MR Characterization of Focal Liver Lesions...2018/12/13 · used to differentiate benign from...

MR Characterization ofFocal Liver Lesions
Pearls and Pitfalls
Evan S. Siegelman, MD*, Anil Chauhan, MD

KEYWORDS

� Focal nodular hyperplasia � Hepatic adenoma � Hepatic steatosis � Hepatocellular carcinoma� Magnetic resonance imaging � Siderotic regenerative nodules

KEY POINTS

� Focal liver lesions that are isointense to hyperintense to liver on in-phase T1-weighted images areusually hepatocellular in origin.

� Focal liver lesions that lose signal intensity on an opposed-phase image compared with thematched in-phase image contain lipid and are usually hepatocellular in origin.

� Focal liver lesions that lose signal intensity on an in-phase image compared with an opposed-phaseimage are most often iron-containing siderotic nodules.

� Focal liver lesions that are isointense to spleen on T2-weighted images are solid and often malig-nant, whereas focal liver lesions that are hyperintense to spleen on heavily T2-weighted images areusually nonsolid benign cysts or hemangiomas.

PEARL 1: THE T1 PEARL: A FOCAL LESIONTHAT IS ISOINTENSE TO HYPERINTENSE TOLIVER ON T1-WEIGHTED IMAGES ISHEPATOCELLULAR IN ORIGIN

The first 3 imaging pearls discussed in this revieware the 3 instances when focal liver lesion charac-terization is possible with T1-weighted gradientecho images.

The 3 most common focal liver lesions encoun-tered in clinical practice are cysts, hemangiomas,and metastatic disease. Nonsolid benign hepaticlesions (cysts and hemangiomas) and almost allmetastatic lesions are hypointense relative to liveron T1-weighted images (Fig. 1). Normal liver hasrelative high signal intensity on T1-weighted im-ages that has been attributed to high concentra-tions of protein, rough endoplasmic reticulum,and paramagnetic substances, such as manga-nese and copper.1–3 One study calculated the

Department of Radiology, Perelman School of Medicine,1st Floor Silverstein, Philadelphia, PA 19104-4283, USA* Corresponding author.E-mail address: [email protected]

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T1 relaxation times of liver at 1.5 T as 547 msand that of solid lesions, hemangiomas, and cyststo be 1004, 1337, and 3143 ms, respectively.Thus, most liver lesions are initially detected onT1-weighted images as being hypointense toliver.4 The authors use other pulse sequences be-sides T1-weighted images in order to differentiateamong cysts, hemangiomas, and solid liverlesions.

If a focal liver lesion is isointense to hyperintenseto liver on a T1-weighted image, then it is mostcommonly hepatocellular in origin. The 5 mostcommon focal hepatocellular lesions encounteredin clinical practice are regenerative nodules (RN),hepatocellular carcinoma (HCC), focal nodular hy-perplasia (FNH), hepatocellular adenoma (HCA),and focal steatosis. In this section, the authorsdiscuss FNH and the inflammatory subtype ofHCA (IHCA). The reader is referred to the articlesby Barr and Hussain and Sirlin in this issue of the

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Fig. 1. Magnetic resonance demonstration of hepatic hemangioma and metastatic breast cancer in a 51-year-oldwoman. Metastases, cysts, and hemangiomas are almost all hypointense relative to liver on T1-weighted images.(A) Axial in-phase T1-weighted image shows low signal intensity hemangioma (white arrow) and infiltrativemultifocal metastases (smaller black arrows). The metastases are isointense and the hemangioma is hypointenseto spleen (S). However, the authors prefer to use T2-weighted images, diffusion-weighted images, and/orenhanced imaging to differentiate solid masses, such as metastatic disease, from nonsolid hepatic cysts and hem-angiomas. (B) Corresponding opposed-phase image shows similar relative signal intensities of the hemangiomaand metastatic disease. Geographic regions of lower signal intensity within the left lobe of liver (black arrows)represent steatosis. (C, D) T2-weighted fast-spin-echo images obtained with effective echo times of 90 (C) and180 ms (D). The hemangioma is hyperintense to spleen, whereas the metastases are isointense. As the echotime increases, the contrast between the hemangioma and the adjacent metastases improve. This improvementis not because the hemangioma lights up or enhances; rather, the improved image contrast is because the hem-angioma loses less signal as the echo time increases compared with liver, spleen, and metastases. (E) Opposed-phase T1-weighted imaging performed 2 years prior shows that the hemangioma (arrow) is hyperintense tothe surrounding liver (L). When trying to establish the hepatocellular origin of a focal liver lesion by showingisointensity or hyperintensity to liver, one should use an in-phase image as steatotic liver can be of low signal in-tensity on opposed-phase imaging and can confound relative signal assessment. (F) Corresponding in-phaseT1-weighted image shows that the hemangioma (black arrow) is hypointense to the steatotic liver.

Siegelman & Chauhan296

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Magnetic Resonance Imaging Clinics of NorthAmerica concerning the evaluation of the cirrhoticliver and how to differentiate RN from HCC. Lipidand fat-containing liver lesions are discussed in“Pearl 2.”

FNH

FNH is the second most common benign hepatictumor in adults after hemangioma. FNH composesapproximately 8% of all primary liver tumors andhas an estimated prevalence between 0.3% and3.0%.5,6 FNH is not considered a neoplasm butinstead is hypothesized to develop as a hyper-plastic response of hepatic parenchyma arounda central developmental vascular malformation.7

Individuals with FNH are more likely to have coex-istent hepatic hemangiomas (20%) than would beexpected by chance8; both hemangioma and FNHinvolve focal abnormalities in the hepatic bloodsupply.

