This review will summarize some of the recent advances in MR imaging of liver masses, focusing on contrast agents and the relative role of MR to CT and US in evaluating patients with liver masses. It has been approved for three (3) hours of category I credit
The last 10 years have seen dramatic changes in the therapeutic
approach to primary and secondary liver malignancies. This has been
due, in part, to the increasing proliferation of new less-invasive
treatments, including percutaneous ablative therapies (ethanol
injection, radio-frequency ablation, laser ablation), angiographic
therapies (segmental chemoembolization), and liver transplantation,
in addition to wider applications of pre-existing treatments
(resection and systemic chemotherapy) either alone or in
conjunction with the new treatments. The broad array of treatments
available requires current medical management to select the
therapeutic approach for each patient, which will provide the
highest success rate while taking into consideration the risks,
costs, and availability of the required technology.
Recent advances in ultrasound (US), computed tomography (CT),
and magnetic resonance (MR) imaging mean that pretreatment imaging
of the liver is now the critical step in evaluating patients with
liver malignancies. The imaging of patients with suspected liver
masses can be viewed as having three purposes: detection,
characterization, and the assessment of intrahepatic and
extrahepatic extent of tumor. Given the high incidence of benign
it is fairly common to detect these lesions both incidentally and
during the work-up of oncologic patients. Thus, while lesion
detection is a principal objective of liver imaging, lesion
characterization is also an important concurrent objective.
Similarly, the accurate staging of disease extent is a prerequisite
for the selection of appropriate therapy.
The advances in diagnostic imaging have enhanced our ability to
detect and characterize focal liver lesions, affording a definitive
diagnosis noninvasively now more than ever before. The information
acquired, combined with appropriate clinical information,
facilitates the preparation of optimal treatment plans for patients
with liver malignancies. This review will summarize some of the
recent advances in MR imaging of liver masses, focusing on contrast
agents and the relative role of MR to CT and US in evaluating
patients with liver masses.
LIVER LESION DETECTION: THE MEDICAL NEED
Liver Lesion Detection in the Noncirrhotic
This is commonly undertaken in two distinct clinical situations:
in patients with known malignancy for whom staging of disease is
required, and in patients with known liver malignancy who are
considered candidates for local resection or interventional
treatment. Patients with a known extrahepatic malignancy require
evaluation for abdominal metastases for staging extent of disease.
In this setting, the imaging modality of choice should be one that
most effectively and efficaciously can simultaneously evaluate the
liver and the extrahepatic abdomen. Contrast-enhanced CT is
generally accepted as the most appropriate modality for such a
screening study, primarily due to the ease of performing and
interpreting large numbers of such examinations, its widespread
availability, and a generally acknowledged superior ability to
evaluate the extrahepatic abdomen.
In addition, if other body parts, such as the head or chest, need
to be evaluated for the spread of disease, they can all be examined
in a single visit according to a cost-effective, efficient protocol
Although MR currently plays only a limited role in this setting,
it is appropriate in certain specific clinical situations. While
not as easily utilized for screening large numbers of patients on a
daily basis, MR can certainly evaluate the abdomen efficiently and
can be utilized in patients who are allergic to iodinated contrast
media. A clinical situation in which MRI is the preferred liver
imaging modality is in the presence of fatty infiltration of the
liver in patients with potential liver malignancies. Fatty
infiltration is a common problem that often results from poor
nutrition, the effects of chemotherapy, or regional differences in
liver perfusion in patients with malignancy. In these situations,
diffuse fatty changes can often obscure the presence of underlying
focal lesions on CT (Figure 2). Moreoever, focal fatty infiltration
or sparing can often create pseudolesions on CT scans.
MR, especially with opposed-phase gradient-echo techniques, is
superior to CT for detecting or confirming the presence of lesions
against a background of fatty liver (Figure 3).
The second important clinical setting in which lesion detection
is vital is in patients with a known liver malignancy who are being
evaluated for liver resection or lesion ablation. This is
particularly relevant in patients with colorectal cancer, where up
to 30% of patients may have isolated liver metastases. It is in
this sub-group that local therapy, in particular liver resection,
can offer the possibility of cure. Studies have shown a 5-year
survival rate of 20% to 40% following partial hepatic resection of
colorectal metastases in selected patients, compared with a 5-year
survival rate of 5% to 10% in untreated patients.
However, successful outcome depends greatly on an accurate
knowledge of the size and location of the tumor burden. Imaging
plays a vital role in differentiating patients with limited local
tumor disease, who may benefit from radical surgery or
interventional treatments, from patients with widespread disease
for whom such treatments are unlikely to be beneficial.
While multidetector helical CT has greatly improved the ability
of CT to evaluate the liver in patients with malignancy,
studies with strong pathologic correlation have yet to demonstrate
adequate capacity for the detection of small (<1.5 cm) tumor
Until recently, CT during arterial portography (CTAP) was widely
used for the preoperative staging of liver disease with a
sensitivity of approximately 90% for lesion detection, compared
with 70% for conventional contrast-enhanced CT (CECT).
The advent of multidetector helical CT has significantly improved
the sensitivity of CT to approaching 90% for dynamic helical CT,
and to >90% for helical CTAP.
However, CTAP is an invasive technique and has low specificity due
to numerous benign perfusion defects.
Moreover, concern over the nephrotoxicity of iodinated contrast
agents and the requisite use of ionizing radiation in all CT
examinations are factors to be considered when referring patients
for diagnostic evaluation of the liver.
Contrast-enhanced MR provides a viable alternative to helical CT
for all liver examinations. Traditionally, contrast-enhanced liver
MR has been performed with conventional gadolinium chelates, which
distribute exclusively to the extracellular space and rely on
differences in perfusion between normal liver and lesion to improve
the detection of liver lesions beyond that achievable on unenhanced
However, while such agents have proven beneficial for the improved
detection of hypervascular tumors, they have not always been shown
to increase the detection of hypovascular metastases.
The development and use of contrast-enhanced MRI using contrast
agents with liver-specific properties is emerging as an appropriate
modality for the preoperative staging of liver malignancy; in most
practices it has replaced CTAP (Figure 4).
Liver Lesion Detection in the Cirrhotic
There is a very high incidence of hepatocellular carcinoma (HCC)
in patients with chronic liver disease, particularly hepatitis B
and C, long-standing cirrhosis, and hemochromatosis. Studies of
patients referred for transplantation have consistently
demonstrated >10% incidence of HCC in patients ultimately
transplanted for severe cirrhosis, and approximately a 20%
incidence in patients with hepatitis B and C.
Despite the use of US and serum alpha-fetoprotein determinations as
screening techniques for the detection of HCC in cirrhotic
patients, both are characterized by low sensitivity when reported
in screening population studies with pathologic correlation.
