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DOI: 10.1148/radiol.2263011623
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(Radiology 2003;226:675-685.)
© RSNA, 2003

Gastrointestinal Imaging

MR Imaging Features of Primary Sclerosing Cholangitis: Patterns of Cirrhosis in Relationship to Clinical Severity of Disease1

Till R. Bader, MD, Kimberly L. Beavers, MD and Richard C. Semelka, MD

1 From the Departments of Radiology (T.R.B., R.C.S.) and Internal Medicine (K.L.B.), University of North Carolina at Chapel Hill, 101 Manning Dr, CB 7510, Chapel Hill, NC 27599-7510; and Department of Radiology, University of Vienna, Austria (T.R.B.). Received October 2, 2001; revision requested December 18; final revision received June 19, 2002; accepted October 9. T.R.B. supported by a grant from the Max Kade Foundation, New York, NY. Address correspondence to R.C.S. (e-mail: richsem@med.unc.edu).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate the spectrum of magnetic resonance (MR) imaging appearances of the liver in primary sclerosing cholangitis (PSC) and to examine their correlation with clinical stage of disease.

MATERIALS AND METHODS: Fifty-two patients (25 female, 27 male; mean age, 43 years; age range, 11–87 years) with PSC underwent nonenhanced and gadolinium-enhanced MR imaging. Two abdominal radiologists retrospectively reviewed all images (independently and then in consensus) for the imaging pattern of the liver parenchyma, presence and grade of intrahepatic biliary ductal dilatation, and presence of areas of parenchymal atrophy or abnormal signal intensity and/or gadolinium enhancement. Imaging findings were correlated with Child class, Child-Turcotte-Pugh score, and Mayo end-stage liver disease (MELD) score. Statistical analyses ({kappa} scoring for interobserver agreement, McNemar test, Mann-Whitney U test, multiple regression analysis, Spearman correlation) were performed.

RESULTS: Of 52 patients, seven (13%) had no imaging findings of cirrhosis, 17 (33%) had a diffuse pattern of cirrhosis, and 28 (54%) had a large macronodular pattern (with nodules >=3 cm) ({kappa} = 0.84). Intrahepatic biliary ductal dilatation was observed in 44 (85%) patients and was general in 18 (35%) and segmental in 26 (50%). Peripheral wedge-shaped areas of parenchyma were observed with atrophy in 23 (44%) and 25 (48%) patients by the two readers ({kappa} = 0.76) and without atrophy in 18 (35%) patients by both readers ({kappa} = 1.00). No correlation was found between imaging findings and clinical scores (P > .05, multiple regression analysis; P = .25–.75, Mann-Whitney U test; Spearman correlation coefficients between -0.33 and 0.33).

CONCLUSION: The spectrum of MR imaging appearances of PSC is diverse and comprises distinct patterns that do not appear to correlate with severity of disease. Large regenerative nodules are a frequent finding and may help to establish the diagnosis.

© RSNA, 2003

Index terms: Bile ducts, MR, 763.12141, 763.12143, 764.12141, 764.12143, 765.12141, 765.12143, 766.12141, 766.12143 • Cholangitis, 76.288 • Liver, cirrhosis, 761.794 • Liver, MR, 761.12141, 761.12143


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Primary sclerosing cholangitis (PSC) is a disease of unknown etiology. It is associated with inflammatory bowel disease in 71% of cases (1,2). PSC is characterized by inflammation and fibrosis of the biliary tree (3). It results in obliterative fibrosis of small, medium, and large bile ducts, which in turn results in cholestasis with progression to secondary biliary cirrhosis and hepatic failure (4). The diagnosis of PSC is established on the basis of clinical history and confirmatory histologic, biochemical, and imaging findings that often include results of endoscopic retrograde cholangiopancreatography (5,6).

Because no specific diagnostic test for PSC has yet been established, the diagnosis is often challenging and necessitates a multimodality approach (2). Magnetic resonance (MR) imaging is an effective tool for the noninvasive investigation of the liver and biliarysystem, and a number of studies have focused on MR cholangiopancreatography in patients with PSC (7–9). To our knowledge, only two studies described in the literature have involved the evaluation of findings in the liver parenchyma in patients with PSC at conventional MR imaging, and only one of these studies involved the use of contrast material–enhanced MR imaging (10,11).

In a study by Dodd et al (12) in which computed tomography (CT) was used, a lobular liver contour caused by large nodules was observed more frequently in patients with cirrhosis secondary to PSC than in patients with other types of cirrhosis. To our knowledge, however, the full spectrum of MR imaging appearances of PSC has not yet been established. The primary purpose of this study was to evaluate the MR imaging appearance of the liver in patients with PSC and to determine whether distinctive morphologic features are present. A secondary purpose was to examine the correlation between the clinical stage of the disease and the MR imaging findings.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population
We cross-referenced the database of the Department of Internal Medicine at the University of North Carolina at Chapel Hill—a referral center for the evaluation of potential candidates for liver transplantation—with the MR imaging database to identify all patients with confirmed PSC who had undergone MR imaging of the liver at our institution. Institutional review board approval was obtained. Informed consent was not required by the institutional review board for this retrospective study. A total of 63 patients who had undergone MR imaging of the liver between May 1994 and January 2001 were identified. Patients with malignant hepatic tumor (eg, hepatocellular carcinoma, cholangiocarcinoma, or liver metastases) at the time of MR imaging or in whom such a tumor was identified within a follow-up period of 6 months after the MR imaging study were excluded. Patients who were lost to follow-up after MR imaging were also excluded.