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FNH is typically detected in women aged 20 to50 years and is uncommon in men (female-to-male ratio 5 10:1).5 Unlike hepatic adenomas,there is no proven association of oral contracep-tive use or pregnancy with the development orgrowth of FNH.9,10 Although up to 15% of FNH le-sions can grow when followed longitudinally,11 thisshould not cause clinical concern. The authors areskeptical of reports of malignant transformation tofibrolamellar hepatoma12 or HCC,13 as most inves-tigators think that malignant transformation of FNHdoes not occur.14

The magnetic resonance (MR) features of FNHcan be considered in 2 parts (Fig. 2). The firstcomponent is the vascular nidus that forms thecentral scar of FNH, and the second is the sur-rounding hyperplastic response of adjacent liver.The vascular scar is hypointense to liver on bothin-phase and opposed-phase imaging and ishyperintense to liver on T2-weighted imaging.The higher T2-weighted signal intensity is

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Fig. 2. MR findings of FNH and lipid-containing hepatocyte nuclear factor-1a inactivated hepatic adenoma in a25-year-old woman. (A, B) Axial in-phase (A) and opposed-phase (B) T1-weighted images show 2 lesions: a largerFNH in segment 8 and a smaller adenoma in segment 2. The FNH has outer components (thick arrow in A) that areisointense to surrounding liver suggesting that it is hepatocellular in origin. There is a lower signal intensity cen-tral scar (thin arrow in A). The adenoma is isointense to liver and not perceptible on in-phase imaging; however, itloses signal and becomes recognizable on opposed-phase imaging (arrow in B). In-phase isointensity and loss ofsignal on opposed-phase image indicate that the lesion is lipid containing and hepatocellular in origin. (C, D)T2-weighted fast-spin-echo images (effective echo time 5 95 ms) shows that both the FNH and adenoma (thickarrows) are hyperintense to liver and relatively isointense to spleen. The central scar of the FNH (thin arrow) ishyperintense to spleen. On the fat-suppressed image (D), there is similar contrast with the exception of lowersignal intensity of the adenoma (thick arrow in D) because of the suppressed lipid. (E) Hepatobiliary-phaseenhanced fat-suppressed T1-weighted image obtained after the intravenous administration of gadoxetate diso-dium shows hyperenhancement of the nonscar components of the FNH (thick arrow) and hypoenhancement ofthe adenoma (thin arrow). The adenoma showed hyperenhancement compared with adjacent liver on dynamicenhanced imaging (not shown).

MR Characterization of Focal Liver Lesions 297

hypothesized to be secondary to slow flow withinvessels. The scar does not enhance during the dy-namic administration of gadolinium but does showdelayed enhancement during the interstitial phaseof enhancement when a conventional extracellulargadolinium contrast agent is used.15,16

The surrounding lesion of FNH itself is usuallyisointense to liver on both in-phase and opposed-phase imaging. Cases of lipid-containing FNH areuncommon and reportable17; many are associatedwith diffuse hepatic steatosis.18 On T2-weightedimaging, FNH is isointense to minimally hyperin-tense relative to liver. On arterial-phase dynamicgadolinium-enhanced imaging, FNH showsmarked homogeneous enhancement, often withrapid washout during the portal and interstitialphases of enhancement.16,19

If a gadolinium contrast agent with hepatobiliaryexcretion is used (eg, gadoxetate disodium), FNHwill typically have components that are isointenseto hyperintense relative to the surrounding liver ondelayed hepatobiliary-phase imaging, which canbe useful for distinguishing FNH from HCA forsome lesions (see Fig. 2E).19–24 In one study of 30


FNH lesions, only 2 showedhomogenous low signalintensity on delayed hepatobiliary-phase images.25

If one uses gadoxetate disodium–enhanced MR tocharacterize FNH, the central scar may not showenhancement during the interstitial phase ofcontrast enhancement.26 The absent enhancementof the central scar is hypothesized to be from themore rapid removal of gadoxetate disodium fromthe circulation compared with other gadoliniumcontrast agents. The reader is referred to the articleby Bashir for a detailed discussion concerning theuse of the various MR contrast agents used for liverimaging.

Diffusion-weighted imaging and apparent diffu-sion coefficient (ADC) values alone should not beused to differentiate benign from malignant focalliver lesions as there can be substantial overlap.For example, many benign FNH and hepatic ade-nomas can show restricted diffusion similar tometastatic disease.27 For a review concerningthe performance and interpretation of diffusion-weighted imaging of the liver, the reader is referredto the article by Taouli in this issue of theMagneticResonance Clinics of North America.



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IHCA

Although pathologists had previously classifiedHCA into a single pathologic entity, recent molec-ular and immunohistochemical markers havedetermined that there are 4 distinct subtypes ofHCAs.28–31 These subtypes include IHCAs and he-patocyte nuclear factor 1a inactivated (HNF-1a),b-catenin–activated, and unclassified HCAs. MRcan often detect and characterize the subtype ofHCA based on specific imaging features.32 Inde-pendent of the subtype, larger (>4 cm) adenomasare at risk of developing intralesional hemor-rhage33 and are usually treated with surgicalresection or with nonsurgical radiofrequencyablation or bland embolization.5,29,34,35 Smalleradenomas can be managed conservatively andfollowed by imaging.35 Women who take oral con-traceptives should discontinue their use as someHCAs may subsequently decrease in size.5,31

Obesity and metabolic syndrome are associatedwith HCA36,37; patients are encouraged to modifytheir diet, develop an exercise program, and loseweight as part of a treatment plan.

Fig. 3. MR imaging findings of pathology-proven hepaticin a 43-year-old woman. The patient stopped taking oralfollowed conservatively for the next 7 years. (A) Axial in-pfoci of increased signal intensity relative to liver (black arloss of signal intensity within the liver confirming the prethat are hyperintense to the steatotic liver (arrows). Givphase imaging, this pattern suggests they are hepatocelluling the opposed-phase image from the in-phase image (incontain both lipid and water protons. The highest signal iinterfaces (eg, junction of left kidney and perirenal fat [thinsteatosis and the absence of lipid within the focal liverphase–enhanced fat-suppressed T1-weighted images showto the surrounding liver. The presence of arterial phase enlike regions of focal sparing of steatosis.


