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SPECIAL ARTICLE Table of Contents   
Year : 1998  |  Volume : 4  |  Issue : 2  |  Page : 67-75
Diagnosis of diseases of biliary and pancreatic ducts with magnetic resonance cholangio pancreatography (MRCP)


Department of Radiology, University of Rome "La Sapienza", Rome

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Date of Submission19-Aug-1997
Date of Acceptance25-Feb-1998
 

   Abstract 

Magnetic Resonance Cholangio Pancreatography (MRCP) is a new noninvasive imaging technique for the evaluation of bilio-pancreatic disorders. Different sequences, using both breth­hold and nonbreath-hold techniques, have been employed in order to obtain MRCP images. The authors discuss the technical aspects, particularly focusing their attention on a nonbreath-hold, threee-dimensional, fat-suppressed Turbo Spin Echo sequence, optimised on a 0.5T magnet with 15 mT/m gradients. Clinical applications of MRCP are evaluated, presenting data from both the literature and the personal experience. The main indication for MRCP study is represented by the evaluation of common bile duct obstruction, with the aim of assessing the presence of the obstruction (accuracy: 91-100%) and, subsequently, the level (accuracy: 85-100%) and the cause. The utility of associating conventional Magnetic Resonance (MR) images to MRCP in malignant strictures, in order to characterize and stage the malignant lesion is also discussed. Finally, data are presented regarding the indictions and the utility of MR-pancreatography in the evaluation of patients with chronic pancreatitis.

How to cite this article:
Pavone P, Laghi A, Panebianco V, Catalano C, Brillo R, Assael F, Passariello R. Diagnosis of diseases of biliary and pancreatic ducts with magnetic resonance cholangio pancreatography (MRCP). Saudi J Gastroenterol 1998;4:67-75

How to cite this URL:
Pavone P, Laghi A, Panebianco V, Catalano C, Brillo R, Assael F, Passariello R. Diagnosis of diseases of biliary and pancreatic ducts with magnetic resonance cholangio pancreatography (MRCP). Saudi J Gastroenterol [serial online] 1998 [cited 2019 Dec 16];4:67-75. Available from: http://www.saudijgastro.com/text.asp?1998/4/2/67/33893


Noninvasive imaging techniques until now have made possible to investigate the biliary tree only by means of bidimensional procedures, as US and CT [1],[2]. Invasive techniques (i.v. cholangiography, endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography) can offer projectional images of the biliary tree, but only by the introduction of contrast medium.

I.v. cholangiography is used in a very limited number of cases due to the incomplete opacification of the biliary system, occurring in about 30-40% of cases and the quite high number of adverse reactions [3],[4] . Thus, only for diagnostic purposes, endoscopic retrograde cholangiopancreatography (ERCP) and, less commonly, percutaneous transhepatic cholangiography (PTC) are often performed. The main advantages of ERCP are the high resolution images and the therapeutical possibilities. But technical limitations can lead to unsuccessful examinations and complications may be observed in a consistent number of patients (asymptomatic hyperamilasemia in 70% of cases, postpancreatographic acute pancreatitis in 0.5% and cholangitis in 1%), with mortality occurring in about 1% of patients [5],[6],[7],[8] . PTC has the same diagnostic and therapeutic role as ERCP, but it is more invasive, risky (incidence of sepsis is around 1.4% of cases) and expensive [9] .

Recently, the development of fast imaging techniques as well as better abdominal image quality allowed MR Cholangiopancreatography (MRCP) to be developed, generating new interest in MR evaluation of bilio-pancreatic diseases. MRCP is a new diagnostic, noninvasive technique for direct visualization of the biliary ducts with images similar to those obtained with invasive cholangiography, but requiring neither the use of contrast medium injection nor any biliary intervention

This paper illustrates the technical aspects of MRCP images as well as the main clinical applications in bilio-pancreatic diseases.


   Technique Top


MRCP technique is based on heavily T2 weighted images whichg result in dramatic increase in contrast between stationary fluids (bile) and background (hepatic and pancreatic parenchymas, abdominal fat). As a result, the bile presents a very high signal intensity compared with low signal intensity background. In addition, no signal comes from flowing blood. Different techniques have been optimized, initially based on gradient echo sequences (GRE) and more recently on fast spin echo (FSE).

