G a s t r o i n t e s t i n a l I m a g i n g R ev i ew

Yaghmai et al.
Imaging Assessment of HCC Response to Therapy

Gastrointestinal Imaging
Review

Imaging Assessment of
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Hepatocellular Carcinoma
FOCUS ON:

Response to Locoregional
and Systemic Therapy
Vahid Yaghmai1 OBJECTIVE. This article focuses on imaging techniques and imaging findings after lo-
Cecilia Besa2 coregional and systemic therapy in patients with hepatocellular carcinoma (HCC). We dis-
Edward Kim 2 cuss currently available locoregional and systemic therapies for HCC, imaging modalities
Joseph L. Gatlin1 and protocols used to assess HCC response, criteria for assessing HCC response, imaging ap-
Nasir A. Siddiqui1 pearances of treated HCC, and future directions.
CONCLUSION. The evaluation of tumor response after systemic and locoregional thera-
Bachir Taouli2
pies is essential in directing management for HCC. An understanding of the various therapeu-
Yaghmai V, Besa C, Kim E, Gatlin JL, Siddiqui NA, tic strategies and of their posttherapy imaging appearances is essential for accurately assessing
Taouli B treatment response. The evaluation of tumor response should include not only anatomic im-
aging biomarkers, such as reduction in tumor size, but also tumor enhancement and necrosis.

Keywords: ablation, CT, hepatocellular carcinoma, MRI,
transarterial chemoembolization
DOI:10.2214/AJR.13.10706
Received February 8, 2013; accepted without revision
February 11, 2013.
1
Department of Radiology, Northwestern University,
Feinberg School of Medicine, Chicago, IL.
2
Department of Radiology, Icahn School of Medicine at
Mount Sinai, Translational and Molecular Imaging
Institute, One Gustave Levy Pl, Box 1234, New York, NY
10029. Address correspondence to B. Taouli
(bachir.taouli@mountsinai.org).
AJR 2013; 201:8096
0361803X/13/201180
American Roentgen Ray Society
H
epatocellular carcinoma (HCC)
is the most common primary he-
patic malignancy and usually de-
velops in the setting of liver cir-
rhosis. Over the past 20 years, the incidence
of HCC in the United States has increased
from 1.5 to 4.9 cases per 100,000 individuals,
with a concomitant 41% increase in the over-
all mortality rate [1]. Radical treatment strat-
egies in HCC involve tumor resection or liver
transplantation. Unfortunately, many patients
have advanced-stage disease or multifocal tu-
mors at presentation and, therefore, are not
candidates for radical treatment options [2].
In these cases, systemic or locoregional ther-
apy is used to treat the disease with promis-
ing results reported in experienced hands [3].
Locoregional therapy such as transarterial
chemoembolization (TACE) is also used as a
bridge to liver transplantation or to down-
stage tumors exceeding Milan criteria [48].
Imaging evaluation of HCC response to
therapy is generally performed with cross-
sectional imaging (CT and MRI). Accurate
assessment of response to therapy, either lo-
coregional or systemic, requires evaluation of
tumor size, tumor margins, and tumor necrosis
as well as early detection of residual or recur-
rent tumor and new tumor. The evaluation of
treatment success is essential for future treat-
ment decisions and for prognosis [9].
Locoregional Treatment Options
for Hepatocellular Carcinoma
Locoregional therapy is an important part of
the management of HCC because tumors are
resectable or meet transplant criteria at the time
of diagnosis in only 510% of patients [10]. In
addition, locoregional therapy has the advan-
tages of preservation of hepatic parenchyma
and overall less morbidity and mortality com-
pared with resection. The Barcelona Clinic Liv-
er Cancer classification has been used recent-
ly as a guideline for therapies directed toward
HCC [11]. The most used locoregional therapy
that will be discussed consists of imaging-guid-
ed percutaneous ethanol or thermal ablation,
such as radiofrequency ablation (RFA) and
microwave ablation, TACE, and transarterial
radioembolization, and the emerging technol-
ogy of irreversible electroporation.
For early-stage HCC, imaging-guided tumor
ablation has been recommended in patients
who are not suitable candidates for resection.
Percutaneous ethanol ablation induces coagu-
lation necrosis through cellular dehydration,
protein denaturation, and chemical occlusion
of small tumor vessels [12]. Ethanol ablation
is now rarely used in the era of efficient RFA
methods because of inhomogeneous injection
and a high recurrence rate in tumors with a di-
ameter of greater than 3 cm [13]. Thermal ab-
lation alters tissue temperature to induce cellu-

