Index words : Bile duct radiography, technology Bile ducts MR Bile ducts surgery Liver, transplantation

Hilar Branching Anatomy of Living Adult Liver Donors: Comparison of T2-MR Cholangiography and Contrast Enhanced T1-MR Cholangiography in Terms of Diagnostic Utility 1 Joon Seok Lim, M.D. 1, Myeong-Jin Kim, M.D. 1,3, Kyung Sik Kim, M.D. 2, Joo Hee Kim, M.D. 1, Young Taik Oh, M.D. 1, Jin Yong Kim, M.D. 1, Hyung Sik Yoo, M.D. 1, Jong Tae Lee, M.D. 1, Ki Whang Kim, M.D. 1 Purpose: To compare T2-weighted MR cholangiography (T2-MRC) and contrast-enhanced T1-weighted MRC (enhanced T1-MRC) in the assessment of biliary anatomy in donor candidates for living related liver transplantation (LRLT). Materials and Methods: Thirty-three potential donors underwent MR examination for preoperative evaluation. Using the single-shot half-fourier RARE sequence, T2-weighted single-section and coronal images were obtained, and enhanced T1-MRC was performed, using 3D GRE sequences after the administration of mangafodifir trisodium. To assess the hilar ductal branching pattern and determine diagnostic confidence, two reviewers first evaluated the unpaired T2-MRC and enhanced T1-MRC images, and then paired T2-MRC and enhanced T1-MRC images together. In particular, in 12 cases in which direct cholangiographys were performed, the feasibility of single duct-to-duct anastomosis was assessed using the unpaired and the paired sets sequentially. Results: The reviewersconfidence tended to be higher for enhanced T1-MRC than T2- MRC, but the difference was not statistically significant. For both reviewers, confidence was significantly higher for the paired set than for T2- or enhanced T1-MRC alone (p <.001). The types of biliary anatomy determined in the paired set matched the consensus reading in 33 (100%) and 30 cases(91%) assessed by reviewer 1 and 2, respectively. The separate interpretation of T2- and enhanced T1-MRC findings matched the consensus interpretation in 30 (91%) and 28 cases (85%), respectively, assessed by reviewer 1, and 26 (79%) and 28 cases (85%), respectively, assessed by reviewer 2. The possibility of single anastomosis was accurately predicted in 91.6% of cases in T2-MRC, and 100% at enhanced T1-MRC and the combined set. Conclusion: In the evaluation of the biliary anatomy of potential donors for LRLT, the combined use of T2-MRC and enhanced T1-MRC may improve diagnostic confidence and decrease the occurrence of a non diagnostic or equivocal interpretation at T2-MRC alone. Index words : Bile duct radiography, technology Bile ducts MR Bile ducts surgery Liver, transplantation 1 Department of Diagnostic Radiology, Yonsei University College of Medicine 2 Department of Surgery, Yonsei University College of Medicine 3 BK21 Project of Medical Science Yonsei University College of Medicine Received June 24, 2003 ; Accepted November 17, 2003 Address reprint requests to : Myeong-Jin Kim, M.D., Department of Diagnostic Radiology, Yonsei University Medical College, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Republic of Korea. Tel. 82-2-361-5843 Fax. 82-2-393-3035 E-mail: kimnex@yumc.yonsei.ac.kr 185

