaging pro-
cess as it produces high-contrast images for supporting an early diagnosis (high sensi-
tivity and specificity) and provides histological information using non-ionizing
radiation.

KEYWORDS
diffusion-weighted imaging, dual-energy computed tomography, liver cancer, review

1 | I N T RO DU CT I O N
Hepatocellular carcinoma (HCC) is the sixth most common malignant
tumor type and the fourth leading cause of cancer deaths worldwide.1
The mortality rate of HCC is high because its initial diagnosis is typi-
cally only made at an advanced stage. In theory, if treatments can be
initiated at an earlier stage, outcomes could be significantly improved.
For patients with HCC symptoms or abnormal blood tests, imaging of
the liver by computed tomography (CT) or magnetic resonance
imaging (MRI) scans could then be requested. These scans can help
physicians identify focal lesions and establish a diagnosis. A pathology
examination may help diagnose, but it involves comparatively more
invasive procedures in the form of a biopsy.
One of the most used imaging modalities for diagnosing HCCs is
multiphasic contrast-enhanced CT. Compared with other diagnostic
imaging techniques, including ultrasound, CT provides better sensitiv-
ity and specificity, and has a shorter scanning time.2 However, the
radiation dose of CT and severe reaction to a high iodinated contrast

862 © 2022 Wiley Periodicals LLC. wileyonlinelibrary.com/journal/jcu J Clin Ultrasound. 2022;50:862–868.


FAN ET AL.
medium dosage remain its major disadvantages. Dual-energy CT
(DECT) has been attempted to reduce radiation and contrast media
doses without jeopardizing image quality. This process includes
two consecutive scans using two different X-ray sources. It can
be combined with the technology of rapid kilovoltage switching
(typically switching between 80 and 140 kVp), thus providing
quantitative information via low monochromatic spectral images,
which can provide better image contrasts while using the same
iodine concentration.3
There has been an increasing interest in diagnosing HCCs using
diffusion-weighted imaging (DWI), a process that is becoming a stan-
dard imaging technique due to its characteristics of having a high soft-
tissue resolution, non-ionizing radiation, and the ability to provide
functional details, thereby allowing the detection and identification of
accurate focal liver lesions. Additionally, DWI can quantitatively mea-
sure the motion of water molecules in tissue to create an apparent
diffusion coefficient (ADC) map, which is directly related to the rate
of water diffusion within the tissue. DWI not only produces a high
lesion-to-background contrast (due to a natural difference in the diffu-
sion properties of normal liver tissue and cancer/tumor cells) but can
also provide selected pathology information.4 The sensitivity of DWI
is influenced by the b-value, which is a factor that indicates the degree
of diffusion weighting applied. Increasing the b-value allows the DWI
machine to detect slower diffusion and shorter diffusion distances
(regions that include more signals); that is, tissue with restricted water
movement (speed or space-based) will still have a high signal intensity,
while tissue with less diffusion restriction will have lower signal inten-
5
sity when the b-value is increased.
While there is significant existing research on the use of DWI and
DECT for diagnosing liver cancer, not many researchers have com-
pared the effectiveness and efficiency of these two imaging diagnostic
methods. The broad aim of the current narrative review is to clarify
how these two imaging diagnostic modalities have been used to help
diagnose liver cancer in the past decade. This review compares the
contributions of DWI and DECT in the diagnosis, treatment, and pro-
spective evaluation of HCCs and provides recommendations con-
