Morphine- and Glucagon-Augmented Magnetic Resonance Cholangiopancreatography To Evaluate Living Liver Donors

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1 LIVER TRANSPLANTATION 15: , 2009 ORIGINAL ARTICLE - and Glucagon-Augmented Magnetic Resonance Cholangiopancreatography To Evaluate Living Liver Donors Yuan Heng Mo, 1,2 Po Chin Liang, 3 Ming Chih Ho, 4 Po Huang Lee, 4 Fu Shan Jaw, and Steven Shinn-Forng Peng 3 1 Institute of Biomedical Engineering, College of Engineering and College of Medicine, National Taiwan University, Taipei, Taiwan; 2 Department of Radiology, Cathay General Hospital, Taipei, Taiwan; and 3 Department of Medical Imaging and 4 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan The purpose of this study was to investigate the effectiveness of the combined use of intravenous morphine and intramuscular glucagon in improving magnetic resonance cholangiopancreatography (MRCP) image quality in donors for living-related liver transplantation. Sixteen healthy donor candidates underwent an MRCP study. Coronal, single-shot, fast spin-echo, heavily T2-weighted dynamic MRCP images were obtained before and 3 minutes after the intravenous administration of morphine HCl with a dose of 0.04 mg/kg. Thirty minutes after the injection of morphine, intramuscular glucagon was used. Another MRCP image of the same pulse sequence was generated 15 minutes after the injection of glucagon with a dose of 1 mg. The diameter, signal intensity, and number of branches of bile ducts in MRCP images taken immediately before and after the injection of morphine and after the injection of glucagon (plus delayed morphine effects) were compared and analyzed. In all 16 donor candidates, the diameters of the right and left hepatic ducts, common bile duct, and main pancreatic duct were significantly increased (P 0.05) in the MRCP images taken 3 minutes after the injection of morphine and 15 minutes after the injection of glucagon (plus delayed morphine effects) in comparison with MRCP images taken before any drug administration. The qualitative grading scores of the signal intensity and order of branches of bile ducts revealed improvements in the MRCP images after the injection of glucagon (plus delayed morphine effects; P 0.05). In conclusion, combining the intravenous administration of low-dose morphine and the intramuscular use of glucagon before MRCP examination improves the visualization of the nondilated biliary ductal anatomy, which is important for the preoperative biliary evaluation of donor candidates for living-related liver transplantation. Liver Transpl 15: , AASLD. Received April 29, 2008; accepted March 4, Magnetic resonance cholangiopancreatography (MRCP) is a popular noninvasive imaging technique for the diagnostic evaluation of biliary disorders. The diagnostic accuracy of MRCP has been reported to be comparable to that of endoscopic retrograde cholangiopancreatography in the evaluation of disorders and identification of anatomic variants of biliary ductal systems. 1-5 Drugs can alter the physiology of the biliary system and improve the quality of MRCP images in patients with biliary diseases and other opiates contract the sphincter of Oddi. Glucagon increases bile flow but relaxes the sphincter of Oddi. 6 In addition to biliary pathology, magnetic resonance imaging including MRCP has been increasingly used for Abbreviations: CBD, common bile duct; HD, hepatic duct; IHD, intrahepatic bile duct; MRCP, magnetic resonance cholangiopancreatography; PD, pancreatic duct. The protocol ID for this study is ( Address reprint requests to Steven Shinn-Forng Peng, M.D., Department of Medical Imaging, National Taiwan University Hospital, 7 Chung Shan South Road, 100, Taipei, Taiwan. Telephone: ; FAX: ; sfpeng@ntuh.gov.tw DOI /lt Published online in Wiley InterScience ( American Association for the Study of Liver Diseases.