The reasons for limiting the use of GRE sequences is due to inherent limitations represented by the poor visualization of small non dilated ducts, the high sensitivity to susceptibility artifacts and the high signal from fat, reducing the contrast between extrahepatic bile ducts and abdominal background. As opposite, compared with GRE sequences, FSE have higher SNR and CNR, lower sensitivity to susceptibility and motion artifacts and blood flow. Moreover, FSE takes advantage of the new techniques that are able to improve image quality, such as gradient moment nulling (reducing artifacts from periodic motion), respiratory triggering and fat-suppression.

Apart from the sequences employed both breath­hold and non-breath-hold ttechniques have been developed.

Breath-hold Techniques:

Several authors explored the possibility to optimize a breath-hold technique for MR Cholangiography. Takehara [12] proposed a breath­hold FSE technique with surface coil and small FOVs in order to increase the SNR and the spatial resolution. The major limitations were represented by the relatively long breath-hold period (44s.), requiring oxygen support in old patients or segmentation of the images, and the evaluation of pancreas in fat patients, when the organ is too deep from the surface coils. In the series from Guibaud [13] , a breath-hold of more than one minute was required, with patients asked to hyperventilate with 100% oxygen for 10 minutes before the examination.

A breath-hold technique with faster acquisition time (18 seconds) by using a fast-inversion recovery sequence in order to get a better CNR was also proposed [14] .

More recently new techniques have been developed, based on modified FSE sequences. This is the case of the experience of Laubenberger [15] with a single-shot RARE technique with acquisition of a single thick slice covering the entire imaging volume within a four second breath-hold. The main disadvantage is the lack of image post-processing, with no availability of source images to be evaluated. The impact of this factor on the diagnosis of small lesions (i.e. small stones) has to be evaluated.

Finally, Sananes [16] stated the feasibility of MR cholangiography with a HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) sequence with a two second breath-hold per slice.

Different techniques have been explored by other authors [17],[18] , but they are not commercially available and therefore of no general interest to date.

Non-breath-hold techniques:

The reasons for investigating the use of non­breath-hold technique are due to the fact that most of the patients are old and noncooperative, so that they cannot hold their breath even for 20 seconds, as required by most of the available breath-hold techniques.

Non-breath-hold techniques are all based on FSE sequences and were firstly proposed in 1993 by Meakem et al and Outwater [19],[20]. Both 2D and 3D acquisition techniques have been developed. Macaulay and Reinhold [21],[22] explored the potential advantages of a 2D FSE technique, the main limitation of which is related to the slice thickness (no less than 3mm) due to gradient restrictions. However, 3D FSE technique used by Barish et al at 1.5T [23] , and by Pavone, Laghi et al at 0.5T [24] may overcome these limitations. The use of three­dimensional acquisition improves the signal-to-noise ratio and spatial resolution and decrease imaging artifacts. Near isotropic resolution allows maximum­intensity-projection images in any plane as well as multiplanar reformatting to be performed.

Personal experience:

In our institution MRCP examinations are performed by using a 0.5 Tesla superconductive magnet with gradient strength of 15mT/meter. The body coil is used for both excitation and signal reception. We have optimised a heavily T2 weighted three-dimensional, fat suppressed (SPIR) Turbo Spin-Echo (TSE) sequence. Imaging parameters, modified during the past three-year experience, are now as follows: TR=2000 ms, TE=700 ms, Echo Train Length (ETL)=123. Images are acquired on the coronal plane with a 3-mm (or 2 mm) partition thickness. Imaging volume is positioned to image both the pancreatic and the biliary ducts using as scout view an axial T2w (TRITE: 3000/120) TSE sequence. A field of view of 240 nun allows to improve spatial resolution and to image only the region of interest, avoiding surrounding fluid structures (i.e. cysts, bowels, etc.). Image matrix size ranges between 83x128 and 184x256, depending on clinical indication (for example higher matrix is used in case of evaluation of secondary pancreatic ducts). Six to eight signal averages are selected for all images with a nominal acquisition time less than six minutes for a 6 cm-volume. Respiratory triggering is used in order to reduce motion artifacts. With respiratory triggering the data are acquired between end-expiration and the beginning of the next inspiratory phase.

