Magnetic resonace imaging (MRI) of the liver has become an effective modality for diagnosing liver disease and evaluating its proress. This article presents the MRI techniques for evaluating the liver and the imaging characteristics of common diffuse liver diseases, including fatty liver, iron overload, cirrhosis, hepatic venous thrombosis, and primary sclerosing cholangitis.
is a third-year resident and
is a Professor of Radiology, Department of Radiology, Thomas
Jefferson University Hospital, Philadelphia, PA.
Magnetic resonance imaging (MRI) of the liver has evolved over
the past 2 decades to become an effective and widely used modality
for diagnosing liver disease and evaluating its progress. This
article presents the MRI techniques for evaluating the liver and
the imaging characteristics of common diffuse liver diseases.
A comprehensive MR imaging examination of the liver should
include T1-weighted images (T1WI), T2-weighted images (T2WI), and
dynamic multiphasic contrast-enhanced images, preferably
supplemented by chemical-shift images and fat-saturation images. A
phased-array torso coil should be used to improve the
signal-to-noise ratio (SNR).
Single-shot fast-spin echo (SSFSE) is recommended for coronal
localizer images. Each of the images is obtained in <1 second,
providing a rapid, motion-independent T2-weighted survey. These
sequences not only give an overview of the liver, but also help
depict fluid and differentiate solid lesions from cystic lesions or
hemangiomas, particularly with the use of a heavily T2-weighted
sequence (effective echo time [TEef] >180 msec). We routinely
include a set of axial SSFSE heavily T2WI for this purpose.
At high field strength (>= 1 Tesla), gradient-echo sequences
are generally used for T1-weighted sequences. Spoiled gradient-echo
(SGE) sequences are advantageous; these allow acquisition of
sufficient sections in one breath hold (about 20 sec) for complete
liver coverage and provide good SNR. For multisection
two-dimensional (2D) SGE techniques, repetition time (TR) is
typically >100 msec, or as high as breath holding will allow,
but always <500 msec to provide heavy T1-weighting. Flip angle
is usually 90°, but is reduced if TR is <100 msec. Echo time
(TE) is as short as possible. Usually, both in-phase and
opposed-phase T1-weighted sequences are obtained, particularly for
evaluation of cellular fat content, such as for the evaluation of
fatty liver. For optimal in-phase effect, TE should be 4.6 msec,
although 4.2 msec is adequate. For optimal fat-water opposed-phase
effect, TE should be close to 2.3 msec.
For T2 weighting, echo-train spin- echo sequences are currently
used because of the shorter sequence duration. Fat suppression is
advantageous because it reduces motion-induced phase and chemical
shift artifacts and improves the dynamic range of tissue signal
intensities. Short tau inversion recovery (STIR) also may be used
to acquire T2WI that are augmented by inverse T1-weighting; these
images have high soft-tissue contrast and minimal signal from
The most commonly used contrast agents are gadolinium chelates,
which are extracellular space agents. They are distributed
initially in the intravascular compartment and diffuse rapidly
throughout the extracellular space, analogous to water-soluble
iodinated contrast agents for computed tomography (CT) scanning. A
multiphasic dynamic contrast-enhanced series includes breath-hold
SGE sequences acquired before the contrast injection, as well as
postcontrast sequences in the arterial phase, portal venous phase,
and delayed extracellular phase. If possible, fat suppression is
applied to ensure the conspicuity of the enhancing tissue and
vessels in relation to abdominal fat. Our current preference for
dynamic multiphasic gadolinium-enhanced images are
three-dimensional (3D) spoiled gradient-echo images using partial
Fourier acquisition, segmented fat suppression through selective
inversion, and zero-fill interpolation in the encoding select axis.
Using this technique, it is possible to obtain fat-suppressed
contiguous images at increments of ¾ 2.5 mm through the entire
liver, during a single suspended respiration. These images are
similar to those obtained for gadolinium-enhanced MR angiography,
and, in fact, clearly depict the hepatic and abdominal arteries and
Fatty liver has many causes, including obesity, diabetes
mellitus, malnutrition, or exposure to ethanol or other chemical
toxins. In fatty liver, fat accumulates in hepatocytes, either
focally or diffusely. On CT or ultrasound, focal fatty change can
be difficult to differentiate from a neoplasm.
With MRI, the confidence of diagnosing fatty liver is greatly
improved by using chemical shift techniques. The most useful
technique involves comparison of in-phase (water + fat) and
opposed-phase (water fat) images.
