MR contrast agents: Applications
in hepatobiliary imaging
Tan Cher, MD, and Janio Szklaruk, MD, PhD
L
iver imaging has improved with
advances in magnetic resonance
imaging (MRI) technology.
With the advent of newer sequences and
higher magnetic fields, which allow for
greater temporal and spatial resolution,
dynamic contrast-enhanced (CE) imag-
ing of the liver now plays a dominant
role in lesion characterization.
There has been much discussion
about the use of CE MRI of liver
masses. 1,2 In this article, we briefly dis-
cuss the various MR contrast agents
used in liver imaging, including classi-
fication, dose and mechanism of action,
and side effects. We also discuss recent
advancements in imaging features of
focal liver lesions.
MR contrast agents have been classi-
fied based on their chemical properties,
mechanism of action and their biological
distribution. They can be divided into
gadolinium-based chelated agents
(GBCA) and non-GBCA. The non-
GBCAs include reticuloendothelial (RE)
agents and hepatobiliary (HPB) agents.
The GBCAs and HPB agents are para-
magnetic, while the RE agents are super-
paramagnetic. Based on the biological
distribution, GBCAs behave similar to
iodinated contrast used in computed
tomography (CT), by distributing into
Dr. C h e r is a Body Imaging Fellow,
and Dr. S z k l aruk is an Associate
Professor, Department of Radiology ,
The Univ ersity of Tex as, M. D. Ander-
son Cancer Center, Houston, TX
26 ■ APPLIED RADIOLOGY ©
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the extracellular compartment. The RE
agents are accumulated in the reticuloen-
dothelial system (i.e., Kupffer cells in the
liver). The HPB agents are accumulated
in the hepatocytes and excretedin bile.
Gadolinium-based chelate agents
The first GBCA to be used in clinical
practice was Gd-DTPA (MAGNEVIST®,
Bayer HealthCare Pharmaceuticals,
Wayne, NJ). This was approved by the
United States Food and Drug Administra-
tion (FDA) for use in humans in 1988. 3
Since then, other GBCAs have been
developed by pharmaceutical companies.
Examples include Gd-DTPA-BMA
(OMNISCAN™, GE Healthcare, Chal-
font, St. Giles, U.K.), Gd-HP-DO3A
(ProHance®, Bracco Diagnostics, Prince-
ton, NJ), Gd-DTPA-BMEA (Optimark™,
Covidien Pharmaceuticals, Hazelwood,
MO), Gd-EOB-DTAP (Eovist®, Bayer
HealthCare Pharmaceuticals) and Gd-
BOPTA (MultiHance®, Bracco Diagnos-
tics). The last 2 agents, Multihance and
Eovist, are partly excreted in bile (here-
after referredto as HPB-Gdagents).
The GBCAs shorten the T1 relaxation
times of the surrounding protons. In
liver imaging, fast gradient recalled echo
T1-weighted (T1W) sequences (such as
dynamic 3D-LAVA, GE Healthcare) pro-
vide sufficient spatial and temporal reso-
lution to allow for lesion
characterization. This should also
include a precontrast phase. Multiphasic
contrast evaluation should be performed
using a bolus tracking technique. 4
The recommended dose for most of
these agents depends on the amount of Gd
and stands at 0.1 µmol/kg (0.2 mL/kg).
Close to 100% of the injected dose is
eliminated through the kidneys, with
the exception of Eovist and MultiHance.
The recommended dose for Eovist is
0.025 µmol/kg (0.1 mL/kg).
The incidence of side effects is low by
comparison with the CT contrast
agents. 5 The rate of adverse events has
been low and reported to be <1%. 5 The
most common side effects include non-
specific symptoms such as nausea,
vomiting and headache. Serious side
effects such as anaphylaxis are rare
(0.005% of patients). 5
A recent concern is the development
of nephrogenic systemic fibrosis
(NSF). This condition was first diag-
nosed in 1997. 6 Symptoms are similar
to that of systemic sclerosis, but with
the exception of facial sparing. Other
symptoms include skin thickening,
which restricts joint mobility and can
lead to contractures and immobility.
The visceral organs may also be
involved, including the lungs, liver,
muscles and myocardium. Mortality
has been estimated at around 5%. 7,8
As of February 1, 2008, there have
been 190 biopsy-proven cases of NSF
published in the peer-reviewed literature
with the following associations:
157 gadodiamide (ONISCAN), 8 gado-
pentetate (MAGNEVIST), 3 gadoverse-
tamide (Optimark), and 18 unspecified
GBCA, and 4 confounded cases with
November 2010