The detection rate of HCC with US is related to the size, location,
and echotexture of the lesions, as well as to the US technology
employed and the experience of the operator. While US HCC detection
rates from 82% to 93% have been reported for tumors measuring
between 2 and 3 cm,
results at these high sensitivities have not been confirmed in
screening populations or in studies with pathologic confirmation.
The reported rate for HCCs <2 cm in diameter is considerably
more variable and is generally accepted as inadequate for tumor
detection. The detection rate on US for HCCs <1 cm is even
lower, ranging between 13% and 37%.
Generally, detection, especially of small nodules, is severely
affected by the location and echogenicity of the tumor and by the
level of expertise on the part of the operator. Additionally,
diffuse HCCs are very difficult to identify and characterize with
US, since the diffuse parenchymal inhomogeneity can be
misinterpreted as being due to cirrhosis (Figure 5). The use of
ultrasound is further complicated by the numerous false-positive
lesions created by the nodular regeneration inherent in cirrhosis.
The sensitivity of US for the detection of HCCs can be
reasonably increased by improving contrast resolution, ie, by
optimizing US beam focalization and frequency, preferably with the
most updated wideband transducers, and/or by the use of tissue
harmonic imaging. The recent advent of contrast agents for
ultrasound (eg, Levovist, Schering AG, Berlin, Germany; SonoVue,
Bracco Imaging SpA, Milan, Italy) may further improve the impact of
US for liver lesion detection,
but the clinical utility of these remain to be proven in large
populations and will need to be compared with CT and MR.
Evaluating the cirrhotic liver for HCC is further confounded by
the multiple causes of nodularity in these patients. First and
foremost, HCC is a multifocal tumor and daughter nodules or
multiple sites of tumor development are common features. All
imaging modalities tend to underestimate the number of multicentric
nodules and daughter HCCs in these patients. This is particularly
evident in studies in which end-stage resected cirrhotic liver with
pathologic examination following transplantation are compared with
previous radiologic findings. A study of 46 patients undergoing
orthotopic liver transplantation with pathologic examination of the
explanted livers, revealed pretransplantation sensitivities of 58%
for CT with iodized oil, 67% for digital subtraction angiography
and 85% for CTAP. Most false-negative diagnoses in this study were
due to either small HCCs (<2 cm) or intrahepatic metastases.
The sensitivity for detecting HCCs <3 cm in diameter has a
wide variability in literature reports. This wide range of
detection rates probably reflects the population being studied more
than the abilities of a modality or the investigator. Screening
studies with pathologic proof in patients without suspected tumor
have consistently shown that the highest detection rate for HCC
detection in cirrhosis for any modality is not accurate. The
diagnostic modality with the highest reported success rate is
intraoperative US, with sensitivities ranging from 90% to 98%.
With intraoperative US, the issue of false-positive diagnoses is
less often of importance, as the issue can be addressed
Currently, biphasic or triphasic helical CT achieves a higher
detection rate than does conventional CT, with the arterial phase
proving more accurate than the portal-venous phase, especially for
the detection of HCCs <2 cm in size.
The sensitivity achieved by current MRI technology is
essentially equal to that of helical CT, especially if conventional
T1- and T2-weighted images with various sequences are coupled with
gadolinium chelate dynamic contrast-enhanced images (Figure 6).
While multidetector CT can obtain two arterial-phase passes (early
and late), which may improve HCC detection,
MRI has the ability to obtain multiple arterial passes and has the
added advantage of doing this without additional radiation. This
can improve HCC detection.
In addition, contrast agents with hepatocyte-specific properties
have been shown to improve the detection of HCC.
LIVER LESION CHARACTERIZATION
The liver is a common repository for many benign and malignant
focal lesions. Many of the benign entities, such as hemangioma,
focal nodular hyperplasia, cysts, and focal fatty change are very
common and the importance for radiologists is to recognize them as
such, since these lesions usually require no further attention. In
contrast, malignant lesions in the liver may require prompt
surgical or interventional attention. The primary malignancies that
occur in the liver may arise from hepatocytes, bile duct
epithelium, endothelial cells, or lymphoid cells. The majority of
malignancies encountered in clinical practice are epithelial in
origin, with HCC and cholangiocarcinoma accounting for nearly all.
Whereas HCC is the most common abdominal primary malignancy
worldwide, the liver is also a very fertile soil for metastases
because of: 1) its dual blood supply from the systemic and
splanchnic systems; 2) the presence of humoral factors that promote
cell growth; and 3) the discontinuous nature of the endothelial
lining of the hepatic sinusoid, which allows open communication
with the extracellular space of Disse.
The predominance of benign lesions in the liver, even in
patients with known malignancies elsewhere, is clear from a recent
retrospective study reporting 2978 cancer patients who had
undergone CT examinations.
Small (<1 cm) hepatic lesions were present in nearly 13% of
these patients. At follow-up, 80% of these small lesions were
determined to be benign and 8% were stable and indeterminate. Only
approximately 12% of these liver lesions were confirmed as
malignant. The high prevalence of benign liver lesions in adults,
and the fact that small subcentimeter lesions are increasingly
being recognized due to advances in CT and MR imaging, make liver
lesion characterization an important objective of imaging.
Incidental liver masses discovered in healthy adults as well as
lesions detected during the work-up of a known malignancy
frequently need to be characterized. Common benign lesions such as
cysts, hemangiomas, focal nodular hyperplasia, focal fatty
infiltration, and sparing need to be differentiated from metastases
and HCC, and from less frequently encountered malignant lesions,
such as fibrolamellar HCC, intrahepatic cholangiocarcinoma,
lymphoma, mesenchymal tumors, and hepatoblastoma.
CT is often used as the initial modality for liver lesion
characterization, and US may also detect and, occasionally,
characterize lesions. Liver masses with US and/or CECT features
typical of simple cysts or hemangiomas that are detected in
patients who are not known or suspected of having a malignancy may
confidently be classified as benign and generally do not need any
further work-up. Similarly, lesions with unequivocal US and/or CECT
signs of a malignant mass may not need additional imaging, but may
sometimes need confirmation by percutaneous biopsy. For lesions
that are indeterminate on US and CECT, MRI is the modality of
choice to best characterize liver lesions (Figure 7).
LIVER LESION DETECTION AND CHARACTERIZATION ON
When MRI first became a practical reality, it was thought that
the administration of exogenous contrast agents would not be
necessary and that native differences in relaxivity between lesion
and normal liver parenchyma would suffice for both lesion detection
and differential diagnosis. This was based on early studies that
demonstrated that normal parenchyma and lesions possess different
T1 and T2 relaxation times. These relaxation times could be used to
differentiate the lesion from the parenchyma and, considering the
difference in signal intensity between one lesion and another,
could be used for the differentiation of these lesions.