cerning the preferred diagnostic technique for the diagnosis of liver
cancer in the future.
2 | METHODS
A database search was performed using the Medline, Scopus, CIN-
AHL, and Embase databases using the search terms “DWI-MRI and
diffusion-weighted image,” “DECT and dual-energy CT,” and “liver
cancer and hepatocellular carcinoma (HCC).”
Peer-reviewed journal articles on the clinical use of DECT/DWI-
MRI in liver cancer cases published in English from 2011 to 2021
were included. Articles based on patients with severe complications
were excluded, as were full-text unavailable articles. A resulting
210 articles were selected after reviewing their titles and abstracts.
Following a careful review, 56 articles were incorporated into this
review.
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863
3 | DI SCU SSION
3.1 | Dual-energy computed tomography
Multiphase contrast-enhanced CT is a first-line diagnostic tool for a
physician to rule out or confirm a liver tumor. Although conventional
multiphase CT has relatively high sensitivity and specificity for diag-
nosing focal hepatic lesions, its diagnostic performance may not be
ideal when it comes to atypical focal liver lesions.6 Studies suggested
that DECT could be used to improve diagnostic performance and pro-
vide more clinical information by introducing quantitative values like
iodine concentration, normalized iodine concentration, and spectral
curve (CT values at different energy levels).2,7–11 Overall, 17 articles
related to DECT are presented in this paper.
3.2 | Diagnostic performance and clinical value
DECT exploits the fact that molecules have varying X-ray attenuation
coefficients at different energy levels. Using two different energy
levels to acquire two sets of images produces much more clinical
information compared with conventional CT scans. Studies conducted
by Anzidei et al. and Altenbernd et al.12,13 demonstrated that when
using DECT, a high-energy beam (140 kVp) provided a high-quality
image, while a low-energy beam (80 kVp) was extremely sensitive in
terms of detecting HCCs due to the attenuation coefficient profile of
iodinated contrast media. Research conducted by Anzidei12 also dem-
onstrated that virtual unenhanced images, reconstructed by combin-
ing the high- and low-energy datasets, are adequate for replacing
conventional CT images and showed slightly higher accuracy. Cecco11
posited that the sensitivity of DECT on a small liver lesion (smaller
than 1 cm) was as high as 69%. However, all three studies included
limitations regarding the patient population and histopathology infor-
mation concerning the detected lesions. Furthermore, in Anzidei's
study, only patients with chronic liver disease were included. Similarly,
Altenbernd's study set the research objectives using diagnosed HCC.
In a study conducted by Wang, the ability to reconstruct a virtual
monoenergetic image at different keV levels by combining low- and
high-energy datasets obtained during a single DECT scan was further
explored.7 Virtual spectral curves (VSCs) were plotted using the CT
value of the tissue of interest against different energy beam levels. It
was found that this curve could provide histological information for
assisting in differentiating between different types of liver lesions
with 100% diagnostic specificity for simple cysts and hemangioma
and approximately 60% for HCCs and metastasis.7 These results are
supported by a study performed by Yang's team.9 However, this study
only included HCC patients, while patients with hemangiomas, HCCs,
metastases, and simple cysts were assessed in the study conducted by
Wang. Furthermore, the staging or treatment efficacy evaluation of
hepatic neoplastic lesions may be applied to determine their clinical
value in future research.
In addition to virtual monoenergetic images and VSCs, DECT can
also be used to generate material density iodine images.8,14 In both