Table 1. Thermodynamic Stability Constants and Dissociation
Rates for Gd-Chelate Contrast Agents12,41
Type Agent
Linear Gadoversetamide
(Optimark)
Gadodiamide
(Omniscan)
Gadopentetate dimeglumine
(Magnevist)
Gadobenate dimeglumine
(Multihance)
Gadoxetate diodium
(Eovist)
Macrocyclic Gadobutrol
(Gadovist)
Gadoteridol
(Prohance)
Gadoterate meglumine
(Dotarem)
*Data from Ersoy and Rybicki.41
**Data from Rofsky, Sherry, and Lenkinski.12
>1 GBCA. Five cases of NSF were
unassociated with GBCA. 9 Recent
FDA warnings on the use of gadolinium
based contrast agents recommends the
avoidance of GBCA in patients suspected
or known to have impaired drug elimina-
tion, unless the imaging is essential and
not available without contrast. In that
case, clinicians should administer only
once during an imaging session, and
monitor for signs and symptoms of NSF
if GBCA is administered to patients with
acute kidney injury, or chronic or severe
kidney disease. An estimate of kidney
function should be performed through
laboratory testing for patients at risk of
having reducedkidney function.10
These reported cases of NSF were
related to advanced renal dysfunction
and appeared to develop over a period of
several days or months. Among
patients with end-stage renal disease,
the incidence of NSF in those who
received Gd-chelate contrast agent
ranged from 2.9% to 5%, and was inde-
pendent of dose. 11
It has been suggested that the dis-
placement of Gd3+ from the chelating
agent, a process known as transmetalla-
tion, is involved in the accumulation
November 2010
MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING
*Stability constant **Disocciation rate
(log10) (0.1 µmol/L HCL)
16.6 >2.2 x 10-2
16.9 >2 x 10-2
22.5 1.2 x 10-3
22.6 Not reported
23.5 Not reported
21 2.8 x 10-6
23.8 6.4 x 10-5
25.6 8.4 x 10-7
of free Gd3+ within the body tissues.
This is one of the mechanisms thought
to provoke an inflammatory response
resulting in NSF. 11 The rate of dissoci-
ation and thermodynamic stability of
the compounds are listed in Table 1.
Based on these factors, macrocyclic
agents are thought to be less likely
related to the release of free Gd3+ in
vivo than the linear agents. 12 Guide-
lines for contrast use, dose, and selec-
tion of contrast have been developed by
the American College of Radiology
(ACR) and various radiology depart-
ments as shown in Table 2.
Reticuloendothelial agents
The RE agents, also known as super-
paramagnetic iron oxide (SPIO), were
designed to accumulate in the Kupffer
cells. These are usually present in nor-
mal liver tissue. In contrast to the Gd-
chelate agents, which serve to accelerate
the T2*-dephasing of protons, leading to
signal loss in areas where they accumu-
late. 13 Tissues that do not contain Kupf-
fer cells, such as metastatic disease,
demonstrate signal-loss lesions in the
liver on T2*-weighted imaging (T2*W).
Alternatively, Kupffer-cell–containing
www.appliedradiology.com
masses will show no significant signal
loss on T2*W imaging.
A prototype of the RE agents is feru-
moxide (Feridex®, Bayer HealthCare
Pharmaceuticals), which contains 0.56
mg of iron per kg of body weight. This
is diluted in 100 mL of 5% dextrose and
injected slowly over a period of 30 min.
Side effects are dose dependent. These
include facial flushing, dyspnea, rash
and lumbar pain. 14 Feridex is no longer
available in the United States. A newer
agent, Ferucarbotran (Resovist®, Bayer
Schering Pharma AG, Leverkusen,
Germany) allowed for immediate imag-
ing of the liver, and therefore reduced the
overall examination time. The rapid
action also meant that dynamic T1
sequences could be performed, 15 how-
ever, development and production of
Resovist ceased in 2009.
Hepatobiliary agents
The main application of the hepato-
biliary (HPB) agents is in the imaging
of the liver parenchyma and the biliary
tree. Like Gd-chelate agents, these also
work by shortening the T1-relaxation
times (paramagnetic effects). The dif-
ference vs. Gd-chelate agents is that
after the blood pool phase, they accu-
mulate within the hepatocytes and are
later excreted in bile.
One of the earliest HPB agents avail-
able was Mangafodipir trisodium. Man-
gafodipir trisodium is a manganese-
based agent that dissociates rapidly
in the blood following slow IV infusion
(2 to 3 mL/min over a 10 to 20 min
period), releasing free Mn2+ ions. 16 The
free ions are then available for uptake
into the cells, particularly in the liver,
pancreas, kidneys and adrenal glands.
Maximum enhancement of the liver is
usually observed after 20 min and lasts
for 4 hours.
There are 2 GBCAs that have shown
excretion of contrast through the biliary
system (HPB-Gd): MultiHance (5%)
and Eovist (55%). Eovist is the first
HPB-Gd agent approved for liver imag-
ing. 17 It behaves as an extracellular
agent on early dynamic imaging, but
also possesses a hepatocyte-selective
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MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

