IMAGING OF DIFFUSE LIVER DISEASE

HEPATIC IMAGING 0033-8389/98 $8.00 + .OO

IMAGING OF DIFFUSE LIVER DISEASE

Patricia J. Mergo, MD, and Pablo R. Ros, MD, FACR

Although the diagnosis of diffuse hepatic disease has traditionally been made by laboratory examination or liver biopsy, cross-sectional image can aid in the diagnosis and characterization of diffuse diseases. Imaging can be used to determine the cause of diffuse hepatocellular disease in many instances, and in others can be used to assess the extent of cirrhosis and associated secondary changes of portal hypertension. In patients with end-stage liver disease, imaging is essential in evaluating for development of complications of cirrhosis, such as portal vein thrombosis, and the development of hepatocellular carcinoma (HCC).

Diffuse hepatocellular diseases that can be further evaluated with CT scan and MR imaging include cirrhosis; iron overload; Wilson’s disease; Budd-Chiari syndrome; fatty change; neoplastic diseases, such as hepatocellular carcinoma, metastases, and lymphoma; sarcoidosis; amyloidosis; and schistosomiasis. In certain instances, the speci- ficity of findings on CT scan or MR imaging is sufficient to obviate the need for histologic examination.

CIRRHOSIS

Many of the diffuse liver diseases have cirrhosis as an underlying finding, because cirrhosis occurs as a chronic response to repeated episodes of hepatocellular injury. It is characterized by repeated episodes of impaired circulation, injury, inflammation, and the key components of regeneration and fibrosis. Cirrhosis must contain these last two ele- ments, fibrosis and regeneration, by definition.

Microscopically, cirrhosis can be characterized as

having either micronodular regenerative change, macronodular change, or mixed change. A fourth type of cirrhosis, incomplete septa1 cirrhosis, also known as posthepatitic cirrhosis, may be classified as macronodular. Micronodular cirrhosis, which is common in alcohol-related liver disease and hemochromatosis, has diffuse nodules less than 3 mm in size, with thin fibrous septa. Viral hepatitis results in macronodular cirrhosis, which is characterized by nodules greater than 3 mm in size, with thick fibrous septa. Both types result in progressive fibrosis; hepatic failure; and portal hypertension, and its associated sequelae of variceal hemorrhage and HCC.

The CT scan findings of cirrhosis are well estab- lished, and include a small fibrotic right lobe of the liver with regenerative enlargement of the caudate and left lobes; a caudate to right lobe ratio equal to or greater than 0.65 (90% specific for the presence of ~irrhosis)’~; and a portal vein diameter greater than 1.3 cm.

Cross-sectional imaging cannot reliably distinguish micronodular from macronodular disease, because of the small size of the regenerative nodules. When nodularity is appreciable by imaging, however, it is most likely secondary to underlying macronodular disease. This nodularity, combined with intervening strands of fibrosis, results in the liver having a characteristic hobnail appearance.

In addition to regenerative nodules, dysplastic nodules and HCC may develop in cirrhosis. Identi- fication, by imaging, of focal masses in a cirrhotic liver is important, because dysplastic nodules are thought to be a precursor of HCC, and the development of HCC has a dismal prognosis and may preclude liver transplantation. MR imaging has

From the Division of Body Imaging and MRI, Department of Radiology, University of Florida College of Medi- cine, Gainesville, Florida (PJM, PRR); currently, Vice Chairman, Department of Radiology, Harvard Medical School/Brigham & Women’s Hospital, Boston, Massachusetts (PRR)

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definite utility in the evaluation of the cirrhotic liver, because it is the most successful imaging technique for differentiating regenerative nodules and dysplastic nodules from HCC, and it provides physiologic information regarding the presence of portal hypertension.