80 AJR:201, July 2013

 Imaging Assessment of HCC Response to Therapy
lar disruption and tissue coagulation necrosis.
RFA has been shown to be an effective thera-
py, with overall survival and disease-free sur-
vival similar to resection [14]. In meta-analy-
ses of randomized controlled trials, RFA was
shown to have greater effectiveness and sur-
vival than percutaneous ethanol injection [15
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17]. Patients with very-early-stage HCC have
complete response rates of 97% with 5-year
survival rates of 68% [18]. A factor that lim-
its the use of RFA is vessel size of greater than
3 mm abutting the target tumor, which causes
heat loss due to perfusion-mediated tissue
cooling [7]. Microwave ablation has recent-
ly emerged as a viable alternative for thermal
ablation. The advantages of microwave abla-
tion over RFA are higher intratumoral tem-
peratures, larger tumor ablation volumes, fast-
er tumor ablation, and increased resistance to
tissue cooling due to adjacent vessels [19].
Because of the recent technologic advances in
microwave ablation, only a small number of
studies regarding its effectiveness have been
published, but the results are promising.
A novel, nonthermal ablative technology
that is undergoing clinical investigation for
early-stage HCC is irreversible electropora-
tion. Irreversible electroporation induces ir-
reversible disruption of cell membrane integ-
rity by altering transmembrane potentials,
resulting in cell death [20]. Because of its
nonthermal technology, irreversible electro-
poration is not susceptible to the cooling that
occurs during thermal ablation of tumors ad-
jacent to vessels. Results of ongoing prospec-
tive clinical trials are needed.
For patients with intermediate-stage HCC,
TACE has been established as the standard of
care on the basis of pivotal randomized con-
trolled trials of TACE compared with best
supportive care [2123]. With the advent of
a drug-eluting beads platform for TACE, pa-
tients have decreased systemic side effects
with significant reductions in serious liver
toxicity [24, 25]. TACE with drug-eluting
beads allows sustained and controlled deliv-
ery of doxorubicin as compared with iodized
oil (Lipiodol, Guerbet)based TACE (con-
ventional TACE). The objective response rate
between conventional TACE and TACE with
drug-eluting beads was not statistically signifi-
cant [24]. Transarterial radioembolization has
emerged as a therapeutic option for patients
with intermediate-stage HCC. This therapy
differs from TACE in that microspheres con-
taining 90Y, a -emitting isotope, are injected
into hypervascular HCC through flow-direct-
ed therapy in which high-energy, low-pene-
AJR:201, July 2013 81
tration radiation causing tumor destruction
(SIR-Spheres, Sirtex; or TheraSpheres, Nor-
dion) [26]. Studies have shown the efficacy
of this therapy to be similar to that of TACE
and have documented its safety [2729].
Lower toxicity and longer time to progres-
sion have been cited as advantages of trans-
arterial radioembolization [30].
Advanced-stage HCC, according to the
Barcelona Clinic Liver Cancer classification,
should be treated with sorafenib, a system-
ic multikinase inhibitor, which we discuss in
the next section [31]. In patients with difficul-
ty tolerating sorafenib, locoregional therapy
may be a viable alternative. In patients with
branch vascular invasion, TACE has provided
an overall survival benefit similar to sorafenib
[32]. In comparison with sorafenib, transarte-
rial radioembolization has also shown similar
overall survival in patients with segmental and
main portal vein invasion [33]. Results from
randomized controlled trials are ongoing to
establish the promising role of transarteri-
al radioembolization in the Barcelona Clinic
Liver Cancer algorithm.
Systemic Therapy Options for
Hepatocellular Carcinoma
Medical treatment options have signifi-
cantly advanced over the past decade because
the biology and the pathogenesis of HCC tu-
morigenesis are better understood [34]. How-
ever, despite this progress, systemic therapy
remains reserved for advanced, unresectable
HCC in which radical therapy or liver-directed
therapy is not possible [35]. Conventional cy-
totoxic chemotherapy has, for the most part,
failed to provide long-term benefits. The fail-
ure of chemotherapy has been attributed large-
ly to tumor cell resistance and the pharmaco-
kinetics in the setting of cirrhosis, which alters
the side effect profile and tolerability of many
nonselective chemotherapy agents [34]. Addi-
tionally, hormonal agents, such as tamoxifen
or octreotide, have failed to show an objective
treatment response in placebo-controlled ran-
domized trials or when added to existing che-
motherapeutic options [36, 37].
Molecular targeted therapies directed against
specific molecular alterations in the patho-
physiology of HCC have shown the most
promise. Unlike conventional chemotherapy,
molecular targeted therapies aim to prevent
the growth and spread of disease by interfer-
ing in the signaling pathways for tumor pro-
gression and viability [34]. These cytostatic
agents are geared toward increased efficacy
and reduced toxicity.
Sorafenib, an oral multikinase inhibitor that
targets both tumor cell viability and tumor an-
giogenesis, has been shown to improve surviv-
al when compared with placebo [31]. These re-
sults have established sorafenib monotherapy
as the reference standard for unresectable HCC.
Variation in efficacy based on the cause of the
HCC has been suggested by preliminary data
that show patients with chronic hepatitis C have
a better response to sorafenib than patients with
HCC from other causes [38]. Additionally, the
synergistic effects of sorafenib combined with
conventional chemotherapeutic agents have
yet to be defined; however, initial studies have
shown that sorafenib combined with doxorubi-
cin has promise in reducing tumor progression
and increasing survival duration [39].
Bevacizumab, a molecular targeted mono-
clonal antibody directed against tumor angio-
genesis, has shown promise both alone and
in combination with TACE [40]. Combined
therapy with TACE offers an intriguing op-
tion because some of the effects of TACE may
be blunted by neoangiogenesis, which would
be impeded by the use of bevacizumab [34].
However, the efficacy of this treatment option
has yet to be verified against standard thera-
pies in randomized controlled trials. Addition-
al molecular targeted agents as well as gene
and cell therapies are being pursued with the
hopes of reducing the carcinogenesis and pro-
liferative behavior of HCC [34]. The challenge
will be to identify objective imaging biomar-
kers that accurately assess treatment response.
In summary, there are several options for
locoregional therapy in HCC, which may in-
clude thermal ablation, microwave ablation,
and TACE with or without drug-eluting beads.
These therapies can be used in synergy with
one another depending on the institution.
Sorafenib is the only systemic drug approved
for use in unresectable HCC that has shown
improved survival compared with placebo.
Imaging Techniques for Assessment
of Hepatocellular Carcinoma
Response
Ultrasound and Contrast-Enhanced Ultrasound
Ultrasound is generally used for HCC screen-
ing [41] and is not recommended for follow-
up of patients with treated HCC. On the other
hand, there has been considerable interest in
using contrast-enhanced ultrasound (CEUS)
to characterize solid liver masses such as HCC
[42, 43]. CEUS has also been studied to as-
sess response to locoregional therapy includ-
ing TACE [44], RFA [45], percutaneous etha-
nol ablation, and combined techniques [46].