Hepatic adenomatosis is a distinct entity thatwas originally described and defined in 1985 asthe presence of greater than 10 HCAs (Fig. 3).38

The HCA associated with adenomatosis is notlimited to any one particular subtype,39,40 althoughpatients with multiple adenomas are more likelyto have steatosis.41 As with single lesions, man-agement is based on lesion size and patients’symptoms.42,43

The IHCA is the most common subtype of HCAand accounts for 40% to 60% of lesions in re-ported series. IHCA is associated with obesity34

and metabolic syndrome.36 In one study of 32women with IHCA, the median body mass indexwas 32.5.44 In this same group of 32 women, stea-tosis was present in 59% on liver biopsies ob-tained distant from the tumor. In another seriescomparing 63 IHCA versus 46 HNF-1a adenomas,there was significantly less intralesional steatosisin the IHCA subgroup (43% vs 82%).34 Ten ofthe 63 patients with IHCA had findings of either in-tralesional or peritumoral hemorrhage, which wasnot significantly different than those found in theHNF-1a subtype.

steatosis and hepatic adenomatosis secondary to IHCAcontraceptives at the time of diagnosis and has beenhase T1-weighted gradient echo image shows subtle

rows). (B) Corresponding opposed-phase image showssence of hepatic steatosis. There are multiple lesionsen that these lesions were isointense to liver on in-ar in origin. (C) Subtraction image created by subtract--phase minus opposed-phase) depicts those voxels thatntensity on the subtraction images occurs at fat-waterarrows]). This image confirms the presence of hepatic

lesions (thick arrows). (D, E) Precontrast and arterialhyperenhancement of the adenomas (arrows) relativehancement assists in differentiating IHCAs from mass-



On T1-weighted images, IHCAs are usually iso-intense to slightly hyperintense to surroundingliver.28,29 On opposed-phase imaging, the sur-rounding liver is more likely to lose signal intensitybecause of steatosis than the inflammatoryadenoma itself (see Fig. 3; Fig. 4).34,44 On T2-weighted images, most IHCAs are minimallyhyperintense relative to liver.28,29 In one series,13 or 30 IHCAs revealed a specific atoll sign,consisting of a hyperintense rim that enhanceson delayed gadolinium-enhanced imaging (seeFig. 4C).29 It is hypothesized that the atoll sign issecondary to dilated sinusoids within the peripheryof the adenoma. Like FNH, HCAs will enhanceafter gadolinium contrast. However, unlike FNH,IHCAs do not have a central scar and almost allIHCAs do not have components that are isointenseto hyperintense to liver on delayed hepatobiliary-phase gadolinium-enhanced imaging.23 Thus, ina noncirrhotic woman with hepatic steatosis whohas a solid enhancing mass that is isointense toliver on precontrast T1-weighted images and hy-pointense on hepatobiliary-phase enhanced im-ages, one should consider an IHCA as the mostlikely cause.

Fig. 4. MR illustration of the atoll sign in a 26-year-old wproven IHCA. Obesity and metabolic syndrome are assocopposed-phase (B) T1-weighted images show a subcapsuhepatocellular in origin. Mild steatosis, which was confirmas lower signal intensity within segment 4 on the opposeT2-weighted image (effective echo time 5 93 ms) shows thto spleen. Not every focal lesion that is isointense to splehave cirrhosis or history of a primary malignancy. A high-shas been termed the atoll sign and is hypothesized toenhanced fat-suppressed T1-weighted image shows hyperof the peritumoral sinusoids.


THE EXCEPTIONSNonhepatocellular Focal Liver Lesions in aLiver Containing Background Moderate orMarked Steatosis

On opposed-phase T1-weighted images, liver thatis involved with moderate or severe steatosis willhave very low signal intensity. Thus, if one wereto evaluate the relative signal intensity of a focalliver lesion with surrounding steatotic liver on anopposed-phase T1-weighted image alone, thenone may come to a false conclusion that the lesionis hepatocellular. For example, a benign hemangi-oma (see Fig. 1E) or even a metastasis can appearhyperintense to steatotic liver on opposed-phaseimaging. Therefore, one should use the in-phaseimage as the T1-weighted reference when usingpearl 1.

Hemorrhagic Metastases to the Liver

Rare hepatic metastases can show T1 hyperinten-sity secondary to the T1 shortening properties ofmethemoglobin within subacute intralesional hem-orrhage.45 This hyperintensity has been describedin cases of metastatic renal, neuroendocrine, and

oman with a body mass index of 39 with a surgicallyiated with hepatic adenomas. (A, B) Axial in (A) andlar hyperintense hepatic mass (arrow) indicating it ised at surgery, is most pronounced and best revealedd-phase image (small arrows). (C) Axial fast-spin-echoat the adenoma is hyperintense to liver and isointenseen is malignant, especially in individuals who do notignal-intensity rim around the adenoma (small arrows)be secondary to dilated sinusoids. (D) Arterial-phaseenhancement of the adenoma and hypoenhancement



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lung cancers as well as choriocarcinoma.2,46 Focalliver lesion hyperintensity can also be secondary tothe paramagnetic metals attached to melanin con-tained within metastatic melanoma (Fig. 5).2,47,48

In these instances, patients’ primary tumor andthe presence of metastatic disease are oftenknown or apparent at the time of imaging.After radiofrequency ablation or chemoem-

bolization of liver malignancies, intratumoral T1hyperintensity can result from hemorrhagic andcoagulative necrosis.49 Once again, the cancerhistory and prior procedures are usually knownat the time of image interpretation. The reader isreferred to the article by Kamel concerning theuse of MR to evaluate treated liver metastases.

