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Published online before print March 4, 2005, 10.1148/radiol.2343040028
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(Radiology 2005;235:250-258.)
© RSNA, 2005

Technical Developments

Biliary Atresia: Feasibility of Mangafodipir Trisodium–enhanced MR Cholangiography for Evaluation1

Hun Kyu Ryeom, MD, Byung Ho Choe, MD, Jong Yeol Kim, MD, Soonhak Kwon, MD, Cheol Woo Ko, MD, Heng Mi Kim, MD, Sang Bum Lee, MD and Duk Sik Kang, MD

1 From the Departments of Radiology (H.K.R., J.Y.K., D.S.K.) and Pediatrics (B.H.C., S.K., C.W.K., H.M.K., S.B.L.), Kyungpook National University School of Medicine, Samduk 2Ga, Jung-Gu, Daegu 700–721, Republic of Korea. Received January 10, 2004; revision requested March 12; revision received May 14; accepted June 15. Supported by a BioMedical Research Institute grant, Kyungpook National University Hospital (2002). Address correspondence to B.H.C. (e-mail: bhchoi@knu.ac.kr).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 Materials and Methods
Results
 Discussion
 REFERENCES
 
The study was approved by the institutional review board, and informed consent was obtained from the patients’ parents. Twenty-three consecutive infants suspected of having biliary atresia (BA) were prospectively examined by using mangafodipir trisodium (Mn-DPDP)–enhanced magnetic resonance (MR) cholangiography. Sequential T1-weighted spoiled gradient-echo MR cholangiograms were obtained 1, 2, and 3 hours after intravenous administration of Mn-DPDP. The possibility of BA was excluded if bowel excretion of contrast material was noted at contrast material–enhanced MR cholangiography. The diagnostic specificity and accuracy of contrast-enhanced MR cholangiography were compared with those of conventional MR cholangiography, technetium 99m Tc (99mTc)–disofenin (DISIDA) scintigraphy, and the triangular cord sign at ultrasonography (US). MR cholangiography was used to accurately distinguish four cases of BA from 19 cases of other cholestatic liver diseases, without false-positive results. Conventional MR cholangiography, 99mTc-DISIDA scintigraphy, and the triangular cord sign at US respectively yielded false-positive results of 42% (eight of 19 infants), 35% (six of 17 infants), and 11% (two of 19 infants) in patients without BA. Mn-DPDP–enhanced MR cholangiography appears to be a promising modality for early diagnosis of BA as the cause of neonatal cholestasis.

© RSNA, 2005


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
Materials and Methods
Results
 Discussion
 REFERENCES
 
Biliary atresia is a progressive obliterative cholangiopathy that occurs in neonates. A number of prenatal or perinatal insults to the biliary tree appear to result in complete obstruction of the lumina of the extrahepatic biliary trees and continued injury and sclerosis of the intrahepatic bile ducts (1). The obstruction of the bile flow then results in worsening cholestasis, hepatic fibrosis, cirrhosis, and hepatic failure within 2 years. However, the natural progression of biliary atresia can be favorably altered by means of early recognition and by performing hepatic portoenterostomy. Nonetheless, biliary atresia remains the leading indication for liver transplantation in children (1). Therefore, for any infant older than 2 weeks who has direct hyperbilirubinemia, prompt evaluation to distinguish biliary atresia from neonatal hepatitis is needed (1,2) because early (<45– 60 days) hepatic portoenterostomy reduces and delays the need for liver transplantation during infancy (3,4). Successful portoenterostomy allows transplantation to be delayed until an older age, when risks of mortality and morbidity are decreased; thus, it also leads to improved health outcome (5).

In difficult cases in which neonatal hepatitis and metabolic disorders are unlikely diagnoses, biliary atresia cannot be excluded by using conventional diagnostic tools such as ultrasonography (US), cholescintigraphy, and magnetic resonance (MR) cholangiography, so exploratory laparotomy with liver biopsy and intraoperative cholangiography may need to be performed (1,2). Thus, to avoid performing unnecessary exploratory laparotomy, a more accurate and noninvasive diagnostic modality is needed.

Mangafodipir trisodium (Mn-DPDP, Teslascan; Nycomed Amersham, Princeton, NJ) is a nonradioisotopic liver-specific contrast medium that is taken up mainly by the liver cells and excreted into the biliary system (6). It has been reported that Mn-DPDP is well tolerated in patients with cholestasis and can be used in patients who have had obstructive jaundice, as long as administration of the agent is followed by successful bile drainage (7,8). Accordingly, the aim of our current study was to prospectively determine the feasibility of performing Mn-DPDP–enhanced MR cholangiography to exclude biliary atresia as the cause of neonatal cholestasis.