864
Muenzel's and Pfeiffer's research, it was found that the generated
material density iodine images could significantly increase the
contrast-to-noise (C/N) ratio compared with conventional CT and
MRI. The diagnostic sensitivity of DECT is thus greater. Pfeiffer
obtained an iodine concentration using a material density image and
suggested that this served as a valuable tool for comparing scan
results independent of the machine used to perform the scan. This
could serve as a valuable tool for monitoring treatment response,
15
which is also suggested by Dai. These findings were limited to small
patient populations.
3.3 | Contrast and radiation reduction
DECT not only has better diagnostic performance but also presents
surprising advantages compared with conventional CT, particularly
in terms of contrast and radiation dose.16,17 This is because it allows
for the reconstruction of virtual monoenergetic imaging by combin-
ing two different datasets (obtained by low- and high-energy tubes).
As the X-ray attenuation coefficient for iodine is much greater in a
low-energy environment, the sensitivity towards iodine is signifi-
cantly higher. The most obvious benefit of this is that the amount of
contrast medium administered to the patient can be significantly
reduced. Parakh17 reported that the contrast medium dosage could
be reduced by 25% for hypovascular lesions and up to 50% for hyp-
ervascular lesions. This is particularly beneficial for patients who
require periodic surveillance CT check-ups and those who have mild
renal impairment.
The above also means that DECT has the potential to achieve
the same results with a much lower radiation dose. As DECT is sig-
nificantly more sensitive to iodine, a lower voltage can be used in
DECT while still receiving the same image quality (unchanged C/N).
Haj-Mirzaian and Altenbernd6,13 reported this phenomenon. If
DECT is used as a first-line assessment tool instead of conventional
CT, many instances of unnecessary follow-up imaging can be
avoided (because DECT can provide a large volume of valuable
clinical information), which can reduce the long-term/overall radia-
tion dose received by the patient.12,18,19 However, image quality is
highly associated with the patient's body size. With increasing
objective thickness, the image noise will be higher. Thus, how this
study relates to obese patients must be addressed in future
research.
3.4 | The limitations of dual-energy computed
tomography
One of the common problems with DECT is that one of the X-ray
tubes has a relatively small field of view (FOV).13,17,20 This was a
factor in the study conducted by Altenbernd,13 in which the FOV of
the low-energy tube was not big enough to cover the entire liver
region; these areas were reconstructed using data obtained by the
high-energy tube. In many cases, full coverage of the liver can be
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FAN ET AL.
obtained by placing patients in an off-center position. As DECT
technology advances, this issue will be resolved; Altenbernd13 sug-
gests that newer machines are gradually beginning to provide a
larger FOV.
Another issue related to using DECT is that due to the low
energy-level X-ray used, the noise on the image can be quite signifi-
cant, particularly for overweight patients.2,17 This issue remains
ongoing. Anzidei12 suggested that this could be resolved by equip-
ping the machine with an advanced tube current modulation/
adaptation function. An increased current can help combat excessive
image noise. Software noise optimization algorithms can also be
helpful in this regard. In a study conducted by Cecco,11 it was
suggested that applying a noise optimization algorithm has the
potential to improve the diagnostic specificity by 11% in detecting
small liver lesions (Figure 1).
4 | D I F F U SI O N - W E I G H T E D I M A G E–
MAGNETIC RESONANCE IMAGING
4.1 | Hepatocellular carcinoma detection with
diffusion-weighted imaging
The potential benefit of using DWI for identifying HCCs has
attracted research attention in recent years. Many studies have
reported the advantages of using DWI to detect HCCs. Some stud-
ies22,24–27 have investigated the diagnostic performance of DWI and
reported that it could enhance the sensitivity and accuracy for HCC
diagnosis compared with CT or routine MRI, including T1-weighted
images (T1WI) and T2-weighted images (T2WI). According to
research published in 2020 by Cha,21 DWI presents higher sensitiv-
ity (90.3% vs. 74.9%) and accuracy (91.9% vs. 76.9%) compared with
normal MRI using hepatobiliary agents (HBA-MRI). A potential rea-
son for this is that HCCs typically have restricted diffusion; accord-
ingly, DWI may be more sensitive in terms of deriving a diagnosis.28
However, in Cha's study, a strict criterion was employed that could
make it difficult to indicate washout features using gadoxetic acid.
This may reduce the sensitivity of HBA-MRI in the detection of liver
lesions.
Furthermore, DWI may be useful as a non-invasive procedure for
differentiating the stages of HCC. A study conducted by Shankar23
published in 2016 found a significant difference in DWI C/N ratio
among all histological grades compared with the T2WI C/N ratio.23 In
this study, the mean ADC values for the decreasing stages of HCC
showed an increasing trend. Although Shankar's study had a small
sample size of only 20 patients, it indicated the significance of apply-
ing DWI when grading HCCs.
DWI is also valuable and useful as a non-invasive diagnostic imag-
ing method of HCC, particularly for patients with liver cirrhosis,
impaired renal disease, and patients who have a contraindication to
the gadolinium contrast.29–31 There remains room for improving DWI
in this regard because recording the standardized b-values and other
parameters is essential.32

