Keywords
gallbladder - cancer - dual-energy CT - CT
Introduction
There is a spectrum of pathologies affecting the gallbladder (GB), ranging from benign
to malignant. Among these conditions, gallstone (GS) disease is the commonest.[1] Therefore, imaging plays an essential role in investigating patients suspected to
have biliary diseases. Imaging modalities that are frequently utilized to evaluate
biliary tract disease include ultrasonography (USG), computed tomography (CT), magnetic
resonance cholangiopancreatography, and hepatobiliary scintigraphy. USG is a cost-effective
and readily available technique for evaluating biliary diseases with estimated sensitivity
and specificity for acute cholecystitis (AC) being 88 to 94% and 78 to 80%, respectively.[2] CT also plays an essential role in diagnosing GB diseases especially complicated
AC and suspected malignancy, although it is less sensitive than USG for the detection
of GS.[3] Dual-energy computed tomography (DECT) is a technical advancement that has been
exploited for clinical applications in various organ systems and pathologies, including
biliary diseases. In this article, we review the role of DECT in the evaluation of
biliary disease.
DECT can overcome some of the limitations of conventional CT in the evaluation of
GB diseases. DECT is based on the concept of scan acquisition with the help of different
X-ray energy levels: one acquired at higher kVp (usually 140 kVp) and the other at
lower kVp (usually 80–100 kVp). We can extract the composition of a substance if we
know how it interacts at different energy levels. The interaction that is most important
for DECT application is the photoelectric effect. The increase in photoelectric absorption
of X-ray photon, which is seen at energy levels higher than k-shell binding energy,
is termed K-edge and forms the basis of dual-energy techniques.[4] The most common methods for acquisition of DECT include dual source, single-source
rapid kilovoltage switching, and dual-layer DECT (sandwich). Postprocessing techniques
can be used to differentiate various structures based on their different X-ray absorption
behavior as a function of X-ray energy.[5] Virtual noncontrast (VNC) images can be generated when the iodine content is subtracted.
Quantitative assessments, including the amount of iodine uptake and degree of enhancement,
can be achieved from single CT image acquisition with the help of pure iodine map
or overlay maps, where iodine content is superimposed. Atomic number map (Rho/Z) is
a newly developed application of DECT that helps calculate the atomic number values
in the lesion, thus allowing the separation of various materials.
Role of DECT in Various Disease
Cholelithiasis
GS disease affects ∼10 to 15% of the adult population, thus constituting a significant
health problem.[1] Individuals may remain asymptomatic throughout their life. The most common presentation
is biliary colic that occurs due to obstruction by calculus at the cystic duct. Complications
of GS include AC (ranging in severity from mild to severe, uncomplicated, or complicated),
GS ileus, acute pancreatitis, and Mirizzi syndrome. Association of GS with GB cancer
has also been reported in a few studies. Although USG is accurate in the diagnosis
of GS, a CT scan is frequently utilized for routine workup. As the majority of GS
are of cholesterol type (70%), these may not be visible on CT as they are isoattenuating
to surrounding bile. Dual-energy postprocessing techniques such as virtual monochromatic
imaging (VMI) and VNC have shown positive results in improved detection of GS on DECT.[6]
[7]
[8]
[9]
[10]
[11] Kim et al found that VNC images were of equivalent quality as true unenhanced images.[7] VNC images showed increased contrast to noise ratio for the cholesterol GS compared
with true unenhanced images. However, the visibility of calcified GS and smaller GS
(<9mm) was negatively affected due to the inaccurate decomposition of calcium and
iodine. Thus, calcified GS are better visualized on true unenhanced images.[7] In a study by Uyeda et al, VMI was useful in distinguishing GS from surrounding
bile.[8] The GS, which are of similar attenuation to bile on conventional CT (120 kVp), becomes
more discernible on higher (200 keV) and lower (40 keV) keV VMI. The reason for better
visualization is that GS has an energy-dependent X-ray attenuation curve different
from surrounding bile.[9] Noncalcified GS has lower attenuation than bile on low keV images and higher attenuation
on high keV images. Low keV images have been found better in the detection of GS as
the contrast difference among noncalcified GS, and surrounding bile is maximum compared
with that at high keV images. Recently, Soesbe et al found that dual-layer DECT generation
of the two-dimensional histogram of Compton and photoelectric attenuation was even
more helpful in differentiating small (<9mm) isoattenuating GS from the bile.[10] Most materials have a different position in the two-dimensional histogram based
upon their Compton and photoelectric ordered pairs. Thus, we can differentiate isoattenuating
GS from bile ([Fig. 1]). Atomic number map (Rho/Z) is another important application of DECT, which can
help identify GS from surrounding fluid in the small bowel in cases of GS ileus.[11]
Fig. 1 Dual-energy computed tomography (DECT) in gallstone disease: (A, B) 80 keV, 140 keV DECT images show hypoattenuating calculus in gall bladder on 80
keV images (arrow) and hyperattenuating calculus on 140 keV images (arrow).