   Materials and Methods
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
Results
 Discussion
 REFERENCES
 
Patient Population
The current study was approved by the institutional review board, and informed consent was obtained from the parents of the patients. To our knowledge, there have been no reported side effects of using Mn-DPDP as a contrast agent thus far.

The study population included 23 consecutive infants (12 male, 11 female) aged 24–139 days (mean, 69 days) who were examined between November 2001 and December 2003. The infants were referred from private clinics or other medical centers, as well as from the neonatal intensive care unit of Kyungpook National University School of Medicine, for further evaluation of prolonged jaundice and lightened stool color. Biliary atresia had not been ruled out clinically in these patients, in whom hypocholic to acholic (clay-colored) stool and prolonged conjugated hyperbilirubinemia had developed within the first 2 months of life. Prolonged conjugated hyperbilirubinemia was defined as a direct bilirubin level higher than 2.0 mg/dL (34 µmol/L) or a fraction greater than 20% of an elevated total bilirubin level (normal values: direct, 0–0.2 mg/dL [0–3.4 µmol/L]; total, 0.2–1.0 mg/dL [3.4–17.0 µmol/L]).

Imaging Examinations
The first precontrast and Mn-DPDP–enhanced MR cholangiography examinations were performed at the same time 1–5 days before technetium 99m Tc (99mTc)–disofenin (DISIDA) hepatobiliary scintigraphy was performed. During each session of contrast material–enhanced MR cholangiography, the infants were sedated, if needed, with an intravenous injection of midazolam (Dormicum; Roche, Basel, Switzerland) (0.1–0.3 mg per kilogram of body weight) without intubation. The images were obtained during quiet respiration while a pediatrician monitored the patients by using electrocardiography and a standard pulse oximetry device placed on the fingertip. To avoid generating any signal intensity enhancement in the gastrointestinal tract on T1-weighted images, the patients were not fed for 4 hours before the MR cholangiography examinations and were not given milk until after the final session of contrast-enhanced MR cholangiography.

Mn-DPDP was the contrast agent used for contrast-enhanced MR cholangiography. The active ingredient in Mn-DPDP is manganese dipyridoxyl diphosphate, a metal chelate of manganese that is essentially a paramagnetic T1 enhancer (6,9). After intravenous administration, a proportion of manganese is slowly released from the chelate and binds to the blood protein, and the main uptake of manganese occurs in the liver (6). Enhancement of the liver parenchyma peaks after 5–10 minutes and plateaus over several hours (10,11). Most of the manganese is then eliminated through the biliary route, with about 20% secreted into the urine (12,13).

The MR imaging examinations were performed by using a 1.5-T unit (Vision Plus; Siemens Medical Systems, Erlangen, Germany), in which the head coil was positioned around the patient’s upper abdomen. In each patient, conventional MR cholangiography was performed by using two data acquisition techniques: a single-section method and a multisection method. For the single-section technique, a single-shot rapid acquisition with relaxation enhancement (RARE) sequence was used with the following parameters: {infty}/87 (repetition time msec/effective echo time msec), a flip angle of 150°, a 170-mm field of view, one signal acquired, and a 240 x 256 matrix. The single-section MR cholangiograms were obtained in the coronal and oblique coronal planes with a section thickness of 15–45 mm within an acquisition time of 1.4 seconds during quiet respiration.

For the multisection technique, a half-Fourier RARE sequence was used with the following parameters: 2816/95, a flip angle of 150°, a 170-mm field of view, one signal acquired, and a 256 x 176 matrix. The multisection MR cholangiograms were obtained in the coronal and oblique coronal planes within a sequential imaging time of 18 seconds during quiet respiration. Multiple 3-mm-thick sequential sections were postprocessed by using a standard maximum intensity projection reconstruction algorithm.