Table 2. M. D. Anderson Cancer Center Guidelines for MRI Contrast Administration

in Patients with Impaired Renal Function (based on estimated GFR readings)

*Calculated glomerular filtration rate (GFR) provided on ClinicStation (“Creatinine Serum” lab results) or can be calculated via serum
creatinine measure and the MDRD GFR calculator at http://www.nephron.com/MDRD_GFR.cgi
**Omniscan: gadodiamide / Magnevist: gadopentetate dimeglumine / ProHance: gadoteridol / Multihance: gadobenate dimeglumine/
Optimark: gadoversetamide

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 MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

range in liver imaging and accentuates

Table 3. Typical Appearances (by phase of T1W imaging)
enhancement. This technique alone
of Focal Liver Lesions Using Gd-chelates
detects most of the clinically relevant
Lesion Pre-contrast Arterial Portovenous Delayed focal liver lesions. Additional liver
Cyst Hypointense Hypointense Hypointense Hypointense examination using unenhanced T1W,
Focal nodular Isointense Hyperintense Isointense Isointense T2W and DWI sequences are helpful for
hyperplasia lesion characterization and detection.
Adenoma Hypointense Hyperintense Isointense Hypointense The 3 phases of dynamic post Gd
Hemangioma Hypointense Hyperintense Hyperintense Hyperintense liver imaging include a late arterial
Hepatocellular Hypointense Hyperintense Isointense Hypointense phase, portal venous phases and excre-
carcinoma tory phase. In general, for the first
Hypervascular Hypointense Hyperintense Isointense Hypointense phase, a bolus tracking technique is rec-
metastasis ommended. The arterial phase should
Hypovascular Hypointense Hypointense Hypointense Hyperintense begin with acquisition of data in the
metastasis center of k space imaging at 8 to 10 sec
after contrast has reached the aorta at the
Table 4. Typical Appearances of Focal Liver Lesions Using level of the celiac axis. 2 A 60 sec and
Reticuloendothelial (RE) and Hepatobiliary (HPB) 180 sec phase are obtained for the portal
Agents at Delayed Phase Imaging venous and excretory phases. At our
institution, a 5 min delayed phase of
Lesion RE (T2*WI) HPB imaging is also routinely added. 1
Cyst Hyperintense Hypointense In the setting of the HPB-Gd agents,
Focal nodular Isointense Hyperintense a hepatocyte-specific delayed phase is
hyperplasia obtained. This is performed at 20 min
for Eovist 23 and at 45 min to 3 hours
Adenoma Isointense Hypointense
for MultiHance. 19
Hemangioma Hyperintense Hypointense The manganese-based agent is not
Hepatocellular Hyperintense Hyperintense used in a dynamic fashion and is pre-
carcinoma dominantly a T1-shortening agent. MR
Hypervascular Hyperintense Hypointense data acquisition should start ≥20 min
metastasis after the end of contrast administration
Hypovascular Hyperintense Hypointense for the best imaging results. However,
metastasis the diagnostic window is broad (≤4
hours) so exact timing is not manda-
profile, and is accumulated in the liver biliary leaks, 20 documenting patency of tory; 1 though this agent is no longer
and biliary system on delayed imaging biliary-enteric anastamoses, 21 and deter- available. The imaging features will
at 20 min. The enhancement on the mining the proximity of lesions to the mimic HPB-Gd during the hepatocyte
hepatocyte phase following the adminis- intrahepatic biliary ducts. phase of enhancement.
tration of Eovist is a function of the Ferumoxide is given as a slow infu-
organic anion transporting polypeptide Imaging protocols sion over 30 min, followed by an inter-
(OATP) in functioning liver cells. 18 With Gd chelates, dynamic imaging val of 30 min for accumulation, and an
MultiHance is excreted to a lesser degree is ideally performed using T1W 3- imaging window of 1 to 4 hours.
by the bile ducts and has been used as an dimensional-gradient recalled echo T2*W GRE, T2W fat-saturated TSE or
HPB-Gd agent as well. 19 Due to its (GRE) pulse sequences with fat satura- turbo-STIR sequences are preferred. 1
smaller percentage of biliary excretion, tion (for example, 3D-LAVA, GE
delayed imaging needs to be performed Healthcare). 22 This technique allows for Imaging of liver lesions
between 45 min to 3 hours. a higher signal-to-noise ratio (SNR) and Common focal liver lesions are clas-
The advent of faster, high-resolution, thinner effective slice thickness, com- sified as benign vs. malignant. Benign
thin-slice MRI has allowed excellent pared with 2-dimensional methods with- lesions include cysts, hemangiomas,
multiplanar reconstruction (MPR) for out interslice gap or crosstalk. The focal nodular hyperplasia (FNH), and
the evaluation of the biliary system. technique also allows for thin-section adenoma, while common malignant
HPB agents have been used in CE coverage of the liver in a single breath- lesions include hepatocellular carci-
assessment of the biliary tree, including hold. Fat saturation is commonly used noma (HCC), as well as hyper- and
visualization of post cholecystectomy because it helps improve the dynamic hypovascular metastases. CE MRI is