Our final study population included 52 patients (25 girls and women, 27 boys and men; mean age, 43 years; age range, 11–87 years). In all patients, the diagnosis of PSC was established if all of the following criteria were present: (a) typical clinical findings, (b) a positive direct cholangiography result, (c) findings at histologic examination of the liver compatible with those of PSC, and (d) exclusion of secondary forms of sclerosing cholangitis. Clinical findings that were considered typical of PSC included cholestatic liver disease of at least 6 months duration and elevation of serum bilirubin and serum alkaline phosphatase levels to at least 1.5 times the upper limit of normal. Findings at direct cholangiography that were considered typical included (a) luminal irregularities, (b) segments of bile ducts with short stenoses alternating with dilated or normal caliber segments ("beading"), and (c) loss of small ducts ("pruning").

Traditionally, the Child-Turcotte-Pugh classification (Child class) and Child-Turcotte-Pugh (CTP) score have been used to designate the severity of liver cirrhosis (13,14). More recently, a new system has been developed at the Mayo Clinic as a severity index for assessment of the 3-month mortality risk of patients with advanced liver disease: the Mayo end-stage liver disease (MELD) score (15,16). The MELD score is calculated on the basis of serum bilirubin and creatinine levels and the international normalized ratio for prothrombin time (16). Child class and CTP scores were available in 49 of 52 patients. Disease was staged as Child class A in 17 (35%) of 49 patients, as Child class B in 24 (49%) of 49 patients, and as Child class C in eight (16%) of 49 patients. The median CTP score was 8 (range, 5–11).

MELD scores were calculated in 43 of 52 patients. In nine patients, not all clinical data necessary for this calculation were available, so MELD scores could not be assigned. Patients were classified into one of three groups according to their MELD score: group 1 consisted of patients with MELD scores below 10, group 2 consisted of patients with MELD scores between 10 and 19; and group 3 consisted of patients with MELD scores between 20 and 29. According to the literature, these score groups reflect 3-month mortality rates of 1%–8%, 13%–26%, and 56%, respectively (16). In our study population, 34 (79%) of 43 patients were classified into group 1, eight (19%) were classified into group 2, and one (2%) was classified into group 3.

MR Imaging
All MR studies were performed at 1.5 T with an SP4000 or Vision MR imaging unit (Siemens Medical Systems, Iselin, NJ) and a phased-array body coil (42 patients) or the system body coil (10 patients). All MR imaging examinations were performed with the following protocol: transverse and coronal in-phase T1-weighted spoiled gradient-echo (SGE) sequences of the upper abdomen (repetition time msec/echo time msec, 120–175/4.0–4.5; flip angle, 80°–90°; 14–22 sections acquired in a 16–27-second breath hold), a transverse out-of-phase T1-weighted SGE sequence (echo time, 2.5 msec), and T2-weighted sequences that included a fat-suppressed turbo spin-echo sequence (2,200–5,700/90 [effective]; 18–28 sections acquired in the transverse plane during approximately 5–12 minutes) and/or a fat-suppressed half-Fourier rapid acquisition with relaxation enhancement (RARE) sequence in the transverse and coronal planes (8/90 [effective], 20–27 sections acquired in a 13–30-second breath hold, two to three acquisitions), which was performed in 45 patients. A T2-weighted short inversion time inversion-recovery sequence (repetition time msec/echo time msec/inversion time msec, 5,110/76/170) was also performed in the 45 patients who were imaged with the half-Fourier RARE sequence. Section thickness was 7–10 mm and matrix size was 128–192 x 256 (phase x frequency encoding) for all sequences.

MR cholangiopancreatography was not routinely performed, and, therefore, MR cholangiopancreatographic results were not evaluated in this study. After nonenhanced MR images were obtained, gadolinium chelate (gadopentetate dimeglumine, Magnevist; Berlex, Wayne, NJ, or gadodiamide, Omniscan; Nycomed, Princeton, NJ) was hand injected at a dose of 0.1 mmol per kilogram of body weight in a rapid bolus. Serial T1-weighted SGE MR images of the upper abdomen were acquired during the hepatic arterial dominant phase starting immediately after completion of the injection and during the portal venous phase 45–60 seconds after the injection. Ninety to 120 seconds after injection, a fat-suppressed SGE series was acquired.

Image Interpretation
All MR images were retrospectively reviewed by two experienced abdominal radiologists (T.R.B., R.C.S.) with additional experience (5 and 13 years, respectively) in MR imaging of the abdomen. These observers first evaluated all MR images independently; they then performed a consensus reading of results of all MR imaging studies. All evaluations were categorized and documented by using standardized data sheets.

At the independent reading, the two observers evaluated the MR images for (a) the presence of imaging findings suggestive of liver cirrhosis, (b) the imaging pattern of the liver parenchyma, (c) the presence and grade of intrahepatic biliary ductal dilatation, and (d) the presence of peripheral wedge-shaped areas of parenchymal atrophy. Imaging findings that were considered suggestive of liver cirrhosis included hypertrophy of the left lobe and/or the caudate lobe, atrophy of the right lobe, irregularity of the liver contour, a nodular or reticular pattern of the liver parenchyma, and signs of portal hypertension such as splenomegaly and the presence of portosystemic collateral vessels (17–21). Left lobe hypertrophy and caudate lobe hypertrophy were noted separately.