For the first contrast-enhanced MR cholangiography session, nonenhanced transverse and coronal T1-weighted spoiled gradient-echo images were obtained immediately after the conventional MR cholangiography examination with the following parameters: 150/4.8 (repetition time msec/echo time msec), a 75° flip angle, a 256 x 170 matrix, a 4-mm section thickness for the transverse images and a 7-mm section thickness for the coronal images, and a 300-mm field of view. The images were obtained for 19 seconds during quiet respiration. Then, sequential T1-weighted spoiled gradient-echo images were repeatedly acquired 1, 2, and 3 hours after the intravenous administration of Mn-DPDP (5 µmol/kg) by using the same pulse sequence and imaging parameters used to obtain the precontrast images. If a patient excreted contrast material before the 3-hour session, delayed imaging was not performed; however, the 3-hour image was required to confirm the diagnosis in the infants with biliary atresia. The parents of the patients were not charged for the sequentially repeated contrast-enhanced MR cholangiography examinations. The total imaging time and examination time for each contrast-enhanced MR cholangiography session were 44 seconds and about 5 minutes, respectively.

In 21 patients, 99mTc-DISIDA hepatobiliary scintigraphy was performed by using a gamma camera scanner (Prism 2000; Picker Marconi, Cleveland, Ohio) 1–5 days after the MR cholangiography examinations were performed. For the scintigraphic examinations, phenobarbital (5 mg/kg/d orally) was given to each patient for 2–5 days in advance of the procedure, and the patients were given no food for 3 hours before the examination. Scanning was performed after the intravenous administration of 99mTc-DISIDA at a dose of 0.25 mCi/kg (9.25 MBq/kg). Sequential anterior scintigrams of the abdomen were then obtained 1, 5, 15, and 30 minutes and 1, 2, 4, and 6 hours after the injection. Delayed scans were obtained 24 hours later if there was still no visualization of intestinal radioactivity after 6 hours.

All patients underwent US on the same day of and just before the MR cholangiography examinations. They were given no food for 4 hours before the US examination. All US examinations were performed by one of the authors (H.M.K.), who had 5 years of experience in pediatric gastrointestinal US. Each patient was examined with 1–4-MHz convex linear-array and 8–5-MHz linear-array transducers (Sequoia 512; Acuson Solutions, Mountain View, Calif). The length of the gallbladder and the presence or absence of the triangular cord sign were evaluated. The triangular cord sign was defined as a triangle- or tube-shaped echogenic lesion just cranial to the portal vein bifurcation and was accepted as a sign positive for biliary atresia when it was more than 4 mm thick (14).

Image Analysis
The MR cholangiograms were independently interpreted by two radiologists (H.K.R., J.Y.K.), who respectively had 10 and 6 years of experience interpreting abdominal MR images and who were blinded to the clinical histories of and other examination results for the patients. The visibility of the extrahepatic bile duct was evaluated on the basis of the source and maximum intensity projection–reformatted image findings. Discrepancies in the interpretations of the conventional and contrast-enhanced MR cholangiograms were resolved by consensus.

Contrast material filling of the gallbladder, extrahepatic bile duct, and duodenum or small-bowel loops (hereafter, referred to as contrast filling) was assessed on sequential contrast-enhanced MR cholangiograms. Precontrast images were compared with corresponding postcontrast images obtained in the same plane to determine the extent of contrast filling, which was defined as an area of intraluminal high signal intensity on contrast-enhanced MR cholangiograms that was not seen on the precontrast images. When the extrahepatic bile ducts were visualized at conventional or contrast-enhanced MR cholangiography, their diameters were measured at the most proximal portion.

For each imaging modality, diagnostic criteria for excluding biliary atresia were established to avoid performing unnecessary exploratory laparotomy. Hence, biliary atresia was excluded if intestinal radioactivity was noted on the 99mTc-DISIDA scans (15) and if a normal extrahepatic biliary system was visualized on the conventional MR cholangiograms (16,17). For contrast-enhanced MR cholangiography, the expected time frame for excretion of Mn-DPDP into the central biliary tract is 10–20 minutes (11). However, to prevent false-positive results, the authors decided that the criterion for the exclusion of biliary atresia would be the excretion of contrast material into the bowel within 3 hours after the administration of Mn-DPDP. The criterion for the diagnosis of biliary atresia at US was the presence of the triangular cord sign (14).

Final Diagnosis
To make a final diagnosis, a combination of surgery, various imaging modalities, and clinical follow-up served as the reference standard. Laparotomy and hepatic portoenterostomy were performed in those patients in whom the imaging findings indicated biliary atresia. One female patient with biliary atresia was referred when she was 130 days old with signs of biliary cirrhosis. Therefore, her parents requested that she be immediately listed as a liver transplantation candidate because it was presumed to be too late to obtain a successful result from portoenterostomy. The diseases in the remaining patients who were believed not to have biliary atresia according to imaging results were diagnosed on the basis of laboratory findings and clinical symptoms, which were confirmed during the subsequent 2–5-month clinical follow-up period until the clearance of jaundice.