Most tissues, including tumors, maintain similar signal intensity
on in-phase and opposed-phase T1WI. Fatty liver, on the other hand,
will have lower signal intensity on opposed-phase images because of
cancellation of water and fat signals within voxels. Fat-suppressed
images can also be helpful in cases of moderate to severe fatty
infiltration. Fatty liver will have lower signal intensity with fat
suppression, although the drop is not as much as on opposed-phase
images (figure 1).
One must consider that certain neoplasms (such as some
well-differentiated hepatocellular carcinomas [HCCs], adenoma,
angiomyolipoma, or lipoma) contain lipid. The differentiation can
be achieved by analyzing the morphology and other imaging
characteristics of these tumors. Even though some
well-differentiated HCCs contain lipid, most HCCs with high T1
signal intensity do not. Hepatocellular carcinomas are usually well
defined, and often have capsules.
Adenomas have low signal intensity on opposed-phase T1WI, similar
to fatty infiltration, but have a round shape and a characteristic
early arterial phase blush postcontrast. Angiomyo-lipoma and lipoma
have gross deposits of fat, which have decreased signal intensity
on fat-suppressed images, but less on opposed-phase images. On
opposed-phase T1WI, instead, there is cancellation of signal
primarily at the edges of these tumors.
In the setting of diffuse fatty infiltration, neoplasms are more
difficult to detect by CT or ultrasound. On the contrary, a diffuse
fatty liver may help MRI detect a tumor. On nonfat-saturated T1WI,
the fatty liver may have higher intensity than a normal liver,
which increases the contrast relative to the low signal intensity
of tumors. On fat-saturated T2WI, the fatty liver has lower
intensity than a normal liver. Again, the contrast between the
liver and high intensity tumors increases.
Iron accumulation in liver is seen in hemochromatosis,
transfusion overload, hemolytic anemias, and cirrhosis.
Intracellular iron is usually superparamagnetic. It reduces T2
and T2* relaxation times, and results in low signal intensity on
both T2WI and T2*-weighted images (T2*WI). This makes MRI a more
sensitive and specific method for diagnosing iron overload;
gradient recalled echo (GRE) T2*WI have greatest sensitivity. To
achieve T2*-weighting, at 1.5 T, 9 msec or more of echo time is
preferred. The flip angle should be ¾ 30° to minimize the T1
differences between tissues. TR is usually minimized to reduce
acquisition time. Normally, liver has higher signal intensity than
skeletal muscle on both T1WI and T2WI. The signal intensity of
skeletal muscle serves as a good internal reference, because it
does not vary over a wide range of iron overload or change with
is an autosomal recessive disorder with a homozygous prevalence of
0.25% to 0.50%.
In hemochromatosis, iron overload results from long-term increased
iron absorption through the intestine. Reticuloendothelial (RE)
function may be deficient. Iron accumulates in liver, pancreas, and
heart, as well as the parenchyma of other organs. In liver, the
iron is incorporated preferentially into the hepatocytes rather
than Kupffer cells of the RE system. Hemochromatosis causes
morbidity and mortality by means of cirrhosis, increased incidence
of hepatocellular carcinoma, diabetes mellitus, and myocardial
dysfunction. Diagnosis of hemochromatosis is difficult because of
the nonspecific symptoms of hepatic, myocardial, and pancreatic
dysfunction. If diagnosed early, normal life expectancy can be
achieved with phlebotomy treatment. Magnetic resonance imaging
detects low signal intensity on GRE T2*WI as evidence of excessive
hepatic iron in preclinical hemochromatosis without cirrhosis,
when treatment is crucial before irreversible damage occurs. As the
disease progresses, low T2* signal intensity can be seen in the
pancreas and heart, but normal signal of the spleen is preserved
(figure 2). Magnetic resonance imaging can be used longitudinally
to monitor disease progress and to evaluate response to treatment.
Liver iron concentration can be measured by calculating T2
relaxation time or intensity ratios.
transfusional iron overload
, iron deposits in RE cells of the liver, spleen, and bone marrow.
In contradistinction to hemochromatosis, iron overload in RE is of
little clinical significance. Magnetic resonance imaging shows low
signal intensity of liver, spleen, and bone marrow on GRE T2*WI,
sparing the heart and pancreas (figure 3).
This finding, as well as a clinical history of multiple
transfusion, helps to differentiate transfusion overload from
primary hemochromatosis. Iron deposition occurs in hepatocytes and
pancreas only when RE cells are saturated (if a patient has
received >100 units of blood).
is also a cause
of hepatocellular iron overload. Thalassemia major patients have
ineffective erythropoiesis, which triggers increased absorption and
decreased excretion of oral iron, similar to that which occurs in
genetic hemochromatosis. Without a history of transfusion, the
pattern of iron overload is indistinguishable from hemochromatosis.