Acute Cholecystitis
In most cases, AC is caused by GS. Few cases occur secondary to stasis.[12] USG is the initial imaging of choice for diagnosing AC because of its high sensitivity.[13] Patients whose diagnosis remains unclear on USG due to limitations of scanning or
impacted stone in the neck or patients with complicated AC may undergo CT.[14] DECT has the potential to be the single best imaging test for patients presenting
with biliary colic because of its ability to identify GS and better visualization
of findings of AC.[15] Iodine maps generated from DECT can easily detect mural hyperemia and hypervascularity
of the adjacent liver parenchyma (hot rim sign). Also, complications such as GB perforation
may be better visualized using VMI and color-coded iodine maps where a nonenhancing
defect in the GB wall can be easily detected ([Fig. 2]).
Fig. 2 Dual-energy computed tomography (CT) in acute cholecystitis. (A) Virtual nonenhanced CT image shows a large calculus impacted at the gallbladder
neck (arrow). (B, C) 80 keV and 140 keV images show mural thickening and continuous mural enhancement
(arrow). (D) Iodine overlap image depicts the discontinuity of mural enhancement better (arrow). This may be a predictor of gallbladder perforation.
GB Polyp
GB polyps are of many types, some of them have malignant potential, and others are
generally benign, thus can be grouped into neoplastic (adenomatous) and nonneoplastic
(cholesterol, inflammatory). USG has a high sensitivity for detecting polyps but cannot
differentiate the histological type of GB polyps. Risk factors that help predict malignancy
are size, female sex, elderly patient, number, and shape of the lesion.[16] Based on previous studies, size >1 cm of the lesion is the most important criteria
for the likelihood of malignant polyp, but a lesion of size <1cm may also turn out
to be adenomatous.[17] Therefore, size cannot be reliably used as the only criteria to differentiate benign
from malignant polyps. Recently, few studies have shown DECT to be a promising modality
that helps in diagnosis and differentiates the polyp types. In a study by Yin et al.,
different energy spectral curves were identified for cholesterol and adenomatous polyp.[17] Cholesterol polyps showed positive mean attenuation value change, whereas adenomatous
polyps had negative mean attenuation value change between 80–140 keV or 40–140 keV
VMI.
GB Cancer
GB cancer is the most common malignancy of the biliary system with a predilection
for specific geographic regions of the world.[18] The presentation is nonspecific. Most patients are diagnosed at an advanced stage
with metastasis and have a poor prognosis.[19] For the diagnosis and staging of GB cancer, imaging plays a crucial role. USG is
the initial investigation of choice as it is cost-effective and readily available.
However, CT and magnetic resonance imaging remain the preferred modalities for accurate
diagnosis and staging. Morphologically, GB cancer has three main patterns; the most
typical pattern is mass occupying or completely replacing the GB lumen (40–65%), followed
by focal or diffuse asymmetric GB wall thickening (20–30%) and polypoid lesion (15–20%)[20] ([Fig. 3]). Additional imaging findings such as associated lymphadenopathy, invasion of surrounding
structures, and distant metastasis help in the diagnosis of wall thickening type of
GB cancer.
Fig. 3 Dual-energy computed tomography (DECT) in gallbladder cancer: mass replacing gallbladder.
(A–C) 80 keV, 140 keV, and mixed (representative of conventional CT) DECT images show
a large mass replacing the gallbladder. The mass is necrotic and shows peripheral
enhancement (arrow). (D) Iodine overlay image (D) shows the peripheral iodine uptake (arrow).
Benign Gallbladder Wall Thickening
Benign conditions like adenomyomatosis, xanthogranulomatous cholecystitis, and cholecystitis
may have similar findings on conventional CT. It is often difficult to accurately
diagnose GB wall thickening.[21]
[22]
[23] Hence, we require advanced imaging modalities to characterize GB wall thickening.
DECT is a potential tool for this problem that has not been investigated. It may show
the mural characteristics, including enhancement pattern and intramural cyst/hypodense
nodules, better than conventional CT, especially on iodine maps. The presence of intramural
cysts/Rokitansky–Aschoff sinuses is diagnostic for adenomyomatosis. The intactness
of mucosa is critical for the diagnosis of benign GB wall thickening and is better
assessed on iodine overlay maps. Finally, adjacent liver infiltration will be better
seen on the iodine overlay images ([Fig. 4]).