The imaging pattern of the liver parenchyma was characterized as follows: pattern A, no imaging findings of cirrhosis; pattern B, a large macronodular pattern of cirrhosis, with nodules 3 cm or larger; or pattern C, a diffuse pattern of cirrhosis, with nodules smaller than 3 cm or no nodules. Nodules were defined as rounded, masslike structures of liver parenchyma with definable borders. The distribution of large (>=3 cm) nodules was evaluated in terms of their lobar location (right, left, or caudate lobe) and whether they were located exclusively in the central portion of the liver (central two-thirds) or in the central and peripheral portions of the liver.

Intrahepatic ductal dilatation was considered present if intrahepatic ducts were of greater diameter than more central ducts or if they were greater than 3 mm in diameter (11). Intrahepatic biliary ductal dilatation was regarded as general when it involved the entire liver and as segmental when it involved only segmental or subsegmental areas. The severity of intrahepatic ductal dilatation was subjectively graded as mild, moderate, or severe, where mild dilatation was regarded as that with a maximum diameter of less than 4 mm, moderate as that with a diameter between 4 and 6 mm, and severe as that with a diameter larger than 6 mm.

At consensus reading, both observers assessed the imaging pattern of the liver, the number of large nodules (the maximum number of nodules counted per patient was five), the maximum size of the large nodules, the signal intensity behavior of the nodules on T1-weighted and T2-weighted MR images, and the gadolinium enhancement of the nodules on MR images obtained immediately after gadolinium chelate administration and 2 minutes after administration. The liver was further evaluated for segmental or subsegmental areas of parenchyma that showed abnormal signal intensity on nonenhanced images and/or abnormal enhancement on gadolinium-enhanced images.

High signal intensity in the periphery of the liver was not considered abnormal if a phased-array body coil was used and the area of high signal intensity appeared to be caused by the proximity of the liver to the coil. Signal intensity and contrast enhancement of large nodules and of abnormal areas of liver parenchyma were compared with those seen in surrounding liver parenchyma, and nodules and abnormal areas were rated as isointense, hyperintense, or hypointense and as isoenhancing, hyperenhancing, or hypoenhancing (10,11). The presence of fatty liver, established by means of observation of a decrease in signal intensity in the liver parenchyma on out-of-phase SGE MR images, was noted as an additional finding.

Statistical Analysis
Descriptive statistical analyses with simple contingency tables were performed to characterize the data and to determine the frequencies of the imaging findings. {kappa} scores were calculated to assess interobserver agreement. {kappa} values less than 0 were considered to represent no agreement; those between 0 and 0.40, poor agreement; those between 0.41 and 0.75, good agreement; and those between 0.76 and 1.00, excellent agreement. The McNemar test was used to test for the statistical significance of findings on nonenhanced and gadolinium-enhanced MR images as indicators of PSC as well as for correlations between imaging patterns of the liver and Child classes and MELD groups. Correlations among pattern of liver cirrhosis, number of large regenerative nodules, presence of segmental liver atrophy and/or fibrosis, and presence and grade of biliary ductal dilatation were evaluated with the {chi}2 test.

Multiple regression analyses were performed to test for correlations between clinical scores (CTP, MELD) and imaging findings (ie, liver pattern, nodule number, nodule diameter, presence of wedge-shaped areas of parenchymal atrophy, and grade of biliary ductal dilatation). Spearman correlation coefficients were calculated for ordinal data. The Mann-Whitney U test was additionally performed to examine differences in clinical scores between patients who had imaging findings of cirrhosis and those who did not. For all tests, P < .05 was considered to indicate a statistically significant difference. Statistical analyses were performed with SPSS 7.5 for Windows (SPSS, Chicago, Ill) and Microsoft Excel 2000 (Microsoft, Redmond, Wash).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
DISCUSSION
 REFERENCES
 
MR imaging findings suggestive of liver cirrhosis were observed in 44 (85%) of 52 patients (23 men and boys and 21 women and girls) by one reader and in 45 (87%) patients (24 men and boys and 21 women and girls) by the other at independent reading of MR images. The readings of the observers differed in only one patient, in whom MR imaging findings were rated as normal by one observer and as indicative of diffuse liver cirrhosis by the other. Histologic examination of the liver was not performed in this patient. Interobserver agreement on findings of liver cirrhosis at independent reading of images, as expressed by the {kappa} score, was 0.92.

At consensus reading, the two readers determined that seven (13%) of 52 patients had no MR imaging findings suggestive of cirrhosis (imaging pattern A) and that 45 (87%) patients had findings of cirrhosis. Hypertrophy of the left lobe was observed at independent reading in 19 (37%) of 52 patients by one reader and in 17 (33%) patients by the other ({kappa} = 0.83). Hypertrophy of the caudate lobe was observed at independent reading in 30 (58%) of 52 patients by one reader and in 33 (63%) patients by the other ({kappa} = 0.81). Fatty liver was observed at independent and consensus reading in four (8%) of 52 patients on the basis of a decrease in signal intensity on out-of-phase SGE MR images.