Specifically, some authors demonstrated that multi-echo heavily
T2-weighted sequences are helpful in differentiating cysts and
hemangiomas from metastases due to the different T2 relaxation
Cysts and hemangiomas have longer T2 relaxation times than
metastases and thus maintain high signal intensity on longer echo
Although the information obtained on unenhanced T1- and
T2-weighted imaging is frequently important for characterization,
the potential overlap of signal intensity between benign and
malignant lesions and between different lesion types within each
group generally renders unenhanced imaging alone insufficient for
accurate differential diagnosis unless a homogeneous, very high
signal intensity lesion characteristic of cyst or hemangioma is
encountered. This is particularly true with the now routine use of
gradient-echo and fast-spin-echo techniques, rather than
conventional T2-weighted imaging, which may lessen the differences
in intensity between benign and malignant liver lesions. The
limitations of the unenhanced approaches to MR imaging have made
the use of contrast agents mandatory for adequate lesion
Contrast Agents for Liver MRI
As shown in Table 1, a number of contrast agents with different
biodistribution patterns and relaxation properties are available
today for liver MRI. Until relatively recently, the purely
extracellular MR contrast agents based on gadolinium were the only
agents available for both liver lesion detection and
characterization. These T1 relaxing contrast agents are usually
administered as a bolus and are used in conjunction with
T1-weighted sequences such as T1-weighted gradient echo (GET1) or,
more recently, volume interpolated breath-hold examination (VIBE).
The lesion enhancement patterns observed derive from the
differential perfusion properties of lesions compared with normal
liver and are frequently specific to individual lesion types. Thus,
lesion characterization is based essentially on differential lesion
morphology and is therefore analogous to that occurring in helical
In addition to the purely extracellular contrast agents, two
distinct categories of MR contrast agents with liver-specific
properties are now available (Table 1). The first category
comprises the hepatocyte-targeted agents and include both
gadolinium- and manganese-based agents (predominantly T1-shortening
agents). The second category comprises the superparamagnetic iron
oxides (SPIO), which are targeted to the reticuloendothelial system
(predominantly T2-shortening agents). Agents of the former category
include the gadolinium-based agents gadobenate dimeglumine
(Gd-BOPTA; Multihance, Bracco Imaging SpA, Milan, Italy) and
gadoxetate (Gd-EOB-DTPA; Eovist, Schering AG, Berlin, Germany), and
the manganese-based agent mangafodipir trisodium (Mn-DPDP;
Teslascan, Amersham-Health, Oslo, Norway). Agents of the latter
category include Ferumoxides (Feridex IV, Berlex Laboratories,
Wayne, NY; and Endorem, Guerbet, Aulnay Sous Bois, France) and SH U
555 A (Ferucarbotran, Resovist; Schering AG).
Unlike CT and MRI enhanced with purely extracellular gadolinium
agents, MRI enhanced with agents with liver-specific properties is
frequently able to make use of functional information to
differentiate one lesion type from another. With Mn-DPDP and some
of the larger SPIO agents (eg, ferumoxides) that cannot be
administered as a rapid bolus, the functional information
attainable is alternative to the morphologic information available
with the extracellular gadolinium agents. With other agents, such
as Gd-BOPTA, Gd-EOB-DTPA and some of the smaller ultrasmall
superparamagnetic iron oxide agents (USPIO; eg, SH U 555A), rapid
bolus administration is possible, and both morphologic and
functional information is attainable.
Mangafodipir trisodium is a manganese-based contrast agent that
dissociates rapidly in the blood following slow intravenous
infusion (2 to 3 mL/min over a 10- to 20-minute period) to release
ion. This free Mn
ion is then available for nonspecific uptake into parenchymal
cells, particularly those of the liver, pancreas, kidneys, and
adrenals in which metabolism of this metal takes place. Maximal
enhancement of the liver is usually observed after approximately 20
minutes and lasts for approximately 4 hours.
Tumors of nonhepatocytic origin show little or no enhancement
resulting in increased lesion conspicuity; several studies have
shown improved lesion detection on images obtained after infusion
of Mn-DPDP compared with precontrast images.
Inherent in its uptake by liver cells is that it is also taken up
by many hepatocellular lesions with well-differentiated hepatocytes
resulting in enhancement, and thus a decreased tumor-liver
contrast-to-noise ratio (CNR). An investigation aimed at evaluating
Mn-DPDP for the study of hepatocellular tumors demonstrated poor
efficacy of this agent for the identification of these lesions, in
large part due to this phenomena.
However, the uptake itself allowed for identification of additional
lesions not seen on unenhanced imaging, but at the expense of
converting other lesions clearly identified to isointense lesions.
Moreover, Mn-DPDP accumulation has also been observed in hepatic
metastases from nonfunctioning endocrine tumors of the pancreas.
In a recent study in 77 patients with histologically confirmed
lesions, Mn-DPDPenhanced MRI had a sensitivity and specificity of
91% and 67%, respectively, for the differentiation of malignant
versus benign liver lesions, and 91% and 85%, respectively, for the
differentiation of hepatocellular versus nonhepatocellular lesions.
Uptake of Mn-DPDP by both benign and malignant hepatocellular
neoplasms limits the possibilities of accurate tumor
differentiation and represents a major shortcoming of this agent.
Moreover, there have also been reports of an increased toxicologic
and neurologic risk in patients with hepatic impairment, and of a
possible depressive action on heart function arising from the entry
of free Mn
into myocardial cells through calcium channels.
Nonetheless, because of excellent liver parenchymal enhancement and
virtually no uptake in common tumors, such as hepatic metastases,
MR imaging with mangafodipir is now often used to replace CTAP for
tumor detection and does allow for moderate tumor
Agents with Combined Perfusion and Hepatocyte-Selective
Other contrast media combine the properties of a conventional
extracellular agent with those of an agent targeted specifically to
the liver. Such compounds distribute initially to the
vascular-interstitial compartment in a manner analogous to that of
the conventional gadolinium chelate agents. Thereafter, a fraction
of the injected dose is taken up into functioning hepatocytes,
causing an increase of the signal intensity of the hepatic tissue.
Agents of this type include gadobenate dimeglumine (Gd-BOPTA),
which is already approved in Europe and elsewhere for clinical use,
and Gd-EOB-DTPA, which is in an advanced phase of development.
Gadobenate dimeglumine is the first of the combined (dual)
second-generation gadolinium agents to become available
Features that distinguish Gd-BOPTA from the conventional
extracellular gadolinium agents are a capacity for weak and
transient interaction with serum albumin, which results in a
two-fold greater T1 relaxation rate in vivo,
and an elimination profile that sees roughly 96% of the injected
dose excreted renally via glomerular filtration and the remaining
dose taken up by functioning hepatocytes and eliminated in the bile
via the hepatobiliary pathway.