The evaluation of the biliary anatomy of donor candidates for adult-to-adult right lobe transplantation is essential. A candidate with biliary variants such as anomalous drainage of the right posterior segmental duct (draining segments and ) or trifurcation can preclude single duct-to-duct biliary anastomosis in the transplant recipient (1). T2 weighted MR cholangiography (T2-MRC) is becoming the modality of choice for the noninvasive evaluation of biliary tract abnormalities, but its diagnostic limitations include poor visualization of the intrahepatic biliary tree compared with the extrahepatic (2), particularly in non-dilated systems such as that seen in healthy donor candidates. The recent development of liver-specific contrast agents which excrete into the biliary tree, such as mangafodipir trisodium, has renewed interest in contrast-enhanced MR imaging of the biliary tree, a procedure that may counter the limitations of heavily T2- weighted MR cholangiography. Lee et al. suggested that T1-weighted MR imaging, particularly when it involves high-resolution volumetric T1-weighted imaging of the liver, may facilitate the definition of intrahepatic bile duct anatomy in healthy liver transplant donor candidates and have a favorable impact on surgical results (3). In our study, contrast-enhanced T1-weighted MR cholangiography after mangafodipir trisodium administration was used as an alternative method for evaluation of the biliary anatomy in a donor candidate for LRLT. The findings were compared with those of the widely used T2-MRC procedure in terms of their ability to diagnose the hilar ductal branching anatomy and detect intrahepatic biliary anomalies, which would preclude single anastomosis. The additional effect of contrast-enhanced MR cholangiography (enhanced T1-MRC) was also investigated. Materials and Methods 186 Donor candidates The study involved of 33 consecutive candidates who underwent T2-MRC and enhanced T1-MRC between April 2001 and April 2002, and were referred for examination as potential living adult-to-adult liver donors. Nine candidates underwent laparotomy and operative cholangiography, and eight underwent uncomplicated hepatectomy (right hepatectomy n=7, left extended hepatectomy, n=1). For the ninth, the transplantation was aborted because intraoperative liver biopsy revealed unfavorable fatty change; however, operative cholangiography was performed. Three candidates underwent endoscopic retrograde cholangiography (ERCP), and a total of 12 including the nine who underwent operative cholangiography and the three in whom ERCP was performed) underwent direct cholangiography. The outcome of this, and the operative reports were reviewed by one investigator (J.S.L.) in terms of the biliary anatomy observed and the feasibility of single duct-to-duct anastomosis. MRI technique All donor candidates underwent both T2-MRC and enhanced T1-MRC using a 1.5-T MRI system (Horizon; GE Medical Systems, Milwaukee, Wis., U.S.A.) and a phased-array multicoil. Breath-hold heavily T2-weighted single-shot fast spin-echo MR cholangiography (T2- MRC), was performed before the administration of mangafodipir trisodium. Initially, localizer images were obtained in the coronal and transverse planes using a spoiled gradient-recalled sequence with the following parameters: repetition time, msec/echo time, msec 130/1.7, a flip angle of 90, a field of view of 362436 cm, section thickness of 10 mm with no gap, a matrix size of 256128, and one acquisition. Subsequently, thin-section T2-weighted images were obtained using a single-shot half-fourier rapid-acquisition and relaxation sequence (single-shot fast spin-echo) with a 260320 mm field of view. The imaging parameters were an effective echo time of 66100 msec, a field of view of 32 24 cm, a section thickness of 5 mm with no gap, a receiver bandwidth of 31.3 khz, a matrix size of 256 256, and half-fourier acquisition. In order to maintain signals from the soft-tissue structure, fat suppression was not used for this sequence. In addition, by using a spatial fat saturation technique, multisection images with a long effective echo time of 645869 msec were obtained. All other parameters were the same as for T2- weighted images. Single thick-section images were then obtained, using the following parameters: an echo time of 8301,050 msec; a section thickness of 30 mm; and a field of view of 2424 cm in the coronal, lateral, and left and right 15, 30, and 45oblique planes. (Eight images were obtained.) Mangafodipir trisodium (Teslascan; Nycomed, Princeton, N.J., U.S.A.) at a standard dose of 5 mol/kg (0.1 ml/kg; maximum dose, 15 ml) was then administered intravenously via a slow injection lasting 12 min prior to a 10-mL saline flush. Between 10 and 15 min after injection, axial and coronal volumetric 3D spoiled