The large macronodular pattern of liver cirrhosis, with nodules 3 cm or larger (imaging pattern B), was observed at independent reading by both readers in 27 (52%) of 52 patients ({kappa} = 0.85) (Fig 1). At consensus reading, this pattern was observed in 28 of 52 patients (54%). The nodules were located only in the central part of the liver, not in the periphery, in 18 (65%) of these 28 patients according to one reader and in 19 (68%) of these patients according to the other at independent reading (Fig 1). Distribution of the nodules throughout the entire liver was observed at independent reading in nine (32%) of these patients by one reader and in eight (29%) of these patients by the other.



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  		Figure 1a. MR images in a 57-year-old man with a large macronodular pattern of liver cirrhosis. Three large nodules (straight arrows), each measuring more than 3 cm, are visible in the central area of the liver and have low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). The rightmost nodule has a small central area of low signal intensity on b that is consistent with an area of iron deposition. The nodules show decreased gadolinium enhancement on (c) a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration and (d) a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. This enhancement behavior is typical of regenerative nodules. The peripheral bile ducts (curved arrows) are dilated, show irregular strictures (beading), and appear to be centrally obstructed by the large nodules.

 


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  		Figure 1b. MR images in a 57-year-old man with a large macronodular pattern of liver cirrhosis. Three large nodules (straight arrows), each measuring more than 3 cm, are visible in the central area of the liver and have low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). The rightmost nodule has a small central area of low signal intensity on b that is consistent with an area of iron deposition. The nodules show decreased gadolinium enhancement on (c) a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration and (d) a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. This enhancement behavior is typical of regenerative nodules. The peripheral bile ducts (curved arrows) are dilated, show irregular strictures (beading), and appear to be centrally obstructed by the large nodules.

 


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  		Figure 1c. MR images in a 57-year-old man with a large macronodular pattern of liver cirrhosis. Three large nodules (straight arrows), each measuring more than 3 cm, are visible in the central area of the liver and have low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). The rightmost nodule has a small central area of low signal intensity on b that is consistent with an area of iron deposition. The nodules show decreased gadolinium enhancement on (c) a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration and (d) a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. This enhancement behavior is typical of regenerative nodules. The peripheral bile ducts (curved arrows) are dilated, show irregular strictures (beading), and appear to be centrally obstructed by the large nodules.

 


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  		Figure 1d. MR images in a 57-year-old man with a large macronodular pattern of liver cirrhosis. Three large nodules (straight arrows), each measuring more than 3 cm, are visible in the central area of the liver and have low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). The rightmost nodule has a small central area of low signal intensity on b that is consistent with an area of iron deposition. The nodules show decreased gadolinium enhancement on (c) a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration and (d) a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. This enhancement behavior is typical of regenerative nodules. The peripheral bile ducts (curved arrows) are dilated, show irregular strictures (beading), and appear to be centrally obstructed by the large nodules.

 
The number of large nodules per patient was between one and five in 16 (57%) of 28 patients and was more than five in 12 (43%) patients. The mean size of the nodules was 6.3 cm ± 2.1 (SD); the maximum size was 13 cm. The signal intensity of the nodules on nonenhanced MR images is described in Table 1. The gadolinium enhancement characteristics of the nodules are described in Table 2.


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  		TABLE 1. Signal Intensity of Large Liver Nodules in 28 Patients

 

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  		TABLE 2. Gadolinium Enhancement of Large Liver Nodules in 28 Patients

 
The diffuse pattern of liver cirrhosis (imaging pattern C) was observed in 17 (33%) of 52 patients by one reader and in 18 (35%) patients by the other at independent reading. The diffuse pattern was observed in 17 (33%) of 52 patients at consensus reading (Figs 2, 3). Interobserver agreement for overall evaluation of the liver parenchyma for all three patterns (A, B, and C) was excellent ({kappa} = 0.84).



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  		Figure 2a. MR images in a 60-year-old woman with a diffuse pattern of liver cirrhosis. The liver contour is minimally irregular, and the caudate lobe is slightly enlarged; these findings are demonstrated on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90). (Because of inhomogeneous fat suppression and use of a phased-array body coil, anterior subcutaneous fat shows relatively high signal intensity in this image). Peripheral wedge-shaped areas (arrows) without parenchymal atrophy show high signal intensity in this image and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) On a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate adminstration, these areas (arrows) are slightly hyperenhancing. (d) This slight hyperenhancement (arrow) persists mildly on a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. Segmental biliary ductal dilatation is visualized as low-signal-intensity tubular structures (arrowheads) in this image.

 


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  		Figure 2b. MR images in a 60-year-old woman with a diffuse pattern of liver cirrhosis. The liver contour is minimally irregular, and the caudate lobe is slightly enlarged; these findings are demonstrated on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90). (Because of inhomogeneous fat suppression and use of a phased-array body coil, anterior subcutaneous fat shows relatively high signal intensity in this image). Peripheral wedge-shaped areas (arrows) without parenchymal atrophy show high signal intensity in this image and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) On a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate adminstration, these areas (arrows) are slightly hyperenhancing. (d) This slight hyperenhancement (arrow) persists mildly on a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. Segmental biliary ductal dilatation is visualized as low-signal-intensity tubular structures (arrowheads) in this image.

 


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  		Figure 2c. MR images in a 60-year-old woman with a diffuse pattern of liver cirrhosis. The liver contour is minimally irregular, and the caudate lobe is slightly enlarged; these findings are demonstrated on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90). (Because of inhomogeneous fat suppression and use of a phased-array body coil, anterior subcutaneous fat shows relatively high signal intensity in this image). Peripheral wedge-shaped areas (arrows) without parenchymal atrophy show high signal intensity in this image and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) On a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate adminstration, these areas (arrows) are slightly hyperenhancing. (d) This slight hyperenhancement (arrow) persists mildly on a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. Segmental biliary ductal dilatation is visualized as low-signal-intensity tubular structures (arrowheads) in this image.