The changes of cirrhosis apparent in the liver by CT scan (Fig. 1) are also seen with MR imaging (Fig. 2) . Overall, the signal intensity of the cirrhotic liver is not significantly different from that of normal liver. Regenerative nodules may have altered signal intensity, however, depending on whether or not they contain hem0siderin.3~ Regenerative nodules without hemosiderin are isointense or slightly hyperintense on T1-weighted images and mildly hypointense on T2-weighted images. Those with hemosiderin are more hypointense on T2- weighted images because of their iron content. Gradient echo imaging is a more sensitive way to demonstrate the presence of hemosiderin, however, compared with spin echo imaging, because gradient-echo images lack a 180-degree refocusing pulse and thus are more sensitive to the magnetic susceptibility effects of the hemosiderh’, 37 T2*- weighted gradient echo imaging with a TE ranging from 15 to 25 millisecond and a flip angle of 10 to 30 degrees maximizes the T2* effects and provides optimal imaging for demonstrating the presence of iron.45

Gradient echo imaging also allows the demon- stration of associated siderotic nodules, termed Gundy-Gamma nodules, in the spleen. These hemosiderin nodules, which occur with portal hypertension, are apparent on gradient echo imaging as tiny foci (3 to 8 mm in size) of abnormal low- signal intensity.29

Dysplastic nodules are seen as low signal in-

Flgure 1. CT scan appearance of cirrhosis. Enhanced CT scan shows a lobulated contour of the liver, splenomegaly, portosystemic collaterals (solid arrows), and ascites. There are enlarged hepatic arterial collateral vessels and thrombus within the portal vein (open arrows).

tensity foci on T2-weighted and gradient echo sequences, with slight hyperintensity on T1- weighted sequences (see Fig. 2). These signal changes reflect the accumulation of iron and hemosiderin products within the nodules. Foci of HCC are distinguishable by their increased signal intensity on T2-weighted sequences and hypointensity on T1-weighted imaging (see Fig. 2).

One entity that can mimic HCC on imaging is confluent fibrosis. This type of massive fibrosis, generally seen in the anterior segment of the right hepatic lobe or the medial segment of the left lobe, has a wedge-shaped appearance and is hypodense on CT ~can .3~ The MR imaging signal characteristics are not unique, however, and thus do not allow differentiation from HCC.36

MR angiography provides useful information regarding the presence of portal vein thrombosis and collateralization of flow in portal-systemic shunts. These findings have been shown to correlate well with those seen by color Doppler ultrasound examination.20

Ultrasound examination is more commonly used for this purpose, however, because it provides an inexpensive means of evaluation of portal venous flow. The changes of cirrhosis are also seen as corresponding changes in the liver configuration and echotexture, but the distinction of mass lesions in the liver is less reliable, often requiring further evaluation with MR imaging.

Other associated imaging signs of cirrhosis include widening of the hepatic interlobar fissure and colonic interposition. Hypoproteinemia related to hepatocellular dysfunction is also evident by the presence of ascites, gallbladder wall thickening, and small bowel edema, and secondary signs of portal hypertension include the presence of splenomegaly and the formation of large or multiple portosystemic collateral vessels (see Fig. 1).

Overall, the diagnosis of cirrhosis is suggested by these changes in the size, configuration, and texture of the liver, combined with the previously mentioned secondary signs of portal hypertension and hepatocellular dysfunction. Focal masses within the cirrhotic liver may then be correlated with serum alpha-fetoprotein levels and further characterized with MR imaging, because it allows the distinction of regenerative nodules (often too small to be seen by imaging) and dysplastic nodules (hypointense on T2) from HCC (hyperintense on T2).

IRON OVERLOAD

Iron overload states can result in hepatic parenchymal or reticuloendothelial deposition of iron, depending on the underlying disease. Hereditary hemochromatosis, cirrhosis, and intravascular he- molysis can all result in hepatic parenchymal iron deposition, whereas chronic overload states associated with multiple transfusions result only in reticuloendothelial deposition of iron. Distinguishing

IMAGING OF DIFFUSE LIVER DISEASE 367

Figure 2. MR image of cirrhosis; distinction between HCC and dysplastic nodule. A, T I weighting (300/30) shows the nodular appearance of the liver secondary to regenerative nodules, giving the liver a hobnail appearance. Low signal intensity bands of fibrosis (arrows) are seen between the nodules. A dominant nodule, representative of a dysplastic nodule, is present in the left lobe (arrowheads). A low signal intensity focus is present in the right lobe from HCC (curved arrow). 5, T1 fat-suppressed image (700/15) better demonstrates the low signal intensity focus of HCC (curved arrow). C, T2 weighting at a slightly different level shows the high signal intensity HCC (arrows). Other associated changes of cirrhosis are seen including a shrunken right hepatic lobe, enlargement of the left hepatic lobe, splenomegaly, varices, and ascites.

these two entities is important, because their prognosis is different. Hepatic parenchymal iron deposition more commonly results in cirrhosis and thus has a higher association with the development of HCC and an overall worse prognosis.

Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism characterized by the abnormal absorption of iron from the gas- trointestinal tract, with subsequent excessive deposition of iron in the liver, pancreas, myocardium, endocrine glands, joints, and skin. The additional organ involvement allows its distinction from the reticuloendothelial form of iron 0verload.4~ The reticuloendothelial cells in patients with hereditary hemochromatosis are also abnormal, however, and are unable to store iron effectively.”

On CT scan, the high atomic number of the excess deposited iron results in overall increased attenuation of the liver (Fig. 3). Hepatic density measurements of iron overload disorder typically range from 75 to 130 H. The CT scan appearance of a hyperdense liver is not specific for iron overload disorder, however, because similar findings can be

seen with Wilson‘s disease; gold deposition; type IV glycogen storage disease; and amiodarone administration (due to its iodine content with subsequent iodine accumulation in the liver).

The MR imaging findings are more specific than the CT scan findings, due to the unique magnetic susceptibility effects of the iron. T2-weighted images show markedly decreased-signal intensity of the liver, secondary to the superparamagnetic effects of the accumulated iron (Fig. 4).49 T2*- weighted gradient echo imaging is the most sensitive technique for the detection of iron overload states, because gradient-echo imaging is more sensitive to magnetic susceptibility effects, secondary to its lack of a 180-degree refocusing pulse. As previously mentioned, a TE of 15 to 25 and a flip angle of 10 to 30 degrees maximizes the T2* effects and provides optimal imaging.45 Comparison of the signal intensity in the liver with that of paraspinal muscle provides an internal control, because iron is not deposited within the skeletal muscle. Thus, if liver signal intensity is less than that of paraspinal muscle, it is considered abn0rma1.l~

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BUDD-CHIARI SYNDROME

Figure 3. CT scan of hemochromatosis. Unenhanced CT scan shows marked increased attenuation of the liver diffusely, secondary to iron deposition, in this patient with hemochromatosis.

In addition, MR imaging enables distinction of hereditary hemochromatosis from reticuloendothelial deposition of iron from transfusion-related iron overload states. In hereditary hemochromatosis, signal intensity changes are demonstrated in other involved organs (pancreas, myocardium, adrenals, and other endocrine glands) (see Fig. 4),43* 44, 49

whereas in transfusion-related iron overload, abnormal-signal intensity is seen only in organs with significant reticuloendothelial activity, including liver, spleen, and bone marrow. Foci of bright signal intensity on TZweighted sequences, in the low-signal intensity background, suggests the development of HCC. Corresponding CT scan images show low-density lesions in an abnormally high-attenuation background.

WILSON’S DISEASE

Wilson’s disease is an autosomal recessive disorder of copper metabolism in which high levels of copper accumulate in the liver, brain, and cornea?’ In the liver, copper deposits along the sinusoids and in the periportal regions and incites an inflammatory reaction that can lead to cirrhosis.

The CT scan appearance of Wilson’s disease is that of a liver with diffusely increased attenuation, due to the high atomic number of copper (Fig. 5).7 The high attenuation from the copper deposition can be offset by abnormal low attenuation from coexistent fatty change; thus, this finding is a variable one. Copper is nonferromagnetic; thus, MR imaging does not show any characteristic signal intensity change within the liver. The most common finding is subsequent changes of cirrhosis in more advanced cases. Overall, though, imaging does not play a major role in the diagnosis of this entity, because it is a diagnosis made on the basis of clinical and laboratory findings.