Hemorrhagic Cysts of the Liver

Most liver cysts have simple fluid content and verylow signal intensity on T1-weighted images. Occa-sionally, intralesional hemorrhage can occur insimple hepatic cysts that appear hyperintense onT1-weighted images secondary to methemoglobinand or intracystic proteins.50 Hemorrhage intosimple hepatic cysts has been described in auto-somal dominant polycystic liver disease51 andlarge bile duct hamartomas.52 The absence of a

Fig. 5. MR depiction of T1 hyperintense melanoma metasorrhagic metastases can be hyperintense to liver and shouorigin. (A) Axial in-phase T1-weighted gradient echo imagthe lesions have central high signal intensity (arrows). (B)high internal signal intensity within 2 of the metastases (suggest intracellular lipid. Had the high signal intensity bepected an etching artifact at the interface of the high sign(see Fig. 11B). (C) Fat-suppressed T2-weighted image (effemetastases (arrows) are isointense to spleen (S). The hemothe liver and spleen (small arrows) are isointense to hypoglobin and/or melanin.


thick fibrous capsule, septa, nodules, and solidenhancing components differentiates the benignhemorrhagic hepatic cyst from biliary cystade-noma-biliary cystadenocarcinoma.51

PEARL 2: THE CHEMICAL SHIFT PEARL: FOCALLIVER LESIONS THAT LOSE SIGNAL INTENSITYON OPPOSED-PHASE IMAGING CONTAINLIPID AND ARE MOST OFTENHEPATOCELLULAR IN ORIGIN

When performing dual-phase in and opposed-phase T1-weighted gradient echo imaging of theliver, the echo time of the opposed-phase imageshould be shorter than the in-phase echo time.This timing will ensure that any loss of signal inten-sity on the opposed-phase image compared withthe in-phase image will be caused by the presenceof lipid and water protons within the samevoxel.53,54 If the opposed-phase echo time islonger than the in-phase echo time, then signalloss could also be secondary to T2* susceptibilityeffects.55 Some manufacturers’ 3-T MR systemscome with configured dual-phase gradient echosequences (eg, echo times of 2.2 and 3.3 ms)that could result in potential diagnostic confusion.

tases to the liver in a 64-year-old woman. Some hem-ld not necessarily be assumed to be hepatocellular ine shows multiple hypointense liver metastases. Two ofOpposed-phase T1-weighted image shows persistent

arrows). There is no loss of internal signal intensity toen secondary to macroscopic fat, one would have ex-al intensity with the adjacent water-containing tissuective echo time [TE] 5 90 ms) shows that most of therrhagic components of the metastases present withinintense to liver secondary to intracellular methemo-



The reader is referred to the article by Wells toensure that an appropriate echo pair is used at 3 T.

Cysts, hemangiomas, and almost all livermetastases do not contain lipid and, therefore,do not lose signal intensity when comparing theopposed-phase image with the corresponding in-phase image. Pearl 2 is similar to pearl 1 in that ituses T1-weighted pulse sequences to charac-terize focal lesions as hepatocellular in origin.Next is the list of those hepatocellular lesionsthat contain microscopic lipid and lose signal in-tensity on opposed-phase images.

Fig. 6. Lipid-containing HCC in a 59-year-old man with cirphase T1-weighted image shows a slightly hypointense liveimage shows subtle loss of signal intensity (arrow) indicatimage (similar technique as described in Fig. 3C) demonstthe presence of lipid. (D) Axial fat-suppressed T2-weightedto spleen (S). In the setting of cirrhosis, this is specific forT1-weighted image obtained after the intravenous adminihypointense relative to the surrounding liver, also suggest(F) Repeat axial in-phase T1-weighted image obtained aftsize of the mass and subtle increase in signal intensity, etreated lesion approach the signal intensity of the adjacto marked loss of signal intensity within the mass (arrowintracellular lipid or intratumoral ethiodized oil. (H) Subtrshows no internal enhancement. No viable tumor wascomputed tomography (CT) examination shows dense etMR images illustrate complementary techniques of showof intratumoral iodine, whereas the MR shows the lipid c


RN and HCC

Both RN and HCC may contain lipid and losesignal intensity on chemical shift imaging (Figs. 6and 7). The presence of intralesional lipid is oneof the ancillary features that favor HCC over RNin the liver imaging reporting and data system clas-sification.5,56 However, intralesional lipid is not100% specific for HCC. Lipid-containing RN canoccur and should be favored when multiple andless than 10 mm.57 Investigators have shownthat lipid-containing HCCs tend to have betterprognosis58 and better differentiation59 compared

rhosis secondary to hepatitis C infection. (A) Axial in-r dome mass (arrow). (B) Opposed-phase T1-weighteding the presence of intracellular lipid. (C) Subtractionrates intralesional signal intensity (arrow) confirmingimage shows that the mass has components isointenseHCC. (E) Hepatobiliary-phase enhanced fat-suppressedstration of gadoxetate disodium shows that the mass ising that it represents HCC as opposed to a benign RN.er transarterial chemoembolization shows decrease inspecially anteriorly (arrow) where components of theent liver. (G) Opposed-phase image shows moderate). In the patient, the signal loss could be either fromaction image obtained after gadolinium enhancementidentified at subsequent transplant. (I) Unenhancedhiodized oil accumulation. The CT and chemical shifting ethiodized oil uptake; the CT shows the presenceontained within the ethiodized oil.


Fig. 7. MR depiction of a lipid-containing, iron-spared HCC, siderotic nodules, and Gamna-Gandy bodies in a66-year-old man with hepatitis C infection and cirrhosis. (A) Axial in-phase image obtained at 3 T (echo time2.48 ms) shows a high-signal-intensity lesion within segment 7 of the liver (arrow). The liver is diffusely of lowsignal intensity secondary to iron deposition. Focal low signal intensity within the liver and spleen (thin arrows)represent siderotic RN and Gamna-Gandy bodies, respectively. (B) Opposed-phase image (echo time 1.24 ms)shows higher signal intensity within those tissues that contain iron, including the diffuse liver parenchymaand both the focal siderotic nodules and Gamna-Gandy bodies. There is loss of signal intensity within the poste-rior aspect of the segment 7 lesion (arrow) indicating the presence of intracellular lipid. (C) Subtraction image(in-phase minus opposed-phase) confirms the presence of intralesional lipid (arrow). The presence of lipid is spe-cific for hepatocellular tissue but is not specific for malignancy. However, the absence of intralesional iron incirrhotic patients with diffuse and focal iron deposition is suspicious for malignancy. A 1.9-cm HCC was confirmedat surgery.