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MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

A B

C D

FIGURE 2. Cyst. T1W GRE fat-suppressed

imaging during the delayed (hepatocyte-spe-
cific) phase, 45 min after MultiHance con-
trast administration. The cyst demonstrates
low signal (black arrow). Note the presence
of contrast within the biliary tree (white
FIGURE 1. Cyst. Multiphasic T1W GRE fat-suppressed imaging shows a cyst (arrows) in seg- arrow).

Hemangioma
ment 5/8 of the liver following Magnevist administration. It remains hypointense in all four
phases: (A) precontrast, (B) late arterial, (C) portal venous, and (D) 3 min delayed.
With Gd-chelate agents, heman-
giomas demonstrate early peripheral
nodular enhancement and delayed cen-
tripetal filling-in on T1W imaging
A B

(dynamic gradient recalled echo), paral-

leling that of CT imaging with iodi-
nated contrast (Figure 4). As with other
benign lesions, there can be some loss
of T2 signal. 24 As they do not contain
hepatocytes, they remain hypointense
in the hepatocyte phase following HPB
agent administration. 25 After RE agent
administration, hemangiomas display
the greatest SNR on T2W imaging
among the focal liver lesions (exclud-
ing cysts).

Focal nodular hyperplasia

FNH is composed of multiple spher-
FIGURE 3. Cyst. Pre- (A) and post Feridex (B) contrast administration on T2*W imaging. The
cyst (arrows) is markedly hyperintense in both phases.
ical aggregates of hepatocytes and pro-
commonly used as a problem-solving do not enhance (Figure 1). The contrast- liferation of disordered biliary
tool for lesions that are indeterminate to-noise ratio (CNR) increases signifi- structures that do not communicate
on other forms of imaging. A summary cantly with contrast administration. with the biliary tree. These lesions typ-
of the MRI imaging features is pro- Hence, both extracellular and HPB-Gd ically show early arterial enhancement
vided in Tables 3 and 4. agents (Figure 2) appear markedly and become isointense with the rest of
hypointense on dynamic T1W GRE the liver on the delayed phase using
Hepatic cyst imaging. With HPB agents (Figure 3), the GBCAs on T1W GRE imaging at 3 to
Cysts are fluid-filled cavities, and are cysts appear as hypointense in all phases. 5 min (Figure 5). A central scar is pre-
typically hypointense on T1W imaging With RE agents, they appear markedly sent in 40% of cases. 26 It consists of
and hyperintense on T2W imaging, and hyperintense on T2*W imaging. fibrous tissue, which appears hyperin-

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 MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

A B A

C
C D

FIGURE 5. Focal nodular hyperplasia (FNH).