 


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  		Figure 2d. MR images in a 60-year-old woman with a diffuse pattern of liver cirrhosis. The liver contour is minimally irregular, and the caudate lobe is slightly enlarged; these findings are demonstrated on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90). (Because of inhomogeneous fat suppression and use of a phased-array body coil, anterior subcutaneous fat shows relatively high signal intensity in this image). Peripheral wedge-shaped areas (arrows) without parenchymal atrophy show high signal intensity in this image and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) On a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate adminstration, these areas (arrows) are slightly hyperenhancing. (d) This slight hyperenhancement (arrow) persists mildly on a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration. Segmental biliary ductal dilatation is visualized as low-signal-intensity tubular structures (arrowheads) in this image.

 


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  		Figure 3a. MR images in a 40-year-old man with a diffuse nodular pattern of liver cirrhosis. Multiple regenerative nodules smaller than 3 cm are seen in the entire liver, resulting in a nodular liver contour. Fibrous tissue between the nodules forms a reticular pattern that shows high signal intensity on (a) a transverse short inversion time inversion-recovery MR image (5,110/76/170) and low signal intensity on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) Some strands of fibrous tissue (arrows) show enhancement on a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration. (d) On a transverse fat-suppressed SGE MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, progressive enhancement of fibrous tissue, revealing a high-signal-intensity reticular patchwork, is seen. This patient’s spleen (S) is enlarged, and perihepatic ascites (A) appears with high signal intensity in a (a T2-weighted MR image) and low signal intensity in b-d (T1-weighted MR images).

 


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  		Figure 3b. MR images in a 40-year-old man with a diffuse nodular pattern of liver cirrhosis. Multiple regenerative nodules smaller than 3 cm are seen in the entire liver, resulting in a nodular liver contour. Fibrous tissue between the nodules forms a reticular pattern that shows high signal intensity on (a) a transverse short inversion time inversion-recovery MR image (5,110/76/170) and low signal intensity on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) Some strands of fibrous tissue (arrows) show enhancement on a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration. (d) On a transverse fat-suppressed SGE MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, progressive enhancement of fibrous tissue, revealing a high-signal-intensity reticular patchwork, is seen. This patient’s spleen (S) is enlarged, and perihepatic ascites (A) appears with high signal intensity in a (a T2-weighted MR image) and low signal intensity in b-d (T1-weighted MR images).

 


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  		Figure 3c. MR images in a 40-year-old man with a diffuse nodular pattern of liver cirrhosis. Multiple regenerative nodules smaller than 3 cm are seen in the entire liver, resulting in a nodular liver contour. Fibrous tissue between the nodules forms a reticular pattern that shows high signal intensity on (a) a transverse short inversion time inversion-recovery MR image (5,110/76/170) and low signal intensity on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) Some strands of fibrous tissue (arrows) show enhancement on a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration. (d) On a transverse fat-suppressed SGE MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, progressive enhancement of fibrous tissue, revealing a high-signal-intensity reticular patchwork, is seen. This patient’s spleen (S) is enlarged, and perihepatic ascites (A) appears with high signal intensity in a (a T2-weighted MR image) and low signal intensity in b-d (T1-weighted MR images).

 


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  		Figure 3d. MR images in a 40-year-old man with a diffuse nodular pattern of liver cirrhosis. Multiple regenerative nodules smaller than 3 cm are seen in the entire liver, resulting in a nodular liver contour. Fibrous tissue between the nodules forms a reticular pattern that shows high signal intensity on (a) a transverse short inversion time inversion-recovery MR image (5,110/76/170) and low signal intensity on (b) a transverse T1-weighted SGE MR image (140/4.1). (c) Some strands of fibrous tissue (arrows) show enhancement on a transverse SGE MR image (140/4.1) obtained immediately after gadolinium chelate administration. (d) On a transverse fat-suppressed SGE MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, progressive enhancement of fibrous tissue, revealing a high-signal-intensity reticular patchwork, is seen. This patient’s spleen (S) is enlarged, and perihepatic ascites (A) appears with high signal intensity in a (a T2-weighted MR image) and low signal intensity in b-d (T1-weighted MR images).

 
Intrahepatic biliary ductal dilatation was observed at independent reading in 42 (81%) of the 52 patients by one reader and in 44 (85%) patients by the other (Figs 1–4). At independent reading, the distribution of the biliary ductal dilatation was rated as general in 17 (33%) of 52 patients by one reader and in 18 (35%) patients by the other. The distribution was rated as segmental in 25 (48%) of the 52 patients by one reader and in 26 (50%) patients by the other. At consensus reading, intrahepatic biliary ductal dilatation was observed in 44 (85%) patients and was general in 18 (35%) and segmental in 26 (50%). The frequencies of general and segmental ductal dilatation were not significantly different. The {kappa} score for interobserver agreement for findings of intrahepatic biliary ductal dilatation was 0.84.