Patients often develop coexisting transfusion iron overload with
transfusion. In sickle cell anemia, patients have rapid hepatic
iron turnover, and will not necessarily have hepatic low signal
intensity, unless they recently received blood transfusion. Due to
renal filtration and tubular absorption of free hemoglobin, they
may have renal cortical low signal, which is independent of
transfusion. Reduced signal intensity of the renal cortex is a
characteristic finding in patients with intravascular hemolysis
from other causes as well, such as paroxysmal nocturnal
from etiologies other than primary hemochromatosis also accumulates
iron in mild degree. In some cirrhotic patients, iron is
concentrated within some large regenerative nodules.
Dominant iron-containing nodules are at risk for HCC. Magnetic
resonance imaging serves as the imaging modality of choice in
detecting early HCC in these regenerating nodules, since these foci
of HCC do not contain iron. This produces a characteristic finding
for a focus of HCC in an iron-containing regenerative nodule, the
"nodule in nodule" sign.
Developing high signal intensity within an iron-containing
low-signal nodule on GRE T2*WI is highly suggestive of
hepatocellular carcinoma. These nodules tend to grow quickly,
doubling their diameter in about 2 months.
Therefore, ablative treatment or rapid follow-up is indicated.
Cirrhosis is a pathologically defined entity characterized by
irreversible chronic injury of the hepatic parenchyma, extensive
fibrosis, and regenerative nodules.
In North America, the leading cause of cirrhosis has been alcohol
abuse, followed by chronic viral hepatitis, hemochromatosis,
autoimmune chronic hepatitis, primary biliary sclerosis, drug
toxicity, etc. However, the incidence of hepatitis C has increased
dramatically in recent years.
Magnetic resonance imaging provides comprehensive evaluation of
a cirrhotic liver, including diagnosis, assessment of disease
progression, as well as detection of dysplastic nodules and
hepatocellular carcinoma. The findings in cirrhosis are liver
surface nodularity, regenerative nodules, change of hepatic
morphology, fatty changes, and iron deposition, as well as ascites,
splenomegaly, varices, and collaterals. These signs are usually
seen in advanced cirrhosis.
The natural course of cirrhosis progresses from compensated
stage (Child's class A) to decompensated stage (Child's class B or
C), then to end-stage cirrhosis. Patients with compensated
cirrhosis can develop features of decompensation at a rate of 10%
per year; the survival rate is lower in patients with decompensated
cirrhosis. In cases of compensated cirrhosis, hypertrophy of the
lateral segment and caudate lobe are predominant findings on
longitudinal MRI exam. Atrophy of the medial segment and the right
lobe are the predominant findings in cases of progressive
These MRI findings help predict a patient's clinical outcome.
Although the cause of the segmental morphologic changes is unclear,
it is thought to be related to altered blood flow in cirrhotic
Many findings of early cirrhosis are caused primarily by
preferential atrophy of the medial segment of the left lobe. As
this segment atrophies, enlargement of the hilar portal space
occurs. This has been described as an early MRI sign of cirrhosis
(figure 4). It has been reported that 98% of patients who had early
cirrhosis have enlargement of the hilar periportal space before the
presence of the conventional signs of cirrhosis.
Medial segment atrophy also causes an expanded gallbladder fossa,
another MR sign of cirrhosis. This finding was reported to have 98%
specificity, although the sensitivity was 68%.
Although there is no effective therapy to reverse the changes of
cirrhosis, detection of the disease at an early stage is still
important. There have been reports of effective interferon therapy,
which reduces or prevents progression of hepatic damage, for
patients with compensated cirrhosis due to hepatitis C.
Other imaging signs, such as ratio of the transverse diameter of
the caudate to right lobe (C/RL > 0.65), have been used to
However, this ratio is not increased in early cirrhotic patients.
Regenerative nodules are regenerated hepatocytes surrounded by
fibrotic septa. Cirrhosis can be classified based on the size of
the nodules as: micronodular (¾ 3 mm), macronodular (>3 mm) or
mixed. Alcoholic cirrhosis is commonly micronodular, and
viral-induced cirrhosis is typically macronodular. Regenerative
nodules are hypointense in relation to hyperintense inflammatory
septa on T2WI and gadolinium-enhanced MR images.
They have variable intensity on T1WI and can be iso- or hypointense
on T2WI, but are not hyperintense on T2WI, with the exception of
those in chronic hepatic vein thrombosis. In contradistinction to
HCC, regenerative nodules are not hyperintense on hepatic
arterial-phase gadolinium-enhanced images.
Dysplastic nodules are premalignant and are found in 15% to 25%
of cirrhotic livers.
These nodules are commonly hyperintense on T1WI and hypointense or
isointense on T2WI.