gradient-echo images of the liver and biliary system (enhanced T1-MRC) were obtained using the following parameters: TR range/te, 58/minimum; flip angle, 20 ; matrix, 256128; field of view, 3224 cm (using a rectangular field of view); and 4 mm slice thickness with no intersection gap. Qualitative image evaluation T2-MRC images and enhanced T1-MRC images were separately analyzed by two radiologists (M.J.K and J.H.K). Images from the 33 unpaired examinations were arranged in random order, and the two observers reviewed the images from 66 examinations. The 33 paired sets of T2-MRC and enhanced T1-MRC images were then arranged randomly, and four weeks later all members of the panel reviewed all the paired sets, completing a standardized data sheet. Each reviewer recorded the anatomic type of each hilar bile duct branching pattern (the orthogonal relationships between the right anterior and posterior segmental duct, and the left and common hepatic duct), grading diagnostic confidence on a 5-point scale (15). The branching pattern and confidence grade for T2-MRC and enhanced T1-MRC image sets were reviewed for each modality separately, and in combination. The consensus subsequently reached was based on the findings for the combined set; the results were used as the gold standard in 21 cases in which direct cholangiography or surgery was not performed. The findings of ERCP (n=3) and surgery, including intraopertive cholangiography (n=9), were used as the gold standard for the remaining cases. In donor candidates who underwent direct cholangiography (n=12), each reviewer used the findings of T2 MRC, enhanced T1-MRC and the combined set to determine the feasibility of single duct-to-duct anastomosis for right lobe donation, respectively. The results obtained by the two reviewers were compared using the k statistic, and interobserver agreement thus determined. Discrepancies were resolved by consensus, and a single conclusion thus obtained. In all these 12 candidates, the results of MRC were compared with the confirmed results of direct cholangiogrphy. Statistical analysis To determine the anatomic type of each hilar branching pattern, the accuracy of T2-MRC, T1-MRC, and the combined set were determined according to the consensual findings of the two reviewers. Wilcoxon s signed 187 rank test was used to assess differences in diagnostic confidence, and a P value less than 0.05 was considered statistically significant. In predicting the possibility of single anastomosis, the Kappa ( ) test was used to assess interobserver variability. Agreement was categorized as follows: value of 00.2, poor; of 0.20.4, fair; of 0.4 0.6, moderate; of 0.60.8, good; and of 0.8 1.0, excellent. For each method, the sensitivity, specificity and accuracy of the results were calculated. Results Biliary variants were identified in nine (27.3%) of 33 candidates. In four of these, the anterior segmental duct drained into the left hepatic duct, and in two, drainage of the posterior segmental duct was aberrant, involving the left duct (Fig. 1). In two candidates had the common hepatic duct trifurcated into two right branches and one left hepatic duct (trifurcation) (Fig. 2), and in one, the lateral segmental duct drained into the right duct (Fig. 3). Diagnostic confidence and accuracy in determining the anatomic types of hilar branching pattern For both reviewers, the mean diagnostic confidence level was higher for enhanced T1-MRC than for T2- MRC, through the difference was not statistically significant. For T2-MRC and enhanced T1-MRC in combination, however, the mean confidence level was significantly higher than for either modality alone in both reviewer 1 and 2 (p<0.001) (Table 1). The accuracy of T2- MRC, enhanced T1-MRC, and the combined set for determining the anatomic types of hilar branching pattern was calculated on the basis of consensual interpretation. The separate interpretation of T2-MRC and enhanced T1-MRC matched the consensual findings in 30 (91%) Table 1. Diagnostic Confidence of Hilar Biliary Branching Anatomy in T2-MRC, Enhanced T1-MRC and the Combined Set for Each Reviewer Reader 1 Reader 2 Mean grade T2-MRC 3.52 3.64 Enhanced T1-MRC 3.97 4 Combined set 4.76 4.52 Comparison of methods T2-MRC vs Enhanced T1-MRC p=0.1 p=0.056 T2-MRC vs Combined set p<0.001 p<0.001 Enhanced T1-MRC vs Combined set p<0.001 p<0.001

Joon Seok Lim, et al : Hilar Branching Anatomy of Living Adult Liver Donors and 28 cases (85%) (reviewer 1), 26 (79%) and 28 cases (85%) (reviewer 2). The types of biliary anatomy determined from the combined set matched the consensual interpretation in 33 (100%) and 30 (91%) cases (reviewer 1 and 2, respectively). A C B Fig. 1. Right posterior segmental duct to left hepatic duct pattern. A. Heavily T2-weighted coronal single shot fast spin-echo thick-section MRC ( /1004 [effective], 30-mm thickness) depicts a branch (white arrow) off left hepatic duct. B. T1-weighted coronal enhanced T1-MRC shows right posterior segmental duct (white arrow) draining aberrantly into proximal left hepatic duct through serial image review from posterior to anterior. Diagnostic confidence of enhanced T1-MRC was higher than that of T2-MRC in both reviewers. C. Intraoperative cholangiography confirmed this anomaly. The single anastomosis was identified to be impossible. Dual ductal anastomosis was performed in the associated recipient. 188

