AJR 2004; 182:1497-1504
© American Roentgen Ray Society
Diagnosing Biliary Complications of Orthotopic Liver Transplantation with Mangafodipir Trisodium–Enhanced MR Cholangiography: Comparison with Conventional MR Cholangiography
Mellena D. Bridges1,
Gerald R. May1 and
Denise M. Harnois2
1 Department of Radiology, Mayo Clinic Jacksonville, 4500 San Pablo Rd.,
Jacksonville, FL 32224.
2 Department of Transplantation, Division of Transplant Medicine, Mayo Clinic
Jacksonville, Joe Adams 1100 Transplant Center, Jacksonville, FL 32216.
Received October 14, 2003;
accepted after revision November 13, 2003.
Address correspondence to M. D. Bridges
(Bridges.Mellena{at}mayo.edu).
Abstract
OBJECTIVE. This study was designed to determine whether the addition
of mangafodipir trisodium–enhanced MRI could improve the image quality,
visualization of ductal structures, and diagnostic confidence provided by
conventional T2-based MR cholangiography (MRC) in patients with suspected
biliary complications after orthotopic liver transplantation.
SUBJECTS AND METHODS. Our study group consisted of 25 consecutive
patients who were referred for MR evaluation of clinically suspected biliary
complications after orthotopic liver transplantation. Conventional MRC in the
axial and coronal planes was performed in each patient, followed by
fat-suppressed volumetric gradient-echo imaging in the same planes both before
and after the IV administration of mangafodipir trisodium. Imaging was
performed in all patients until the contrast agent was seen in the bowel.
Images were then graded for quality, visualization of bile ducts and
anastomoses, presence of significant stricture or leak, and level of
diagnostic confidence.
RESULTS. Mangafodipir trisodium–enhanced MRC tended to
outperform conventional MRC in overall image quality and extrahepatic duct
visualization; it was also more effective in delineating biliary anastomoses,
and the difference was statistically significant (p < 0.001). All
25 enhanced examinations were considered diagnostic. Diagnostic confidence was
scored as poor or lacking in 14 of the conventional MRC examinations for
biliary stenosis and in 12 examinations for biliary leak.
CONCLUSION. Enhancement with mangafodipir trisodium improves the
performance of MRC for the detection and exclusion of biliary abnormalities
after orthotopic liver transplantation. Future investigations should compare
the performance of mangafodipir trisodium–enhanced MRC with the
performance of more invasive techniques.
Introduction
Orthotopic liver transplantation has become the treatment of choice for
end-stage liver disease, with more than 5,000 transplantations performed in
the United States in 2002 [1].
Since 1988, more than 57,000 orthotopic liver transplantation procedures have
been performed in the United States alone
[1].
As the frequency of liver transplantation procedures rises, so do the
associated complications and, consequently, the need for accurate, rapid
diagnosis [2,
3]. Biliary complications,
especially anastomotic stricture and leak, are an important and common cause
of morbidity and graft failure. Frequencies vary among centers, with recent
larger cohorts ranging from 11% to 30% and reported ranges overall of
9–50%
[4–8].
Because biliary complications do not present specific clinical or
laboratory findings, the posttransplantation patient is often referred for
diagnostic imaging. Analysis of the postoperative biliary system has
traditionally been the purview of endoscopic retrograde cholangiography (ERC)
or percutaneous transhepatic cholangiography
[9–14].
These methods have the advantage of being both diagnostic and potentially
therapeutic techniques. Unfortunately, they are also invasive, expensive, and
subject to their own inherent complications. Furthermore, ERC is of little
value in the patient with a biliary–enteric anastomosis.
MR cholangiography (MRC), a technique dependent on the high T2 signal
intensity of bile, is recognized as a noninvasive alternative to these methods
for evaluation of the biliary system
[15–17].
In our experience, however, conventional MRC has been less than satisfactory.