Budd-Chiari syndrome is the manifestation of hepatic venous outflow obstruction,31 often clini- cally evident by the presence of hepatomegaly, ascites, and abdominal pain, with nonspecific ele- vation of hepatic enzymes. Two forms exist: (1) acute and (2) chronic. The acute form occurs secondary to acute thrombosis of the inferior vena cava or main hepatic veins. The thrombosis is often attributable to hypercoagulable states, such as with polycythemia Vera, pregnancy, myeloproliferative disorders, or oral contraceptive but can also be secondary to tumor thrombosis. In the chronic form of Budd-Chiari syndrome, fibrosis of the intrahepatic veins occurs, presumably related to inflammation. Both the acute and chronic forms result in severe centrilobular congestion and hepatocellular necrosis and atrophy.

Two other entities that have similar clinical man- ifestations are severe right-sided heart failure and

Figure 4. MR image of hemochromatosis. A, T2-weighted image (000/90) shows marked decreased signal intensity of the liver, secondary to iron deposition. Some nodularity and contour changes are also evident, as well as ascites, indicative of cirrhosis. 6, T2 weighting at a different level shows abnormal low signal intensity in the pancreas (arrows) in this patient with hereditary hemochromatosis. Abnormal low signal intensity was also evident in the adrenal glands.


syndrome, such as narrowing, nonvisualization, or thrombosis of the hepatic veins and inferior vena ~ a v a . ~ ~ , 48 In addition, comma-shaped intrahepatic varices are a characteristic finding not appreciable with other modalities (Fig. 7)?* These collaterals are formed in an attempt to bypass the ob- structed flow.

Severe congestive failure and right-sided failure may result in a similar patchy enhancement pattern and congestive changes of the liver; however, the hepatic veins are enlarged and distended rather than diminished.

FAlTY CHANGE

Figure 5. Wilson’s disease. A, Unenhanced CT Scan Fatty change can from decreased hepatic demonstrates multiple hyperdense nodules secondary to copper deposition with associated cirrhotic change.

Of fatty acids from hepatocellular or from increased production or mobilization of fatty acids. Common etiologies include alcohol, obesity, diabetes mellitus, hepatitis, drugs, hyper- alimentation, and liver transplantation. hepatic veno-occlusive disease. Hepatic veno-oc-

clusive disease is characterized by inflammation of The distribution of fatty change can be quite the postsinusoidal venules, whiGh results in their obliteration and occlusion.

The findings of Budd-Chiari syndrome are seen with both CT scan and MR imaging, as well as ultrasound.28 The underlying hepatic congestion prevents contrast material from readily diffusing throughout the liver in a normal fashion. Thus, by CT scan, a mottled enhancement pattern is typical, with delayed enhancement in the periphery of the liver and around the hepatic veins (Fig. 6). Because the caudate lobe has a separate venous drainage, it compensitorily enlarges and has increased enhancement compared with the rest of the liver. This accounts for the finding of a hot caudate lobe appearance, with increased activity in the caudate lobe, on Tc-99m sulfur colloid scan.

MR imaging angiography can demonstrate the changes in hepatic venous flow of Budd-Chiari

Figure 7. Budd-Chiari syndrome. A, T2 weighting shows a mottled appearance of the liver with areas of abnormal increased signal intensity secondary to edema. The hepatic veins and inferior vena cava are obliterated. B, Gradient echo image shows no flow within the hepatic veins and the presence of intrahepatic comma-shaped

Figure 6. Budd-Chiari syndrome. Enhanced CT scan shows a mottled appearance of the liver secondary to vascular congestion. No contrast is seen in the hepatic veins because they are thrombosed. The caudate lobe is enlarged as well. collaterals (arrows).

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Figure 8. Fatty change. Enhanced CT scan demonstrates diffuse fatty infiltration of the liver. Note the increased visibility of the normal hepatic vessels.

variable, ranging from focal, to multifocal, or diffuse. Diffuse involvement can be either uniform (Fig. 8) or patchy and non~niform.~, l2

On CT scan, normal liver measures 8 H greater than the spleen on noncontrast CT scan. Areas involved with fatty change show abnormally decreased attenuation (see Fig. 8), typically 10 H less than the spleen on non-contrast-enhanced CT scan, and 25 H less than the spleen on contrast- enhanced CT scan.’, Classically, vessels course through involved areas unaltered. This is a useful distinguishing feature, although one that can occasionally be mimicked by malignant lesions?