Whereas the former feature permits lower overall doses to be used
compared with conventional agents to obtain equivalent diagnostic
information on dynamic imaging,
the latter feature leads to a marked and long-lasting enhancement
of the signal intensity of normal liver parenchyma, resulting in an
additional, delayed imaging window beginning 40 min after Gd-BOPTA
Studies have shown that Gd-BOPTA behaves in an analogous way to
conventional gadolinium agents during the dynamic phase of contrast
and as a liver-specific agent in the delayed phase when accentuated
liver-lesion contrast differences not only improve the impact of
MRI for the detection of focal liver lesions,
but also contribute to the improved characterization of detected
lesions, particularly lesions demonstrating atypical enhancement on
Gadolinium-ethoxybenzyl-DTPA behaves in a similar manner to
Gd-BOPTA in distributing initially to the vascular-interstitial
compartment after injection. However, whereas only approximately 4%
of the injected dose of Gd-BOPTA is thereafter taken up by
hepatocytes and eliminated in the bile, approximately 50% of the
injected dose of Gd-EOB-DTPA is taken up and eliminated via the
hepatobiliary pathway after approximately 60 minutes. The maximum
increase of liver parenchyma signal intensity is observed
approximately 20 minutes after injection and lasts for
approximately 2 hours.
During the perfusion phase, the dynamic enhancement patterns seen
after injection of Gd-EOB-DTPA are similar to those seen with
conventional agents and Gd-BOPTA. During the hepatobiliary phase,
Gd-EOB-DTPA-enhanced images have been shown to yield a significant
improvement in the detection rate of metastases, HCCs, and
hemangiomas compared with unenhanced and Gd-DTPAenhanced images.
It is not yet clear whether the additional hepatocytic uptake that
this agent provides, as compared with Gd-BOPTA, will have any
advantage in routine clinical practice.
Agents Targeted to the Reticululoendothelial
Agents that distribute specifically to the reticululoendothelial
system (RES) include the SPIO particles and the USPIO particles.
These agents are cleared from the blood by phagocytosis
accomplished by the RES, which is abundant in the liver parenchyma
but is usually deficient or lacking in most malignant liver
lesions. After SPIO injection, a darkening of the normal liver
parenchyma surrounding focal liver lesions increases the CNR of
these lesions, which, through having deficient RES, appear more
hyperintense on delayed T2-weighted images compared with the
decreased intensity of normal liver parenchyma.
Ferumoxides is an example of a larger type of SPIO agent with a
diameter between 50 and 180 nm for which bolus injection and
dynamic imaging are generally precluded. Thus, while this agent has
proven effective for liver lesion detection,
it has proven less effective for lesion characterization due to the
overlap of diverse liver lesion types able to take up this agent.
SH U 555A, on the other hand, is a smaller USPIO agent with a
diameter between 45 and 60 nm. Unlike ferumoxides, this agent can
be administered as a fast bolus to observe the early perfusion
characteristics of the liver using T1- or T2*-weighted sequences.
Unfortunately, the enhancement observed on SH U 555Aenhanced
images is quite weak due to the small dose that can be
AMI-227 is another example of a USPIO agent with a mean particle
diameter between 17 and 20 nm. Because of the comparatively long
intravascular half-life of this agent, AMI-227 is considered a
As is typical of iron oxide contrast agents, AMI-227 shows
preferential or selective accumulation in the liver parenchyma
resulting in signal loss on T2-weighted images. With the long
intravascular half-life, however, vascular lesions will also
enhance for extended periods of time. This can aid in
characterizing lesions, but may reduce liver-lesion contrast when
compared with unenhanced images and may obscure some vascular
BEHAVIOR OF FOCAL LIVER LESIONS IN RESPONSE TO CONTRAST
In the past, a practical approach to the characterization of
focal hepatic lesions on CT and MR has focused on the distribution
of conventional iodine and gadolinium chelates to the extracellular
fluid spaces. This approach facilitates both the detection and
characterization of lesions, the latter relying upon the
recognition of distinctive patterns of enhancement of liver
lesions. Lesions are broadly separated into categories of
hypervascular or hypovascular on the basis of their handling of
these contrast agents.
Hypovascular liver lesions include clearly avascular lesions,
such as cysts and abscesses, and tumors that demonstrate only
marginal peripheral enhancement, if any, compared with surrounding
liver parenchyma. The majority of metastases to the liver are
hypovascular lesions from primary sources such as colon, lung,
pancreas, and others. The few primary sites that reproducibly
demonstrate hypervascular liver metastases include renal, thyroid,
neuroendocrine (pancreatic islet cell), and sarcomas. Breast and
melanoma metastases to the liver may be vascular, but are generally
less reproducibly so than the other tumors. Imaging of hypovascular
tumors on CT or dynamic gadolinium-enhanced MR relies on imaging
the liver during the peak liver enhancement, at which point
liver-lesion contrast is maximal. Beyond this point, the CNR
decreases as the equilibrium phases are reached (beginning at
approximately 90 to 100 seconds postinjection). The hypovascular
solid tumors, whether benign or malignant, all have a similar,
noncharacteristic appearance and cannot be characterized
Hypervascular liver lesions include a wide number of lesion
types ranging from physiopathologic to pathologic. These lesion
types comprise benign and malignant lesions of both hepatocellular
and nonhepatocellular origin. The enhancement characteristics of
these lesions can aid in the differential diagnosis or, in some
cases, can achieve a definitive diagnosis.
Benign Focal Masses Derived From Hepatocellular
Focal nodular hyperplasia
Focal nodular hyperplasia (FNH) is the second most common benign
liver tumor, surpassed only by hemangioma. It is present in 3% to
5% of the population and is more common in women of child-bearing
The cellular structure of FNH is similar to that of normal hepatic
parenchyma apart from the presence of an abnormal biliary system.
In more than a third of cases, the lesion develops asymptomatically
as a result of a hyperplastic process
and is discovered in an entirely incidental manner. In roughly 85%
of cases, only a single nodule of FNH is present. The margins of
the lesion are usually well-defined, and its size is generally
<5 cm, although lesions between 8 and 10 cm can be encountered.
Given the lack of clinical symptomatology associated with these
lesions and the lack of malignant potential, FNH is most often left
untreated, albeit with follow-up examinations to confirm the
Since FNH contains the same elements as normal liver but with a
disordered architecture, it mimics the appearance of normal liver
and may be difficult to detect without exogenous contrast. On
unenhanced MR imaging, the lesion is isointense to hypointense to
normal liver on T1-weighted images, frequently with a hypointense
central fibrous scar. On T2-weighted images, it is isointense to
mildly hyperintense to normal liver with a hyperintense central
scar. On dynamic gadolinium-enhanced T1-weighted images, the
lesions show intense homogeneous enhancement in the arterial phase
that washes out rapidly thereafter. This characteristic aids in
differentiating these lesions from fibrolamellar hepatocellular
Typical of fibrous tissues, the central scar is slower to allow
entry of extracellular-type contrast agents and slower to allow
their washout. Thus, the scar appears characteristically
hypointense on dynamic phase images, but iso- or hyperintense to
the liver parenchyma on equilibrium and later images. This is
frequently a distinguishing feature from the tumor necrosis often
seen in malignant tumors.