For example, although the biliary anastomosis is easily seen, most
reconstructions show some degree of narrowing. Furthermore,
donor–recipient mismatches in duct size occur commonly, which makes
analysis of anastomotic narrowing more difficult. At issue in both of these
situations is not only morphologic narrowing but also functional significance,
especially because significant donor duct dilatation is not seen often enough
in our population to be a useful predictive sign. As a technique that depends
on the high signal intensity of bile to depict ducts, conventional MRC can
also be limited by conflicting signals from ascites, perihepatic fluid
collections, and soft-tissue edema, all of which are common in the
postoperative period. Similarly, conventional MRC cannot easily distinguish
between a biloma and a simple perihepatic collection.
Mangafodipir trisodium (Teslascan, Amersham) is an IV-administered,
T1-shortening contrast agent developed for hepatic imaging. Its safety has
been shown in multicenter trials
[18]. The agent is primarily
excreted in the bile and has been applied to T1-weighted biliary imaging, with
investigators addressing its potential in several recent studies
[19–22].
In combination, these investigations suggested that mangafodipir
trisodium–enhanced MRC could provide the high-quality anatomic imaging
that is necessary for the evaluation of small-caliber ductal structures, even
in the setting of intraabdominal fluid and soft-tissue edema. Detection of
strictures and intraductal debris, and direct visualization of anastomotic
leaks, might be possible. Furthermore, if a correlation between delay in
contrast excretion into the bile ducts and the physiologic significance of an
anastomotic stricture could be shown, and if exclusion of excretion delays
caused by synthetic dysfunction could be accomplished, then the technique
could add information previously unavailable with MRI.
The purpose of this study was to examine the usefulness of incorporating
mangafodipir trisodium–enhanced imaging into our MRC protocol in cases
of suspected posttransplantation biliary complications. Specifically, our
intent was to determine whether this approach could improve ductal
visualization or diagnostic confidence over that provided by conventional MRC
alone, to evaluate the effect of ascites or edema and the type of anastomotic
reconstruction on diagnostic confidence for the two techniques, and to
determine whether delay in contrast excretion could be correlated with
functional significance of ductal narrowing.
Subjects and Methods
The study group consisted of 25 sequential patients who were referred for
MRI evaluation of biliary complications after orthotopic liver
transplantation. Fourteen of these patients had a biliary–enteric
anastomosis (hepaticojejunostomy or choledochojejunostomy), and the remainder,
a primary duct-to-duct reconstruction (choledochocholedochostomy). The average
time elapsed since the transplantation procedure was 5.1 months. When the two
patients whose transplantations were more than 1 year previous are excluded
from the calculations, this interval is only 2.3 months. The study period
extended from September 2002 through January 2003. Institutional review board
approval was sought and granted for this prospective study. Because the
protocol we describe in the following text was already in clinical use for
evaluation of the posttransplantation biliary system, the institutional review
board waived the requirement for written patient consent.
MRI was performed on a 1.5-T scanner (Symphony or Sonata, Siemens Medical
Solutions) using a phased array torso coil. Imaging sequences included axial
and coronal HASTE sequences through the entire abdomen for ductal localization
as well as for a general survey of the abdominal structures and potential
fluid collections. MRC sequences were then obtained as follows: axial and
coronal multislice HASTE imaging through the central biliary tree (TR/TE,
1,000/89; refocusing angle, 180°; slices, 20; slice thickness, 3 [coronal]
or 4 [axial] mm with a 10% gap; matrix, 168–192 x 256; field of
view, 220–340 mm [depending on body habitus]). We also obtained six
projectional HASTE images in the coronal and coronal oblique planes (TR/TE,
2,800/1,100; refocusing angle, 150; single slice per breath-hold; slice
thickness, 40 mm; matrix, 256 x 256; field of view, 240–340 mm).
Images were obtained either during suspended respiration (20- to 25-sec
breath-hold) or using a free-breathing navigator echo-gated technique,
depending on patient ability.