No patient preparation and sedation are required. In our experience, we administered an antiperistaltic drug (i.m. 20 mg of hyoscine butylbromine, Buscopan; Boehringer Ingelheim, Florency, Italy) to reduce motion artifacts resulting from peristalsis and tap water (around 200 cc) in order to obtain a complete filling and visualization of the duodenum.

Image reconstruction techniques:

Image reconstruction with multiple projections is performed at the console, after all the source images have been acquired, either with 2D or 3D techniques. Different reconstruction techniques can be used: MIP (Maximum Intensity Projection), Targeted MIP, MPR (MultiPlanar Reformations) and, if available, SSD (Shaded Surface Display) [25],[26] .

We have studied 430 patients with bilio-pancreatic disorders. The results of our work are reported in the following [Table 1],[Table 2],[Table 3],[Table 4].

Normal anatomy, anatomic variants and congenital anomalies

MR cholangiography is able to image a normal caliber common bile duct (CBD) [Figure - 1], although the larger is the caliber of the CBD, the better will be the quality of the reconstructed images. Right and left hepatic duct as well as the common hepatic duct are always evident on MRCP images, and better displayed on MIP-reconstructed images using a right anterior oblique projection. Intrahepatic segmentary ducts are evident only up to the first-order branches. More peripheral ducts, due to small caliber, can be visualized only in case of dilatation. A distended gallbladder is clearly visible on MRCP images as well as the cystic duct and its insertion to the CBD.

The main limitation of MR cholangiography is represented by the lack of detailed evaluation of the papillary region. A useful trick to obtain a better depiction of the papilla is to administer tap water prior to the examination. In this way, with consistent filling of the duodenum the distance between the distal CBD and the duodenum can be clearly evaluated, in order to rule out the presence of expansile lesion in this region.

Anatomic variants and developmental anomalies are rare findings and represented by aberrant drainage or congenital dilatation of the biliary ducts [27] . Congenital dilatation can involve either the extrahepatic or the intrahepatic biliary tree, or both of them. In case of Caroli's disease, particularly, MRCP can be extremely important and could be proposed as the only diagnostic examination, because it offers an optimal visualization of the intrahepatic cystic dilatations and it can demonstrate, by the analyzis of the source images, the communication among the multiple cysts, that is mandatory for the differential diagnosis with cystic disease of the liver and multiple abscesses [28] .

Bile duct obstruction

Biliary obstruction represents the main indication for MRCP study because of the ability of this technique in assessing the presence, the site and the cause of the obstruction. The accuracy in diagnosing the presence of the obstruction ranges between 91 and 100% whereas the level of the obstruction can be correctly evaluated in 85-100% of cases [29],[30] . The advantages of MRCP are mainly related to routine visualization of bile ducts above and below the obstruction with a very consistent demonstration of intrahepatic biliary branches [Figure - 2]. At ERCP tight strictures may not be overcome by the guide and overdistension of bile ducts above is usually avoided due to the risk of septic complications, with a consequent poor image quality. In high obstructions MRCP provides a complete map of the biliary system, with depiction also of excluded segmentary ducts, possibly not evaluated at PTC. Finally, MRCP offers evaluation of bile ducts with physiological filling condition as opposite to ERCP where overfilling or underfilling of contrast medium injection may modify the real anatomical situation.

Lithiasis:

Biliary stones, independently of calcium content, present almost always a low signal intensity on MR images [31] . Therefore, the stone is identified as a round or oval-shaped "filling defect" within the CBD, surrounded by the high signal intensity bile, with semeiologic criteria similar to conventional cholangiography, although based on different physical basis. When the stone is wedged at the level of the papilla, a typical "meniscus sign" can be observed.

Although spatial resolution of MRCP is lower than ERCP, the higher contrast resolution allows 2-3 mm stones to be easily detected [Figure - 3] a & b. In case of obstruction stone at the level of the papilla, with impossible cannulation of the CBD at ERCP, MRCP is able to depict the biliary tract above the obstruction, showing additional stones.

The diagnostic accuracy of MRCP in choledocholithiasis is very high, ranging between 89% and 97% (sensitivity 81-95%, specificity 85­-98%), as reported by several studies [32],[33],[34],[35] .

Nevertheless different pitfalls can be observed which require correct identification in order to avoid wrong diagnoses. They are represented by: 1) lack of evidence of stones on MIP reconstructed images; 2) CBD completely filled with stones; 3) pneumobilia; 4) differential diagnosis between air bubbles and small stones.