J Korean Radiol Soc 2004;50:185-193 A B C D Fig. 2. Unfavorable trifurcation pattern that single anastomosis cannot be performed. A. The junction of right posterior segmental duct and right hepatic duct cannot be accurately visualized on heavily T2-weighted single shot fast spin-echo MRC ( /1,088 [effective], 30-mm thickness) T2-MRC was interpreted as normal biliary anatomy. B, C. But enhanced T1-MRC depicts the unfavorable trifurcation pattern or very short right hepatic duct to disable a single duct to duct anastomosis in recipient (B is posterior to C). D. Intraoperative cholangiography confirmed this biliary anomaly. Extended left hepatectomy was performed in this donor. 189

Joon Seok Lim, et al : Hilar Branching Anatomy of Living Adult Liver Donors A B C D Fig. 3. Left lateral segmental duct to right hepatic duct pattern. A. Heavily T2-weighted single shot fast spin-echo MRC ( /995 [effective], 30-mm thickness) depicts a branch (white arrow) off right hepatic duct. B, C. T1-weighted coronal enhanced T1-MRC shows the left lateral segmental duct (white arrow) to right hepatic duct pattern (B is posterior to C). D. This left lateral segmental duct (white arrow) to right hepatic duct pattern well visualized on intraoperative cholangiography 190

Table 2. Assessment of Possibility for Single Duct to Duct Anastomosis Examination TP* TN* FP* FN* Sensitivity Specificity Accuracy T2-MRC 7 4 1 0 100 80 91.6 T1-MRC 7 5 0 0 100 100 100 Combined set 7 5 0 0 100 100 100 * Data are numbers of patients, out of a total of 12, with false negative (FN), false positive (FP), true negative (TN), and true positive (TP) of determination on performance possibility of single anastomosis. Sensitivity, specificity and accuracy values are cited as percentages. Assessement of the possibility of single duct to duct anastomosis In four of twelve cases in which direct cholangiography was performed, biliary anomalies were visualized (one case each of anterior duct to left duct, posterior duct to left duct, unfavorable trifurcation, and lateral duct to right duct). Singe duct-to-duct anastomosis for right lobe donation was found to be impossible in all four cases. In three recipients who received donations from three of four candidates with biliary anomalies, double anastomosis was performed in two cases, and left lobe transplantion in the other. Liver donation did not proceed in the candidate with lateral duct to right duct anomaly. Overall interobserver agreement in determining the possibility of single anastomosis showed good or excellent agreement ( =1.0 for T2-MRC, =0.657 for enhanced T1-MRC, and =0.824 for the combined set). Table 2 shows the sensitivity, specificity and accuracy of the findings, with each imaging technique assessed for possible single duct-to-duct anastomosis for right lobe donation.t2-mrc showed 100% sensitivity, 80% specificity, and 91.6% accuracy, with no false negative cases, one false positive and seven true positives. Enhanced T1-MRC and the combined set showed 100% sensitivity and 100% specificity and 100% accuracy. Discussion Most current MRC techniques are based on variants of heavily T2-weighted fat-suppressed rapid acquisition using relaxation enhancement (RARE) pulse sequences. The spatial resolution of current MRC techniques is, however, limited owing to the use of thick sections and blurring from the use of multiecho techniques with long echo trains. Because of relatively low spatial resolution, the depiction of intrahepatic biliary anatomy is often inadequate in individuals without a dilated biliary system, and for this reason, a new approach to MR cholangiography which permits its accurate delineation is clearly 191 needed. Several studies have suggested that a new approach should rely on contrast agents that are excreted into the bile ducts for delineation of intrahepatic biliary anatomy using 3D T1-weighted imaging (3, 4), and in this regard, the spatial resolution of MRC can be potentially improved by using rapid 3D T1-weighted gradientecho techniques with contiguous or overlapping thin sections in which bile has been enhanced by the administration of a suitable biliary contrast medium such as mangafodipir trisodium. In particular, in the preoperative assessment of living liver donor candidates, enhanced T1-MRC can play an important role in the accurate depiction of hilar branching bile duct anatomy. Carlos et al. (5) reported that combining T2-MRC and enhanced T1-MRC (using gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid as an intrabiliary contrast agent) significantly improved biliary visualization compared with each test alone. The improvement was small, however, and the perceived added value of an intrabiliary contrast agent was modest. Their study, though, assessed the utility of the agent only in terms of ductal depiction; we tried to evaluate the added effect in terms of the confidence with which the hilar branching ductal anatomy was diagnosed during the preoperative assessment of donor candidates. Our degree of confidence was not significantly different between T2-MRC and enhanced T1-MRC. For reviewer 1, accuracy tended to be lower for enhanced T1-MRC (91% in T2-MRC and 85% in enhanced T1-MRC) than T2-MRC, though for both reviewers, diagnostic confidence for the combined set was significantly higher than for T2-MRC or enhanced T1-MRC alone. With regard to accuracy, for both reviewers 1 and 2 this was also higher for the combined set than for T2-MRC or enhanced T1-MRC alone. These findings suggest that the combination of images obtained at standard T2-MRC and enhanced T1-MRC improved both diagnostic confidence and accuracy in determining the anatomic type of a hilar branching pattern. In donor candidates, the preoperative assessment of