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with non–lipid-containing HCCs. Imaging featuresthat would favor HCC over an RN would includelarger size, restricted diffusion, isointensity tospleen on T2-weighted images, arterial phaseenhancement, and portal venous washout with apseudocapsule. The reader is referred to the arti-cles by Barr and Hussain and Sirlin in this issueof the Magnetic Resonance Clinics of North Amer-ica for further discussion concerning lipid-containing HCC.

HNF-1a Hepatic Adenoma

In “Pearl 1,” the authors discuss that the IHCA wasassociated with hepatic steatosis and lacked intra-cellular lipid. The HNF-1a adenoma has oppositequalities; the lesions themselves contain lipid, butthe surrounding liver usually does not have hepaticsteatosis (see Fig. 2; Fig. 8). The accumulation ofintracellular lipid within HNF-1a adenomas ishypothesized to be secondary to the aberrant pro-motion of lipogenesis secondary to gene inactiva-tion.60 Some investigators have suggested thatHNF-1a subtype adenomas are less hyperintenseon T2-weighted images and show greater con-trast washout on interstitial gadolinium-enhanced


imaging compared with IHCA.28,34,39 However,van Aalten and colleagues29 did not confirm thesefindings. It is probably more clinically important toestablish a diagnosis of HCA and exclude a diag-nosis of intralesional hemorrhage or HCC than it isto be able to establish the specific subtype of HCA.There are unusual instances of FNH that contain

intracellular lipid.17,61 Fortunately, most of theseFNH demonstrate a central scar. However, inthose lipid-containing FNH lesions whereby noscar is depicted, differentiation from an HNF1-aadenoma may be difficult. In such cases, per-forming a gadolinium-enhanced study with a hep-atobiliary contrast agent should be helpful inseparating these entities.If an HCA undergoes intralesional hemorrhage,

high T1 signal intensity that persists on opposed-phase and fat-suppressed images can be presentsecondary to the T1 shortening effects of methe-moglobin (see Fig. 8).45

Nodular Steatosis

Chemical shift imaging methods can readily bothqualify and quantify the presence and degree ofhepatic steatosis.56,62 One of the causes of


Fig. 8. MR findings of a surgically proven lipid-containing HNF-1a hepatic adenoma with intralesional hemor-rhage in a 40-year-old man who presents with 3 days of severe left upper quadrant pain. (A) Axial in-phaseT1-weighted gradient echo image shows an 11-cm left lobe liver mass that has central components that areboth hypointense and hyperintense to surrounding liver and peripheral tissue that is minimally hyperintenseto liver. (B) Corresponding opposed-phase image shows loss of signal intensity within the periphery of themass (arrow), establishing the presence of intracellular lipid. There is no loss of signal intensity within the centralhigh signal intensity components, which are secondary to methemoglobin within subacute hemorrhage (H). It isthe presence of lipid and not hemorrhage that is specific for characterizing the mass as hepatocellular in origin.(C) Subtraction image (in-phase minus opposed-phase; see Fig. 3 legend) confirms the presence of intracellularlipid not only within the segment 1 and 2 nodules (arrow) but also in the remainder of the liver to a variabledegree.


steatosis is chemotherapy.63 In oncology patients,hepatic steatosis can either mask or mimic livermetastases on computed tomography (CT).64

Some patients have undergone liver biopsy oreven wedge resections based on suspicious imag-ing findings.65,66 Fat has shorter T1 values thanliver at both 1.5 and 3.0 T.67 Thus, nodular steato-sis should be hyperintense to surrounding liver onin-phase T1-weighted imaging (Fig. 9), suggestingit is of hepatocellular origin based on pearl 1. Theloss of signal on opposed-phase imaging estab-lishes the presence of lipid. On all other pulse se-quences, nodular steatosis should follow theexpected behavior of steatotic non-neoplasticliver and, thus, should not be confused with anHNF-1a adenoma or well-differentiated lipid-con-taining HCC.

THE EXCEPTIONSClear Cell Renal Cell Carcinoma

Clear cell renal cell carcinomas were namedbecause of the transparency of the cytoplasm on


hematoxylin and eosin staining. Intracellularglycogen and lipids are removed during the stain-ing process. Chemical shift MR can detect andcharacterize the lipid content of primary clear cellrenal cell carcinomas68 as well as metastaticdisease to the adrenal gland69 and pancreas.70

Although there are no published case reports ofchemical shift imaging of hepatic metastatic clearcell renal cell carcinomas, the authors have seenexamples (Fig. 10). Metastatic clear cell renal cellcarcinoma to the liver should not be misdiagnosedas a benign lipid-containing hepatocellular lesion,as these patients often have a known primary renalcancer and other sites of metastatic disease.

Liposarcoma and Germ Cell Neoplasms

Retroperitoneal and extremity liposarcomas canrarely metastasize to the liver. Liposarcoma meta-static to the liver can have variable amounts of fatthat can be characterized with chemical shiftimaging and fat-suppressed imaging techniques.Examples of these metastases are rare and