Focal nodular hyperplasia lesions contain Kupffer cells and thus
take up both SPIO and USPIO agents, demonstrating diminished signal
intensity on postiron-oxide scans. However, this finding is not
specific, as well-differentiated HCCs may also take up iron oxides,
although usually to a lesser degree.
In equivocal cases with SPIO agents, biopsy or surgical resection
may be required.
Although gadolinium-enhanced MRI is considered the most
sensitive method for the characterization of FNH, atypical features
are frequently seen. For example, in a recent study, 86% of small
(¾3 cm) FNH did not have a visible scar on unenhanced or enhanced
dynamic phase scans.
Although the absence of a scar in small FNH cannot be considered
wholly atypical, it may make it more difficult to distinguish these
lesions from other hypervascular neoplasms on dynamic imaging
alone. Hence, the availability of MR contrast agents with
liver-specific properties, such as iron oxide agents, Gd-BOPTA, or
Gd-EOB-DTPA, may be helpful for the accurate characterization of
Unlike the iron oxide agents, Gd-BOPTA and Gd-EOB-DTPA offer the
possibility to perform both dynamic and delayed-phase imaging. The
enhancement of FNH on dynamic imaging after Gd-BOPTA is
indistinguishable from that after administration of conventional
nonspecific gadolinium agents. However, on delayed T1-weighted
images, substantial enhancement is noted within the parenchyma of
the lesion, indicative of hepatocyte uptake (Figure 8), while the
central scar, which is the principal site of biliary metaplasia,
appears consistently hypointense. Similar findings have been
observed with Mn-DPDP,
although the inability to perform dynamic imaging with this agent
is an obvious limitation.
Since Kupffer cells are usually observed within FNH, uptake of
SPIO is common, with the lesions showing significant decreases in
signal intensity on postcontrast T2-weighted images.
Unfortunately, the amount and distribution of Kupffer cells within
the nodules can vary, yielding different patterns of signal
decrease: some small FNH (<3 cm) show homogeneous signal drop
similar to that observed in the surrounding parenchyma, while large
FNH may show heterogeneous signal drop. A recent intra-individual
comparison of Gd-BOPTA and ferumoxides in 50 patients with 83 FNH
revealed that while all 83 FNH (100%) were seen during the
examination with Gd-BOPTA, only 62 FNH were seen during the
examination with ferumoxides. Importantly, Gd-BOPTA detected, and
was able to correctly diagnose, all 17 FNH in 12 patients with
previous neoplasia, while ferumoxides was able to detect only 9 of
these 17 lesions (52.9%) and accurately characterize only 7.
Nodular regenerative hyperplasia
Nodular regenerative hyperplasia (NRH) of the liver does not
represent a specific entity but is a secondary and nonspecific
tissue adaptation to heterogeneous distribution of blood flow,
characterized by multiple monoacinar regenerative nodules without
fibrous septa. These lesions can be imaged when the nodules achieve
a macroaggregation of sufficient size to be visualized. Nodular
regenerative hyperplasia occurs in 5% to 6% of individuals >80
years of age and with increased frequency in patients with
Budd-Chiari syndrome, systemic arthritis, polymyalgia rheumatica,
massive tumor infiltration, mineral oil deposition, and other
disorders of liver blood flow.
On unenhanced MRI, NRH displays a broad spectrum of signal
intensity characteristics capable of appearing hypo-, iso-, or
hyperintense with liver parenchyma on T1- and T2-weighted images.
On dynamic-phase MRI with Gd-BOPTA and other extracellularly
distributed gadolinium agents, approximately 90% of these lesions
exhibit enhancement and appear hyperintense during the arterial
phase and iso- or slightly hyperintense in the portal-venous and
With both Gd-BOPTA and Mn-DPDP the lesions appear iso- or
hyperintense to the surrounding liver parenchyma in the
hepatobiliary phase. The appearance of NRH after SPIO
administration has not yet been described completely, but due to
the histologic characteristics of NRH, its behavior can be expected
to be similar to that of FNH (Figure 9).
Hepatic adenoma (HA) is a benign neoplasm typically found in women
with a history of oral contraceptive use,
and in patients with type I glycogen storage disease.
In these latter subjects, the HAs tend to be multiple and more
prone to malignant transformation, although this is still
considered quite rare.
Other predisposing conditions have been described, such as iron
Hepatic adenoma consist of plates or cords of cells that are
larger than normal hepatocytes and contain large amounts of
glycogen and lipid. The plates are separated by dilated sinusoids,
which are thin-walled capillaries perfused by arterial pressure. A
portal-venous supply is lacking in HAs. Kupffer cells are often
found in HA but in reduced numbers and with little or no function,
as reflected by the absent or diminished uptake of technetium
(Tc)99m sulfur colloid.
Even though HAs have functioning hepatocytes, they lack bile ducts,
a key histologic feature that helps distinguish HA from FNH.
Thus, bilirubin metabolism is blocked within HAs, as confirmed by
the absence of bile within resected HAs.
Most patients are asymptomatic with normal liver function. The
classic clinical manifestation for large or multiple adenomas is
spontaneous rupture or hemorrhage leading to acute abdominal pain,
and possibly hypotension or death.
Thus, there is a clinical indication for the surgical removal of
large (>5 cm) HAs.
The appearance of HA on unenhanced MR imaging has been variously
described as hyperintense, isointense, and hypointense.
Areas of increased signal intensity on T1-weighted MR images can
result from fat and hemorrhage,
while low signal intensity areas correspond to necrosis, old
hemorrhage, or calcifications.
Many HAs are predominantly hyperintense on T2-weighted images,
while the remainder are isointense or hypointense. Most lesions are
heterogeneous, demonstrating a combination of hyper- and
hypointensity on T2-weighted images relative to hemorrhage and
necrosis. One-third of HAs have a peripheral rim corresponding to a
which is typically hypointense on T1- and T2-weighted images.
Dynamic gadolinium-enhanced MR imaging often reveals early
arterial enhancement. On portal-venous phase images, this early
enhancement usually fades, revealing an iso- or hypointense lesion.
In lesions with previous hemorrhage, the arterial enhancement will
On delayed-phase images after injection of Gd-BOPTA or
Gd-EOB-DTPA, there is little evidence of CM uptake by HAs which
On the other hand, the liver-specific contrast agent Mn-DPDP is
able to enter the abnormal hepatocytes producing an iso- or
hyperintense appearance on delayed-phase images (Figure 10).