FAN ET AL.
F I G U R E 1 Diagnostic imaging pathways suggestion for liver lesions. DECT, dual-energy computed tomography; DWI, diffusion-weighted
imaging; MRI, magnetic resonance imaging
4.2 | Differentiation of malignant and benign
lesions using diffusion-weighted imaging
33 34 35–40
Battal, Testa, and others agreed that DWI could differentiate
malignant from benign lesions (78% accuracy for all benign lesions
and 71% for solid liver lesions in Testa's study34). This was because
space-occupying liver lesions presented different DWI and ADC
values on imaging. Thus, significant differences between ADC values,
based on the nature of the lesions, can be detected by DWI.41 For
42
example, Granata stated that malignant tissue would show a
hyperintense signal on a DWI with a hypointense signal on the ADC
map.42 Furthermore, Parsai's43 research showed that for liver lesions,
benign lesions had a significantly higher ADC value than malignant
lesions (1.994 ± 0.63810  10 3
, and 1.070 ± 0.237  10 3 2
mm /s,
respectively). However, Parsai's study showed that the ADC values of
benign solid lesions might not indicate any significant differences
compared with malignant lesions.
Several studies reported DWI to be superior compared with
T2WI for focal lesion detection and image quality,5,36,39,40 as well as
having enhanced sensitivity to detecting metastatic cancer rather than
HCCs.40 These studies also stated that DWI with a low b-value
showed better lesion detection performance than T2WI.
4.3 | Small liver lesion detection with diffusion-
weighted imaging
In terms of small liver lesions, DWI can be used as an additional tool
for diagnosing such lesions at an early stage.26,44 Particularly for small
HCCs (<1 cm), DWI combined with geodetic acid-enhanced MRI has
90.0% specificity and higher sensitivity for differentiating between
abnormal nodules compared with conventional MRI only.45,46
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865
Moreover, the combination of DWI and enhanced MRI is also rec-
ommended for detecting small HCCs (≤2 cm) due to higher sensitivity
and diagnostic accuracy.27,46
4.4 | The limitations of diffusion-weighted imaging
Regarding the detection performance stated above, some studies
presented opposing views. Studies conducted by Shankar,23
Galea,31 and Saito47 reported that DWI has limitations for evaluat-
ing the differentiation between HCC/liver lesion grades because
the tumor grade does not significantly change the ADC values. Fur-
thermore, Sutherland48–50 concluded that using DWI to differenti-
ate between solid benign and malignant lesions and different sorts
of hypervascular hepatic lesions remains challenging because the
differences in ADC values were not statistically significant. For
example, Sutherland reported an overlap between the cellularity of
focal nodular hyperplasia and malignant liver lesions in low ADC
values.48
Some important limitations of DWI should be noted. One of its
most significant disadvantages is that its parameters (such as the cal-
culation methods for ADC and b-values) used in different institutions/
medical centers may not be consistent; accordingly, a lack of stan-
dardized parameters can result in the degraded diagnostic efficacy of
DWI.24,32,35,42,51 For example, the results of DWI for differentiating
between benign and malignant lesions may vary when using different
b-values.52 Another important drawback is the process's high suscep-
tibility to motion artifacts, particularly for lesions near the diaphragm
where cardiac motion can affect DWI detection.24,42,46,53 Finally,
since the parameters are not standardized, the consistency of ADC
values between scans using the same or a different machine is
another limitation for the widespread use of DWI.53
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866 FAN ET AL.