Fig. 4 Dual-energy computed tomography (DECT) in gallbladder cancer: wall thickening type.
(A–C) 80 keV, 140 keV, and mixed (representative of conventional CT) DECT images show
mural thickening of the gallbladder body (arrow). Note that the enhancement characteristics are better seen at 80 keV images. (D) Iodine overlap image shows that the enhancement is asymmetric and heterogeneous
(arrow) features favoring malignant nature.
The critical characteristics of DECT studies evaluating biliary diseases are summarized
in [Table 1].
Table 1
Studies highlighting the role of DECT in the evaluation of biliary diseases
|
Authors
|
Year
|
Country
|
Scanner
|
Technique of DECT
|
Aim
|
Key results
|
|
Kim et al[7]
|
2011
|
Korea
|
Somatom definition, Siemens Healthcare
|
Dual-source DECT scanner
|
To assess whether VNC images are equally good as nonenhanced images for evaluation
of biliary stones and compare VNC images obtained during LAP and PVP with true nonenhanced
images
|
VNC images have moderate accuracy for detection of biliary stone. However, limited
role in detection of smaller GS (<9mm) and relatively radiolucent CBD stones of attenuation
<78HU
|
|
Lee et al[6]
|
2015
|
Korea
|
Somatom definition Flash, Siemens Healthcare
|
Dual-source DECT scanner
|
To compare GS on VNC and true unenhanced images acquired with DECT
|
VNC images allow better visualization of cholesterol GS, but calcium and small GS
are better seen on true unenhanced images
|
|
Yang et al[9]
|
2016
|
China
|
Discovery CT750 HD scanner
|
Single tube, dual-energy fast-switching spectral imaging mode
|
To investigate whether spectral CT can differentiate cholesterol GS from surrounding
bile
|
VMI images at lower and higher keV provide significant attenuation difference between
cholesterol GS and surrounding bile
|
|
Uyeda et al[8]
|
2017
|
USA
|
Siemens FLASH, Forchheim Germany
|
Dual-source 128 × 2 slice scanner
|
To assess whether VMI allow better detectability of noncalcified GS on DECT in comparison
with conventional CT imaging
|
Noncalcified stones are better visualized on low keV VMI images
|
|
Soesbe et al[10]
|
2019
|
USA
|
IQon; Philips Healthcare, Best, the Netherlands
|
Dual-layer DECT
|
To develop a dual-energy technique for differentiation of iso-attenuating GS from
bile
|
Segmented images improved the detection of isoattenuating GS from bile with good accuracy
even for smaller GS (<9mm)
|
|
Yin et al[17]
|
2020
|
China
|
Somatom definition Flash, Siemens, Erlangen, Germany
|
Dual-source DECT
|
To investigate whether DECT can differentiate between cholesterol and adenomatous
polyp
|
DECT scans with their unique energy spectrum information can differentiate cholesterol
and adenomatous polyps 1.0–2.0 cm in size
|
Abbreviations: CBD, common bile duct; DECT, dual-energy computed tomography; GS, gallstones;
HU, Hounsfield unit; keV, kiloelectron voltage; LAP, late arterial phase; PVP, portal
venous phase; VMI, virtual monoenergetic images; VNC, virtual noncontrast.
Future Directions
DECT may provide quantitative data for texture analysis and radiogenomics in GB cancer.
A recent study showed the incremental value of the radiomics model for detecting serosal
invasion in preoperative restaging for locally advanced gastric cancer.[24] Another study reported a DECT-based nomogram for detecting HER 2 status in gastric
cancer.[25] Furthermore, DECT may allow accurate differentiation of metastases from cholangitic
abscess in the setting of GB cancer. This has enormous prognostic and therapeutic
implications as metastatic GB cancer has a dismal prognosis and receives the best
supportive care. In a recent study comprising 28 patients with multiple malignancies
(GB cancer) and 23 patients with liver abscesses, DECT had sensitivity and specificity
of 89.3 and 93.3% and area under the curve of 0.963 for differentiating liver abscess
from metastases.[26] The comparative performance of different DECT scanners/techniques needs full exploration
before confident clinical applications.
Conclusion
DECT is a promising tool for the evaluation of biliary diseases. It has the potential
to provide a one-stop solution to the detection of intraluminal and intramural pathologies,
including differentiation of benign and malignant pathologies. However, there is limited
data available on individual biliary tract pathologies. Therefore, future research
must focus on knowing the potential of this application of CT scan.