Fig. 9. Nodular steatosis and a hepatic cyst in a 49-year-old woman with acute alcoholic hepatitis. (A) EnhancedCT examination detected nodular and regional foci of decreased attenuation (arrows) for which MR was re-quested for further evaluation. (B) Axial in-phase image shows that lesions of the caudate and posterior aspectof segment 2 (black arrows) are hyperintense to the remainder of the left lobe of the liver suggesting hepatocel-lular origin. An 8-mm cyst of the subcapsular portion of segment 4 (small white arrow) is hypointense to bothliver and spleen. (C, D) Corresponding opposed-phase image (C) and subtraction image (in-phase minusopposed-phase; see Fig. 3 legend) (D) not only confirms the presence of intracellular lipid within the caudateand segment 2 nodules (arrows) but also shows mild regional and diffuse steatosis of the remainder of the liver.(E, F) Axial T2-weighted fast-spin-echo images with effective echo times of 94 (E) and 180 ms (F) show that thenodular lesions are isointense to spleen (S), whereas the 8-mm cyst (arrow) is hyperintense to spleen and isoin-tense to cerebrospinal fluid and ascites. The higher signal intensity of the nodular steatosis compared with sur-rounding liver is from the T2 lengthening effects of fat. (G) Fat-suppressed T2-weighted image with an effectiveecho time of 94 ms shows a change in contrast; the hepatic nodules (arrows) are now moderately hypointense tospleen (S). One would have expected a lipid-containing HCC to have components that were isointense to spleenon this pulse sequence (see Fig. 6C). These foci of nodular steatosis did not restrict diffusion or show arterialphase enhancement and did enhance on hepatobiliary-phase enhanced imaging (not shown), all of which sup-ported a benign diagnosis.


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reportable.71,72 There are also rare reports of he-patic metastases from malignant mature cysticteratoma or from an immature ovarian tera-toma.73,74 Like peritoneal extension of otherovarian neoplasms, these lesions are centeredon the peritoneal surface of the liver as opposedto intrahepatic lesions from hematogenous orlymphatic spread. Primary hepatic teratomas areeven rarer than peritoneal spread of an ovarianteratoma, with only 25 reported cases.18,75


Ethiodized Oil

Ethiodized oil (e.g., lipiodol) is a compound thatcontains both iodine and long-chain fatty acids.76

Hepatic malignancies treated with ethiodized oilchemoembolization can show loss of signal inten-sity on chemical shift imaging secondary to thelipid components of the agent. Unenhanced CTcan be used to evaluate the distribution and accu-mulation of high-attenuation iodine within treated


Fig. 10. Chemical shift MR findings of metastatic clear cell renal cell carcinoma in a 52-year-old man. (A) Axial in-phase T1-weighted image shows hypointense liver dome (arrow) and left chest wall (large arrows) masses. (B)Opposed-phase T1-weighted image shows subtle signal loss within both lesions indicating the presence of intra-cellular lipid. (C) Subtraction image (similar technique as described in Fig. 3C) shows signal within both lesion(arrows) confirming the presence of lipid. (D) T2-weighted fast-spin-echo image (effective echo time [TE] 5 79ms) shows that the liver metastasis (arrow) is isointense to spleen (S), whereas the chest wall mass is slightly hyper-intense to spleen. A small focus of increased signal intensity (small arrow) is present within the metastasis. (E)Heavily T2-weighted image (effective TE 5 179 ms) shows that the liver lesion remains isointense to spleenwith continued punctuate central hyperintensity (arrow). This focus did not enhance after contrast (not shown)and is in keeping with central necrosis. Note the decreased contrast between the liver metastases with both thesurrounding liver and spleen. This pulse sequence is ideal for characterizing cysts and nonsolid lesions but shouldnot be relied on for solid lesion detection.


lesions (see Fig. 6I).77 Although the loss of signalintensity within malignancies after chemoemboli-zation has not been formally reported, the authorshave observed this phenomenon in HCC and met-astatic disease after chemoembolization (seeFig. 6F–H).

Hepatic Angiomyolipoma

Hepatic angiomyolipomas (HAML) are raremesenchymal neoplasms composed of variableamounts of fat, smooth muscle, and blood ves-sels.78 Although HAML is a primary hepatic lesion,it does not contain hepatocytes and, thus, is nothepatocellular in origin. HAMLs with greater than70% fat content have been termed lipomatousHAMLs that compose 20% of all HAMLs.79

Chemical shift MR can categorize these lipoma-tous HAMLs by depicting an etching artifact atthe interface of the HAML and the adjacent liveron opposed-phase imaging (Fig. 11).80 The pres-ence of macroscopic fat can then be confirmed byshowing marked loss of internal signal intensity ona corresponding fat-suppressed T1-weighted im-age, similar to how one diagnoses fat-containingrenal AMLs. Opposed-phase imaging can detectsmaller amounts of lipid, so-called microscopic


fat, present within the nonlipomatous HAMLs.The signal loss within these HAMLs onopposed-phase imaging can appear similar tothe examples of focal steatosis and HNF-1a ade-nomas as discussed earlier.81 Lipid-poor HAMLsmay not be definitely characterized by imagingand may require tissue sampling. For example,in a single-institution experience of 178 resectednonlipomatous HAMLs, less than 10% of the le-sions were considered HAML at preoperative im-aging.78 The resected HAMLs were mostcommonly misdiagnosed as HCC. Other lesscommon fat-containing lesions, such as lipomaand pseudolipoma of Glisson capsule, are dis-cussed and illustrated elsewhere.18,72,82

PEARL 3 (IN 3 PARTS): THE IRON PEARLS

A. Focal liver lesions that diffusely lose signal in-tensity on an in-phase image compared withthe corresponding opposed-phase image aresiderotic nodules.

B. A siderotic nodule that contains an iron-sparedregion within it is an HCC until provenotherwise.

C. In an iron overloaded cirrhotic liver, an iron-spared lesion is suspicious for HCC.


Fig. 11. Chemical shift imaging illustration of a primary HAML in a 37-year-old woman with tuberous sclerosis.Not every T1 hyperintense or lipid-containing liver lesion is hepatocellular in origin. (A, B) Axial in (A) andopposed-phase (B) T1-weighted images show a focal liver lesion (arrows) that is hyperintense to liver at bothecho times. The lesion can be characterized as containing macroscopic fat because of the presence of an etchingartifact (arrows) at the interface between the mass and the surrounding liver indicating a fat-water interface. Asthe liver is almost never composed of more lipid than water, one can conclude the mass is composed of mostly fatand that the residual signal with the lesion is from fat protons. (C) Subtraction image (in-phase minus opposed-phase; see Fig. 3 legend) confirms the presence of both lipid and water protons within the HAML and the absenceof hepatic steatosis. Even though this HAML is composed mostly of fat, the amount of signal intensity present onthis subtraction image is minimal. The maximal signal on the subtraction image corresponds to those voxels thathave maximum signal loss on the opposed-phase image (eg, at the interface of the HAML with the adjacent liver[arrows]); this corresponds to those voxels that have similar signal contributions from lipid and water protons.