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  		Figure 4a. MR images in a 35-year-old woman with a peripheral wedge-shaped area of parenchymal atrophy. Large nodules (straight arrows) in the central area of the liver show low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). A peripheral wedge-shaped area of parenchymal atrophy (curved arrows) in the left lobe of the liver shows high signal intensity in a, low signal intensity in b, and some heterogeneity. (c) Hyperenhancement (arrows) is revealed on a transverse MR image (140/4.1) obtained immediately after gadolinium chelate administration. A small central area of fibrosis is spared. (d) On a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, the central large nodules are minimally hypoenhancing and the rest of the liver is isoenhancing. Dilated bile ducts (arrowheads) in the periphery of the liver are best visualized on this image.

 


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  		Figure 4b. MR images in a 35-year-old woman with a peripheral wedge-shaped area of parenchymal atrophy. Large nodules (straight arrows) in the central area of the liver show low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). A peripheral wedge-shaped area of parenchymal atrophy (curved arrows) in the left lobe of the liver shows high signal intensity in a, low signal intensity in b, and some heterogeneity. (c) Hyperenhancement (arrows) is revealed on a transverse MR image (140/4.1) obtained immediately after gadolinium chelate administration. A small central area of fibrosis is spared. (d) On a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, the central large nodules are minimally hypoenhancing and the rest of the liver is isoenhancing. Dilated bile ducts (arrowheads) in the periphery of the liver are best visualized on this image.

 


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  		Figure 4c. MR images in a 35-year-old woman with a peripheral wedge-shaped area of parenchymal atrophy. Large nodules (straight arrows) in the central area of the liver show low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). A peripheral wedge-shaped area of parenchymal atrophy (curved arrows) in the left lobe of the liver shows high signal intensity in a, low signal intensity in b, and some heterogeneity. (c) Hyperenhancement (arrows) is revealed on a transverse MR image (140/4.1) obtained immediately after gadolinium chelate administration. A small central area of fibrosis is spared. (d) On a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, the central large nodules are minimally hypoenhancing and the rest of the liver is isoenhancing. Dilated bile ducts (arrowheads) in the periphery of the liver are best visualized on this image.

 


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  		Figure 4d. MR images in a 35-year-old woman with a peripheral wedge-shaped area of parenchymal atrophy. Large nodules (straight arrows) in the central area of the liver show low signal intensity on (a) a transverse fat-suppressed T2-weighted half-Fourier RARE MR image ({infty}/90) and isointense signal on (b) a transverse T1-weighted SGE MR image (140/4.1). A peripheral wedge-shaped area of parenchymal atrophy (curved arrows) in the left lobe of the liver shows high signal intensity in a, low signal intensity in b, and some heterogeneity. (c) Hyperenhancement (arrows) is revealed on a transverse MR image (140/4.1) obtained immediately after gadolinium chelate administration. A small central area of fibrosis is spared. (d) On a transverse fat-suppressed MR image (147/4.1) obtained 2 minutes after gadolinium chelate administration, the central large nodules are minimally hypoenhancing and the rest of the liver is isoenhancing. Dilated bile ducts (arrowheads) in the periphery of the liver are best visualized on this image.

 
At independent reading, ductal dilatation was rated as mild in 11 (21%) of 52 patients by one reader and in 14 (27%) patients by the other, as moderate in 18 (35%) patients by one reader and in 17 (33%) patients by the other, and as severe in 13 (25%) patients by both readers ({kappa} = 0.74). At independent reading, each observer classified 15 (29%) of 52 patients as having central intrahepatic biliary obstruction that appeared to be caused by the presence of large central nodules (Fig 1) ({kappa} = 1.00).

Peripheral wedge-shaped areas of parenchymal atrophy were observed at independent reading in 25 (48%) of 52 patients by one reader and in 23 (44%) patients by the other ({kappa} = 0.76) (this finding was observed at consensus reading in 24 [46%] patients). These 25 and 23 patients represented 56% and 51%, respectively, of the 45 patients who had additional imaging findings suggestive of cirrhosis (Fig 4). The signal intensity characteristics of these wedge-shaped areas on nonenhanced T1-weighted and T2-weighted MR images are described in Table 3. The gadolinium enhancement patterns of these wedge-shaped areas on MR images obtained after gadolinium chelate administration are described in Table 4.


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  		TABLE 3. Signal Intensity of Peripheral Wedge-shaped Areas of Parenchymal Atrophy

 

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  		TABLE 4. Gadolinium Enhancement of Peripheral Wedge-shaped Areas of Parenchymal Atrophy

 
In 18 (35%) of 52 patients, areas of abnormal signal intensity and/or gadolinium enhancement that were not associated with wedge-shaped atrophy were observed at consensus reading (Fig 2). The signal intensity characteristics of these areas on nonenhanced T1-weighted and T2-weighted MR images and their enhancement patterns on gadolinium-enhanced MR images are described in Tables 5 and 6, respectively.


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  		TABLE 5. Signal Intensity of Abnormal Areas of Liver Parenchyma without Atrophy in 18 Patients

 

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  		TABLE 6. Gadolinium Enhancement of Abnormal Areas of Liver Parenchyma without Atrophy in 18 Patients

 
The pattern of liver cirrhosis had statistically significant correlations with the presence of wedge-shaped areas of parenchymal atrophy and/or fibrosis (P < .01), the number of large regenerative nodules (P < .01), and the degree of biliary ductal dilatation (P = .011). The number of large regenerative nodules, the presence of parenchymal atrophy, and the presence of parenchymal fibrosis also had statistically significant correlations with each other (P < .01 in all cases). The presence of wedge-shaped parenchymal atrophy and the presence of parenchymal fibrosis also correlated with each other (P < .01). The combination of a macronodular pattern of liver cirrhosis and the presence of wedge-shaped areas of parenchymal atrophy was observed in 21 (40%) of 52 patients. The finding of large nodules appearing to obstruct central bile ducts was observed in 15 (29%) of 52 patients. The combination of a macronodular pattern, peripheral wedge-shaped atrophy, and biliary obstruction was observed in 12 (23%) of 52 patients.