On postablation CEUS, nodules showing no
contrast enhancement in the arterial phase cor-
relate with complete necrosis on CT and nod-
ules with persistent arterial vascularization are
considered viable tumor deposits [46].
The potential benefits of CEUS include its
ease of use during or immediately after locore-
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gional therapy and the fact that high-densi-
ty iodized oils used during TACE do not limit
CEUS interpretation, as can be the case with
CT [44]. Some investigators have reported
CEUS to be more sensitive than contrast-en-
hanced CT (CECT) for the detection of small
foci of residual tumor after TACE [44]. How-
ever, to date, microbubble contrast agents for
the evaluation of liver lesions have not re-
ceived approval by the U.S. Food and Drug
Administration (FDA), and this technique re-
mains rarely performed in the United States.
MDCT
CT has long been a mainstay of liver and
HCC imaging for both initial tumor charac-
terization and posttreatment follow-up for re-
sponse assessment. Biphasic scanning in the
hepatic arterial and portal venous phases is gen-
erally used for HCC detection [4749]. MDCT
uses 16, 64, 128, or more contiguous detectors
to increase effective pitch without consequent
loss of spatial resolution along the axis of scan-
ning. These scanners allow thin-section imag-
es to be obtained in a single breath-hold with
greatly improved speed and longitudinal res-
olution, which results in nearly isotropic im-
age acquisition and subsequent high-resolution
multiplanar reformations. For patients suspect-
ed of having HCC, the United Network for Or-
gan Sharing currently recommends the use of a
quadruple-phase CT protocol that includes un-
enhanced images (to characterize residual en-
hancement in posttreatment cases), a single late
arterial phase based on a bolus-tracking meth-
od (for accurate peak arterial enhancement), a
portal venous phase at 60 or 70 seconds after
iodine contrast injection at a rate of 45 mL/s,
and a late venous phase ( 120 seconds) after
iodine contrast injection [50].
Recently, dual-energy CT (DECT) has be-
come available and its utility in imaging hy-
pervascular liver masses such as HCC is being
evaluated. DECT provides additional infor-
mation about how tissues of differing densi-
ties behave at differing tube voltages. DECT
can be performed with either two x-ray sourc-
es of differing tube voltages or a single source
with rapidly alternating tube voltages [51].
The omission of a true unenhanced phase to
be replaced with a virtual unenhanced phase
82 AJR:201, July 2013
Yaghmai et al.
may be feasible and has potential dose reduc-
tion advantages [52]. Increased detection of
hypervascular lesions with DECT has also
been reported [53] and DECT may improve
characterization of indeterminate subcentime-
ter lesions using a generated iodine map [51].
DECT may also have utility in evaluating
HCC response to locoregional therapy, such
as RFA, with higher lesion-to-liver contrast-
to-noise ratio on iodine maps, which aids in
the detection of residual tumor [54].
MRI
State-of-the-art protocols using 1.5- or 3-T
MRI systems include breath-hold sequences
for routine MRI examination of the liver (ac-
quisition time for whole-liver imaging < 30
minutes). The following sequences are recom-
mended: axial gradient-recalled echo (GRE)
in phase and opposed phase T1-weighted im-
aging, axial fast spin-echo T2-weighted imag-
ing with fat saturation, axial and coronal T2-
weighted HASTE imaging, diffusion-weighted
imaging (DWI), and axial 3D fat-suppressed
GRE T1-weighted imaging before and after
dynamic injection of extracellular gadolini-
um-based contrast agents (GBCAs) or a liver-
specific GBCA (such as gadoxetate disodium
[Eovist or Primovist, Bayer HealthCare Phar-
maceuticals]) or gadoxetic acid using an MR-
compatible automatic injector. The volumetric
T1-weighted imaging sequence is the most im-
portant sequence for HCC detection and char-
acterization; acquisitions are performed at the
hepatic arterial phase using either a test bolus of
contrast material or a bolus-tracking method for
accurate timing [55]. The portal venous phase
is at 1 minute after contrast injection late ve-
nous or equilibrium phase, at 3 minutes (for ga-
doxetic acid); and hepatobiliary phase, at 10 or
20 minutes (for gadoxetic acid) [56, 57]. Con-
trast-enhanced dynamic T1-weighted imaging
with DWI can be advantageous in assessing
treatment-related changes in HCC and has been
shown to be superior to CECT in evaluating
patients who have undergone Lipiodol-based
TACE therapies [58, 59]. The beam-hardening
effects of high-attenuation Lipiodol on CT may
obscure small enhancing tumors. However,
Lipiodol does not adversely affect MR signal-
intensity characteristics, so residual enhance-
ment can be detected, especially when image
subtraction is used [58, 59].
Lesions treated with RFA or TACE typically
undergo coagulative hemorrhagic necrosis that
may appear hyperintense on unenhanced T1-
weighted imaging, making contrast-enhanced
evaluation difficult [60]. Image subtraction
techniques with MRI have been shown to be
beneficial in depicting residual enhancement,
with excellent correlation with histopatho-
logic degree of tumor necrosis [61]. The add-
ed value of gadoxetic acid over extracellular
GBCAs after HCC locoregional therapy is un-
clear. A recent study suggested no benefit of
using the hepatobiliary phase over dynamic
phases after gadoxetic acid administration for
the detection of local recurrence of HCC after
RFA [62], whereas another study comparing
CT with gadoxetic acidenhanced MRI after
RFA showed higher interobserver agreement
for MRI than CT and a better performance in
general for MRI [63]. The added potential val-
ue of gadoxetic acid may be in the detection of
new lesions and in the differentiation of small
areas of viable tumor from pseudolesions en-
hancing during the arterial phase by assess-
ing washout on the late venous phase or lack
of functioning hepatocytes (hypointensity) on
the hepatobiliary phase [64].
PET
FDG PET has limited sensitivity for HCC
detection ( 60%) and its role in assessing
HCC response to therapy needs to be validat-
ed [65]. Studies have shown a higher sensi-
tivity of 18F-fluorocholine for detecting HCC,
especially well-differentiated HCC, when
compared with FDG [66]. However, the lack
of tumor specificity of FDG PET, limited
quantitative data on the role of the standard-
ized uptake value in predicting overall sur-
vival of patients with HCC, and limitations
in reproducibility of semiquantitative meth-
ods in FDG PET support the need for addi-
tional studies to establish its role in the man-
agement of patients with HCC.
Summary
There is no clear evidence showing the su-
periority of MRI or CT for assessing HCC re-
sponse to therapy. Therefore, the choice of CT
or MRI depends on local expertise and avail-
ability. However, we recommend that MRI
with subtraction be used for the follow-up of
patients treated with Lipiodol-based TACE
and in patients with questionable areas of re-
sidual enhancement on CT after locoregion-
al therapy. Regarding the choice of an ex-
tracellular GBCA or a liver-specific GBCA,
because the role of MRI for the diagnosis of
recurrence relies on the dynamic phases of en-
hancement, there is no compelling evidence
to use a liver-specific agent for follow-up of
treated HCC other than for detecting new tu-
mor foci away from the treated lesion.
 Imaging Assessment of HCC Response to Therapy

TABLE 1: Comparison of European Association for the Study of the Liver (EASL) Criteria [72] and Modified Response
Evaluation Criteria in Solid Tumors (RECIST) [73] for the Assessment of Hepatocellular Carcinoma (HCC)
Response to Locoregional and Systemic Therapy
Assessment Category EASL Criteriaa Modified RECISTb
CR Disappearance of all known disease and no new lesions determined by Disappearance of any intratumoral arterial
two observations not less than 4 weeks apart enhancement in all target lesions
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PR At least 50% reduction in total tumor load of all measurable lesions At least 30% decrease in the sum of diameters of viable
determined by two observations not less than 4 weeks apart target lesions
SD Any cases that do not qualify for either PR or PD Any cases that do not qualify for either PR or PD
PD At least 25% increase in size of one or more measurable lesions or the At least 20% increase in the sum of the diameters of
appearance of new lesions viable target lesions
NoteBoth methods are based on CT or MRI using contrast-enhanced arterial phase images (see also Fig. 1). CR = complete response, PR = partial response, SD =
stable disease, PD = progressive disease.
aBidimensional measurements.
bUnidimensional measurements.