Statistical Analyses
The diagnostic sensitivity, specificity, false-positive rate, and accuracy of contrast-enhanced MR cholangiography were compared with those of conventional MR cholangiography, 99mTc-DISIDA scintigraphy, and the triangular cord sign at US. For all comparisons, Fisher exact tests were performed by using statistical software (SAS, version 8.2; SAS Institute, Cary, NC) and a standard personal computer system (Samsung Magic Station M2950; Samsung, Seoul, Republic of Korea). P < .05 was considered to indicate statistical significance.


   Results
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
Results
Discussion
 REFERENCES
 
No infant was excluded from this study owing to medical reasons. Good-diagnostic-quality images of the biliary tract were obtained in all patients without complications or side effects from the administration of Mn-DPDP or sedatives.

Four patients received a diagnosis of biliary atresia on the basis of laparotomy (n = 3) and clinical (n = 1, biliary cirrhosis at 130 days old) findings, while the 19 patients without biliary atresia were given a diagnosis of neonatal hepatitis (n = 13) or total parenteral nutrition–associated cholestasis (n = 6) because the jaundice cleared during the 2–5-month follow-up period (Table 1).


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  		TABLE 1. Clinical and Radiologic Findings in Infants Suspected of Having Biliary Atresia

 
The diagnostic sensitivity, specificity, false-positive rate, and accuracy of contrast-enhanced MR cholangiography were 100%, 100%, 0%, and 100%, respectively. These values were 100%, 58%, 42%, and 65%, respectively, for conventional MR cholangiography; 100%, 65%, 35%, and 71%, respectively, for 99mTc-DISIDA scanning; and 75%, 89%, 11%, and 87%, respectively, for the triangular cord sign at US (Table 2). As such, the specificity, false-positive rate, and accuracy of contrast-enhanced MR cholangiography were significantly superior (P < .01, Fisher exact test) to those of conventional MR cholangiography and 99mTc-DISIDA scanning (Table 2).


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  		TABLE 2. Imaging Results and Accuracy

 
Conventional MR cholangiography did not depict the extrahepatic bile ducts and major intrahepatic ducts in eight (42%) of the 19 patients without biliary atresia, whereas 99mTc-DISIDA scintigraphy yielded false-positive results (no intestinal radioactivity) in six (35%) of 17 patients without biliary atresia. The US finding of a triangular cord sign was seen in two (11%) of the 19 patients without biliary atresia but in three (75%) of the four patients with biliary atresia. No false-positive results were obtained at contrast-enhanced MR cholangiography, as compared with the false-positive results obtained in 42%, 35%, and 11% of the patients at conventional MR cholangiography, 99mTc-DISIDA scanning, and US, respectively (Tables 1, 2).

At Mn-DPDP–enhanced MR cholangiography, the excreted contrast material had high signal intensity and filled the bowel lumen; these findings were not seen on the precontrast images obtained in the patients without biliary atresia. The signal intensity of the excreted contrast material was so conspicuous that there were no discrepancies in the interpretations of the contrast-enhanced MR cholangiograms. In all 23 patients, there was noted contrast enhancement of the normal pancreatic parenchyma, as described in a previous report (6).

The filling of the duodenum or proximal small bowel with excreted contrast material was noted in all 19 patients without biliary atresia (six with total parenteral nutrition–associated cholestasis, 13 with neonatal hepatitis) but not in any of the patients who had biliary atresia. Contrast agent filling of the gallbladder and extrahepatic bile duct was noted, respectively, in 12 (63%) and 11 (58%) of the 19 patients without biliary atresia but not in any of the patients who had biliary atresia.

The mean diameter of the contrast material–filled extrahepatic bile ducts was 2.9 mm (range, 2.1–3.6 mm). Thus, results show that when we applied the contrast-enhanced MR cholangiography–based criterion for the exclusion of biliary atresia—that is, the appearance of contrast material in the bowel within 3 hours after the administration of Mn-DPDP—an accurate distinction between biliary atresia (in four patients) and other cholestatic liver diseases (in 19 patients) could be made without any false-positive results (Table 1). Most patients without biliary atresia (except patients 1 and 20) exhibited intestinal excretion of contrast material within 1 hour after the intravenous injection of Mn-DPDP and did not need an examination performed 2 or 3 hours after the injection.