Axial and coronal volumetric spoiled gradient-echo imaging with chemical
fat-suppression pulses was then performed (TR range/TE range,
3.2–3.6/1.3–1.5; flip angle, 12°; partitions, 64; slice
thickness, 1.5 mm; matrix, 156 x 256; field of view, 260–340 mm;
phase oversampling on the coronal images). Each of these acquisitions was
obtained in a breath-hold (20–25 sec). Except that the asymmetric echo
parameter was enabled to decrease TR and slice thickness was diminished, the
parameters were identical to our protocol for gadolinium-enhanced imaging of
the liver.
Total scanning time averaged 45 min in uncomplicated cases, which is the
time allotted in our practice for a single MRI examination. All 25
examinations were technically adequate. No adverse events clearly attributable
to the administration of mangafodipir trisodium were encountered.
After a standardized IV injection of 10 mL of mangafodipir trisodium
administered slowly over several minutes and followed by a 20-mL saline flush,
the axial and coronal 3D imaging sequences were repeated at 5 and 15 min, with
the delay interval calculated from the completion of injection. After 15 min
of scanning, the radiologist was consulted. If the study was considered
adequate for evaluating ductal and anastomotic anatomy, excretion into bowel,
and bile leak, imaging was ended and maximum-intensity-projection (MIP)
reconstructions of the best coronal data set were created. In cases in which
excretion had not yet been visualized, or when anastomotic leak remained in
question, delayed imaging was performed up to 1 hr. If visualization was still
not documented, further scanning was done the next morning.
Each MRI examination was stored in digital archives as two sets of images,
with the conventional MRC sequences constituting one set and the volumetric
mangafodipir trisodium–enhanced sequences the second set. The latter
included source images as well as MIP reconstructions. All image review was
performed on a diagnostic interpretation workstation (MagicView 1000, Siemens
Medical Solutions), and each set of images was evaluated separately during a
different consensus interpretation session.
Two radiologists who were experienced in the interpretation of abdominal MR
images, interpreting in consensus and unaware of the specifics of the
patient's clinical status, subjectively evaluated image quality and
visualization of anastomoses, intrahepatic bile ducts, and extrahepatic bile
ducts using a 5-point scale (with 1 being poor and 5, excellent). The
radiologists also determined the presence or absence of significant
anastomotic stenoses or leaks (yes, no, indeterminate) and graded their
confidence (none, poor, good) regarding each diagnostic determination.
Decisions regarding stenotic significance were subjectively based, drawing
from experience with ERC and percutaneous cholangiography. In our endoscopy
practice, the biliary reconstruction is considered within normal limits if an
8.5-mm occlusion balloon can be passed easily across the anastomosis. On the
other hand, dilatation is routinely attempted if the anastomosis will not
permit passage of a balloon larger than 4 mm. Intermediate results are
considered indeterminate. Diameter measurements were not attempted on the MR
images because the ERC standard refers more to ease of passage than to exact
measurements and because no accepted measurement standards exist for
percutaneous cholangiography.
For the enhanced image sets, the reviewers also examined the time delay
between completion of mangafodipir trisodium administration and its appearance
in the bowel; failure of copious excretion by 15 min was considered definitely
abnormal and suggestive of significant stenosis. Type of anastomotic
reconstruction, presence of ascites or focal fluid near the anastomosis, and
presence of soft-tissue edema at the liver hilum were also recorded. The data
gathered during these interpretations was then entered into a spreadsheet.
To allow correlation of laboratory measures of hepatic dysfunction with the
imaging results, concurrent liver function test values were obtained from the
medical records for all patients and were added to the spreadsheet data.
To compare the two techniques, we extracted the patients for whom quality
or confidence scores differed and examined the proportion of those for whom
the mangafodipir trisodium–enhanced images had the better score. An
exact binomial test of the null hypothesis was performed on the basis of the
observed proportion. A p value of less than 0.05 was considered
significant. Finally, to investigate whether diagnostic confidence was
associated with the presence or absence of a specific feature, we performed a
Fisher's exact test.