Due to the deficient Kuppfer cell activity, HAs usually do not show
uptake of SPIO particles, resulting in an increased tumor-liver CNR
ratio on T2-weighted images. However, on occasion, HAs may show
some degree of uptake,
leading to a heterogeneous signal drop similar to that seen in FNH.
Uptake of SPIO in HA appears to be due to pooling of the contrast
agent within the peliosis-like dilated vessels.
Unlike isolated HA, liver adenomatosis (LA) is distinguished by the
presence of multiple adenomas, lack of correlation with steroid
medication, occurrence in both men and women, and abnormal
increases in serum alkaline phosphatase and
gamma-glutamyltransferase levels, in an otherwise normal liver and
in patients without glycogen storage disease.
Histologically, the lesions consist of sheets of hepatocytes
with foamy cytoplasm and uniform round nuclei. Portal tracts and
bile ducts are absent, but Kupffer cells and fatty components can
be present in some of the nodules. Many of the nodules can show
evidence of subacute or chronic hemorrhage. Two different types of
LA can be distinguished: a massive form and a multifocal form.
Of these, the former has an increased risk of malignant
degeneration and hemorrhage, and hence surgical intervention is
On T2-weighted MR images, most of the adenomas in LA are
heterogeneously moderately hyperintense or homogeneously
isointense. Noncomplicated lesions are generally isointense to the
liver parenchyma on T1-weighted images.
Dynamic contrast-enhanced MR imaging with gadolinium contrast
agents reveals most adenomas as hyperintense on arterial and early
portal-venous phase images, and as isointense or homogeneously
hypointense on late portal-venous and equilibrium phase images. On
delayed-phase images after injection of Gd-BOPTA, most lesions
appear hypointense, indicating a lack of uptake by the lesions. On
the other hand, Mn-DPDP is able to enter the abnormal hepatocytes,
resulting in a hyperintense appearance on delayed-phase images.
Adenomas show variable uptake of SPIO, with lesion conspicuity
decreasing at intermediate-weighted and T2-weighted imaging.
MR imaging is seldom required for characterization of hepatic
cysts, but when performed, it reveals these lesions to be
hypointense on T1-weighted images and hyperintense on T2-weighted
images with the signal increasing markedly on heavily T2-weighted
images. However, since hemangiomas also exhibit this behavior, a
lack of enhancement of the cyst on postgadolinium T1-weighted
images is able to distinguish between them if clinically
Malignant Focal Liver Lesions: Hepatocyte Origin
Hepatocellular carcinoma (HCC) is the most frequent primary tumor
of the liver and represents >5% of all cancers worldwide, with
an incidence of more than 500,000 new cases per year throughout the
There are considered to be three steps in the development of HCC:
regenerative nodule, dysplastic nodule (low-grade; high-grade; with
focus of HCC), and small HCC (<2 cm).
Regenerative nodules are benign lesions with exclusive
portal-venous blood supply that occur nonspecifically in response
to a variety of insults to the liver. Low-grade dysplastic nodules,
on the other hand, show slight cytologic atypia, mainly large cell
changes, while high-grade dysplastic nodules are considered
pre-malignant lesions. The development of new nontriadal arterial
flow to dysplastic nodules and small HCC can result in some
enhancement on contrast-enhanced CT and MR and simulate HCC,
although this is comparatively rare.
In approximately one-third of high-grade dysplastic nodules, small
foci of carcinoma can be found.
Dysplastic nodules are commonly encountered in severe cirrhosis,
but only approximately 15% of such nodules are detected on MR
When visualized, dysplastic nodules are generally hyperintense on
T1-weighted images and hypointense on T2-weighted images.
Whereas arterial-phase enhancement can increase the sensitivity for
characterization, this is at the expense of decreased specificity
because of the overlap with the much more commonly seen arterial
phase enhancement in HCC (Figures 11 and 12).
Although nodular regeneration and the development of dysplastic
nodules increases the possibility of false-positive diagnoses of
HCC, MRI is widely considered the most successful imaging modality
for differentiating these nodules from HCC.
On the basis of histological differentiation, HCC can be
classified as belonging to one of four grades, from I to IV.
Factors affecting the visualization of primary HCC during
unenhanced and/or contrast-enhanced MRI of the liver include the
dimensions, composition, and degree of vascularization of the
lesion, the functionality of the normal hepatic parenchyma, and the
residual hepatic functionality of the neoplastic cells themselves.
Unfortunately, such factors vary from patient to patient, often
making the behavior of a given HCC lesion difficult to predict.
Studies aimed at correlating the appearance of HCC on MR imaging
with the pathologic characteristics of the lesion reflect the
difficulty in drawing firm conclusions on the behavior of such
Many small HCC lesions are isointense on unenhanced T1- and
T2-weighted imaging and, thus, are not easily seen. When
visualized, HCCs are typically mildly to moderately hyperintense on
T2-weighted images. On T1-weighted images, increased signal
intensity correlates with a more well-differentiated histologic
grade than isointensity or hypointensity.
Dynamic T1-weighted imaging during the arterial phase improves the
detection of small HCCs, which may be occult at other pulse
sequences and on portal-venous and equilibrium phase images.
Frequently, larger HCC lesions display a pseudocapsule
constructed from connective fibrous tissue around the tumor and
internal septations. The pseudocapsule may derive from an
interaction between tumor and host liver and may interfere with the
growth and invasion of the HCC.
The internal septation process (as well as heterogeneity inherent
within larger lesions due to macroscopic fat accumulation,
hemorrhage, necrosis, and fibrosis) creates a relatively
characteristic mosaic appearance.
The pseudocapsule of HCC appears hypointense on unenhanced T1-
and T2-weighted MR images. On enhanced MR imaging with
gadolinium-based agents enhancement is seen principally on
portal-venous phase images, although late arterial-phase images may
also demonstrate enhancement. Typical of fibrous tissue,
enhancement persists into the equilibrium phase after washout from
the normal liver parenchyma has begun (Figure 13).
Kupffer cells are present in HCCs. Although there are no
statistically significant differences in the numbers of Kupffer
cells between small well-differentiated HCCs and noncancerous
tissues, the numbers tend to decrease in cancerous tissue compared
with noncancerous tissue as the tumor size increases and histologic
While dynamic imaging of HCC with Gd-BOPTA provides similar
information to that obtained with conventional gadolinium agents,
delayed-phase imaging performed approximately 1 hour after contrast
injection provides additional information for lesion
characterization. Generally, moderately differentiated lesions tend
to enhance to a greater extent on delayed images compared with both
well-differentiated lesions and poorly differentiated lesions
(Figure 14). This finding reflects the retention of sufficient
hepatocytic activity by these lesions to take up Gd-BOPTA: A
significant correlation was observed between the presence of
intralesional bile and the degree of lesion enhancement after
With the hepatobiliary agent Mn-DPDP, all hepatocellular tumors
demonstrate enhancement, and HCCs frequently show heterogeneous
Well-differentiated HCCs enhance to a greater extent than poorly
PostMn-DPDP MR imaging has been shown to result in a more
accurate differentiation between benign (FNH) and malignant (HCC)
hepatocellular tumors than unenhanced MR imaging, although absolute
values for sensitivity, specificity, and accuracy were relatively
low (64.5%, 66.7%, and 65.1%, respectively).