hilar branching patterns is essential. Ductal anomalies such as aberrant drainage of the right posterior segmental duct into the left hepatic duct or at the level of the bifurcation (trifurcation) preclude performance of single duct-to-duct biliary anastomosis and require additional biliary anastomoses that may incur an increased risk of biliary complication (6, 7). In order to determine whether single anastomosis was possible, we therefore determined the sensitivity and specificity of each imaging method (T2-MRC, enhanced T1-MRC and the combined set), finding that the sensitivity, specificity, and accuracy of enhanced T1-MRC and the combined set were excellent. In the case of T2-MRC, the trifurcation pattern was not identified in one candidate, and single anastomosis was thus at first considered possible. On the basis of the findings of enhanced T1-MRC and the combined set, however, the reviewers considered that single anastomosis might be impossible. Intraoperative cholangiography demonstrated insufficient right hepatic duct length for single biliary anastomosis without jeopardizing the donor s biliary system (Fig. 2). Our study suffered several limitations. First, with regard to diagnostic confidence analysis, we found that as with many small studies examining technological advances, the expected bias was toward the new technique (in this case, enhanced T1-MRC). Despite this, the diagnostic confidence rate was not significantly different between T2-MRC and enhanced T1-MRC. Only the combined set showed significantly higher diagnostic confidence than either of the two modalities alone. Second, in evaluating the possibility of single anastomosis, we selected from among the 33 candidates the twelve who underwent direct cholangiography. This was not perfored in those in whom on T2-MRC or enhanced T1-MRC depicted a definitely unfavorable biliary anomaly, a fact which indicated selection vias. Thirld, the combined set was in a few cases helpful in hilar branching pattern typing and determining the feasibility of single anastomosis. Because of the small sample size, statistical analysis was, however, limited. In the future, further data collection from a larger number of subjects may help determine whether findings for the combined set are likely to have a favorable impact on surgical results. However, we believe our study is the first to focus on the clinical application of enhanced T1- MRC to a situation in which donor candidates for living related liver transplantation are assessed. In conclusion, enhanced T1-MRC has the potential to enhance the reliability of the preoperative evaluation of hilar biliary anatomy in donor candidates or to lessen the occurrence of a non-diagnostic or equivocal interpretation at T2-MRC alone. References 1. Morgan GR, Lee V, Krinsky G, et al. Duct to duct biliary anastomosis with t-tube drainage in adult right lobe living donor liver transplantation without bile leaks. (abstr) Hepatology 2000;32: 214A 2. Hintze RE, Adler A, Veltzke W, et al. Clinical significance of magnetic resonance cholangiopancreatography (MRCP) compared to endoscopic retrograde cholangiopancreatography (ERCP). Endoscopy 1997;29:182-187 3. Lee VS, Rofsky NM, Morgan GR, et al. Volumetric mangafodipir trisodium-enhanced cholangiography to define intrahepatic biliary anatomy. AJR Am J Roentgenol 2001;176:906-908 4. Mitchell DG, Alam F. Mangafodipir trisodium: effects on T2- and T1-weighted MR cholangiography. J Magn Reson Imaging 1999;9: 366-368 5. Carlos RC, Hussain HK, Song JH, Francis IR. Gadolinium- Ethoxybenzyl-Diethylenetriamine Pentaacetic Acid as an intrabiliary contrast agent: preliminary assessment. AJR Am J Roentgenol 2002;179:87-92 6. Marcos A, Fisher RA, Ham JM, et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation 2000;69:2410-2415 7. Marcos A, Ham JM, Fisher RA, Olzinski AT, Posner MP. Singlecenter analysis of the first 40 adult-to-adult living donor liver transplants using the right lobe. Liver Transpl 2000;6:296-301 192

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