Six months after completion of data collection, examination of the medical
records of all 25 patients was undertaken, and note was made of interval
imaging studies (including cross-sectional and cholangiographic examinations),
biliary interventions, and repeated transplantation procedures. Eight patients
had undergone subsequent ERC, four had percutaneous transhepatic
cholangiography, six had abdominal CT, and three had repeated MRC. Six
patients have had no further abdominal imaging other than sonography. Of
these, four have had at least one liver biopsy, and the other two have been
followed up clinically. Also noted for each patient were relevant laboratory
values and subsequent clinical status.
Results
Table 1 summarizes the data
for image quality and anatomic visualization. In the original data, overall
diagnostic image quality was rated higher for the mangafodipir
trisodium–enhanced image set in 12 patients, equivalent in eight
patients, and inferior in five when compared with conventional MRC. These
results did not achieve statistical significance (p = 0.14). In
contrast, when scored for anastomotic visualization, the contrast-enhanced
technique performed significantly better (Fig.
1A,
1B,
1C,
1D): of the 17 cases in which
the two techniques received different scores, the mangafodipir
trisodium–enhanced images had the higher scores in all but one
(p < 0.001). Visualization of the extrahepatic duct also tended to
be better (p = 0.02), although to a lesser degree. In contrast, for
visualization of the intrahepatic ducts, enhanced MRC showed no benefit; in
fact, in 10 of the 14 patients for whom scores differed for this measure, the
conventional MRC sequences performed better.
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Fig. 1A. —60-year-old man 2 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis and hepatocellular
carcinoma who presented with serum alkaline phosphatase level of 1,025 U/L and
bilirubin of 3.9 mg/dL. MRI diagnosis was minimal narrowing of
choledochocholedochal anastomosis with no stricture. Clinical improvement
occurred after medication was adjusted. Coronal T2-weighted HASTE image
(TR/TE, 2,800/1,100; slice thickness, 40 mm) depicts recipient and donor
ducts, as well as pancreatic duct, but suggests a long anastomotic stricture
(arrow). Note neighboring fluid collections and edema.
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Fig. 1B. —60-year-old man 2 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis and hepatocellular
carcinoma who presented with serum alkaline phosphatase level of 1,025 U/L and
bilirubin of 3.9 mg/dL. MRI diagnosis was minimal narrowing of
choledochocholedochal anastomosis with no stricture. Clinical improvement
occurred after medication was adjusted. Thin-slice coronal HASTE image
(1,000/89; slice thickness, 3 mm) through liver hilum partially shows
low-signal-intensity common duct walls (arrows), but adjacent fluid
compromises conspicuity. Arrowhead indicates signal void of portal vein.
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Fig. 1C. —60-year-old man 2 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis and hepatocellular
carcinoma who presented with serum alkaline phosphatase level of 1,025 U/L and
bilirubin of 3.9 mg/dL. MRI diagnosis was minimal narrowing of
choledochocholedochal anastomosis with no stricture. Clinical improvement
occurred after medication was adjusted. Axial HASTE image (1,000/89; slice
thickness, 4 mm) shows common duct (arrow) in cross section
surrounded by edematous hilar tissue.
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Fig. 1D. —60-year-old man 2 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis and hepatocellular
carcinoma who presented with serum alkaline phosphatase level of 1,025 U/L and
bilirubin of 3.9 mg/dL. MRI diagnosis was minimal narrowing of
choledochocholedochal anastomosis with no stricture. Clinical improvement
occurred after medication was adjusted. Maximum-intensity-projection image
from coronal mangafodipir-enhanced T1-weighted MR cholangiogram shows
minimally narrowed and irregular anastomosis (long arrow) and
duodenal excretion of contrast-enhanced bile (short arrows) within 5
min.
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The data for diagnoses of anastomotic stenoses and leaks are summarized in
Tables 2 and
3. For each patient, the pairs
of image sets were consistent with one another, in the sense that on no
occasion was there a clearly positive diagnosis for one set contradicted by a
negative diagnosis for the other set. However, diagnoses were made with
greater confidence on the basis of the contrast-enhanced MRC (p <
0.001 for both stricture and leak): in all 25 patients, the reviewers had good
confidence in their exclusion or inclusion of significant stenosis or leak on
the basis of the mangafodipir trisodium–enhanced images. In contrast,
56% and 48% of the unenhanced MRC image sets were found to be either poorly
diagnostic or nondiagnostic for stenosis (Fig.
2A,
2B,
2C) and leak (Fig.
3A,
3B,
3C), respectively.
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TABLE 2 Reviewers' Confidence in Diagnosis of Biliary Stenosis: Comparison of
Enhanced and Conventional MR Cholangiography
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TABLE 3 Reviewers' Confidence in Diagnosis of Biliary Leak: Comparison of
Enhanced and Conventional MR Cholangiography
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Fig. 2A. —70-year-old man 6 weeks after retransplantation and
biliary–enteric reconstruction who presented with serum alkaline
phosphatase level of 3,560 U/L and bilirubin of 3.2 mg/dL. MRI diagnosis was
distal common duct and anastomotic narrowing with no physiologically
significant stricture. Subsequent liver biopsy found acute cellular rejection.
Coronal HASTE MR cholangiogram shows central intrahepatic biliary radicles and
small segment of common hepatic duct (arrow). Neither
biliary–enteric anastomosis nor inferior common duct is clearly seen.
Note high-signal-intensity postoperative collections, edema, and bowel
contents.
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Fig. 2B. —70-year-old man 6 weeks after retransplantation and
biliary–enteric reconstruction who presented with serum alkaline
phosphatase level of 3,560 U/L and bilirubin of 3.2 mg/dL. MRI diagnosis was
distal common duct and anastomotic narrowing with no physiologically
significant stricture. Subsequent liver biopsy found acute cellular rejection.
Single 3-mm-thick coronal MR cholangiogram better delineates structures at
liver hilum, including low-signal-intensity duct wall (arrow), but
distal common duct and anastomosis are not visualized. Note perihilar
edema.
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Fig. 2C. —70-year-old man 6 weeks after retransplantation and
biliary–enteric reconstruction who presented with serum alkaline
phosphatase level of 3,560 U/L and bilirubin of 3.2 mg/dL. MRI diagnosis was
distal common duct and anastomotic narrowing with no physiologically
significant stricture. Subsequent liver biopsy found acute cellular rejection.
Coronal maximum-intensity-projection image from mangafodipir
trisodium–enhanced MR cholangiogram shows attenuated distal duct
(arrowheads). Excretion into Roux-en-Y limb (solid arrow) is
well documented by 5 min. Note high-signal-intensity material that represents
evolving postoperative hematoma (open arrows).
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Fig. 3A. —54-year-old woman 6 days after orthotopic liver
transplantation for cryptogenic cirrhosis who presented with abdominal pain,
elevated WBC, serum alkaline phosphatase of 515 U/L, and bilirubin of 7.8
mg/dL. MRI diagnosis was biliary anastomotic leak, confirmed by next-day
endoscopic retrograde cholangiography. At surgical conversion to
biliary–enteric anastomosis 2 days later, small focus of anastomotic
necrosis and peritonitis was noted. Axial thin-slice MR cholangiogram depicts
nonspecific perihepatic fluid and hilar edema. Note common duct
(arrow) in cross section.
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Fig. 3B. —54-year-old woman 6 days after orthotopic liver
transplantation for cryptogenic cirrhosis who presented with abdominal pain,
elevated WBC, serum alkaline phosphatase of 515 U/L, and bilirubin of 7.8
mg/dL. MRI diagnosis was biliary anastomotic leak, confirmed by next-day
endoscopic retrograde cholangiography. At surgical conversion to
biliary–enteric anastomosis 2 days later, small focus of anastomotic
necrosis and peritonitis was noted. Coronal MR cholangiogram shows
fluid-signal bands at anastomosis (arrow) that, in retrospect,
probably represent site of leak.