The results of cross-tabulation of liver parenchyma patterns versus Child class and MELD group are listed in Tables 7 and 8, respectively. The clinical scores (CTP, MELD) and imaging findings did not have a linear relationship (P > .05, multiple regression analysis; the 95% CIs of the regression coefficients included zero in all cases). Spearman correlation coefficients for number and size of large nodules, grade of biliary ductal dilatation, and Child class and MELD group were low and between -0.33 and 0.33 for both observers. No statistically significant difference was revealed between the clinical scores of patients who had imaging findings suggestive of cirrhosis and those who did not (P = .25–.75, Mann-Whitney U test).


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  		TABLE 7. MR Imaging Findings in the Liver versus Child Class in 49 Patients

 

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  		TABLE 8. MR Imaging Findings in the Liver versus MELD Score in 43 Patients

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
REFERENCES
 
Eighty-seven percent of all patients in our study population had classic imaging findings of liver cirrhosis (17–21). The MR imaging appearance of the liver parenchyma, however, was not uniform but showed one of three patterns: pattern A, no findings of liver cirrhosis (seen in 13% of patients); pattern B, a large macronodular pattern (seen in 54% of patients); and pattern C, a diffuse pattern of liver cirrhosis (seen in 33% of patients). Hypertrophy of the caudate lobe has been described to occur more frequently in cirrhosis caused by PSC than in other forms of cirrhosis and was observed in our study in a very high percentage of patients (in 58% of patients according to one reader; in 63% according to the other) (11).

Although the imaging appearance and histologic features of liver cirrhosis are highly variable and can differ from patient to patient, cirrhotic livers by definition contain regenerative nodules; it is according to the size of these nodules that such livers are classified (21–23). Regenerative nodules are defined as collections of regenerating hepatocytes surrounded by fibrous septa and are visualized at MR imaging in approximately 50% of patients with cirrhosis (24,25). Very large regenerative nodules measuring several centimeters in diameter are rare in the more common types of cirrhosis, including viral cirrhosis and alcohol-related cirrhosis (20,26).

In our study, more than half (54%) of the patients were found to have nodules 3 cm or larger. In contrast, Revelon et al (10) suggested that an absence of nodules at MR imaging may be typical for PSC. The results of our study, however, indicate the opposite and are in accord with those of Dodd et al (12), who found nodules larger than 3 cm in 73% of patients with PSC at CT. The lower prevalence of this finding in our study may reflect the wider range of disease stages in our patient population compared with that in the population in the study by Dodd et al (12). In our study, the combined findings at nonenhanced and gadolinium-enhanced MR imaging of these large nodules were typical of regenerative nodules (19,21,22,24,25,27–30). Two patients had one nodule each that was larger than 3 cm and showed atypically intense enhancement on MR images obtained immediately after gadolinium chelate administration and isoenhancement on MR images obtained 2 minutes after gadolinium chelate administration. These nodules were probably severely dysplastic because they remained unchanged over the entire observation period (which consisted of 9 months for one patient and 12 months for the other) (27,31–33).

In the present study, large nodules were confined to the central portion of the liver in more than two-thirds of cases (67% according to one reader, 70% according to the other). To our knowledge, this propensity of large regenerative nodules to occur in the central portion of the liver has not been described before. We can only speculate as to the explanation for this. PSC leads to obliterative fibrosis of intra- and extrahepatic bile ducts and to bile duct loss, which in turn leads to cholestatic damage in the liver parenchyma (34). It has been shown that involvement of small intrahepatic bile ducts (so-called small-duct PSC) may be the only and/or the earliest manifestation of PSC and that classic fibro-obliterative lesions in medium-sized and large ducts (so-called large-duct PSC) occur at a later stage of the disease (34,35). Hence, cholestasis and parenchymal liver damage may be expected to occur earlier in peripheral than in central regions of the liver parenchyma. Hepatic parenchymal hypertrophy occurs in response to the diminished hepatic function that accompanies parenchymal damage and probably occurs in areas with no or less severe damage (36,37). Therefore, regenerative nodules would have a tendency to form in the central portion of the liver, where the parenchyma is less damaged, rather than in the peripheral portion. The variability in the pattern of bile duct lesions in PSC, however, is high (4,34). In the setting of a more uniform distribution of bile duct lesions throughout the entire liver, a diffuse pattern of liver cirrhosis may develop, as was observed in 33% of the patients in this study.

Biliary ductal dilatation is a typical finding in PSC and was observed in more than 80% of patients in our study (10,11). We did not evaluate biliary ductal beading and pruning because these can be better visualized with MR cholangiopancreatography, which was not routinely performed in our study. A segmental distribution of dilated bile ducts was observed slightly more often than was general involvement of the entire intrahepatic biliary tree. Notably, peripheral biliary dilatation that appeared to be caused by compression of central ducts by large regenerative nodules was observed in 29% of patients. Because this imaging finding was observed in a relatively high percentage of patients in our study, we suggest that this finding may be typical of PSC.