A study intended to determine the efficacy of Mn-DPDP for the
evaluation of HCC revealed minimal advantages compared with
unenhanced MRI for the identification of lesions.
With SPIO and USPIO agents, HCCs generally do not show a
significant decrease in signal intensity, although signal intensity
loss has been seen in some individual HCCs.
The conspicuity of HCCs after SPIO depends on differences in the
number of Kupffer cells between the lesion and the surrounding
liver. Typically, moderately or poorly differentiated HCCs show
large differences in the number of Kupffer cells and thus
demonstrate a high CNR on SPIO-enhanced MRI, particularly in
cirrhotic livers. Dysplastic nodules and most well-differentiated
HCC, on the other hand, contain nearly the same number of Kupffer
cells as the surrounding cirrhotic hepatic parenchyma and,
therefore, are not well-depicted on T2-weighted MR images.
As with Mn-DPDP, the lack of a dynamic imaging capability limits
the possibilities for lesion characterization with SPIO-enhanced
MRI. With smaller USPIO agents, dynamic evaluation can be
performed, but the conspicuity on enhanced images is generally
weaker than with gadolinium-based agents (Figure 15).
Fibrolamellar HCC (FLC) is a sharply defined, lobulated and
nonencapsulated tumor, whose characteristic microscopic features
include fibrolamellar bands of collagen and fibrocytes arranged in
a lamellar pattern between nests of tumor cells, which often
coalesce to form a central scar.
Typically, FLC occurs in a noncirrhotic liver, primarily in young
adults, with no clear gender predominance.
On MR imaging, the majority of tumors are hypervascular with a
heterogeneous pattern. The heterogeneity of FLC permits its
differentiation from FNH, another lesion with a fibrous central
scar. The fibrous tissue within the scar and radial septa
demonstrate persistent enhancement on contrast-enhanced MR images
obtained 10 to 20 minutes after contrast administration.
On Gd-BOPTA-enhanced images, FLC tend not to show delayed
enhancement at 1 to 3 hours postcontrast.
Benign Nonhepatocitic Focal Lesions
Hemangioma is the most common benign tumor of the liver, with a
reported incidence of up to 20%. Although hemangiomas may be
present at all ages, they are seen more commonly in premenopausal
They are usually well-circumscribed, and represent tortuous caverns
of blood-filled spaces, ranging in size from a few millimeters to
>20 cm. Although frequently a solitary tumor, multiple
hemangiomas occur in approximately 10% to 20% of cases.
Frequently they occur in conjunction with FNH (in 15% to 20% of
Marked hyperintensity on T2-weighted images is frequently
diagnostic for hemangioma, although high signal intensity on
heavily T2-weighted sequences with long echo delay times can
sometimes be seen in cystic tumors and uncommonly in hypervascular
metastases from sarcoma, islet cell tumor, pheochromocytoma,
carcinoid, and renal cell carcinoma. On precontrast T1-weighted
images, hemangiomas are commonly well-defined, slightly hypointense
lesions with lobulated borders. Currently, gadolinium-enhanced MRI
is the most sensitive technique for diagnosing hemangiomas. Three
enhancement patterns of hemangioma with gadolinium-enhanced
gradient-echo imaging have been noted: 1) immediate and complete
enhancement of small lesions (so-called capillary hemangiomas); 2)
peripheral nodular enhancement progressing centripetally to uniform
enhancement; and 3) peripheral nodular enhancement with persistent
central hypointensity due to central fibrosis.
In the majority of cases the combination of T2-weighted and serial
dynamic T1-weighted gadolinium images allows a confident diagnosis
Dynamic imaging characteristics of hemangiomas with Gd-BOPTA and
Gd-EOB-DTPA are the same as with conventional gadolinium agents
On delayed-phase images after these agents and Mn-DPDP, hemangiomas
tend to be hypointense compared with the surrounding liver
as the delayed liver enhancement exceeds the eventual washout from
the lesion blood pool.
Because hemangiomas do not contain Kupffer cells, no
reticuloendothelial uptake is expected with SPIO imaging. However,
hemangiomas do take up USPIO particles due to their blood-pool
effect and may lose signal intensity on USPIO-enhanced T2-weighted
Malignant Nonhepatocytic Focal Lesions
Hypervascular metastases derive from highly vascular tumors such as
carcinoid, islet cell tumor, renal carcinoma, thyroid carcinoma,
pheochromocytoma, melanoma, and breast carcinoma. These lesions are
usually hypointense on unenhanced T1-weighted images, and slightly
hyperintense on T2-weighted images compared with background liver
tissue. Frequently, these lesions demonstrate heterogenous signal
intensity. Some hypervascular metastases may have higher signal
intensity on T2-weighted images and thus mimic hemangiomas.
Hypervascular metastases exhibit significant enhancement during
the arterial phase after gadolinium injection, and as such can be
distinguished from hypovascular lesions, which are best imaged
during the portal-venous phase. In the portal-venous phase,
hypervascular metastases usually show rapid peripheral contrast
agent washout, which, on subsequent images, results in a
hypointense halo appearance.
Larger hypervascular metastases receive arterial blood mainly in
the periphery of the lesion, and may thus demonstrate a peripheral
rim of enhancement.
The dynamic enhancement pattern of hypervascular metastases on
Gd-BOPTA and Gd-EOB-DTPAenhanced dynamic MR imaging is the same as
that seen with conventional Gd-based contrast agents. However, in
the delayed hepatobiliary phase, all metastases are seen as
hypointense to the surrounding enhanced normal liver parenchyma
Although some contrast agent pooling may occasionally be observed
in the necrotic center of the lesion on delayed images, repetition
of the delayed sequence 2 to 3 hours after Gd-BOPTA injection, when
complete washout from the interstitial space has occurred, is
sufficient to confirm that this central enhancement is not due to
As in the case of Gd-BOPTA, hypervascular metastases are
typically hypointense to the surrounding liver parenchyma on
delayed images after Mn-DPDP infusion. However, uptake of Mn
after Mn-DPDP infusion has been observed in hepatic metastases from
nonfunctioning endocrine tumors of the pancreas.
On SPIO-enhanced T2- or T2*-weighted images, hypervascular
metastases appear hyperintense compared with the low signal
intensity of the surrounding normal liver parenchyma due to the
lack of significant contrast agent uptake.
Hypovascular metastases are the most frequent malignancies in the
In the United States, colon cancer is the most common primary site
and approximately 50,000 cases of hepatic colorectal metastases are
Lesion detection is size-related; lesions <1 cm are difficult to
identify with conventional techniques.
A postmortem assessment of the size of liver metastases has shown
that the ratio between metastases >1 cm and those <1 cm is
approximately 1:1.6 for metastases of colorectal adenocarcinoma and
1:4 for other liver metastases.
Thus, an ability to accurately detect and characterize metastases
<1 cm in size is clearly warranted.
Hypovascular metastatic lesions tend to have a round appearance,
although large (>3 cm) metastases from colorectal adenocarcinoma
commonly have a cauliflower aspect. The signal intensity of these
metastases is lower than that of surrounding hepatic tissue on
unenhanced T1-weighted images and typically moderately higher on
T2-weighted images. In approximately 25% of colorectal hepatic
metastases, a hypointense peripheral rim is observed in the
parenchyma around tumor nodules on T2-weighted images. The
associated histopathologic changes are compression of hepatic
parenchyma, hepatocellular atrophy, fibrosis, inflammation, and
It is currently a matter of debate whether conventional
gadolinium contrast agents increase the detection of hypovascular
metastases over unenhanced imaging.
On hepatic arterial-phase images, metastases can show a fleeting
ring enhancement that blurs the margins of the lesions. This
corresponds to a desmoplastic reaction, inflammatory infiltration,
and vascular proliferation in the tumor-liver parenchyma margin;
enhancement progresses centrally with concomitant peripheral
washout. In the equilibrium phase, approximately 10 min after
contrast administration, some lesions may show a peripheral
hypointense rim (peripheral washout sign).
Dynamic-phase imaging after Gd-BOPTA administration reveals
identical enhancement patterns to those obtained with conventional
extracellular gadolinium-based contrast agents. However, since the
lesions are unable to take up Gd-BOPTA, they appear as homogenously
hypointense on delayed T1-weighted images (Figure 18).
When there is a desmoplastic reaction to the lesion, an
accumulation of contrast agent in the fibrotic part may be
observed, which can remain for several hours; in these cases, the
observation of a peripheral hypointense halo is highly suggestive
of the malignant nature of the lesion.
A similar appearance is observed after Mn-DPDP infusion when the
lack of contrast agent uptake leads to an increase of the
Since metastases do not contain Kuppfer cells, the CNR, and
hence lesion detection and conspicuity, is improved after SPIO
injection when compared with unenhanced T2-weighted images.
Due to the nonspecific behavior of malignant liver lesions after
SPIO injection, some authors have proposed a dualcontrast-agent
study to improve lesion characterization. With this approach, pre-
and post-SPIO images are obtained and followed, after bolus
injection of a conventional Gd agent, by multiphasic dynamic
T1-weighted gradient-recalled echo (GRE) images.
The advantages of contrast agents such as Gd-BOPTA that have an
inherent dynamic and delayed imaging capability may render the
dual contrast-agent approach superfluous.
Cholangiocellular carcinoma (CCC) is a malignant hepatic tumor of
the biliary epithelium and is the second most common form of
primary hepatic malignancy in adults after HCC.
Nevertheless, it represents <1% of all newly diagnosed cancers
in North America.
Cholangiocarcinoma is usually divided into intrahepatic and
extrahepatic, depending on the site of origin. Intrahepatic
cholangiocarcinoma (ICC) is a malignant neoplasm arising from the
epithelium of the intrahepatic bile ducts and represents
approximately 10% of all cholangiocarcinomas; hilar (Klatskin's)
and bile duct cholangiocarcinoma account for the remaining 90%.
This neoplasm is usually a large, firm mass, and in 10% to 20% of
cases there are several satellite nodules around the main
Intrahepatic cholangiocarcinoma has a nonspecific appearance on
MR imaging. On precontrast T1-weighted images, it is generally iso-
to hypointense relative to the normal liver, while on T2-weighted
images, the signal intensity of the tumor ranges from markedly
increased to mildly increased. Tumors with high fibrous content
tend to have lower signal intensity on T2-weighted images,
and those with a high mucin content very high signal intensity.
On serial dynamic T1-weighted images enhanced with conventional
gadolinium agents, ICCs usually show minimal or moderate incomplete
rim enhancement at the tumor periphery on arterial-phase images
with progressive central contrast enhancement on portal-venous and
early equilibrium phase images.
Rarely, small homogeneously enhancing tumor nodules can be seen
during arterial-phase imaging simulating HCC. Contrast enhancement
on MR and CT is frequently better seen on delayed equilibrium
images in patients with dense fibrous stroma.
Imaging with Gd-BOPTA is similar to imaging with conventional
nonspecific Gd-based contrast agents during the dynamic phase of
contrast enhancement. However, delayed imaging with Gd-BOPTA during
the hepatobiliary phase may reveal contrast enhancement in the
fibrotic areas of the lesion. The degree of enhancement depends on
the type of cholangiocarcinoma: poor enhancement is noted in large
nonfibrotic cholangiocarcinomas (Figure 19), whereas greater
delayed enhancement is noted in the hepatobiliary phase in the
fibrous core of the scirrhous cholangiocarcinomas.
No significant uptake of Mn-DPDP is observed on delayed
T1-weighted images and, hence, ICC lesions generally appear
hypointense although some peripheral rim enhancement may be
The hepatobiliary phase after administration of liver-specific
contrast media may add useful information for identification of
small satellite lesions.
Analogously, no significant uptake is observed after SPIO
administration due to the absence of Kuppfer cells within the
lesion. Consequently, there is increased liver-to-lesion CNR on
Due to its physiologic location and function, the liver is a
potential repository of a greater number and variety of focal
lesions than any other organ in the body. Apart from malignant and
benign tumors of primary hepatic origin, the liver is also a
principal target for metastatic disease from malignant tumors
elsewhere in the body. The role of diagnostic liver imaging,
therefore, is not only to identify and quantify the presence of
lesions, but also to differentiate lesions requiring immediate
surgical or therapeutic intervention from lesions considered not to
pose a significant clinical risk.
Among the diagnostic imaging modalities available,
contrast-enhanced MRI is generally considered the most sensitive
and accurate technique for the evaluation of focal liver disease.
The variety of contrast agents now available permits accurate
differentiation of benign from malignant lesions on the basis of
morphologic information (ie, with conventional extracellular
gadolinium agents), functional information (ie, with hepatobiliary
and SPIO agents) or both (ie, with second-generation gadolinium
agents, such as Gd-BOPTA).