2 1022 MO ET AL. detailed evaluations of living liver donors because of its noninvasiveness However, difficulties are often encountered in identifying the fine anatomy of nondilated intrahepatic bile ducts. Therefore, we proposed this study to evaluate the combined efficacy of intravenous morphine and intramuscular glucagon in augmenting the quality of MRCP images of liver donor candidates with normal biliary and pancreatic systems. PATIENTS AND METHODS Patients Sixteen liver donor candidates (male:female, 9:7; age range, years; mean age, years old) were prospectively evaluated. Informed consent for diagnostic procedures and data analysis for scientific purposes was obtained from all patients before inclusion in the study. Approval of the institutional ethics committee was obtained before the start of the study. Imaging Techniques Magnetic resonance imaging was performed on a 1.5-T magnetic resonance scanner (Sonata, Siemens Medical, Inc., Erlangen, Germany). A torso phased array coil was used for data acquisition. single-shot, fast spinecho, T2 coronal localization, images were acquired with a T2-weighted, fast spin-echo rapid acquisition with relaxation enhancement pulse sequence. MRCP images were acquired in coronal and coronal oblique planes with a heavily T2-weighted, fast spin-echo pulse sequence with the following imaging parameters: effective echo time, 1400 ms; repetition time, 4800 ms; matrix, ; field of view, 28 cm 28 cm; slice thickness, 30 to 40 mm; single slice; and receiver bandwidth, 32 khz. The acquisition time was 2 s. An oral contrast medium was not used in the MRCP examination. Intravenous morphine HCl was then injected at a dose of 0.04 mg/kg and injected within 10 seconds for the first 2 patients. Because the first 2 patients experienced dizziness after the morphine injection, the other 14 donors received the same dosage of morphine diluted in 10 cc of normal saline and injected for more than 1 minute. Images in the best oblique coronal plane were acquired 3 minutes later. Each patient left the examination table after undergoing MRCP for a second time and receiving morphine with a landmark at the substernal region. Fifteen minutes after the administration of morphine, 1 vial (1 mg) of glucagon was injected intramuscularly through the deltoid region, and rapid acquisition with relaxation enhancement images were acquired 30 minutes after the administration of glucagon. All patients were observed for drug-related side effects for at least 30 minutes after the study. The additional cost of morphine and glucagon was $0.30 and $35 (US dollars), respectively. Image Analysis Biliary ductal anatomy shown on MRCP was correlated with operative cholangiography. For those patients with a right posterior hepatic duct (HD) draining to the left HD and for those patients with right HDs leading directly into the common HD or triple confluence of the common HD on MRCP, quantitative and qualitative assessments of the right HDs were not done to avoid underestimation of the diameter and visualization grading scores of the right HDs. For quantitative analysis, transverse diameters of the common bile duct (CBD; 5 cm proximal to the duodenal orifice), pancreatic duct (PD; 0.5 cm proximal to the pancreaticobiliary junction), and right and left HDs (0.5 cm proximal to the confluence of the right and left HDs) were measured at corresponding points on the images before and after the use of glucagon and morphine. Qualitative assessment was based on an evaluation by the naked eye. Criteria for qualitative assessment were clarity of duct visualization and extent of peripheral duct visualization. On the basis of these criteria, the ductal image was graded as follows: 0, not visible; 1, barely visible with only points of signal; 2, signal present in less than 50% of the length of the duct; 3, signal present in more than 50% of the length of the duct, though discontinuously; and 4, visible with signal present throughout the entire length of visualization of the pancreatobiliary ductal system. Two radiologists blinded to the clinical data analyzed the images independently, and the images taken before and after the use of morphine or glucagon were graded separately while mixed with other patients images. In the case of a disagreement, a consensus was achieved by