Peripheral wedge-shaped areas of parenchymal atrophy were observed in more than half of those patients who had imaging findings suggestive of cirrhosis. These areas demonstrated signal intensity characteristics on T1-weighted and T2-weighted MR images and enhancement patterns on gadolinium-enhanced MR images that were consistent with those of areas of confluent fibrosis, a recognized feature of PSC (38,39).

Focal areas of liver parenchyma that showed abnormal signal intensity and/or gadolinium enhancement characteristics but no atrophy were observed in 35% of patients. These areas did not fulfill the criteria for areas of confluent fibrosis because they did not show atrophy and frequently appeared hyperenhancing on MR images obtained immediately after gadolinium chelate administration; such findings are atypical in fibrous tissue. The MR imaging findings in these focal areas, however, were typical of parenchymal edema and hyperperfusion secondary to focal parenchymal inflammation. Similar areas have been described in other types of inflammatory bile duct disease (ie, infectious cholangitis and recurrent pyogenic cholangitis [40,41]), and these findings are in accord with findings observed in PSC in a study by Ito et al (11).

In the present study, statistical analysis revealed correlations among the pattern of liver cirrhosis, number of large regenerative nodules, presence of wedge-shaped liver atrophy, presence of wedge-shaped fibrosis, and presence of biliary ductal dilatation. This is consistent with the fact that all of these findings are imaging features of liver cirrhosis and can frequently be observed together in patients with PSC.

PSC progresses to end-stage liver cirrhosis with a highly variable clinical course, and models for predicting prognosis are of limited use (4,42–44). However, most such models involve a determination of histologic stage based on the results of needle biopsy. Use of needle biopsy results is problematic because it may lead to underestimation of disease severity and unreliable staging in an individual patient owing to the heterogeneous involvement of the liver by the disease (45,46). Many patients with PSC require liver transplantation. Currently, the CTP classification is used for determination of medical urgency (47,48). The recently introduced MELD score is a reliable predictor of the short-term prognosis of patients with end-stage liver disease of diverse etiologies and severity and has been suggested as a replacement for the CTP score for liver transplantation purposes (15,16).

We used both the MELD score and the traditional CTP system to assess the clinical stage of PSC. The results of our study revealed no correlation between MR imaging findings and the clinical severity of disease. We were, however, able to demonstrate that a spectrum of appearances is observed at MR imaging in patients with different clinical stages of PSC. It is important for radiologists to know the variety of MR imaging appearances of PSC and to understand that these appearances do not correlate with the clinical severity of disease so that they can avoid unwarranted assumptions about the severity of the disease.

Observational studies have inherent limitations. We did not evaluate the sensitivity and specificity of the observed MR imaging findings for establishing the diagnosis of PSC. This should be evaluated in a randomized blinded trial. The consistent and high interobserver agreement in our study, however, shows that these findings can be recognized with a high degree of accuracy. Moreover, the purpose of our study was to evaluate the full spectrum of MR imaging appearances of PSC; this spectrum, to our knowledge, has not yet been described in the literature (10,11).

Another limitation of our study was that no histopathologic correlation for the imaging findings was available. This correlation, however, can usually be obtained only in patients who undergo liver transplantation, and inclusion of patients selected for liver transplantation alone would have biased the study population toward patients with end-stage liver disease. On the other hand, the MR imaging findings observed in our study correlated well with established pathologic entities, as explained above.

In summary, the spectrum of MR imaging appearances of PSC is diverse and comprises distinct patterns. Large regenerative nodules are a frequent finding in patients with PSC, and their presence may help to establish the diagnosis. A high percentage of patients in this study had a combination of a macronodular pattern of liver cirrhosis and parenchymal atrophy, or a combination of a macronodular pattern, parenchymal atrophy, and obstruction of bile ducts by large central nodules. The sensitivities and specificities of these patterns for the diagnosis of PSC should be evaluated in future studies. Serial gadolinium-enhanced MR images are essential in demonstrating the full spectrum of imaging findings of PSC and should be acquired for a full assessment of this disease. MR imaging findings, however, do not appear to correlate with the clinical stage of the disease.


   ACKNOWLEDGMENTS
 
We thank Professor Peter Bauer, PhD, Chairman of the Department of Medical Statistics at the University of Vienna, for his expertise and help with the statistical analyses.


   FOOTNOTES
 
Abbreviations: CTP = Child-Turcotte-Pugh, MELD = Mayo end-stage liver disease, PSC = primary sclerosing cholangitis, RARE = rapid acquisition with relaxation enhancement, SGE = spoiled gradient echo

Author contributions: Guarantors of integrity of entire study, T.R.B., R.C.S.; study concepts, T.R.B., R.C.S.; study design, T.R.B.; literature research, T.R.B.; clinical studies, K.L.B.; data acquisition, T.R.B., K.L.B., R.C.S.; data analysis/interpretation, T.R.B., R.C.S.; statistical analysis, T.R.B.; manuscript preparation, T.R.B.; manuscript definition of intellectual content, T.R.B., R.C.S.; manuscript editing, T.R.B.; manuscript revision/review, K.L.B., R.C.S.; manuscript final version approval, T.R.B., R.C.S.


   REFERENCES
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 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
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