Criteria for Response Assessment
in Hepatocellular Carcinoma
WHO Guidelines and RECIST
Conventional oncologic imaging has fo-
cused on anatomic biomarkers to assess tu-
mor response. The World Health Organization
(WHO) guidelines, incorporating bidimen-
sional perpendicular measurements [67], and
the Response Evaluation Criteria in Solid Tu-
mors (RECIST) (Fig. 1), incorporating uni-
dimensional measurements, were intended to
evaluate change in tumor size over months to
years after systemic treatments and do not take
into account changes in tumor vascularity or
necrosis [68, 69]. However, because the ob-
jective of effective locoregional therapy is to
obtain tumor necrosis regardless of the pres-
ence of changes in size, response based on size
changes may not be achieved by the new cy-
tostatic and locoregional therapies, especially
in the first few weeks after therapy, because
tumor shrinkage may be delayed. In fact, after
locoregional therapy, a treated HCC can possi-
bly increase in size secondary to intratumoral
edema, hemorrhage, or necrosis [70]. There-
fore, better criteria adapted to these new thera-
pies have been developed.
EASL Criteria and Modified RECIST
Given the limitations of the WHO guidelines
and RECIST, new criteria taking into account
a decrease in enhancing tumor and tumor ne-
crosis on CT and MRI have been proposed [71,
72]. The criteria proposed by the European As-
sociation for the Study of the Liver (EASL) are
based on modified WHO bidimensional mea-
surements to estimate tumor response (Table
1 and Fig. 1).
The recently introduced modified RECIST
classification [73] addresses many of the short-
comings of the EASL criteria by defining
methods for newer image acquisitions, target
selection, and target measurement by adapt-
ing many of the strengths of RECIST. Modi-
fied RECIST uses the single largest diameter
of the viable tumor (defined as the compo-
nent enhancing during the arterial phase) and
is more practical for clinical use (Table 1 and
Fig. 1). The EASL and European Organisa-
tion for Research and Treatment of Cancer
(EORTC) [74] have recently endorsed the
use of the modified RECIST criteria for the as-
sessment of HCC response based on dynamic
CT or MRI performed 1 month after locore-
gional therapy or systemic therapy.
Several studies have shown modified RECIST
to be superior to RECIST in predicting HCC
response to TACE and antiangiogenic therapy
[7577]. Measurements of the two largest tar-
get lesions have been shown to be adequate for

RECIST EASL Modified RECIST

Fig. 1Diagrams compare different imaging response criteria used in evaluation of hepatocellular carcinoma (HCC) after treatment: Response Evaluation Criteria in
Solid Tumors (RECIST) [68, 69], European Association for the Study of the Liver (EASL) criteria [72], and modified RECIST [73, 74]. A partially necrotic (black) HCC with an
enhancing component (white) is shown. Arrows illustrate measurements obtained for response assessment. RECIST measures single largest dimension of lesion; EASL
measures two dimensions of enhancing viable tumor; modified RECIST measures single largest dimension of enhancing viable tumor. Both EASL criteria and modified
RECIST are based on measurements obtained on CT or MRI using contrast-enhanced arterial phase images.

AJR:201, July 2013 83

 Yaghmai et al.
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A B C
Fig. 259-year-old man with cirrhosis from chronic hepatitis C virus infection and hepatocellular carcinoma (HCC) who presented for follow-up imaging after undergoing
microwave ablation.
A, Pretreatment axial arterial phase CT image shows hypervascular HCC (arrow) in right hepatic lobe.
B and C, Immediate postprocedural axial unenhanced (B) and contrast-enhanced (C) arterial phase CT images show central high density (arrowhead, B) related
to hemorrhage and tiny air bubbles (arrowhead, C) within ablation zone and surrounding liver. Air bubbles are expected finding immediately after ablation due to
boiling of tissue.

the assessment of HCC response to TACE when
using modified RECIST guidelines [78, 79]. In
two recent studies of patients with HCC treated
with TACE, modified RECIST and EASL criteria
independently predicted overall survival [77, 78].
Response assessments based on EASL criteria
and modified RECIST performed approximately
1 month after therapy with TACE using drug-elut-
ing beads have been shown to predict survival,
with better performance for the modified RECIST
guidelines [76]. In addition, a recent study [80]
showed a significant association between overall
survival and EASL and modified RECIST re-
sponses, whereas there was no significant associa-
tion between survival and RECIST 1.1 response.
Data on the performance of modified RECIST
in assessing HCC response to systemic thera-
pies are limited. In a study of 53 patients treat-
ed with sorafenib, responders based on modi-
fied RECIST showed longer overall survival
than nonresponders [75]. The combination of
-fetoprotein level and modified RECIST has
been shown to predict prognosis in patients with
advanced HCC treated with sorafenib [81].
The modified RECIST criteria have limita-
tions: They have not been validated for assess-
ing HCC after transarterial radioembolization
and RFA. Also, it is difficult to measure with
confidence diffusely necrotic lesions with inter-
vening viable components. Finally, many pa-
tients with multiple HCCs are treated in stages,
so tumors are treated at different time points,
which decreases the value of these criteria
when assessing locoregional therapy.
Summary
The modified RECIST criteria take into ac-
count size and vascularity (on arterial phase
CT or MRI) of residual enhancing tumor and
are appropriate for use in HCC treated with lo-
coregional therapy. However, there are cases
(e.g., infiltrative tumors, heterogeneous ne-
crosis) and situations (e.g., after ablation) in
which the modified RECIST criteria are diffi-
cult or impossible to apply.
Imaging Appearances of Treated
Hepatocellular Carcinoma
General Imaging Considerations
The ultimate goal of locoregional therapy of
HCC is tumor cell death and necrosis [82]. Sys-
temic therapies in HCC are typically cytostatic,
leading to little change in tumor size. Because
of the complexities in therapeutic approaches,
a therapy-tailored imaging evaluation of HCC
after therapy is of paramount importance [83].
Accurate interpretation of posttherapy changes
in tumor by evaluating lesion margins and vi-
ability is essential for assessing response and
determining the need for future treatment [64].
The EASL-EORTC [74] guidelines rec-
ommend performing dynamic CT or MRI 4
weeks after locoregional therapy or after the
start of systemic therapy. They also recom-
mend performing imaging follow-up for the
detection of recurrence and new lesions ev-
ery 3 months during at least the first 2 years
after treatment begins. Afterward, ultrasound
is recommended every 6 months.
Appearance After Locoregional Therapy
Evaluation during and immediately after
locoregional therapyPeriprocedural evalu-
ation of transcatheter therapies such as TACE or
transarterial radioembolization can be challeng-
ing because the target tumor may have a vari-
able blood supply. Identification of the vessels
that perfuse the tumor is essential in directing
these therapies and ensuring that an adequate
ablative response is achieved with minimal col-
lateral damage [84]. Conventional digital sub-
traction angiography is limited in assessing the
variable vascular supply to a tumor and also in
determining therapeutic efficacy [85]. In some
centers, imaging during locoregional therapy
may be performed with C-arm cone beam CT.
This technique offers reconstructed CT-like im-
ages from a flat-panel C-arm unit during the ab-
lative therapy, thereby allowing visualization of
the soft-tissue tumor and feeding vessels [84].
Additionally, the distribution of embolic ma-
terials such as Lipiodol can be evaluated imme-
diately or within 24 hours after the procedure