Multiphasic T1W GRE fat-suppressed imag-
ing shows an FNH (arrows) in segment 8 of
FIGURE 4. Hepatic hemangioma. Multiphase T1W GRE fat-suppressed imaging shows a the liver following Magnevist administration.
hemangioma (arrows) in segment 5 of the liver following Magnevist administration. Precon- Precontrast (A) is hypointense, late arterial
trast (A) is hypointense, late arterial (B) shows peripheral nodular enhancement, portal (B) is hyperintense, portal venous and 3 min
venous (C) shows centripetal filling-in, and 3 min delayed phase (D) is completely filled in. delayed (C and D) are mildly hyperintense.

A B C

FIGURE 6.FNH. Multiphase T1W GRE fat-

suppressed imaging shows an FNH (arrows)
D E

in segment 8 of the liver following MultiHance

administration. Precontrast (A) is hypo-
intense, late arterial (B) is hyperintense, por-
tal venous (C) is mildly hyperintense and
3 min delayed (D) is isointense. In E, the FNH
is isointense to the liver in the hepatocyte
phase at 45 min post contrast administration.

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MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

A B A

FIGURE 7. FNH. Feridex contrast administration on T2*W imaging. FNH (arrow) is hyperin-
tense on the precontrast phase (A). The same lesion takes up Feridex, and becomes isoin-
tense with the rest of the liver on the delayed phase (B).

A B

D
C D

FIGURE 8. Hepatic adenoma. Multiphase

T1W GRE fat-suppressed imaging shows a
FIGURE 9. Hepatocellular carcinoma (HCC). Multiphase T1W GRE fat-suppressed imaging hepatic adenoma (arrows) in segment 4 of
shows the HCC lesion (arrows) in the right lobe of the liver following Magnevist administration. the liver following Magnevist administration.
Precontrast (A) is hypointense, late arterial (B) is hyperintense, portovenous and 3 min Precontrast (A) is hypointense, arterial (B) is
delayed (C and D) are hypointense. Progressive washout is observed in the portovenous and mildly hyperintense, portovenous and 3 min
delayed phases (C and D). delayed (C and D) are hypointense.

tense on T2W imaging and may show
delayed enhancement in some cases.
Differential diagnoses include hepatic
adenomas and fibrolamellar HCC.
Some atypical FNHs present without
arterial enhancement but show
enhancement in the portal venous and
equilibrium phases. 27
With the HPB agents, FNH typi-
cally demonstrates avid enhancements
on the arterial phase. The difference
from extracellular agents is that they
are also taken up by the hepatocytes,
and therefore remain hyperintense to
the liver on hepatocyte phase imaging
(Figure 6). Lesion conspicuity is
reported to be higher than with the RE
agents on delayed imaging. 28 Even
though the central scar is supposed to
be rich in biliary ducts, these are disor-
ganised and poorly functioning, lead-
ing to a persistent lack of
enhancement on hepatocyte phase
imaging. 24 With Eovist, enhancement

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MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

in the hepatocyte-phase after 10 and 20

min can be observed in 88% and 90% of
lesions, respectively. 29
A B

FNH lesions are mildly T2*-hyperin-

tense on the precontrast phase. As they
also contain Kupffer cells, there is
uptake of the RE agents, resulting in
marked signal intensity loss (Figure 7)
that may be less than that of surround-
ing liver (30% in FNH vs. 68% in nor-
mal liver). 19 This may distinguish them
from other lesions such as HCC and
adenoma, which show a signal drop of
3.3% and 6.6%, respectively. 24