Like regenerative nodules, they are not hyperintense on T2WI.
Occasionally, dysplastic nodules may be hyperintense on early
Hepatocellular carcinoma is the most common primary cancer of
liver. The 5-year survival rate is <5%, due to late presentation
and large tumor burden. Early diagnosis with resection and
transplantation can cure both the cancer and the cirrhosis.
Magnetic resonance imaging is the most effective diagnostic imaging
tool to detect small foci of HCCs, with the sensitivity and
specificity ranging from 75% to 100%.
Small HCCs have variable signal intensities on both T1WI and T2WI.
Nevertheless, most well-differentiated HCCs are hyperintense on
TIWI. The presence of moderate T2 hyperintensity is specific for
distinguishing HCC from regenerative or dysplastic nodules, and
homogeneous enhancement during arterial phase with rapid washout
during the portal phase is characteristic
(figure 5). Other features of HCC include presence of a capsule,
size >3 cm, and rapid growth.
As cirrhosis progresses, portal venous flow is compromised
secondary to liver parenchymal distortion. Portosystemic
collaterals frequently develop as a result of portal hypertension.
Gadolinium-enhanced axial thin-section MR images can depict the
collateral vessels in these patients (figure 6). The vessels around
the gastro-esophageal junction are the most visible and are the
major cause of gastrointestinal bleed, as well as mortality. Other
collateral vessels include collaterals to the left renal vein,
paraumbilical vein, and abdominal wall.
Budd-Chiari syndrome results from obstruction of the hepatic
venous outflow, causing portal hypertension, ascites, and hepatic
failure. Most often there is atrophy of the peripheral liver, and
hypertrophy of the caudate lobe and central liver. It is best
diagnosed by multiphasic gadolinium-enhanced MR images, which show
a thrombosed or absent hepatic vein and altered hepatic
enhancement. In acute onset of the Budd-Chiari syndrome, the
periphery of the liver has moderately low signal on T1WI and
moderately high signal on T2WI relative to the central liver.
Severe congestion causes decreased peripheral enhancement during
the arterial and portal venous phase.
In the subacute setting, the T1 and T2 signal characteristics are
similar to those with acute disease. During early and late phases
of contrast enhancement, there is heterogeneously increased
enhancement at the periphery. In chronic disease, signal
differences between the central and peripheral part of the liver on
T1WI and T2WI and post-gadolinium contrast images are minimal.
Varices may be present in chronic Budd-Chiari syndrome. Curvilinear
intrahepatic collaterals and capsular collaterals are
characteristic. In patients with chronic Budd-Chiari syndrome,
hyperplastic nodules may develop (figure 7).
These nodules are hyperintense on T1WI, variable on T2WI, and
enhance early on post-gadolinium images.
They resemble focal nodular hyperplasia in some respects and do not
appear to have malignant potential.
Primary sclerosing cholangitis
Primary sclerosing cholangitis (PSC) is a disease of unknown
etiology characterized by inflammation and fibrosis of the liver
and the bile ducts. Endoscopic retrograde cholangiopancreatography
(ERCP) is the standard reference for diagnosis of PSC, because the
clinical, biochemical, and hepatic histologic findings are usually
nonspecific. Good correlation between MR cholangiopancreatography
(MRCP) and ERCP in diagnosing PSC has been demonstrated.
Comparing MRCP with ERCP has potential advantages: 1) it depicts
bile ducts that are not seen at ERCP; 2) it noninvasively detects
progressive ductal abnormalities in asymptomatic patients; 3) it
identifies the group of patients who might benefit from therapeutic
ERCP; and 4) supplemental MR sequences detect early
cholangiocarcinoma. The main criticism of MRCP is that the care may
be delayed in patients who need therapeutic endoscopic or
percutaneous intervention of obstructing bile ducts. The most
common MRCP findings are intrahepatic ductal dilatation, stenosis,
and a beaded appearance
(figure 8). The key feature of PSC is randomly distributed annular
strictures out of proportion to upstream dilatation.
As the fibrosing process progresses, stricture increases and the
peripheral ducts are obliterated, producing a characteristic pruned
appearance. Wall-thickening and enhancement of the extrahepatic
bile duct are frequent findings as well, which cannot be seen on
MRCP. Instead, they are best seen on the contrast-enhanced dynamic
images. Magnetic resonance images of the liver in patients with PSC
often have patchy peripheral areas of atrophy and abnormal signal
intensity and enhancement.
MR imaging is a superior modality for diagnosing diffuse liver
disease andfollowing disease progress. It is particularly useful
for the evaluation of fatty liver, iron overload, cirrhosis,
hepatic venous thrombosis, and primary sclerosing cholangitis.