In cases where an area of abnormal low attenuation on CT scan needs to be further evaluated to distinguish fatty change from focal lesions, MR imaging can be helpful. On T1-weighted spin echo imaging, areas of fatty change show higher-signal intensity than normal liver (Fig. 9). Fat-suppression imaging shows subsequent decrease in the signal intensity of involved areas. The most sensitive technique, however, for detection of fatty change uses gradient echo imaging.

Figure 9. MR image of hepatic steatosis. T1 weighting (300/30) shows abnormal increased signal intensity in the left hepatic lobe, which is geographic in distribution.

The technique that best demonstrates fatty change is the use of in-phase and opposed-phase imaging. This can be achieved with spin echo imaging using the Dixon technique, which changes the timing of the 180-degree refocusing pulse.8 Gradient echo imaging, however, is more commonly utilized, because gradient echo images are more rapidly obtained and can be accomplished in a single breath-hold. With gradient echo imaging, there is no 180-degree refocusing pulse, and thus chemical shift between lipids and fat can be demonstrated by varying the TE to image water and fat in and out of phase. Typically, in-phase and out-of-phase gradient echo imaging are obtained with a TE of 4.2 millisecond and 2.1 millisecond, respectively? With in-phase imaging, the fat and water protons are in phase and their signal intensi- ties are cumulative, whereas with out-of-phase imaging the fat and lipid protons are opposed (and a refocusing pulse has not been applied to re-align them). Thus, on out-of-phase imaging, areas with significant fat have lower signal intensity than on corresponding in-phase imaging, because the fat and water signal cancel each other out.21,30

Overall, the imaging characteristics of fatty change on CT scan are usually easily identified. At times, however, focal fatty change can have a confusing appearance (mimicking a hepatic lesion) or can make the identification of concomitant malignancy difficult. In these instances, either ultrasound or MR imaging can be utilized to distinguish focal fat from malignancy.

DIFFUSE NEOPLASTIC DISEASE

HCC

HCC most commonly presents as a solitary mass, but can also have multifocal involvement, and can rarely present as a diffuse disease. The diffuse form, also known as the cirrhotomimetic form, is characterized by small foci of malignancy present throughout the liver, giving the liver a nodular appearance mimicking that of cirrhosis. With this form, vascular invasion of the portal vein, and to a lesser degree, the hepatic veins is also common.

By imaging, this cirrhotomimetic form of HCC can give the liver a lobular contour that mimics that of cirrhosis. The underlying neoplastic infiltration, however, results in abnormal increased- signal intensity on T2-weighted MR imaging. This neoplastic infiltration may not be as evident on CT scan, because both foci of HCC and areas of fibrosis from cirrhosis appear as abnormal areas of low attenuation (Fig. 10). These low-attenuation foci variably enhance on contrast-enhanced CT scan, but to a lesser degree than normal liver.

As previously discussed, with MR imaging, foci of HCC are distinguishable from regenerative nodules or dysplastic nodules, because HCC has high-signal intensity on T2-weighted sequences,


Figure 10. CT scan of diffuse HCC. Enhanced CT scan shows diffuse and multifocal areas of abnormal low attenuation (arrows) corresponding to areas of involvement with HCC. There is also tumoral invasion of the portal vein (arrowheads).

whereas regenerative nodules and dysplastic nodules are isointense to hypoinse on T2-weighted images. Differentiation of HCC from diffuse metastatic disease is aided by the identification of signs of underlying cirrhosis, because HCC is very common in the cirrhotic liver and metastases are un- common in the setting of cirrhosis.