Hepatic adenoma
C D

Adenoma cells are larger than normal

hepatocytes and contain large amounts
of glycogen and lipid. A heterogeneous
appearance of adenoma is most likely
due to fat, a hemorrhage, a necrosis or
calcification. 30 Three types have been
described: the steatotic form that con-
tains variable foci of fat, and hence fat
signal; peliotic, which shows avid and
persistent hypervascularity; and the
mixed form, which is a combination of
FIGURE 10. HCC. Multiphase T1W GRE fat-suppressed imaging shows the HCC lesion the steatotic and peliotic forms. With
(arrows) in the right lobe of the liver following Magnevist administration. Precontrast (A) is
GBCAs, the peliotic form shows early
and persistent enhancement, while the
hypointense, late arterial (B) is hyperintense, and portovenous and 3 min delayed (C and D)
are hypointense. Progressive washout is observed in the portovenous and delayed phases
(C, D). Cavernous transformation of the hepatic vessels is evident. steatotic form shows minimal enhance-
ment (Figure 8). 31
Accurate differentiation of FNH from
adenomas is often not possible on the
basis of precontrast or dynamic phase
A B

images alone. Use of delayed T1W

GRE imaging, with partially hepato-
cyte-selective agents, may differentiate
adenomatous tissue from FNH. Both
types of lesions may show avid
enhancement on conventional CE pro-
tocols, but at 1 hour delayed imaging,
most adenomas become hypo-intense
while FNHs retain signal hyperinten-
sity. 29 Adenomas generally do not take
up RE agents, even though there are a
variable number of Kupffer cells within
the lesions. This makes them appear as
hyperintense on both pre- and post con-
trast T2*W imaging. Even though they
consist of hepatocytes, the cells are of
FIGURE 11. HCC. Pre- and post administration (A and B) of Feridex contrast on T2*WI. HCC
decreased function and adenomas do not
(arrows) is hyperintense in both phases. It may not be possible to distinguish this from other accumulate HPB agents and appear
non-hepatocyte containing lesions such as hepatic adenomas or metastases. hypointense. 32

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 MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

Hepatocellular carcinoma
Although rare in Canada and the
United States, hepatocellular carcinoma
A B

(HCC) ranks as the eighth-most com-

mon cancer in the world. 33 On multi-
phase imaging with GBCAs, HCCs
typically display arterial enhancement
and washout on 5 min delayed imaging.
Lesion conspicuity can be improved on
delayed imaging at 3 to 5 min (Figures
9 and 10). Other features such as a
pseudocapsule, a nodular or mosaic
C D

appearance, and fatty metaplasia may

also be present.
Most HCCs demonstrate early
enhancement during the arterial phase
of contrast administration with GBCA.
The portal venous phase and delayed
phase show washout. The hepatobiliary
agents have been utilized to distinguish
FIGURE 12. Hypervascular neuroendocrine metastases showing transient arterial hypervas-
cularity. Multiphase T1W GRE fat-suppressed imaging shows the metastases (arrows) in the
right lobe of the liver following Magnevist administration. Precontrast (A) is hypointense, late HCC from other malignancies that are
arterial (B) is hyperintense, and portal venous and 3 min delayed (C and D) are hypointense. of non-hepatocellular origin. 34 HCC
will more commonly show low signal
on the hepatocyte phase of contrast
administration. This is thought to be
determined by the expression of
A B

OATP. 35 However, as their signal is

variable, it is not always possible to
distinguish between hypervascular
metastasis and HCC. A combination of
clinical history, laboratory data, and
imaging features on T1W and T2W
imaging will be key contributors to the
correct diagnosis.
With RE agents, HCCs appear as T2
hyperintense lesions post contrast (Figure
11). 36 Since the decrease in T2 signal is
dependent on the number of Kupffer cells,
RE agents have been reported to distin-
C D

guish between well-differentiated and

poorly differentiated HCC. 37 Quantitative
analysis of the SPIO intensity index has
been shown at significantly higher value
in dysplastic nodules and well-differenti-
ated HCC, when compared with moder-
ately differentiated and poorly
differentiated HCC. 38 Double contrast
MRI with SPIO and bolus injection of
GBCA improves the diagnosis of HCC.39
FIGURE 13. Multiple bilobar hypervascular metastases showing transient arterial hypervas-
cularity. Multiphase T1W GRE fat-suppressed imaging shows one of the lesions (arrow) fol- Metastases
lowing MultiHance contrast administration. Precontrast (A) is hypointense, arterial (B) is
Common hypervascular metastases
include those from renal and thyroid pri-
hyperintense, portal venous (C) is isointense. These changes parallel the signal changes with
the use of GBCA. On delayed (hepatocyte) phase imaging at 45 min (D), the lesion is
hypointense, due to the absence of normal hepatocytes within it. maries. On multiphase dynamic imaging