For what concern artifacts due to MIP reconstructions, usually there are no difficulties in detecting large size stones (more than 1 cm in diameter) even on MIP reconstructed images, where a filling defect can be easily recognized. But the identification of small stones needs the evaluation of source images, that is a "tomographic-like" image analyzis. This pitfall is well known to endoscopists who can miss small stones at ERCP, due to overfilling of the bile ducts with contrast medium. Multiple stones in the main bile duct may determine inhomogeneous signal with poor depiction of the CBD; also in this case the evaluation of source images is very helpful in detecting thin lines of bile surrounding the multiple stones. Another problem is related to pneumobilia, which determines susceptibility artifact in our experience, only in one patient out of more than 400, there was such a large amount of air in the CBD determining susceptibility artifacts and avoiding the visualization of a small stone. Finally, in case of air bubbles, the use of images on the axial plane (obtained either with a second acquisition on the axial plane or with multiplanar reformation, in case of 3D acquisition) can establish the differential diagnosis between a small stone (usually in the dependent part of the biliary duct) and air bubble (found in the non­dependent part).

Benign biliary strictures:

Benign biliary strictures are the result of surgical injury in 90-95% of cases (laparoscopic cholecystectomy, gastric and hepatic resection, biliary enteric anastomoses, post liver transplantation), external penetrating or blunt trauma, inflammation associated with lithiasis, chronic pancreatitis, stricture of the papillary region, toxic or ischemic lesion of the hepatic artery or primary infection, such as in primary sclerosing cholangitis [36] .

latrogenic strictures:

The major cause of iatrogenic strictures is due to injuries inflicted during cholecystectomy. In particular, the increase in biliary injuries has come with the advent of laparoscopic cholecystectomy (0.1% in open surgery vs. 0.3% in laparoscopic procedures) [37] . The availability of new mini­invasive therapeutical procedures, represented by interventional radiology and endoscopy, greatly increases the need for a complete preoperative overview of the patient's biliary tree, in order to plan the adequate approach (either percutaneously or endoscopically). MRCP can easily and noninvasively provide all the necessary information regarding the biliary stricutre, such as the location of the stricture (according to Bismuth's type classification) as well as the extent and the degree [Figure - 4]. It can also avoid a common pitfall of ERC, that is the lack of visualization of dilated ducts above the stricture, so only a cut-off can be visualized or alternatively in case of intrahepatic stricutre ERC can overlook the unopacified or excluded bile duct segment.

Papillary strictures:

MRCP may play a very important role in the identification of papillary disease. In fact, these clinical entity do not present specific symptoms and a differential diagnosis has to be established with other bile duct diseases, including stones and neoplasms. Papillitis often represents a clinical dilemma, if treating the patient or not.

MRCP may provide the correct diagnostic information in this group of patients with high accuracy. In fact, it can rule out other possible causes of symptoms, it can provide an accurate evaluation of the biliary anatomy and it can define the presence of biliary dilatation and the papillary stricture. Diagnosis of papillitis is based only on morphologic features, represented by dilation of CBD (>1 cm) and papillary stricture with typical "flute-beak" appearance in a minority of cases or alternatively with tight obstruction [Figure - 5]; in both the cases there is no evidence of solid lesions in periampullary region on conventional T1w images. Probably, based only on morphologic features, overestimation can occur, thus great importance has to be given to symptoms. However, including MRCP in the diagnostic protocols will limit the role of ERCP, whose interventional role would be limited to highly selected cases.

Liver transplantation:

In liver-transplanted patients, the major role of MRCP is related to late complications, mainly represented by either anastomotic or nonanastomotic strictures, bile duct stones and papillary dysfunction. Early complications, in fact, are easily diagnosed and managed with US, CT and interventional procedures. The goal of MRCP in late complications is to avoid useless invasive procedures in patients, when sonographic findings and clinical symptoms are nonspecific, and suspicion of bile ducts obstruction is still an issue. In these cases cholangiographic examination is mandatory and it can nowadays be completely replaced by MRCP [38] .

Follow-up of biliarv-enteric anastomoses:

The role of MRCP in the diagnostic algorithm of patients with biliary-enteric anastomoses is in assessing patients with mild symptoms, in order to avoid unnecessary invasive imaging modalities [39]. In fact, in patients with hepaticojejunostomy, the only cholangiographic examination to be performed is MRCP which can also help serve as a screening method with patients requiring treatment or further evaluation with ERC or PTC. MRCP images may also be used as a guide for subsequent interventional procedure.