A single conventional MR cholangiography examination revealed the extrahepatic bile ducts in 11 (58%) of the 19 infants without biliary atresia. Discrepancies in the interpretations of the conventional MR cholangiograms in terms of visualization of the extrahepatic bile ducts occurred in two cases and were resolved by consensus. The mean diameter of the extrahepatic bile ducts was 2.4 mm (range, 2.1–3.5 mm). In eight (42%) of the 19 patients without biliary atresia, conventional MR cholangiography did not depict the extrahepatic bile ducts. Contrast-enhanced MR cholangiography, however, clearly depicted not only the excreted contrast material in the bowel loops in all 19 patients without biliary atresia but also the common bile duct filling in three patients whose extrahepatic bile ducts were not visualized at conventional MR cholangiography (Table 1, Fig 1).



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  		Figure 1a. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1b. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1c. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1d. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1e. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1f. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1g. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 


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  		Figure 1h. Images obtained in 99-day-old girl with total parenteral nutrition-associated cholestasis. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective]; flip angle, 150°) shows intrahepatic bile ducts (arrows) but no extrahepatic bile duct. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic head (black arrows) shows gallbladder (arrowhead) and pancreatic portion of common bile duct (white arrow). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of gallbladder (arrowhead), common bile duct (straight white arrow), and proximal jejunum (curved arrows). Also note the contrast-enhanced pancreatic parenchyma (black arrows). (e) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP at level slightly lower than d shows contrast material-filled third portion of duodenum (arrowheads). In d and e, contrast agent filling appears as area of high signal intensity, which is not seen on c. (f) Coronal precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of porta hepatis. (g, h) Coronal T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of extrahepatic bile duct (straight white arrows in g), duodenum (arrowheads), and proximal jejunum (curved arrow). Contrast agent filling appears as area of high signal intensity, which is not seen on f. Note the contrast-enhanced pancreatic parenchyma (*).

 
Scintigraphy with 99mTc-DISIDA was performed in only 21 of the 23 patients because the possibility of biliary atresia was ruled out in two patients on the basis of their conventional and contrast-enhanced MR cholangiography results. For these two patients, conventional MR cholangiography unequivocally depicted the extrahepatic bile ducts, while contrast-enhanced MR cholangiography clearly depicted contrast material excreted into the extrahepatic ducts and bowel loops (Fig 2). In all four patients with biliary atresia, no intestinal radioactivity was noted. However, the 99mTc-DISIDA scans—even the 24-hour delayed images—showed false-positive findings (ie, no intestinal radioactivity) in six (35%) of 17 patients without biliary atresia (Fig 1).



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  		Figure 2a. Images obtained in 65-day-old boy with cytomegalovirus hepatitis. (a) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective], 150° flip angle) shows intrahepatic ducts (arrows), gallbladder (white arrowheads), and common bile duct (black arrowhead). (b, c) Transverse T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of gallbladder (black arrowhead), pancreatic portion of common bile duct (arrow in b), and duodenal loops (white arrowheads) as areas of intraluminal high signal intensity. (d) Coronal T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of common bile duct (arrows) and duodenal loops (arrowheads) as areas of intraluminal high signal intensity. 99mTc-DISIDA scanning was not performed in this patient because the possibility of biliary atresia was ruled out at both conventional MR cholangiography and contrast-enhanced MR cholangiography.

 


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  		Figure 2b. Images obtained in 65-day-old boy with cytomegalovirus hepatitis. (a) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective], 150° flip angle) shows intrahepatic ducts (arrows), gallbladder (white arrowheads), and common bile duct (black arrowhead). (b, c) Transverse T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of gallbladder (black arrowhead), pancreatic portion of common bile duct (arrow in b), and duodenal loops (white arrowheads) as areas of intraluminal high signal intensity. (d) Coronal T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of common bile duct (arrows) and duodenal loops (arrowheads) as areas of intraluminal high signal intensity. 99mTc-DISIDA scanning was not performed in this patient because the possibility of biliary atresia was ruled out at both conventional MR cholangiography and contrast-enhanced MR cholangiography.