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Loss of signal intensity within the liver on an in-phase image when compared with the corre-sponding opposed-phase image is usually fromthe susceptibility effects of excess iron,assuming the in-phase image is acquired at alonger echo time as was suggested in “Pearl 2.”The 2 most common causes of diffuse excessliver iron are from prior transfusions, where liveriron accumulates primarily in the Kupffer cells,or genetic hemochromatosis, where iron selec-tively deposits within hepatocytes.83,84 Loss ofsignal intensity on an in-phase image within afocal liver lesion in cirrhotic patients is almost al-ways secondary to a siderotic RN (see Fig. 7;Fig. 12). Gradient echo images obtained with alonger echo time (eg, >10 ms) and a lower flipangle (eg, <30�) or susceptibility-weightedgradient echo images have higher sensitivity fordetecting siderotic nodules than routine in-phase and opposed-phase gradient echo im-ages85,86 and could be used if more sensitivedetection is desired.


It is not fully understood why some cirrhotic pa-tients develop siderotic nodules. One hypothesissuggests that the presence of siderotic nodulescorresponds to inflammatory liver activity.87 In aseries of 77 cirrhotic patients who went to trans-plant, 35 (45%) had siderotic nodules, of which80% were detected using T2* sensitive gradientecho imaging.86 Although the presence of iron(either diffusely or focally within a siderotic nodulein a cirrhotic liver) may not increase the risk ofHCC,86 the focal absence of iron within a sideroticnodule is suspicious for malignancy. In 1991,Mitchell and colleagues88 noted that an iron-spared focus within an iron-rich siderotic nodulewas specific for HCC and named this finding the“nodule in nodule” sign (Fig. 13). A subsequentreport shows that the iron-spared focus withina siderotic nodule will grow rapidly in time ifnot treated, with a diameter doubling time of29 weeks.89

Although some cirrhotic patients have increasediron present focally within nodules, others with


Fig. 12. Chemical shift depiction of iron-containing siderotic nodules of the liver and Gamna-Gandy bodies of thespleen in a 56-year-old man with a history of cirrhosis. (A) Axial opposed-phase image obtained at 3 T (echo time1.28 ms) shows subtle low-signal-intensity foci of the liver and spleen (arrows). (B) In-phase image (echo time2.48 ms) shows lower-signal-intensity blooming within the hepatic and splenic lesions (arrows) in keeping withsusceptibility effects from intralesional iron. (C) Fat-suppressed enhanced T1-weighted image obtained with aneven longer echo time of 3.69 ms shows further blooming of the iron-containing nodules (arrows). Siderotic nod-ules often have low signal intensity on delayed enhanced MR imaging that should not be interpreted as washoutkinetics of HCC. A recanalized umbilical vein and abdominal wall varices are present (double arrows).


cirrhosis can develop diffuse increased liverparenchymal iron. In one pathology study of 447livers with cirrhosis, stainable iron was present inapproximately one-third of patients.90 Only 5 pa-tients were homozygous for the hemochromatosisgene. Suggested reasons for the increased ironwithin cirrhotic livers include the presence of intra-hepatic shunts90 or an increase in Kupffer cell ironobtained from ferritin released from damaged he-patocytes.85 Although once thought that the pres-ence of pancreatic iron in cirrhotic patients wasspecific for genetic hemochromatosis,91 it is nowrecognized that some cirrhotic patients withouthemochromatosis can have not only increasedliver iron but also increased extrahepatic iron in or-gans, such as the pancreas and myocardium.92

The increased iron present in cirrhotic patientscan act as a useful intrinsic contrast agent. Justas pathologists look for iron-spared nodules ongross evaluation of explanted livers with iron over-load, radiologists can search for iron-spared nod-ules within livers with iron overload. If patients arecirrhotic, an iron-spared nodule should be consid-ered suspicious for HCC. The reader is referred to


the concurrent review by Sirlin concerning the LI-RADS classification whereby an iron-spared lesionin an iron-overloaded liver is considered an ancil-lary feature that supports a diagnosis of HCC(see Figs. 7 and 13).

PEARL 4 (IN 3 PARTS): THE T2 PEARLS

A. Focal liver lesions that are hypointense to liveron routine T2-weighted (eg, 80–120 ms) im-ages have a limited differential diagnosis.

B. Focal liver lesions that are isointense to spleenon T2-weighted images are malignant.

C. Focal liver lesions that are hyperintense tospleen on T2 and heavily T2-weighted imagesare benign, usually cysts or hemangiomas.

Normal liver parenchyma has relatively low signalintensity on T2-weighted images. The T2 relaxa-tion times of liver at 1.5 T have been shown to bein the range of 51 to 54 ms, whereas those of solidlesions, hemangiomas, and cysts are in the rangeof 80 to 85, 155 to 178, and 517 to 583ms, respec-tively.4,93 The T2 relaxation time of normal splenic