In our experience, image quality was graded as optimal to good in 21 (88%) of 24 cases and poor in three (13%) of 24 cases. The degree of bile duct dilation was correctly assessed with complete agreement between the two observers in all patients. MRCP correctly showed: bile duct irregularities in six of eight patients affected by cholangitis; anastomotic strictures in all the 19 patients with strictures; and 3 to 15 mm stones in nine of 10 patient. A slight overestimation of the strictures occurred in four of the 19 cases with strictures [40] .

Malignant biliary strictures:

In the evaluation of malignant strictures MRCP semeiologic criteria are similar to ERCP, with some inherent limitations. Usually, the morphology and the length of the strictures are clearly evaluated by MRCP, although limitations are due to fine details regarding asymmetry and wall irregularities. Moreover, at ERCP contrast medium injection can provide additional information concerning the stricture, not available with MRCP. But, MRCP in malignant strictures has to be considered as part of complete abdominal evaluation, together with conventional MR images. Therefore, the role of MR imaging is to diagnose the obstruction, to characterize the cause and to provide all the additional information necessary for therapeutical planning, thus replacing both CT and ERCP. In a study of 79 biliary obstructed patients MR was able to diagnose the presence of malignant obstruction with a sensitivity of 86% and specificity of 98% [32] .

Cholangiocarcinoma:

The role of imaging modalities in cholangiocarcinoma is to identify the lesion, stage it and, if unresectable, to plan the adequate palliative treatment. Cholangiocarcinoma may present as a stricture, involving the common bile duct (30-36%), the common hepatic duct (15-30%), the biliary bifurcation, with the typical aspect of Klatskin tumour (10-26%) and the intrahepatic ducts (8-13%) with no evidence of mass lesion or as a nodular process with intrahepatic solid mass.

MRCP features are a sudden biliary obstruction with dilatation of bile ducts above. MRCP can provide a detailed map of the biliary tree above the stricture, also demonstrating isolated segmental ducts, not directly evaluated at ERCP or PTC. In case of Klatskin tumors, infouuation regarding the involvement only of the right or left biliary system or both can be easily obtained, with important consequences on therapeutical approach. As for the other neoplastic lesion, conventional MR images are needed for correct lesion identification and staging. In particular, for cholangiocarcinoma, Tlw images after contrast medium injection can be very helpful in correct identification of the lesion and of its relationship with surrounding organs. Usually, in case of infiltrating lesion, no expansile process is usually identified, whereas solid parenchymal lesion can be observed in intrahepatic forms.

Pancreatic head carcinoma:

The typical cholangiographic appearance of pancreatic head carcinoma is represented by sudden obstruction at the level of the head of the pancreas with a double duct sign, due to biliary and pancreatic ducts dilatation, and evidence of mass effect [Figure - 6]a & b. In case of long-lasting dilatation, the dilated CBD assumes a tortuous aspect with prestenotic horizontal tract. The morphology of the obstruction can be helpful in the differential diagnosis between pancreatitis and neoplastic lesion, although not pathognomonic. In general, the obstruction secondary to pancreatic cancer presents with "mouse tail" pattern or with sudden reduction of the caliber of the bile duct. In case of pancreatitis the biliary duct stenosis has a tapered aspect. For what concerns pancreatic duct, in neoplastic lesions it is usually homogeneously dilated, whereas in chronic pancreatitis an irregular dilatation with a beaded appearance (alternation of dilated and stenotic segments) can be observed. As for cholangiocarcinoma, also in case of pancreatic head lesions the evaluation of conventional MR images is mandatory for a corrrect diagnosis.

Secondary biliarv involvement:

It can be caused by hilar lymphadenopathies or hepatic metastases with occlusion of segmental or subsegmental branches. In these cases MRCP can demonstrate the intrahepatic duct dilatation and the level of the occlusion, intrahepatic, hilar or subhilar. The role of MRCP in these cases is confined to the demonstration of the biliary map with evaluation dilated segments which may require percutaneous drainage.