 


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  		Figure 2c. Images obtained in 65-day-old boy with cytomegalovirus hepatitis. (a) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective], 150° flip angle) shows intrahepatic ducts (arrows), gallbladder (white arrowheads), and common bile duct (black arrowhead). (b, c) Transverse T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of gallbladder (black arrowhead), pancreatic portion of common bile duct (arrow in b), and duodenal loops (white arrowheads) as areas of intraluminal high signal intensity. (d) Coronal T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of common bile duct (arrows) and duodenal loops (arrowheads) as areas of intraluminal high signal intensity. 99mTc-DISIDA scanning was not performed in this patient because the possibility of biliary atresia was ruled out at both conventional MR cholangiography and contrast-enhanced MR cholangiography.

 


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  		Figure 2d. Images obtained in 65-day-old boy with cytomegalovirus hepatitis. (a) Coronal half-Fourier RARE conventional MR cholangiogram (2816/95 [effective], 150° flip angle) shows intrahepatic ducts (arrows), gallbladder (white arrowheads), and common bile duct (black arrowhead). (b, c) Transverse T1-weighted spoiled gradient-echo MR cholangiograms (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP show contrast agent filling of gallbladder (black arrowhead), pancreatic portion of common bile duct (arrow in b), and duodenal loops (white arrowheads) as areas of intraluminal high signal intensity. (d) Coronal T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 1 hour after intravenous injection of Mn-DPDP shows contrast agent filling of common bile duct (arrows) and duodenal loops (arrowheads) as areas of intraluminal high signal intensity. 99mTc-DISIDA scanning was not performed in this patient because the possibility of biliary atresia was ruled out at both conventional MR cholangiography and contrast-enhanced MR cholangiography.

 
For the four patients with biliary atresia, the results of conventional MR cholangiography, contrast-enhanced MR cholangiography, and 99mTc-DISIDA scanning allowed an accurate diagnosis: No intestinal radioactivity was noted on the radionuclide scans, and the extrahepatic biliary system was not visualized at conventional or contrast-enhanced MR cholangiography. Furthermore, no excretion of contrast material into the bowel was noted within 3 hours after the administration of Mn-DPDP (Fig 3). In four patients without biliary atresia, both 99mTc-DISIDA scanning and conventional MR cholangiography yielded false-positive results; thus, exploratory laparotomy would have been considered without positive contrast-enhanced MR cholangiography results. In all four of these patients, the jaundice subsequently resolved during the 2–5 month follow-up period (Table 1, Fig 3).



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  		Figure 3a. Images obtained in 24-day-old girl with biliary atresia. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal single-shot RARE MR cholangiogram ({infty}/87 [effective], 150° flip angle) shows gallbladder (arrowheads) but no intra- or extrahepatic bile ducts. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic body (arrowheads). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 3 hours after intravenous injection of Mn-DPDP shows no contrast material excretion into the biliary system or bowel loops. Note the contrast enhancement of the pancreatic parenchyma (arrowheads).

 


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  		Figure 3b. Images obtained in 24-day-old girl with biliary atresia. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal single-shot RARE MR cholangiogram ({infty}/87 [effective], 150° flip angle) shows gallbladder (arrowheads) but no intra- or extrahepatic bile ducts. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic body (arrowheads). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 3 hours after intravenous injection of Mn-DPDP shows no contrast material excretion into the biliary system or bowel loops. Note the contrast enhancement of the pancreatic parenchyma (arrowheads).

 


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  		Figure 3c. Images obtained in 24-day-old girl with biliary atresia. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal single-shot RARE MR cholangiogram ({infty}/87 [effective], 150° flip angle) shows gallbladder (arrowheads) but no intra- or extrahepatic bile ducts. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic body (arrowheads). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 3 hours after intravenous injection of Mn-DPDP shows no contrast material excretion into the biliary system or bowel loops. Note the contrast enhancement of the pancreatic parenchyma (arrowheads).

 


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  		Figure 3d. Images obtained in 24-day-old girl with biliary atresia. (a) Coronal 99mTc-DISIDA scan shows no radioactive bowel activity. (b) Coronal single-shot RARE MR cholangiogram ({infty}/87 [effective], 150° flip angle) shows gallbladder (arrowheads) but no intra- or extrahepatic bile ducts. (c) Transverse precontrast T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained at level of pancreatic body (arrowheads). (d) Transverse T1-weighted spoiled gradient-echo MR cholangiogram (150/4.8, 75° flip angle) obtained 3 hours after intravenous injection of Mn-DPDP shows no contrast material excretion into the biliary system or bowel loops. Note the contrast enhancement of the pancreatic parenchyma (arrowheads).

 
The US finding of a triangular cord sign was seen in three (75%) of the four patients with biliary atresia and in two (11%) of the 19 patients without biliary atresia. The gallbladder was seen at US in all 23 patients. The mean length of the gallbladder was 2.2 cm (range, 1.2–3.7 cm) in the patients without biliary atresia and 1.9 cm (range, 1.2–2.6 cm) in those with biliary atresia. Only one of the four patients with biliary atresia had a small gallbladder (<1.5 cm in length) at US, whereas one (5%) of the 19 patients without biliary atresia had a small gallbladder.


   Discussion
TOP
 ABSTRACT
 INTRODUCTION
 Materials and Methods
Results
 Discussion
REFERENCES
 
The definitive diagnosis of biliary atresia is based on the demonstration of a fibrotic extrahepatic biliary tree at exploratory laparotomy or intraoperative cholangiography. However, no single noninvasive examination that can be used to satisfactorily exclude biliary atresia as the cause of neonatal cholestasis is currently available, even though early diagnosis is critical for the prognosis and even more important for determining the treatment for biliary atresia. Hence, a number of imaging examinations, including US (18–20), radionuclide cholescintigraphy (21,22), and MR cholangiography (23), have been used together to establish a more accurate diagnosis of biliary atresia less invasively and thereby reduce the need for open liver biopsy and exploratory cholangiography.

The US finding of a triangular cord sign is a simple and useful diagnostic tool for the early detection of biliary atresia when a cone-shaped periportal fibrous mass is observed as a triangular or bandlike periportal area of echogenicity just cranial to the bifurcation of the portal vein (19). Kanegawa et al (24) reported seeing a triangular cord sign in 27 (93%) of 29 infants with biliary atresia and in one of 26 infants with neonatal hepatitis or other causes of infantile cholestasis. Tan Kendrick et al (25) observed a triangular cord sign in 24 (77%) of 31 infants with biliary atresia. However, US enables only limited anatomic delineation of the biliary system (18) and yields variable results owing to the bias related to the experience of the given radiologist. Furthermore, early in the course of postnatal biliary atresia, theoretically it may be difficult to find advanced periportal fibrosis at US. Also, the absence of a triangular cord sign does not exclude the possibility of biliary atresia (24). The gallbladder generally is thought to be abnormal if it is not detectable or is less than 1.5 cm long. However, owing to its low sensitivity and specificity, the gallbladder length cannot be used to diagnose biliary atresia (24).

In the diagnosis of neonatal cholestasis, hepatobiliary scintigraphy has high sensitivity (100%) yet lower specificity (75%) (26). However, 99mTc-DISIDA scanning is beset by frequent false-positive findings and delays secondary to phenobarbital administration (21,22). Also, with this examination, biliary atresia can be ruled out only if the scan shows intestinal radioactivity in a patient with hypocholic to acholic stools; it cannot be excluded if there is no intestinal radioactivity (26).

Although not used routinely, MR cholangiography reportedly has been used in preliminary studies involving infants with cholestasis. Biliary atresia can be ruled out if the complete extrahepatic biliary duct is identified at MR cholangiography (23). However, with MR cholangiography, one relies on the production and excretion of bile for visualization of the biliary system (27). Thus, the insufficient production or secretion of bile due to other severe cholestatic diseases can yield a false-positive result. In addition, the spatial resolution of images obtained in neonates with shallow respiration allows visualization of abnormal dilated ducts but cannot be used to reliably confirm the absence of ducts because image degradation of normal ducts can occur in infants, who cannot hold their breath.

Several previous reports have indicated that MR cholangiography is a very reliable noninvasive imaging modality that can be used to visualize the biliary tract and define the major biliary structures in neonates and small infants and thus exclude biliary atresia as the cause of neonatal cholestasis (16,17). However, contrary to these reports, Norton et al (27) reported both false-positive and false-negative findings and an overall accuracy of only 82% when they used MR cholangiography. In patients with biliary atresia, MR imaging can reveal periportal thickening that is thought to be related to periportal fibrosis (23). However, periportal fibrosis is not specific to biliary atresia; it can also be seen with other conditions such as severe neonatal hepatitis (28).