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Fig. 3C. —54-year-old woman 6 days after orthotopic liver
transplantation for cryptogenic cirrhosis who presented with abdominal pain,
elevated WBC, serum alkaline phosphatase of 515 U/L, and bilirubin of 7.8
mg/dL. MRI diagnosis was biliary anastomotic leak, confirmed by next-day
endoscopic retrograde cholangiography. At surgical conversion to
biliary–enteric anastomosis 2 days later, small focus of anastomotic
necrosis and peritonitis was noted. Axial maximum-intensity-projection image
from enhanced MR cholangiogram shows copious contrast material flowing from
anastomosis (long arrow) and accumulating over liver surface
(short arrows).
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The data regarding the diagnostic impact of type of anastomosis are
outlined in Table 4, and for
ascites and edema in Table 5. Anastomotic type had no statistically significant effect on diagnostic
confidence for either technique, nor did the presence of ascites or edema for
the enhanced technique. However, ascites or edema did tend to have a negative
impact on the confidence of reviewers interpreting the conventional MRC
sequences. Although this tendency did not achieve statistical significance for
diagnosis of stenosis (p = 0.51), the evidence was clear for a
negative impact on confidence in diagnosing leak (p = 0.004).
Several other observations regarding the enhanced image sets are of
interest. First, in 21 of the 25 patients, appearance of the contrast agent in
the recipient's common duct and small bowel was documented within 15 min after
completion of the IV injection. This group included two patients in whom the
reviewers diagnosed mild strictures because of the degree of narrowing, an
impression confirmed on subsequent ERC. Of the rest of this group, none was
diagnosed with morphologic strictures on mangafodipir trisodium–enhanced
MRC, and none was subsequently proven to have a stricture during a follow-up
period of 4–6 months. Alternative diagnoses have included biopsy-proven
cellular rejection, biliary necrosis, and drug-related hepatitis.
In two of the remaining four patients, visualization was delayed to 45 min
and 1 hr, respectively; subsequent ERC showed high-grade anastomotic
strictures in both patients (Figs.
4A,
4B and
5A,
5B,
5C). In neither of these
patients was postoperative synthetic dysfunction thought to be responsible for
the delay because their transplantation procedures had been performed 4 and 8
months previously. Direct serum bilirubin levels were only mildly elevated
(0.4 and 0.6 mg/dL, respectively). In the final two patients, one with
hemorrhagic graft necrosis and the other with extensive bile duct necrosis
(Fig. 6A,
6B,
6C), both surgically proven,
next-day imaging finally documented visualization.
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Fig. 4A. —58-year-old man 2.5 months after orthotopic liver
transplantation for cryptogenic cirrhosis who presented with alkaline
phosphatase level of 1,150 U/L and bilirubin of 0.4 mg/dL. MRI diagnosis was
moderately severe high-grade anastomotic stricture. Diagnosis was confirmed by
subsequent endoscopic retrograde cholangiography, during which stricture was
dilated and stented. Coronal MR cholangiogram shows nondilated intrahepatic
ducts (open arrows), donor's common duct (thin arrow),
recipient's common duct (large arrowhead), and pancreatic duct
(small arrowhead). Long discontinuity is suggested at anastomosis
(thick arrow).
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Fig. 4B. —58-year-old man 2.5 months after orthotopic liver
transplantation for cryptogenic cirrhosis who presented with alkaline
phosphatase level of 1,150 U/L and bilirubin of 0.4 mg/dL. MRI diagnosis was
moderately severe high-grade anastomotic stricture. Diagnosis was confirmed by
subsequent endoscopic retrograde cholangiography, during which stricture was
dilated and stented. Coronal subvolume maximum-intensity-projection image from
mangafodipir trisodium–enhanced MR cholangiogram more clearly shows
anastomotic stricture (thick arrow), its significance confirmed by
45-min delay in contrast excretion into recipient's duct. Arrowhead indicates
recipient's cystic duct remnant; thin arrow indicates duodenal contrast
material.
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Fig. 5A. —71-year-old man 8 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis who presented with
alkaline phosphatase level of 1,899 U/L and bilirubin of 0.6 mg/dL. MRI
diagnosis was high-grade anastomotic strictures. Diagnosis was confirmed, and
stricture was dilated and stented next day on endoscopic retrograde
cholangiography (ERC). Stricture eventually necessitated conversion to
biliary–enteric reconstruction. Coronal HASTE MR cholangiogram shows
mild intrahepatic ductal dilatation (short arrows) and marked
dilatation of donor's common duct. Tight anastomotic stricture (long
arrow) is suggested. Note remnant (arrowhead) of donor's cystic
duct.
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Fig. 5B. —71-year-old man 8 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis who presented with
alkaline phosphatase level of 1,899 U/L and bilirubin of 0.6 mg/dL. MRI
diagnosis was high-grade anastomotic strictures. Diagnosis was confirmed, and
stricture was dilated and stented next day on endoscopic retrograde
cholangiography (ERC). Stricture eventually necessitated conversion to
biliary–enteric reconstruction. Coronal subvolume
maximum-intensity-projection image from mangafodipir trisodium–enhanced
MR cholangiogram shows similar findings. Contrast material was finally
documented in recipient's common duct 1 hr after injection. Note poor
depiction of more peripheral intrahepatic ducts.
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Fig. 5C. —71-year-old man 8 months after orthotopic liver
transplantation for hepatitis C–related cirrhosis who presented with
alkaline phosphatase level of 1,899 U/L and bilirubin of 0.6 mg/dL. MRI
diagnosis was high-grade anastomotic strictures. Diagnosis was confirmed, and
stricture was dilated and stented next day on endoscopic retrograde
cholangiography (ERC). Stricture eventually necessitated conversion to
biliary–enteric reconstruction. ERC image obtained next day confirms MRI
findings.
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Fig. 6A. —48-year-old man 2 months after orthotopic liver
transplantation with biliary–enteric reconstruction as result of
hepatitis B–related cirrhosis and recurrent hepatocellular carcinoma who
presented with serum alkaline phosphatase level of 1,057 U/L and bilirubin of
4.9 mg/dL. At explantation, bile ducts were necrotic. Coronal HASTE MR
cholangiogram depicts intra- and extrahepatic biliary tree containing casts of
necrotic debris (arrowhead).
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Fig. 6B. —48-year-old man 2 months after orthotopic liver
transplantation with biliary–enteric reconstruction as result of
hepatitis B–related cirrhosis and recurrent hepatocellular carcinoma who
presented with serum alkaline phosphatase level of 1,057 U/L and bilirubin of
4.9 mg/dL. At explantation, bile ducts were necrotic. Coronal subvolume
maximum-intensity-projection image from mangafodipir trisodium–enhanced
MR cholangiogram clearly depicts debris as low-signal-intensity filling
defects (arrow) in contrast-filled central ducts.
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Fig. 6C. —48-year-old man 2 months after orthotopic liver
transplantation with biliary–enteric reconstruction as result of
hepatitis B–related cirrhosis and recurrent hepatocellular carcinoma who
presented with serum alkaline phosphatase level of 1,057 U/L and bilirubin of
4.9 mg/dL. At explantation, bile ducts were necrotic. Axial source image from
contrast-enhanced MR cholangiogram shows debris in cross-sectioned ducts
(arrows) and patchy enhancement of transplanted liver.
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Discussion
Our study of 25 consecutive patients showed that mangafodipir
trisodium–enhanced imaging performed better than conventional MRC for
overall image quality and for visualization of the extrahepatic duct, with
improvement in anastomotic visualization being statistically significant.
Improvement was most striking in the presence of ascites or substantial
perihepatic edema. Although 14 (56%) of the 25 patients had
biliary–enteric reconstructions, that did not prove to be an independent
predictor for diagnostic difficulty.
On the other hand, depiction of the intrahepatic biliary tree was not
usually improved by the enhanced technique. In fact, in a number of cases
conventional MRC received higher scores, results at odds with the impression
of Lee et al. [18] that
T2-based MRC was often inadequate to define anatomic variants in the central
intrahepatic biliary radicles. Several possible explanations exist for this
discordance. First, patient motion—primarily respiratory—is a
significant challenge in our postsurgical population. Also worth considering
would be the hepatic synthetic dysfunction present to one degree or another in
our patients: excretion of the contrast agent might not be as copious as in
healthy prospective donors. Finally, our reviewers were evaluating the small
peripheral as well as the central intrahepatic ducts.
Perhaps most important, in a number of cases (56% for stenosis, 48% for
leak) reviewer diagnostic confidence increased significantly when they were
given the mangafodipir trisodium–enhanced images. In no case was
diagnostic confidence poor or lacking for significant stenosis or for leak at
review of the enhanced sequences. However, in roughly half the cases,
conventional MRC images resulted in poor or absent diagnostic confidence.
In our study group, prompt excretion (within 15 min) of mangafodipir
trisodium into distal duct and bowel accurately indicated the absence of
significant ductal stenosis. Of the four patients in whom excretion was
delayed beyond 15 min, two subsequently required intervention for anastomotic
strictures, and two required retransplantation because of graft failure. These
results suggest a potential for establishing a time threshold for contrast
visualization below which the ductal reconstruction is predictably normal.
Our experience with the mangafodipir trisodium–enhanced MRC protocol
since the study period has suggested several drawbacks of the technique.
Although acquired in less than 25 sec, the 3D gradient-echo sequences we use
for enhanced imaging are motion-sensitive and depend heavily on the patient's
ability to breath-hold, and image quality has suffered in a few patients. For
these, single-shot T2-weighted images have been especially valuable. Clearly,
if these patients had been included in our study group, diagnostic confidence
for the enhanced technique would not have been 100%. To address this issue, we
are working with parallel imaging techniques to shorten imaging times for very
ill patients, as well as experimenting with gated sequences, which show some
promise, especially for detecting leaks.
This imaging protocol can be time-consuming. Because mangafodipir trisodium
is not injected until after the conventional sequences are acquired, an
imaging hiatus of several minutes occurs. When that delay is added to the time
needed to acquire the postinjection sequences and to create the MIP
reconstructions, another half hour may be added to an approximately 30-min MRC
protocol. However, because mangafodipir trisodium decreases the T2 of bile,
leading to signal loss in the ducts
[23], this order of imaging is
appropriate. Additionally, we believe that T2-weighted imaging will remain
important because of its ability to depict fluid collections, because of the
relative motion insensitivity of its single-shot variants, and because of its
good performance for the intrahepatic ducts.
Another potential issue is the patient with a long delay in ductal contrast
visualization. Hopefully, as more experience accumulates concerning patients
with cellular hepatic dysfunction, a threshold will be established beyond
which only conventional MRC would be indicated, obviating unproductive
repeated imaging.
Limitations of our study derive from its focus on comparison between two
MRI techniques and from its lack of a gold standard. Consequently, although
some patients did have correlative studies in a short period of time, those
diagnosed as normal on MRI often did not undergo ERC or percutaneous
transhepatic cholangiography. On the other hand, examination of the medical
records for the subsequent 6 months revealed no patient who later required
biliary intervention. Additionally, all but two patients either had
crosssectional imaging follow-up (often multiple examinations) or underwent
diagnostic liver biopsy. None of these examinations was interpreted as
suggesting biliary obstruction or extravasation. At least four patients had
follow-up MRC, with no change in findings.
Only one biliary leak was diagnosed among our cohort, but it was well
depicted by mangafodipir trisodium–enhanced MRC. This is congruent with
the excellent results reported by Vitellas et al.
[20] in detecting leaks after
cholecystectomy.
In conclusion, the addition of mangafodipir trisodium–enhanced
T1-weighted MRC to our MRC protocol for the detection and characterization of
biliary complications after orthotopic liver transplantation provided an
improvement in visualization of extrahepatic ducts and biliary reconstructions
when compared with conventional MRC. Mangafodipir trisodium–enhanced MRC
also improved diagnostic confidence significantly. Further study is needed to
determine when and if this approach can supplant more invasive procedures.
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Abstract
Introduction