T A B L E 1 Advantages and disadvanteges of dual-energy 5.1 | Dual-energy computed tomography

computed tomography and diffusion-weighted imaging in the context
of liver cancer
Since DECT can reduce the amount of contrast media needed and
Advantages Disadvantages produces a higher quality image than conventional CT,2 it can be used
Dual-energy Higher accuracy than A relatively small field as a first-line tool for assessing liver lesions rather than CT. DECT pro-
computed conventional CT of view (FOV) vides significant quantitative information and allows computer-aided
tomography Ability to distinguish Noise is more diagnostics to achieve higher efficiency. Although DWI may have bet-
between different pronounced on ter diagnostic value, DECT may become the first option when MRI is
types of liver lesions images
unavailable in clinical practice environments or for patients with
Ability to generate
claustrophobia.
material density
iodine images
Reduce the dose of
contrast medium 5.2 | Diffusion-weighted imaging
used
Less radiation The use of DWI has become a crucial aspect in detecting liver lesions.
Diffusion- Higher sensitivity and DWI has limitations in Clinical medical workers can consider performing DWI for patients
weighted accuracy than assessing following several considerations. For example, DWI is a non-invasive
imaging conventional MRI differences imaging method and can be an option for patients with contraindica-
between the grades
tions to contrast media. This is also a better option for vulnerable
of HCC/liver lesions
patients, based on its feature of non-radiation. Detecting early-stage
DWI may be useful as Lack of standardized
a non-invasive parameters small liver lesions can be a challenge; DWI used for detecting small
procedure for lesions (≤2 cm), particularly when combined with geodetic acid-
differentiating the enhanced MRI, can achieve high specificity and sensitivity.46 Further-
stages of HCC
more, DWI is useful for deciding treatment schemes and post-surgery
Noninvasive follow-up routines. It can also predict the presence of microvascular
diagnostic imaging
invasion using the quantitative ADC parameter.55
value for HCC
The advantages and disadvantages of DECT and DWI in liver can-
Higher accuracy in
distinguishing cer are shown in Table 1.
benign from
malignant lesions
Superior to T2WI in 6 | RECOMMENDATIONS FOR
focal lesion FU RT H E R S T U D Y
detection and image
quality
6.1 | Dual-energy computed tomography
It can be used as an
early diagnostic tool
for small liver The high-energy tube in DECT has a small FOV. The region of interest
lesions must be positioned at the center of the FOV to achieve the best con-
trast.20 This may be problematic for patients with low mobility. In
addition, low-energy images have a reduced quality because of the
presence of more noise.17 Although imaging centers can include
5 | RECOMMENDATIONS FOR CLINICAL reconstructive algorithms to reduce noise,11 obtaining better quality
PRACTICE images may still be problematic, particularly in low-energy environ-
ments at approximately 40 keV.56 Therefore, future studies and tool
Currently, conventional CT, ultrasound, and MRI are the primary manufacturers must aim to derive solutions to these problems.
image modalities for detecting liver lesions. A study conducted by
Dulku54 discussed the role of imaging for patients with liver lesions
and suggested that contrast-enhanced ultrasonography could be a 6.2 | Diffusion-weighted imaging
first-line approach for diagnosing liver lesions, if available. While
Dulku stated that using dynamic contrast-enhanced MRI and four- Although DWI can provide quantitative parameters, such as ADC and
phase multidetector CT scans to screen small hepatic lesions and ini- b-value indicators, it lacks standardization to establish consistent per-
tial evaluation of the lesion of interest is sufficient, we believe that formance in different imaging centers; additionally, it can be challeng-
DWI or DECT can provide better performance for detecting liver ing to diagnose the grade of liver tumors using a specific value.
lesions and can be advantageous in several contexts. Therefore, additional studies may find it challenging to develop a set

FAN ET AL.
of standards for the quantitative parameters of DWI. Additionally,
since DWI is a sensitive tool, the image quality may be reduced
because of diaphragmatic and cardiac motion. This technical problem
should be addressed in future studies.
7 | C O N CL U S I O N
The early diagnosis of liver cancer remains a challenge for the modern
medical system. In this article, we closely reviewed relevant literature
published in the past decade to gain a better understanding of the
clinical value of DECT and DWI-MRI in the context of defining HCCs.
The imaging approach of choice is DWI-MRI because it has higher
sensitivity and specificity than conventional MRI, even for HCCs
smaller than 1 cm (when contrast media is used). Additionally, DWI-
MRI also has the advantage of using non-ionizing radiation, the ability
to avoid using contrast media without significantly compromising sen-
sitivity, and providing histological information without performing
invasive procedures. Conversely, DECT has the potential to replace
conventional CT as a fast, reliable, and cheap HCC surveillance tool
because it has higher sensitivity and specificity with reduced contrast
medium and lower radiation doses long-term. It also provides stan-
dardized quantitative parameters that enable inter-scan comparisons
and a degree of histological information.
DATA AVAI LAB ILITY S TATEMENT
The data that support the findings of this study are available from the
corresponding author upon reasonable request.
ORCID
Pei-Lin Fan https://orcid.org/0000-0001-6155-7580
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How to cite this article: Fan P-L, Chu J, Wang Q, Wang C. The
clinical value of dual-energy computed tomography and
diffusion-weighted imaging in the context of liver cancer: A
narrative review. J Clin Ultrasound. 2022;50(6):862‐868.
doi:10.1002/jcu.23197