In two relatively recent studies (29,30), contrast-enhanced MR cholangiography depicted biliary enhancement on T1-weighted images obtained 10–20 minutes after the intravenous administration of Mn-DPDP. Contrast-enhanced MR cholangiography can also yield functional information similar to that obtained with hepatic scintigraphy, anatomic information similar to that yielded by conventional contrast-enhanced cholangiography, and cross-sectional information similar to that obtained at computed tomography and US (31). Therefore, in the current study, Mn-DPDP was used as the contrast medium for contrast-enhanced MR cholangiography to obtain better images of the biliary system and detect biliary enteral excretion and thus to determine the feasibility of performing contrast-enhanced MR cholangiography to exclude biliary atresia as the cause of neonatal cholestasis.

So far, we have found no clear reason why 99mTc-DISIDA and Mn-DPDP, when administered for imaging in the same patient, had different excretion patterns, since both agents are taken up by hepatocytes and excreted through the biliary tree. Therefore, the better diagnosis with contrast-enhanced MR cholangiography was probably due to superior resolution compared with that achieved with nuclear scanning. However, two distinct mechanisms also may explain this phenomenon: (a) a difference in the uptake into hepatocytes between the two agents in the presence of severe neonatal hepatitis, which can lead to diminished excretion of radionuclides into the gastrointestinal tract, and (b) the 6-hour half-life of 99mTc. Another hypothesis is that Mn-DPDP itself may enhance biliary excretion. Because bilirubin conjugates are excreted from the hepatocytes through the canalicular membrane into the bile, the excretion of DISIDA from the hepatocytes may be more impaired in the presence of severe inflammation.

In the current study, contrast-enhanced MR cholangiography enabled the identification of neonatal cholestasis in the 19 patients without biliary atresia with no false-positive results and in the four patients with biliary atresia with no false-negative results. Thus, contrast-enhanced MR cholangiography was shown to be a potential new diagnostic modality for excluding biliary atresia as the cause of neonatal cholestasis. On the basis of the current study results, no exploratory laparotomies were performed in those patients who exhibited no intestinal radioactivity at 99mTc-DISIDA scanning yet had positive contrast-enhanced MR cholangiography findings. All of these patients were subsequently found to be free of jaundice at clinical follow-up.

There were several limitations to the current study. First, the infants had to be sedated and could not be given milk for 4–7 hours before the examination because contrast-enhanced MR cholangiography is performed at multiple time points. For the infants without biliary atresia, however, the time during which there was no oral intake was not very long because contrast material excretion into the bowel mostly occurred within an hour after the Mn-DPDP injection. Second, because contrast-enhanced MR cholangiography was performed at multiple time points, conventional MR cholangiography also should have been performed repeatedly; at the least, multiple MR cholangiogram acquisitions should have been performed. In addition, the sensitivity of the US triangular cord sign was relatively low in the current study compared with the US results at several other centers (14,20). Third, the actual number of patients with biliary atresia was small, and the diagnosis for one patient with biliary atresia was based not on laparotomy findings but on clinical and radiologic follow-up results. Therefore, MR cholangiography findings were factored into the diagnosis of biliary atresia in this case, and this action could have caused an element of bias.

One more possible limitation is that the exclusion criteria used in the current study should be expanded in further studies. For example, if contrast-enhanced MR cholangiography depicts duodenal excretion and an equivocally visible extrahepatic bile duct more than 3 hours after the contrast material injection, there is a risk that biliary atresia will be definitively excluded, even though the duct may be progressing to complete obliteration in this stage of biliary atresia. Therefore, confirmation of the diagnosis with follow-up contrast-enhanced MR cholangiography should be considered if the infant has jaundice or persistent other clinical symptoms. However, it is believed, at least, that a prominent gallbladder and extrahepatic bile duct filling, together with duodenal excretion of Mn-DPDP within 1 hour, are definite exclusion criteria that merit further examination.

Although larger clinical trials are needed to determine whether the current diagnostic criteria can be used to definitively avoid performing unnecessary exploratory laparotomy, it appears that Mn-DPDP–enhanced MR cholangiography is a promising modality for the early exclusion of biliary atresia as the cause of neonatal cholestasis.


   ACKNOWLEDGMENTS
 
The authors thank William Balistreri, MD, and Stavra Xanthakos, MD, of the Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Ohio, for their review of the manuscript and helpful comments.


   FOOTNOTES
 
Abbreviations: DISIDA = disofenin, Mn-DPDP = mangafodipir trisodium, RARE = rapid acquisition with relaxation enhancement

Authors stated no financial relationship to disclose.

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


   REFERENCES
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 ABSTRACT
 INTRODUCTION
 Materials and Methods
Results
 Discussion
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