Metastatic Disease

Metastases are the most common malignant lesion encountered in the liver. They are rare, however, in the setting of cirrhosis.13, 14, =, 24, 27, 41 The imaging appearance of diffuse metastases can, however, mimic cirrhosis, as has been a reported finding with treated breast cancer metastases.=

CT scan is the most commonly used modality for detection of metastases, with a reported sensitivity of 38% to 96%.6, la 39, 50 Studies have shown MR imaging to be at least as sensitive as contrast- enhanced CT scan for the detection of metastatic involvement, with lesions typically appearing hyperintense on TZweighted sequences (Fig. 11).6, lo, 16,

39,50 Diffuse involvement of the liver with metastases can be particularly difficult to identify, with subtle features including architectural and vascular distortion and diffuse parenchymal heterogene- ity. With hypervascular metastases, arterial phase imaging, in addition to portal phase imaging, may aid in image detection secondary to increased lesion conspicuity (Fig. 12).

Lymphoma

Lymphomatous involvement of the liver can occur either primarily or secondarily. The primary form is extremely rare and most often presents as a focal hepatic Secondary involvement is much more common, and occurs with both

Hodgkin's and non-Hodgkin's lymphoma. Thirty percent to 40% of patients with lymphomatous involvement of the liver show either a diffuse infiltrating form or a mixed pattern of focal mass with parenchymal The remainder are evident as a focal mass.

Diffuse lymphomatous involvement of the liver can be difficult to detect by any modality, because the underlying hepatic architecture is usually not appreciably altered. The CT scan appearance is nonspecific, with lesions appearing as low-attenuation foci (Fig. 13) with variable contrast enhancement.55 MR imaging findings include foci of increased-signal intensity on T2-weighted sequences, with relatively decreased-signal intensity on T1- weighted sequences. An overall slight increase in signal intensity on TZ-weighted sequences may be present with diffuse infiltrating A report by Weissleder et a152 described no overall signal intensity changes in the three patients in their study with diffuse involvement. In the same study, a mixed pattern of involvement was present in two patients, and was evident on MR imaging as hypointense foci on T1-weighted imaging and hyperintense foci on T2-weighted imaging, with underlying geographic zones of intermediate signal intensity.

SARCOIDOSIS

Sarcoidosis is the most common reported cause of hepatic granulomas.18 Involvement of the periportal regions is characteristic, rather than parenchymal involvement. This results in the development of portal hypertension, which is treatable with steroids in the early stages. Thus, the early reversibility of sarcoidosis-related portal hypertension makes it unique among causes of portal hypertension. Without effective treatment, however, periportal fibrosis occurs, leading to cirrhosis and subsequent irreversible portal hypertension.

The imaging findings of hepatic sarcoidosis are

Figure 11. Diffuse metastases to the liver, MR imaging appearance. There is diffuse abnormal increased signal intensity in the liver secondary to metastases from small cell carcinoma.

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Figure 12. CT scan of diffuse metastases. A and 6, Hepatic arterial and portal venous phase contrast-enhanced CT scans, respectively, show diffuse involvement of the liver with metastases in this patient with a neuroen- docrine tumor. The lesions are much more conspicuous on hepatic arterial phase imaging because of their hypervascular nature.

nonspecific, including hepatomegaly, splenomegaly, and eventually changes of cirrhosis (Fig. 14). Sarcoid granulomas in the liver are usually too small to be discerned by either CT scan or MR imaging and do not result in appreciable signal intensity change of the hepatic parenchyma. One study of 10 patients with MR imaging of hepatic sarcoidosis showed normal-signal intensity of the liver in 8 of 10 patients, although there was increased signal intensity in the periportal regions on T2-weighted images in 7 of 10 patient^.'^ Evi- dence of cirrhosis related hemosiderin deposition was seen in two patients who had diffusely abnormal decreased signal intensity in the liver.

Thus, although imaging changes can be seen with hepatic sarcoidosis, the findings are variable and nonspecific, and imaging does not play a significant role in the diagnosis of this entity.

AMYLOl DOSlS

In hepatic amyloidosis, protein-mucopolysac- charide complexes are deposited along the hepatic

Figure 13. CT scan of diffuse hepatic lymphoma. Multiple low-attenuation nodules are present throughout the liver (arrowheads) and there is extensive periportal involvement with lymphoma (arrows).

sinusoids, within the space of Disse. The liver is the third most common solid abdominal organ to be involved, after renal and splenic involvement.u Amyloidosis is classified using a system based on the biochemical composition of the amyloid fibrils involved.40 This has little radiographic significance, because the types cannot be distinguished by their imaging appearance. In fact, amyloidosis has a very nonspecific imaging appearance, and in most cases no focal abnormality is seen.