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MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING

of the liver following administration of
GBCAs, they show avid enhancement
on the arterial phase and usually become
hypointense to the rest of the liver on the
subsequent phases (Figure 12). With the
HPB-Gd agents, they show low signal
A B
intensity on delayed imaging on T1W
imaging, due to a lack of Kupffer cells
(Figure 13). And, with the RE agents,
they remain hyperintense on T2W imag-
ing, differentiating them from hypervas-
cular lesions of hepatocellular orgin,
such as typical FNH and some HCCs
(Figure 14).
Hypovascular metastases—such as
colon and breast carcinoma—appear as
hypointense on T1W imaging through-
out all post Gd dynamic phases of the
scan, though they often show peripheral
rim enhancement. With RE agents, there
is no loss of T2* signal in the post con-

trast scans (Figure 15). With the use of

hepatocyte-specific agents, the effects of
contrast washout in the lesions and con-
trast accumulation in normal surrounding
liver increases tumor conspicuity,
improving lesion detection (Figure 16).40

Recent MR advances
Recent advances in MRI, including
FIGURE 14. Hypervascular neuroendocrine metastasis. Pre- and post administration (A and B) of

the use of parallel imaging and 3-dimen-

Feridex contrast on T2*W imaging. The metastasis (arrows) is nearly isointense in A but becomes
markedly hyperintense in B. This is an example where Feridex improves lesion conspicuity.
sional volume gradient echo sequences,
have allowed for the shortening of liver
imaging time to <15 sec, without sig-
A B
nificant loss of in-plane resolution, and a
decrease in slice thickness.
Multiphase imaging has been a work-
horse of liver imaging both in CT and
MRI. As this technique continues to pro-
vide faster sequences, future imaging will
include double arterial, or improved-reso-
FIGURE 15. Hypovascular breast carcinoma metastases. Pre- and post administration (A and lution imaging, without significant loss
of spatial resolution. In this setting, the
B) of Feridex contrast on T2*W imaging. The metastases (arrows) are mildly hyperintense in

familiarity of the appearance of common

the precontrast phase. Lesion conspicuity improves on delayed post contrast imaging in B. It
may not be possible to distinguish this from other non-hepatocyte containing lesions such as
hepatic adenomas or HCC. liver lesions, following contrast adminis-

A B C

FIGURE 16. Recurrent cholangiocarcinoma

following liver resection. Multiphase T1W
GRE fat-suppressed imaging shows the
D E
recurrent tumor (arrows) following Eovist
contrast administration. Precontrast (A) is
hypointense, arterial, portal venous, and 3
min delay (B-D) are hypointense with pro-
gressive peripheral enhancement. These
changes parallel the signal changes with the
use of GBCAs. On delayed (hepatocyte)
phase imaging at 20 min (E), the lesion is
hypointense, due to the absence of normal
hepatocytes within it.

40 ■ APPLIED RADIOLOGY ©
www.appliedradiology.com November 2010
MR CONTRAST AGENTS: APPLICATIONS IN HEPATOBILIARY IMAGING
tration, is required and will become the
cornerstone of liver imaging by MRI.
Hepatocyte agents have allowed for the
addition of a new biological property of
these agents to complement the initial
faster sequences.
Conclusion
The use of contrast in MRI improves
liver lesion detection. This is possible
because of recent advances in image
acquisition techniques that allow for
excellent spatial and temporal resolu-
tion. Contrast agents that reflect the
issue composition provide further infor-
mation that can assist in characterizing
the lesions. A sound knowledge of the
behavior and limitations of each agent
enables the radiologist to optimize MRI
as a problem-solving tool in the assess-
ment of liver lesions.
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