   MR Pancreatography Top


MRCP is valuable technique for the evaluation of the pancreatic duct. Normal nondilated pancreatic duct can be depicted, as reported in a study by Soto et al [41] , with accuracy of 69% on MIP reconstructed images and 81% when evaluating source images. Congenital anomalies (i.e. accessory ducts, pancreas divisum) are easily evaluated at MRCP, with an accuracy ranging between 67% and 100% [41] .

The role of MRCP in chronic pancreatitis has to be discussed. In fact, due to lower spatial resolution, abnormalities in cases of mild pancreatitis cannot be assessed. Probably this also depends upon the different condition of the pancreatic system compared with ERCP examinations: in fact during retrograde pancreatography, contrast medium injection creates overdistension of the ducts, whereas MRCP reflects the physiologic condition. Nevertheless, an important role for MRCP can be proposed, especially in the diagnosis and follow-up of advanced cases. Criteria for diagnosing chronic pancreatitis are represented by tapered stricture of the CBD, if involved, and irregular dilatation with a beaded appearance [Figure - 7] (alternation of dilated and stenotic segments) of the pancreatic duct. Other common findings include filling defects within the pancreatic duct (stones, casts) and pseudocysts. Sensitivity in detection of pancreatic duct dilatation ranges between 87% and 100%, whereas stones are identified in 92-100%, depending on the location (tail 92%, head and body 100%) [12],[41] ; detectability, improved by examination of source images, is also highly dependent on the size of the filling defects. For what concerns cystic masses, fundamental for a correct treatment planning is the proof of a communication between the cyst and the pancreatic duct, not always provided at MRCP, because of the absence of intraluminal contrast medium injection. At MRCP, the contemporary evaluation of conventional MR images together with MIP­reconstructed and source images may show the relationship among the cystic lesion, the pancreatic parenchyma and the ductal system.


   Conclusions Top


In summary MRCP is a new noninvasive important tool in the diagnosis of bilio-pancreatic diseases, to be considered part of a comprehensive MR study of the upper abdomen. MRCP may easily discriminate between patients with malignant and benign lesions, suggesting the more appropriate therapy. In case of malignant diseases, MRCP together with conventional MR images may completely replace the role of CT and ERCP in pre­surgical evaluation of the patients.

Finally, the widespread diffusion of these new techniques requires availability of MR equipment and cost-reduction of the examinations. Therefore, cost-effective studies are needed in order to propose a definite role for MRCP in clinical flow chart of bilio-pancreatic diseases.

 
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34.Chan Y, Chan ACW, Lam W WM, et al. Choledocholithiasis: comparison of MR Cholangiography anbd Endoscopic retrograde Cholangiography. Radiology 1996;200:85-9.  Back to cited text no. 34    
35.Regan F, Fradin J. Khazan R, et al. Choledocholithiasis: evaluation wtih MR Cholangiography. AJR 1996:167:1441-5.  Back to cited text no. 35    
36.Lillemoe KD, Pitt HA, Cameron JL. Current management of benign bile duct strictures. Adv Surg 1992;25:119-73.  Back to cited text no. 36  [PUBMED]  
37.Crist DW, Gadacz TR. Complications of laparoscopic surgery. Surg Clin North Am 1993;73:265-89.  Back to cited text no. 37  [PUBMED]  
38.Laghi A, Pavone P, Catalano C, et al. Role of MR cholangiography in liver transplant recipients. Radiology 1996, 201:351.  Back to cited text no. 38    
39.Papp J, Tulassay Z, Bielawski J, et al. Diagnostic value of endoscopic retrograde cholangiopancreatography in bilio­digestive anastomoses. Acta Hepatogastroenterol 1977;24:41-3.  Back to cited text no. 39    
40.Pavone P, Laghi A, Catalano C, et al. MR Cholangiography in the evaluation of patients with biliary-enteric anastomoses. AJR 1997, in press.  Back to cited text no. 40    
41.Soto JA, Barish MA, Yucel EK, et al. Pancreatic duct: MR Cholangiography with a three-dimensional fast spin echo technique. Radiology 1995;196:459-64.  Back to cited text no. 41  [PUBMED]  

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Correspondence Address:
Paolo Pavone
Department of Radiology, University of Rome "La Sapienza", Policlinico Uniberto I, Viale Regina Elena 324, Rome

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Source of Support: None, Conflict of Interest: None


PMID: 19864772

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    Abstract
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