Fig. 13. MR illustration of the “nodule in nodule” sign in a 63-year-old man with cirrhosis secondary to hepatitis Cinfection and multifocal HCC. An iron-spared focus within a siderotic nodule should be considered specific forHCC. (A) Axial opposed-phase image obtained at 1.5 T (echo time [TE] 2.38 ms) shows a low-signal-intensitynodule (arrow) at the junction of segments 6 and 7 that contains a higher-signal-intensity component (small ar-row). The liver is of low signal intensity. On this single opposed-phase image, it is not possible to determinewhether this is from steatosis or liver iron. (B) In-phase image (echo time 4.76 ms) shows lower signal intensityboth within the hepatic parenchyma and to a greater degree within the nodule, which can now be characterizedas siderotic. The iron-spared focus within the nodule is well depicted (arrow). (C) Fat-suppressed respiratory-trig-gered T2-weighted image (effective TE 5 90 ms) shows that the siderotic nodule is minimally hypointense relativeto surrounding liver (arrow), whereas the iron-spared focus is hyperintense (thin arrow). (D) Arterial-phase,contrast-enhanced, fat-suppressed, T1-weighted image shows hyperenhancement of the iron-spared focus (ar-row). The iron-spared focus was isointense to spleen on T2-weighted images and showed washout on delayedimages (not shown). (E, F) Opposed and in-phase images obtained more superiorly within the liver shows aniron-spared 1.5 cm mass (arrows) that had imaging characteristics of HCC on other pulse sequences.


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tissue is similar to solid liver lesions and has beencalculated to be 81 ms at 1.5 T.94

Thus, most focal liver lesions encountered indaily practice are T2 hyperintense to liver. Whena focal liver lesion is hypointense to liver on T2-weighted images, there is a narrow differentialdiagnosis.95 A siderotic nodule is diffusely hypoin-tense on T2-weighted images relative to surround-ing liver secondary to the T2* susceptibility effectsof iron. In the authors’ routine abdominal imagingprotocol, they find that the in-phase T1-weightedimages are more sensitive in showing T2* suscep-tibility effects than T2-weighted fast spin echo im-ages (see Fig. 13B, C).


Other causes of T2-hypointensity in focal liverlesions include hemorrhage,45 melanin (seeFig. 5),48 coagulative necrosis and desmoplasticresponse present centrally within liver meta-stases,96 as well as intralesional fibrosis presentcentrally within mass-forming intrahepatic cholan-giocarcinoma.97 The reader is referred to the illus-trated examples from a Radiographics article byCurvo-Semedo and colleagues95 for other exam-ples of T2-weighted hypointensity from densecalcium, necrosis, smooth muscle, and othermacromolecules.It is a fortuitous coincidence that a typical solid

liver malignancy is isointense to spleen on routine


Fig. 14. MR illustration ofmucinous adenocarcinoma of the colonwith T2 hyperintense livermetastases.Mucinoustumors can have similar T2 signal intensity to nonsolid liver lesions. (A) Coronal T2-weighted image (effective echotime [TE] 5 90 ms) shows multiple liver lesions (arrows) that are hyperintense to spleen (S). The primary tumor ispresent in the descending colon (double arrows). A splenic cyst is also present (small arrow). (B) Axial heavilyT2-weighted fast-spin-echo images (effective TE 5 178 ms) shows persistent hyperintensity of the liver metastases(arrows) relative to spleen. Note decreased contrast between liver and spleen comparedwith the lower TE image in(A). Benign splenic cyst (small arrow) is isointense to gallbladder bile and cerebrospinal fluid.


T2-weighted images. In patients with knowncirrhosis, a focal liver lesion that is isointense tospleen is suspicious for HCC. In patients with aknown primary malignancy, a focal liver lesionthat is T2 isointense to spleen should be consid-ered malignant until proven otherwise, especiallywhen there are other imaging findings of metasta-tic disease. When metastatic disease involves thespleen, it sometimes can be difficult to discernbecause of the similar T1 and T2 values of normalspleen and metastatic disease (see Fig. 5).98

If a focal liver lesion is hyperintense to spleen onroutine T2-weighted images, then one shouldconfirm that it remains hyperintense relative tospleen on a heavily T2-weighted sequence. Asspleen and metastatic disease have shorter T2relaxation times than nonsolid cysts and hemangi-omas, the latter should lose less signal intensity onlonger echo time T2-weighted images than splenicand malignant tissue (see Figs. 1 and 9). Studiesperformed in the 1990s that used echo times ofat least 160 ms showed an improved ability todifferentiate between solid malignancies andnonsolid hemangiomas.99–101 The heavily T2-weighted sequence can be considered a “metas-tases suppression sequence” (Donald MitchellMD, personal communication, 1993) as metasta-ses tended to lose signal intensity and show lesstissue contrast with the surrounding liver.

THE EXCEPTIONSHepatic Adenomas and FNH Can HaveComponents That Are Isointense to Spleen

As discussed and referenced earlier, both HCAand FNH (see Figs. 2 and 4) can have T2 signal in-tensity that is isointense to spleen. The absence of


a known primary malignancy and the presence ofeither isointensity on in-phase T1-weighted im-aging (pearl 1) or loss of signal intensity onopposed-phase T1-weighted imaging (pearl 2)should help in excluding a diagnosis of metastaticdisease and help establish a diagnosis of a benignhepatocellular lesion.

Mucinous Adenocarcinoma Metastases CanBe Hyperintense to Spleen on Heavily T2-Weighted Images and Can Mimic NonsolidBenign Lesions

Mucinous adenocarcinomas can have high T2signal intensity when composed of low viscositymucin with high free-water content.102,103 Meta-static mucinous adenocarcinoma can mimic ahemangioma on moderately and heavily T2-weighted images (Fig. 14).104,105 Knowledge ofthe histology of the primary tumor and use oncontrast-enhanced images can usually establishthe correct diagnosis and avoid characterizingmucinous metastases as a benign nonsolid lesion.

SUMMARY

The authors present the aforementioned pearlsand pitfalls to facilitate tissue characterizationand accurate diagnoses of focal liver lesions.Through the appropriate performance and inter-pretation of the T1 chemical shift and moderateand heavily T2-weighted and hepatobiliaryphase–enhanced imaging, one can often charac-terize lipid and iron-containing hepatocellulartissue, benign hepatocellular lesions, HCC, meta-static disease, and nonsolid benign cysts andhemangiomas.



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MR Characterization of Focal Liver Lesions...2018/12/13 · used to differentiate benign from...

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