simultaneous assessment by both radiologists. Statistical Analysis Visualization of the pancreatobiliary ducts before and after morphine and glucagon administration was statistically evaluated with the paired t test for quantitative diameter changes and with the Wilcoxon signed-rank test for qualitatively grading branching changes to determine any statistically significant differences between images before and after drug administration. All data were analyzed with STATA software, and a P value less than 0.05 was considered statistically significant. RESULTS Of the 16 patients, 9 underwent intraoperative cholangiography, which revealed a classic confluence pattern of common HDs in 6 of the 9 donors. Images obtained before and after the use of morphine or glucagon showed aberrant right posterior HDs draining to the left HD in a donor, aberrant right posterior HDs draining to the common HD in another donor, and a triple confluence of the common HD (confluence of the right anterior and posterior HDs and left HD) in yet another donor. In 1 patient with an aberrant right posterior HD draining to the left HD, intraoperative cholangiography did not

3 MORPHINE- AND GLUCAGON-AUGMENTED MRCP 1023 Figure 1. A 23-year-old female donor with an aberrant right posterior hepatic duct draining to the left hepatic duct. (A) Plain magnetic resonance cholangiography (with rapid acquisition with relaxation enhancement) was performed in the coronal plane. (B) With the same pulse sequence, an image was obtained 3 minutes after the intravenous morphine injection. The distal aberrant right posterior hepatic duct (arrowhead) was demonstrated. (C) 30 minutes of waiting for the morphine effect, glucagon was given intramuscularly. Then, an image acquired 15 minutes after the injection of glucagon disclosed distended right anterior and left hepatic ducts (arrows). The aberrant right posterior hepatic duct (arrowheads) drained to the left hepatic duct. (D) An intraoperative cholangiogram confirmed that the aberrant right posterior hepatic duct (arrowheads) drained to the left hepatic duct. However, the right anterior hepatic ducts were not opacified during the operation. optimally show the right anterior HD because of incomplete filling (Fig. 1A-D). The branching patterns of the common HD and CBD disclosed by images before and after the use of morphine or glucagon were all correctly confirmed by intraoperative cholangiography performed in all 9 donors undergoing transplantation. Among the 7 of 16 patients who did not receive intraoperative cholangiography, 5 had a classic confluence pattern of the common HD. Augmented and plain MRCP revealed an aberrant right posterior HD leading to the left HD in the other 2 patients. In the quantitative analysis, the mean diameters of the right and left HDs, CBD, and PD, measured at

4 1024 MO ET AL. TABLE 1. Ductal Diameter (Mean Standard Deviation) Before and the of and Glucagon and Abbreviations: CBD, common hepatic bile duct; IHD, intrahepatic bile duct; PD, pancreatic duct. Paired t-test P Value TABLE 2. Signal Grading of the Bile Duct Before and the of and Glucagon and Paired t-test P Value Pre- (1) (2) Glucagon (3) Diameter of the right IHD (cm) Diameter of the left IHD (cm) Diameter of the CBD (cm) Diameter of the PD (cm) Pre- (1) (2) Glucagon (3) Right IHD* Right anterior IHD Right posterior IHD Left IHD Left medial IHD Left lateral IHD CBD NOTE: The grading was scored as follows: 0, not visible; 1, barely visible with only points of signal; 2, signal present in less than 50% of the length of the duct; 3, signal present in more than 50% of the length of the duct, though discontinuously; and 4, visible with signal present throughout the entire length. Abbreviations: CBD, common hepatic bile duct; IHD, intrahepatic bile duct. *Five patients were excluded because they had variation of the branching pattern (the right posterior branch draining to the left IHD in 4 and triple confluence of the common hepatic duct in 1). corresponding points, were , , , and mm, respectively. The diameters of the right and left intrahepatic bile ducts, CBD, and PD significantly increased (P 0.05) immediately after the injection of intravenous morphine ( , , , and mm) and after the use of glucagon and morphine ( , , , and mm) in all 16 donors (100%; Table 1). The right HD