84 AJR:201, July 2013

 Imaging Assessment of HCC Response to Therapy

[86]. However, these practices vary from center
to center, are beyond the scope of this article,
and will not be discussed here.
For ablation techniques, success is defined
as a nonenhancing ablation zone encompassing
the entire tumor and an ablative safety margin
of at least 5 mm of the nontumor hepatic paren-
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lation site (Fig. 3). This coagulative necrosis
will result in a hyperdensity within the treated
HCC on CT and hyperintense signal on T1-
weighted imaging, thus limiting assessment
for residual tumor enhancement. However,
these findings frequently will have resolved on
subsequent imaging [89] (Fig. 2). Subtraction
of residual tumor may be obscured by tran-
sient hyperemia, so cases showing persistent
arterial enhancement with washout on delayed
phase images at short-term follow-up should
be evaluated further to determine whether ad-
ditional directed therapy is needed [82].
Regardless of the mode of therapy, nodular

chyma [87]. Moreover, tiny air bubbles that re-
sult from the boiling of tissue can be seen im-
mediately after RFA and will typically have
resolved by 1-month follow-up [88] (Fig. 2).
The air bubbles should be differentiated from
the mottled persistent air densities seen with a
hepatic abscess or within a peripheral wedge-
shaped defect of a hepatic infarct [88]. How-
ever, we will not describe complications of lo-
coregional therapy in this article.
Follow-up evaluation after locoregional
therapyA central area of coagulative necro-
sis is often seen within the tumor or the ab-
images can be a helpful adjunct for differen-
tiating hemorrhage from enhancing tumor on
MRI [61] (Figs. 4 and 5). Transient hyperemia
manifested by thin, uniform enhancement of
the treated zone is an expected finding after
RFA, TACE, or transarterial radioemboliza-
tion and represents a transient physiologic re-
sponse to thermal injury and embolization to
the hepatic parenchyma [82] (Figs. 4 and 5).
This finding should be differentiated from re-
sidual malignancy [89]. Typically transient en-
hancement resolves within several months on
follow-up imaging [89]. However, small foci
or thick areas of arterial enhancement along
the margin of a treated HCC are consistent
with residual tumor, especially when there
is associated washout, and require additional
treatment [60, 88] (Fig. 6). In a recent retro-
spective study, a lack of tumor enhancement,
peripheral ring enhancement, and peripheral
nodular enhancement on arterial phase CT
after TACE with drug-eluting beads showed
progressively greater correlation with tumor
progression (i.e., 8%, 17%, and 83%, re-
spectively) [90]. However, in cases with in-
conclusive imaging findings, short-term fol-

TACE or 1. Ablation 1.
transarterial
radioembolization HCC HCC

CR PR or recurrence CR PR or recurrence

2. 3. 2. 3.

* *

4. 4. 5.

Tumor shrinkage Cavity shrinkage

A B
Fig. 3Diagrams illustrate changes in hepatocellular carcinoma (HCC) after treatment. CR = complete response, PR = partial response.
A, Treatment changes after transarterial chemoembolization (TACE) or transarterial radioembolization. Hypervascular HCC before treatment is illustrated as white circle
in diagram 1. Diagrams 2 and 4 shown below CR label illustrate appearances of successful locoregional therapy: lack of enhancement of treated lesion compatible with
complete necrosis (black circle, diagram 2) with possible surrounding geographic arterial enhancement, rim enhancement, or both (asterisk, diagram 2) corresponding to
posttreatment changes. Enhancement may be segmental or lobar for transarterial radioembolization and rim enhancement surrounding lesion is possible, especially after
transarterial radioembolization. Soon after TACE or transarterial radioembolization, treated lesion shows no changes in size but can decrease in size over time (diagram
4); delayed shrinkage may be seen after transarterial radioembolization. Diagram 3 under PR or recurrence label shows residual enhancing tumor.
B, Treatment changes after ablation. Hypervascular HCC before treatment is illustrated as white circle in diagram 1. Diagrams 2 and 4 below CR label show ablation
cavity (double-headed arrow) is larger than original tumor because of ablation margin. Surrounding geographic arterial enhancement, rim enhancement, or both (asterisk,
diagram 2) corresponding to posttreatment changes is shown. Diagrams 3 and 5 under PR or recurrence label show small nodule that increases in size on follow-up
imaging.

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 Yaghmai et al.
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Fig. 456-year-old man with cirrhosis from chronic hepatitic C virus infection and hepatocellular carcinoma (HCC). Axial fat-suppressed MR images obtained before
(AD) and 7 months after (EH) transarterial chemoembolization (TACE) with drug-eluting beads and stereotactic radiation therapy are shown.
A, T2-weighted image obtained before therapy shows 3.8-cm hyperintense HCC (arrow) in segment VIII (see also Fig. 13).
B, Unenhanced 3D gradient-recalled echo (GRE) T1-weighted image shows that HCC (arrow) is hypointense.
C and D, Three-dimensional GRE T1-weighted images obtained during arterial phase (C) and portal venous phase after injection of extracellular gadolinium-based
contrast agent (D) show HCC (arrow) exhibiting wash-in and washout and that capsule is visible.
E, T2-weighted image obtained 7 months after therapy shows that HCC (white arrow) is hypointense and smaller (2.4 cm). There is also capsular retraction (black arrow).
F, Unenhanced 3D GRE T1-weighted image shows increased signal intensity in treated HCC (arrow).
G, Subtracted arterial phase 3D GRE T1-weighted image after injection of gadoxetic acid shows HCC (long arrow) is completely necrotic with geographic arterial
enhancement of surrounding liver parenchyma (short arrows), which became isointense to liver parenchyma, compatible with perfusion abnormalities.
H, Three-dimensional GRE T1-weighted image obtained at hepatobiliary phase shows hypointense necrotic lesion (long arrow) and decreased uptake of surrounding liver
parenchyma (short arrows); these findings are likely secondary to external beam radiation therapy and TACE.