Diffuse hepatomegaly is the most common finding (Fig. 15), resulting from the massive amyloid deposition. On CT scan, occasionally focal low- attenuation areas can be detected, which corre- spond to sites of amyloid deposition. These areas can have delayed enhancement on contrast-enhanced CT scanz6

The MR imaging appearance of amyloidosis is not well characterized. The two reports that do

Figure 14. Sarcoidosis. The imaging findings of sarcoidosis are nonspecific including changes of cirrhosis (in long- standing or severe cases of sarcoidosis) and associated splenomegaly. In this case, the spleen is massively enlarged and the liver has a cirrhotic appearance. There are also extensive periportal collaterals, indicative of portal hypertension (arrowheads).


exist show no characteristic features that distinguish amyloidosis from other diffuse diseases?, 38

No signal intensity changes were seen on T2- weighted images in either report. One author found some increase in signal intensity on T1- weighted images in a study of nine patients: but this is nonspecific, because hepatic steatosis can cause similar findings. Thus, imaging does not play a significant role in the assessment of hepatic amyloidosis.

SCHlSTOSOMl ASIS

Schistosoma japonicum and Schistosoma mansoni are two species of schistosomes that are known to cause significant hepatic disease. The schistosomes live in the bowel lumen and lay eggs in the mesen- teric veins. The eggs may then embolize to the portal vein, where they incite an inflammatory reaction, causing a granulomatous response, even- tual fibrosis, and presinusoidal hypertension. The eggs themselves do not survive, and may subse- quently calcify. Long-standing infections with either S. japonicum or S. mansoni result in the formation of cirrhosis and risk of development of HCC.

S. japonicum infection results in the formation of a characteristic calcified, septated appearance of the periportal and pericapsular regions of the liver on CT scan and ultrasound, referred to as the tortoise shell appearance (Fig. 16).33 MR imaging plays less of a role in the diagnosis of this entity, because it cannot identify the characteristic calcifications. In one report of 18 patients, the fibrous septa, which were often calcified by CT scan, had abnormally low-signal intensity on T1-weighted images in nine patients and abnormally high-signal intensity in 13 patients with T2-weighted images with gradient-moment

Infection with S. mansoni does not cause the characteristic tortoise shell calcifications, but does

Figure 16. Schistosomiasis from Schistosoma japonicum infection. Characteristic pericapsular and periportal calcifications are present (arrowheads) giving a tortoise shell appearance to the liver. The calcifications form as a result of embolization of the schistosome eggs to these areas in the liver, with ensuing inflammatory reaction and fibrosis.

cause periportal fibrosis.g The periportal bands of fibrosis are echogenic on ultrasound, and low attenuation on CT scan, with marked enhancement after contrast administration. The MR imaging findings are limited to one case which describes the periportal bands as being hyperintense on T2-weighted images and isointense to normal liver on T1-weighted images, with bright enhancement following intravenous injection of gadolinium-pentetic acid.

SUMMARY

Imaging can play an important role in the diagnosis and planning of treatment for patients with diffuse liver disease. In certain entities, such as iron overload disorders, fatty change, Budd-Chiari syndrome, and schistosomiasis, the imaging findings are characteristic and diagnostic. In others, the findings are less specific, but imaging still has utility in assessment for associated changes of cirrhosis and portal hypertension. In either case, fa- miliarity with these diffuse hepatic diseases and their expected imaging findings enables an orga- nized and thoughtful assessment, with careful at- tention paid to the key diagnostic features and the important sequlae, such as portal hypertension and the development of HCC.

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Figure 15. Amyloidosis. Enhanced CT scan shows nonspecific findings of hepatomegaly. There are subtle areas of low attenuation in the spleen (arrows), but these findings are also nonspecific.

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Address reprint requests to Patricia J. Mergo, MD

Harvard Medical School Brigham & Women’s Hospital

75 Francis Street Boston, MA 02215

IMAGING OF DIFFUSE LIVER DISEASE

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