was not evaluated in 3 patients with a right posterior HD leading to the left HD, in 1 patient with an aberrant right posterior HD draining to the common HD, and in 1 patient with a triple confluence of the common HD. A qualitative analysis showed that the mean grading scores of visualization and branching of the right anterior, right posterior, left medial, and left lateral HDs and CBD were 3, 3, 2, and 4 respectively. The mean grading scores of visualization and branching generation significantly improved (P 0.05) after glucagon injection (plus delayed morphine effects) in all 16 patients, except for the right and left HDs and CBD (Tables 2 and 3). However, there was no significant difference in the grading scores (4 0 versus 4 0 for the right and left HDs and CBD) of the right and left HDs and CBD acquired before and immediately after the administration of morphine. DISCUSSION Our results revealed that the transverse diameters of the right and left HDs, CBD, and PD significantly increased after the use of morphine and glucagon. Delayed effects of intravenous morphine and glucagons improved the qualitative grading of visualization and branching at the right anterior and posterior HDs and left medial and lateral HDs. MRCP is a noninvasive modality and has been widely applied to demonstrate the structural abnormalities of

5 MORPHINE- AND GLUCAGON-AUGMENTED MRCP 1025 TABLE 3. Order of Branching of Intrahepatic Ducts Before and the of and Glucagon and Paired t-test P Value Pre- (1) (2) Glucagon (3) Right anterior IHD Right posterior IHD Left medial IHD Left lateral IHD NOTE: The branching score shows the order of branching; each bifurcation adds 1 digit. Abbreviation: IHD, intrahepatic bile duct. the biliary tract, 18,19 especially in patients suffering from choledochal cysts and choledocholithiasis. 2,20-25 Because identification of the pertinent biliary anatomy and variations helps to reduce the complication rate of liver transplantation, MRCP is becoming a popular imaging modality for detailed preoperative imaging of biliary trees in living liver donors MRCP can show intrahepatic ducts in many projectional images of variable angles, but intraoperative cholangiography can provide only several projectional images. However, it is usually difficult to show small-caliber, nondilated intrahepatic ducts, especially in liver donors, with MRCP. High-resolution, isotropic, 3-dimensional T2-weighted MRCP images 29 would likely improve visualization of small HDs and provide multiplanar reformatted images, which were not available at our institution when the study started. Several techniques can alter the physiology of the pancreatic and biliary systems and enhance the image quality of MRCP. 9,30,31 and opiates induce contraction of the sphincter of Oddi 7,9 and help with better visualization of the biliary ducts and PD. has been used to augment the sensitivity and specificity of cholescintigraphy. 32,33 The dose of morphine commonly used to augment cholescintigraphy is 0.04 mg/kg. 32,33 However, a previous study 9 examining MRCP using low-dose morphine to improve the visualization of biliary trees was based on the results of a small sample of 5 patients. 9 In the present study, we used the same low-dose morphine for 2 reasons: the low cost and the well-known pharmacological dynamics and side effects. Our first 2 donor candidates experienced the side effect of dizziness after receiving an injection of low-dose morphine. Later, morphine was diluted with 20 ml of normal saline and injected slowly. No more patients suffered from dizziness after this modification of the morphine procedure. According to our results, the extrahepatic biliary trees dilated significantly 3 minutes after the injection of morphine. However, morphine does not have much of an immediate impact on the visualization grading of intrahepatic biliary branches. seems to have no direct effects on biliary secretion. It takes time to accumulate bile above the contracted sphincter of Oddi. Previous investigators have found that the optimal imaging delay after the intravenous injection of morphine is 10 to 30 minutes. 9 Glucagon increases the bile flow and dilates the biliary trees. 