low-up in 3 months may be necessary to assess
the resolution or progression of residual dis-
ease in the treated lesion or cavity.
Next, we discuss some findings specific to
the locoregional therapy used. After TACE
using Lipiodol, unenhanced CT could be per-
formed to assess Lipiodol distribution. In
general, complete retention of iodized oil has
high correlation with complete lesion necro-
sis and incomplete retention corresponds to
a range of responses from complete necro-
sis to residual viable tumor [91, 92] (Fig. 7).
Lack of iodized oil uptake immediately after
therapy may also indicate an aberrant vascu-
lar supply to the tumor and will require re-
peat treatment as soon as possible [93, 94].
However, multiphasic MDCT must still be
performed to assess areas lacking iodized oil
[91]. Necrotic nonviable tumor tissue will
continue to retain the oil indefinitely but will
decrease in size over time. However, it is
preferable to perform an MRI study because
MRI is more accurate for assessing residual
or recurrent tumor than CT [59].
After ablation, residual viable tumor or tu-
mor regrowth tends to be detected at the pe-
riphery of the treated cavity either as irregu-
lar thickening at the margin or as a new tumor
nodule [95] (Figs. 6 and 8). Hyperintense ap-
pearance on T2-weighted imaging or DWI
with associated nodular enhancement is char-
acteristic of tumor or incompletely treated tu-
mor (Figs. 6 and 8). Care should be taken not
to diagnose peripheral regrowth when a thin,
regular rim of progressive enhancement is
present because this finding is a sign of simple
vascularized inflammation or fibrosis [96]. In
addition, after RFA, arterioportal shunts can
be seen due to thermal injury to small vessels
in the hepatic parenchyma but will resolve on
follow-up evaluation [97].
After transarterial radioembolization, the
radiation effect is manifested as heterogene-
ous enhancement of the liver in a perivascu-
lar distribution in a treated segment or lobe.
This posttherapy finding is unique to trans-
arterial radioembolization and could be eas-
ily mistaken for tumor progression [98, 99].
An explant correlation study assessing HCC
after transarterial radioembolization showed
that decreased enhancement and size of treat-
ed lesions correlate with pathologic necrosis,
whereas peripheral nodular enhancement indi-
cates the presence of viable tumor (Fig. 9). The
same study showed that the presence of rim
enhancement had 93% positive predictive val-
ue and specificity for the prediction of necro-
sis and is not necessarily indicative of viable
tumor [98]. It is also important to emphasize
the delayed effect of transarterial radioembo-
lization on tumor necrosis and shrinkage, with
reported median times to response of approx-
imately 30 and 120 days, using necrosis and
size criteria, respectively [100] (Fig. 10).
In summary, when interpreting the first post-
procedural imaging study, usually obtained
4 weeks after the procedure, it is important to
differentiate normal posttreatment appearance
(shunting surrounding the lesion, thin rim of
enhancement, T1 hyperintense or hyperdense
cavity or treated tumor, heterogeneous per-
itumoral enhancement) from residual tumor
and recurrent tumor (nodule with wash-in and
washout, with or without T2 hyperintensity,
with or without diffusion restriction).
Appearance After Systemic Therapy
At MDCT, sorafenib has been shown to de-
crease HCC enhancement without necessarily
affecting tumor size [101]. The predominant
patterns of HCC response after sorafenib on
MRI are T1 and T2 tumor hyperintensity and
necrosis [102] (Fig. 11). An increase in tumor
size due to necrosis has also been reported.

86 AJR:201, July 2013

 Imaging Assessment of HCC Response to Therapy

Therefore, quantification of necrosis appears

to be a better method of treatment response
assessment than tumor size in HCC treated
with multikinase inhibitors [102]. A recent pi-
lot study showed a statistically significant im-
provement in time to progression of disease
in patients with advanced HCC treated with
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sunitinib when tumor density decreased 15%

or more [103]. After systemic therapy, simi-
lar to after locoregional therapy, residual thick
and nodular foci of arterial enhancement with-
in HCC suggest residual nontreated tumor.
In summary, even without a decrease in
tumor size, a decrease in enhancement or the
presence of tumor necrosis is an indicator of A B
treatment response after systemic therapy.

Novel Imaging Biomarkers

of Response
Volumetric Evaluation
The anatomic imaging biomarkers assume
that tumors are spherical before and after treat-
ment [104]. In both RECIST and modified
RECIST, a 30% decrease in diameter of tu-
mor, defined as the threshold for partial re-
sponse, is presumed to correspond to a 65%
decrease in tumor volume. Similarly, a 20%
increase in diameter of viable tumor, which
defines the threshold for defining disease pro-
gression, corresponds to an approximately 73%
increase in spherical volume. These cut points
are rather arbitrary and may not be applicable
to all therapies. Furthermore, both RECIST and
modified RECIST measurements are only es-
timates of the tumor volume and are prone to
interobserver measurement variability. In a ret-
rospective study of 45 HCCs, diameter based
on 3D measurements was significantly differ-
ent than diameter based on conventional 2D
measurements [105]. Similarly, in a study
of 29 HCCs treated with transarterial radio-
embolization, a significant difference in the
mean calculated necrosis proportions based
on 2D and volumetric methods was observed
[105]. Volumetric evaluation of HCC and its
necrotic component eliminates this limitation
and, when available, offers the most compre-
hensive anatomic evaluation for determining
treatment response [106]. Voxel-by-voxel vol-
umetric analysis of tumor density and necrosis
has been shown to be more reproducible than
2D analysis [105, 107] (Fig. 12). Volumetric
quantification is particularly helpful in cas-
es in which necrosis is heterogeneously dis-
tributed in HCC and cannot be assessed using
modified RECIST. However, to date, volum-
etry has not been incorporated into RECIST
or other commonly used size-based response
criteria in HCC.
C D
Fig. 561-year-old man with cirrhosis from chronic hepatitic C virus infection and hepatocellular carcinoma
(HCC) after transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) treatments.
A, Axial unenhanced fat-suppressed 3D gradient-recalled echo (GRE) T1-weighted image obtained 8 months after
TACE and RFA shows hyperintense treatment cavity (arrow) in right hepatic lobe; this finding is compatible with
posttreatment hemorrhage.
B, On contrast-enhanced fat-suppressed 3D GRE T1-weighted image obtained at arterial phase after injection of
gadoxetic acid, it is difficult to detect any residual enhancement in cavity (arrow).
C, Subtracted 3D GRE T1-weighted image obtained at arterial phase shows no evidence of enhancement (long
arrow); this finding is compatible with completely necrotic tumor. Peripheral geographic enhancement (short
arrows) is noted adjacent to treatment cavity.
D, Axial fat-suppressed fast spin-echo T2-weighted image shows heterogeneous signal intensity, with areas of hypo-
and hyperintensity, in treated cavity (long arrow) and adjacent geographic high T2 signal intensity (short arrows).
In summary, volumetric evaluation of HCC Diffusion-weighted imagingDWI has re-
and its degree of necrosis is a very promis- cently shown potential for HCC detection (Fig.
ing tool because it is more accurate and repro- 13) compared to or combined to contrast-en-
ducible than the currently used bidimensional hanced T1-weighted imaging [109, 110]. DWI
measurement. However, volumetric measure- is also increasingly used to evaluate tumor re-
ment is not easily feasible in the routine clin- sponse to chemotherapy, radiotherapy, and lo-
ical setting and is still not included in tumor coregional therapy [111, 112]. There are sev-
response criteria. eral reports about the use of DWI to evaluate
HCC response to TACE and transarterial ra-
Functional Imaging dioembolization [58, 113117]. These studies
Functional imaging, unlike anatomic im- have shown differences in apparent diffusion
aging, provides information on tumor viabil- coefficient (ADC) values between viable and
ity, cellularity, vascularity, and metabolism necrotic portions of HCCs after treatment and
[108]. These changes can be detected earlier measurable differences before and after treat-
than anatomic changes and are more applica- ment (Fig. 13). In a prospective study, Kamel
ble in assessing treatment response after lo- et al. [117] observed an increase in tumor ADC
coregional therapy or systemic therapy. value that was significant 12 weeks after ini-

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 Yaghmai et al.
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Fig. 639-year-old man with cirrhosis from chronic hepatitic B virus infection and hepatocellular carcinoma (HCC). MR images obtained 2 months after first cycle (AF)
and 2 months after second cycle (GI) of transarterial chemoembolization (TACE) with drug-eluting beads are shown.
A, Axial fat-suppressed T2-weighted image shows 3.4-cm HCC in segment IV with areas of high signal intensity (short arrow) and intermediate signal (long arrow).
B and C, Single-shot echo-planar respiratory-triggered diffusion image obtained using b value of 1000 s/m2 (B) and apparent diffusion coefficient (ADC) map obtained
using b values of 0, 50, 500, and 1000 s/m2 (C) show right-sided nodule (short arrow) to be strongly hyperintense with very low ADC corresponding to coagulative and
hemorrhagic necrosis, whereas viable tumor (long arrow) is less hyperintense with ADC isointense to liver parenchyma.
DF, Three-dimensional gradient-recalled echo (GRE) T1-weighted images (unenhanced, D; contrast-enhanced arterial phase, E; hepatobiliary phase after gadoxetic
acid injection, F) show enhancement of left-sided nodule (long arrow), with lack of contrast retention on hepatobiliary phase compatible with viable tumor, and lack of
enhancement in right-sided nodule (short arrow) compatible with necrosis.
G, Axial fat-suppressed T2-weighted image shows decreased size of treated HCC (arrow) with T2 hypointensity and minimal residual focus of hyperintensity.
H, Axial unenhanced fat-suppressed 3D GRE T1-weighted image shows increased signal intensity in lesion (arrow).
I, Axial contrast-enhanced fat-suppressed 3D GRE T1-weighted arterial phase subtracted image obtained after gadoxetic acid injection shows lack of enhancement in
lesion (arrow); this finding is compatible with complete tumor necrosis.

tial TACE, borderline significant 3 weeks af- was present 12 weeks after TACE. Thus, they gators observed that ADC had a significant cor-
ter therapy, and insignificant 24 hours and 4 recommend the use of contrast-enhanced T1- relation with tumor necrosis assessed with his-
weeks after therapy. They also showed that the weighted imaging and DWI 12 weeks after topathology [118]. For prediction of complete
maximum difference in tumor enhancement TACE. In an explant correlation study, investi- tumor necrosis after TACE, an area under the

88 AJR:201, July 2013

 Imaging Assessment of HCC Response to Therapy
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A B C
Fig. 763-year-old man with cirrhosis from chronic hepatitic C virus infection and hepatocellular carcinoma.
A, Pretreatment axial arterial phase CT image shows hypervascular HCC (arrow) in segment IV.
B, Axial unenhanced CT image obtained 24 hours after transarterial chemoembolization (TACE) shows homogeneous dense accumulation of iodized oil (Lipiodol,
Guerbet) in HCC (arrow) and less dense accumulation of Lipiodol in adjacent parenchyma.
C, Axial contrast-enhanced CT image at arterial phase obtained 1 month after TACE shows continued Lipiodol retention in HCC (arrow) while surrounding parenchyma no
longer retains Lipiodol. Lesion has significantly decreased in size, which is compatible with response to therapy. However, enhancement is difficult to assess on CT after
Lipiodol injection.

A B C

D E F
Fig. 867-year-old man who had undergone right hepatectomy for hepatocellular carcinoma (HCC), with recurrent HCC treated with microwave ablation. Follow-up MR
images obtained 2 months after microwave ablation of caudate lobe HCC are shown. DF were obtained slightly superior to AC during same examination.
A, Unenhanced 3D gradient-recalled echo (GRE) T1-weighted image shows treatment cavity (arrow) in caudate lobe with T1 hyperintense rim.
B, Three-dimensional GRE T1-weighted image obtained at arterial phase after injection of gadoxetic acid shows no enhancement (arrow).
C, Subtracted image confirms finding of no enhancement (arrow) seen in B.
D and E, Unenhanced 3D GRE T1-weighted image (D) and arterial phase 3D GRE T1-weighted image after injection of gadoxetic acid (E) show enhancing lesion (arrow) in
caudate lobe adjacent to treatment cavity; this finding is compatible with recurrent HCC.
F, Single-shot echo-planar diffusion image (b value = 1000 s/m 2 ) shows hyperintense nodule (arrow) compatible with restricted diffusion corresponding to recurrent
tumor.

AJR:201, July 2013 89

 Yaghmai et al.

Fig. 972-year-old man with hepatocellular

carcinoma (HCC) treated with 90Y radioembolization
with good response. Axial fat-suppressed 3D
gradient-recalled echo T1-weighted images obtained
before and after treatment are shown.
A, Pretreatment contrast-enhanced image at
portal venous phase after injection of extracellular
gadolinium chelates shows HCC (arrow) in segment
VIII.
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B, Three-month follow-up contrast-enhanced image

at late venous phase after injection of extracellular
gadolinium chelates shows complete tumor necrosis.
Central high signal intensity(arrowhead) was also
present on unenhanced T1-weighted image (not
shown) and represents coagulative necrosis. Note
right pleural effusion.
C and D, Six-month (C) and 18-month (D) follow-up
images at portal venous phase after injection of
extracellular gadolinium chelates show persistent
lack of enhancement and progressive decrease in
A B size of HCC. These findings are compatible with
response to therapy.

curve (AUC) of 0.85 was observed for ADC

compared with an AUC of 0.820.89 for im-
age subtraction, without significant difference
between the two techniques [118]. The use of
DWI in combination with conventional MRI
shows promising results in increasing the sen-
sitivity for detecting viable tumor [58] (Figs.
6 and 8). Diffusion restriction (hyperintensity
on imaging performed with high b values and
low ADC values) suggests viable tumor com-
ponents [118, 119]. However, a study showed
lower performance of DWI compared with
contrast-enhanced imaging, with lower sen-
sitivity for detection of local HCC recurrence
C D (60.7% vs 82%, respectively) [120]. Regard-
ing the use of pretreatment ADC as a marker
of response to TACE, the data are limited, and
two studies published to date report conflict-
ing results [121, 122]. In a prospective study by
Yuan et al. [121], nonresponding HCCs had
a significantly higher pretreatment ADC than
HCCs that responded. On the other hand, a re-
cently published retrospective study showed
that HCCs with poor or incomplete response
to TACE had significantly lower pretreatment
ADC and lower post-TACE ADC values than
HCCs with good or complete response [122].
A B
Fig. 1062-year-old man with unresectable
hepatocellular carcinoma (HCC) treated with 90Y
radioembolization with good response.
A, Pretreatment axial arterial phase CT image shows
large enhancing mass (arrow) in left hepatic lobe.
B, Axial posttreatment arterial phase CT image
obtained 1 month after procedure shows progressive
decrease in tumor size and persistent enhancement
(asterisk).
C and D, Follow-up CT images obtained at 3 months
(C) and 12 months (D) after procedure show
continued decrease in size of HCC and capsular
retraction (D). Patient underwent no further therapy.
Response to procedure was good despite areas of
persistent enhancement on early follow-up scans.
C D

90 AJR:201, July 2013

 Imaging Assessment of HCC Response to Therapy
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A B
Fig. 1175-year-old woman with multifocal metastatic hepatocellular carcinoma (HCC) treated with sorafenib and 90Y radioembolization.
A and B, Pretreatment MRI. Axial fat-suppressed 3D gradient-recalled echo (GRE) T1-weighted images at portal venous phase after injection of extracellular gadolinium
chelates show two HCCs (arrow, A; and short arrow, B) in right hepatic lobe. There is large extrahepatic metastatic mass (asterisk) and lung metastasis (long arrow, B).
C, MR image obtained after sorafenib therapy and 90Y radioembolization shows that segment VII lesion (long white arrow) has decreased significantly in size and segment
VIII lesion (short white arrow) has become necrotic but that there has been interval progression of lung metastasis (black arrow). Asterisk = extrahepatic metastatic
mass.
A B
C D
Both studies showed an increase in ADC in Regarding the changes in ADC values af-
HCC with good response compared with HCC ter ablation, the data are limited. A prior study
with poor response [121, 122]. Given the con- assessed the role of DWI after RFA of liver
flicting results from these two studies, the val- tumors including HCCs; the results suggested
ue of pre-TACE ADC in predicting response that measuring ADC in focal hyperintense ar-
should be verified in a large prospective study. eas inside the ablation zone had value for the
AJR:201, July 2013 91
C
Fig. 1264-year-old man with hepatocellular
carcinoma (HCC) treated with 90Y radioembolization.
A and B, Pretreatment axial contrast-enhanced
CT (CECT) images show enhancing HCC (arrow, A;
orange line, B) in left hepatic lobe. HCC measures 40.5
mm in maximum dimension. Corresponding volume is
15.5 mL after semiautomated segmentation (B).
C and D, Axial CECT images obtained 40 days after
90 Y radioembolization show interval tumor necrosis
(red, D). Maximum size of tumor (arrow, C; orange line,
D) is 33.9 mm. In this case, decrease of 16.2% should
be considered stable disease according to Response
Evaluation Criteria in Solid Tumors. However,
tumor volume has decreased to 8.66 mL (44.1%)
and residual enhancing component (viable tumor)
constitutes only 7.7% of tumor.
diagnosis of tumor recurrence, whereas mea-
suring the ADC of the whole ablation zone
was not helpful [123].
The limitations of DWI relate to image qual-
ity, with possible echo-planar imagingrelated
artifacts, and to limited knowledge on ADC
reproducibility in liver tumors [124, 125].
In summary, despite promising results, DWI
cannot replace contrast-enhanced T1-weighted
imaging and subtraction for assessment of HCC
response. The role of baseline ADC and early
changes in ADC values as markers of tumor
response and time to tumor progression should
be determined in a large prospective study.
Perfusion imagingDynamic contrast-en-
hanced MRI (DCE-MRI) [126128] and perfu-
sion CT [129, 130] involve the use of contrast
agents with high-temporal-resolution imag-
ing to capture changes in MR signal intensity
or CT attenuation as a function of time; these
changes are used to quantify tissue and tumor
vascular characteristics. Perfusion CT has the
advantage of a direct linear relation between
enhancement change and iodine concentra-
tion, whereas the relationship between MR sig-
 Yaghmai et al.

have not been completely validated for routine

clinical use. It is not yet known whether DWI
or DCE-MRI can be used prospectively for the
prediction of subsequent response when used
at baseline and for the early detection of re-
sponse before changes or lack of changes in
size occur. This will help individualize ther-
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apy depending on different tumor profiles.

A B
However, given the lack of standardization
and evidence for utilizing these novel imag-
ing methods, morphologic criteria using RE-
CIST or modified RECIST should still be used
in clinical practice and for drug trials.

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