6 Moreover, glucagon can eliminate gastrointestinal peristalsis that is related to artifacts on MRCP images. According to our results, the delayed effects of morphine plus the effect of glucagon (about 45 minutes after the injection of morphine) dilate the biliary tree and PD with statistical significance. The delayed effects of morphine plus the effect of glucagon improve the signal and branching identification of MRCP with statistical significance. Glucagon promotes the secretion of bile and distends HDs by relaxing the sphincter of Oddi. The secreted bile may not accumulate within the biliary trees above the relaxed sphincter of Oddi. In contrast, morphine will enhance contraction of the sphincter of Oddi. The combined effect of glucagon and delayed effects of morphine will help to hold increased secretions of bile within the intrahepatic and extrahepatic biliary trees. Therefore, the optimal time interval for performing MRCP imaging in order to get better contraction of the sphincter of Oddi by morphine and increased bile flow by glucagon may be longer than 30 minutes. The discrepancy between the quantitative and qualitative evaluations of HDs exists because the naked eye is less sensitive to the small changes in the diameters of HDs and CBDs after the use of morphine or glucagon in the qualitative evaluation versus the quantitative evaluation. The confluence pattern of segmental intrahepatic ducts may have been more obvious in the qualitative assessment when more bile secretion accumulated above the contracted sphincter of Oddi, induced by the use of glucagon and morphine. In contrast, our quantitative assessment focused on the change in the calibers of the central HDs and CBDs, which more readily distended when the sphincter of

6 1026 MO ET AL. Oddi contracted after the use of morphine. However, the interpretation of confluence patterns of HDs on MRCP mostly depends on findings with the naked eye. A qualitative assessment can be still important for the clinical assessment of potential donors for living-related liver transplantation. In conclusion, the intravenous administration of morphine and intramuscular administration of glucagon before MRCP improve the visualization of biliary trees both qualitatively and quantitatively, especially for the nondilated intrahepatic biliary ductal anatomy. This is a simple and safe technique that may be of great value in the detailed evaluation of living-related liver donor candidates. REFERENCES 1. Hintze RE, Adler A, Veltzke W, Abou-Rebyeh H, Hammerstingl R, Vogl T, Felix R. Clinical significance of magnetic resonance cholangiopancreatography (MRCP) compared to endoscopic retrograde cholangiopancreatography (ERCP). Endoscopy 1997;29: Irie H, Honda H, Jimi M, Yokohata K, Chijiiwa K, Kuroiwa T, et al. Value of MR cholangiopancreatography in evaluating choledochal cysts. AJR Am J Roentgenol 1998;171: Adamek HE, Albert J, Weitz M, Breer H, Schilling D, Riemann JF. A prospective evaluation of magnetic resonance cholangiopancreatography in patients with suspected bile duct obstruction. Gut 1998;43: Sica GT, Braver J, Cooney MJ, Miller FH, Chai JL, Adams DF. Comparison of endoscopic retrograde cholangiopancreatography with MR cholangiopancreatography in patients with pancreatitis. Radiology 1999;210: Taylor AC, Little AF, Hennessy OF, Banting SW, Smith PJ, Desmond PV. Prospective assessment of magnetic resonance cholangiopancreatography for noninvasive imaging of the biliary tree. Gastrointest Endosc 2002;55: Dalal PU, Howlett DC, Sallomi DF, Marchbank ND, Watson GM, Marr A, et al. Does intravenous glucagon improve common bile duct visualisation during magnetic resonance cholangiopancreatography? Results in 42 patients. Eur J Radiol 2004;49: Agarwal S, Nag P, Sikora S, Prasad TL, Kumar S, Gupta RK. Fentanyl-augmented MRCP. Abdom Imaging 2006;31: Wu SD, Zhang ZH, Jin JZ, Kong J, Wang W, Zhang Q, et al. Effects of narcotic analgesic drugs on human Oddi s sphincter motility. World J Gastroenterol 2004;10: Silva AC, Friese JL, Hara AK, Liu PT. MR cholangiopancreatography: improved ductal distention with intravenous morphine administration. Radiographics 2004;24: Mariani A, Curioni S, Zanello A, Passaretti S, Masci E, Rossi M, et al. Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis. Gastrointest Endosc 2003;58: Saremi F, Jadvar H, Siegel ME. Pharmacologic interventions in nuclear radiology: indications, imaging protocols, and clinical results. Radiographics 2002;22: Limanond P, Raman SS, Ghobrial RM, Busuttil RW, Lu DS. The utility of MRCP in preoperative mapping of biliary anatomy in adult-to-adult living related liver transplant donors. J Magn Reson Imaging 2004;19: Lee VS, Krinsky GA, Nazzaro CA, Chang JS, Babb JS, Lin JC, et al. Defining intrahepatic biliary anatomy in living liver transplant donor candidates at mangafodipir trisodium-enhanced MR cholangiography versus conventional T2-weighted MR cholangiography. Radiology 2004;233: Kapoor V, Peterson MS, Baron RL, Patel S, Eghtesad B, Fung JJ. Intrahepatic biliary anatomy of living adult liver donors: correlation of mangafodipir trisodium-enhanced MR cholangiography and intraoperative cholangiography. AJR Am J Roentgenol 2002;179: Lee VS, Morgan GR, Teperman LW, John D, Diflo T, Pandharipande PV, et al. MR imaging as the sole preoperative imaging modality for right hepatectomy: a prospective study of living adult-to-adult liver donor candidates. AJR Am J Roentgenol 2001;176: Fulcher AS, Szucs RA, Bassignani MJ, Marcos A. Right lobe living donor liver transplantation: preoperative evaluation of the donor with MR imaging. AJR Am J Roentgenol 2001;176: Cheng YF, Chen CL, Huang TL, Chen TY, Lee TY, Chen YS, et al. Single imaging modality evaluation of living donors in liver transplantation: magnetic resonance imaging. Transplantation 2001;72: Irie H, Honda H, Tajima T, Kuroiwa T, Yoshimitsu K, Makisumi K, Masuda K. Optimal MR cholangiopancreatographic sequence and its clinical application. Radiology 1998;206: Wallner BK, Schumacher KA, Weidenmaier W, Friedrich JM. Dilated biliary tract: evaluation with MR cholangiography with a T2-weighted contrast-enhanced fast sequence. Radiology 1991;181: Kejriwal R, Liang J, Anderson G, Hill A. Magnetic resonance imaging of the common bile duct to exclude choledocholithiasis. ANZ J Surg 2004;74: Sharma SK, Larson KA, Adler Z, Goldfarb MA. Role of endoscopic retrograde cholangiopancreatography in the management of suspected choledocholithiasis. Surg Endosc 2003;17: Rösch T, Meining A, Frühmorgen S, Zillinger C, Schusdziarra V, Hellerhoff K, et al. A prospective comparison of the diagnostic accuracy of ERCP, MRCP, CT, and EUS in biliary strictures. Gastrointest Endosc 2002;55: Matos C, Cappeliez O, Winant C, Coppens E, Deviere J, Metens T. MR imaging of the pancreas: a pictorial tour. Radiographics 2002;22:e Ly JN, Miller FH. MR imaging of the pancreas: a practical approach. Radiol Clin North Am 2002;40: Chaudhary A, Negi SS, Puri SK, Narang P. Comparison of magnetic resonance cholangiography and percutaneous transhepatic cholangiography in the evaluation of bile duct strictures after cholecystectomy. Br J Surg 2002;89: Mortele KJ, Ros PR. Anatomic variants of the biliary tree: MR cholangiographic findings and clinical applications. AJR Am J Roentgenol 2001;177: Choi JW, Kim TK, Kim KW, Kim AY, Kim PN, Ha HK, Lee MG. Anatomic variation in intrahepatic bile ducts: an analysis of intraoperative cholangiograms in 300 consecutive donors for living donor liver transplantation. Korean J Radiol 2003;4: Imamura H, Makuuchi M, Sakamoto Y, Sugawara Y, Sano K, Nakayama A, et al. Anatomical keys and pitfalls in living donor liver transplantation. J Hepatobiliary Pancreat Surg 2000;7: Morita S, Ueno E, Suzuki K, Machida H, Fujimura M, Kojima S, et al. Navigator-triggered prospective acquisition correction (PACE) technique versus conventional

7 MORPHINE- AND GLUCAGON-AUGMENTED MRCP 1027 respiratory-triggered technique for free-breathing 3D MRCP: an initial prospective comparative study using healthy volunteers. J Magn Reson Imaging 2008;28: Vitellas KM, Keogan MT, Spritzer CE, Nelson RC. MR cholangiopancreatography of bile and pancreatic duct abnormalities with emphasis on the single-shot fast spinecho technique. Radiographics 2000;20: Matos C, Metens T, Devière J, Nicaise N, Braudé P, Van Yperen G, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997;203: Sho M, Nakajima Y, Kanehiro H, Hisanaga M, Nishio K, Nagao M, et al. A new evaluation of pancreatic function after pancreatoduodenectomy using secretin magnetic resonance cholangiopancreatography. Am J Surg 1998; 176: Kim EE, Pjura G, Lowry P, Nguyen M, Pollack M. -augmented cholescintigraphy in the diagnosis of acute cholecystitis. AJR Am J Roentgenol 1986;147: