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Pediatric Imaging |
1 From the Departments of Radiology (R.M., B.G., M.G.B., A.V., G.M., P.M.) and Endoscopic Surgery (G.C.), A. Gemelli University Hospital, 8 Largo A. Gemelli, Rome 00168, Italy; and Departments of Gastroenterology (V.L.) and Endoscopic Surgery (L.D.), Bambino Gesù Children’s Hospital, Rome, Italy. From the 2000 RSNA scientific assembly. Received June 20, 2001; revision requested August 15; revision received November 5; accepted March 25, 2002. Address correspondence to R.M. (e-mail: rmanfredi@rm.unicatt.it).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Fifteen children (mean age, 11.3 years; range, 6–17 years) with at least three recurrent episodes of idiopathic acute pancreatitis prospectively underwent MR cholangiopancreatography before and after secretin administration. Image analysis included visualization of side branches, ductal narrowing, endoluminal filling defects, irregular ductal contour, cavities, and pancreas divisum. All patients underwent endoscopic retrograde cholangiopancreatography (ERCP).
RESULTS: Dilated side branches were detected in three (20%) of 15 patients on MR cholangiopancreatograms obtained before secretin administration and in seven (47%) of 15 patients on images obtained after secretin administration. Ductal narrowing was detected in one (7%) of 15 patients on images obtained before secretin administration and in two (13%) of 15 patients on images obtained after secretin administration. Endoluminal filling defects in one (7%) of 15 patients were observed on MR cholangiopancreatograms obtained both before and after secretin administration. Irregular contour of the main pancreatic duct was present in four (27%) of 15 patients on MR cholangiopancreatograms obtained before secretin administration and in five (33%) of 15 patients on images obtained after secretin administration. Cavities and pancreas divisum were detected in one (7%) of 15 patients and in two (13%) of 15 patients, respectively, only on MR cholangiopancreatograms obtained after secretin administration.
CONCLUSION: Secretin improves the sensitivity of MR cholangiopancreatography in diagnosing early-onset idiopathic chronic pancreatitis.
© RSNA, 2002
Index terms: Bile ducts, MR, 774.12141 • Children, gastrointestinal system, 77.291 • Endoscopic retrograde cholangiopancreatography (ERCP), 774.1222 • Magnetic resonance (MR), cholangiopancreatography, 774.12141 • Pancreatitis, 77.291
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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ICP has a bimodal distribution according to the age of onset of symptoms—whether early or late (4,5). In early-onset ICP (median age, 19.2 years), pain occurs more frequently and is more severe compared with that in the late-onset form (median age, 52.2 years), which is characterized by a rapid development of calcification and pancreatic insufficiency (4). Therefore, a prompt diagnosis of ICP in patients with recurrent episodes of idiopathic acute pancreatitis may help in predicting the natural history of the disease and planning adequate treatment.
However, early-onset ICP may be difficult to diagnose because symptoms appear in children and are most often nonspecific; furthermore, laboratory findings may be transient, and noninvasive imaging modalities such as ultrasonography (US) or computed tomography may not be able to depict subtle pancreatic duct abnormalities.
Therefore, endoscopic retrograde cholangiopancreatography (ERCP) is frequently required in patients with recurrent episodes of idiopathic acute pancreatitis when early-onset ICP is suspected. However, ERCP is operator dependent, has a 5% complication rate (6), and frequently necessitates the use of general anesthesia in pediatric patients.
Magnetic resonance (MR) cholangiopancreatography is a noninvasive imaging modality that is able to accurately depict pancreatic duct abnormalities in adults with chronic pancreatitis (7–10). Dynamic MR cholangiopancreatography after secretin administration improves ductal visualization (11–13) and enables the noninvasive assessment of pancreatic exocrine function (13,14).
The aim of our study was to assess the accuracy of dynamic MR cholangiopancreatography after secretin administration in detecting pancreatic duct abnormalities typical of early-onset ICP in children with recurrent episodes of idiopathic acute pancreatitis.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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We excluded from the study those patients whose pancreatic inflammation was the result of another cause, such as viral infection, hyperlipidemia or other metabolic disease, cystic fibrosis, or a biliary cause of inflammation such as an anomalous pancreaticobiliary junction.
None of the patients had pancreatic insufficiency according to the fatty stool test (ie, steatorrhea-to–ingested fat ratio, 
93%). Five patients had a strong family history of pancreatic disease: Two patients had family members with cystic fibrosis, and three patients had family members with chronic pancreatitis.
All patients underwent dynamic MR cholangiopancreatography before and after secretin administration between July 1997 and August 2000. We explained to the parents and to the children in detail the purpose of the study and the risks involved in it and obtained their consent.
All patients also underwent ERCP with general anesthesia, results of which constituted the standard of reference for ductal abnormalities. One patient was excluded from the study because of an unsuccessful ERCP procedure. Therefore, our study population consisted of 15 children. The mean interval between MR cholangiopancreatography before and after secretin administration and ERCP was 3.5 months (range, 8 days to 1.4 years).
The mean interval between the clinical onset of symptoms and ERCP was 2.1 years (range, 0.1–7.3 years); the mean age at diagnosis was 10.5 years (range, 5.8–16.4 years).
MR Imaging
MR imaging was performed with a 1.5-T MR imager (Signa Horizon Echospeed; GE Medical Systems, Milwaukee, Wis) and a phased-array surface coil. None of the patients required sedation or anesthesia.
Transverse T1-weighted images of the pancreas, both without and with fat saturation, were acquired with a spin-echo or fast multiplanar spoiled gradient-echo pulse sequence, according to the ability of the child to hold his or her breath for the entire duration of the pulse sequence. A spin-echo pulse sequence was performed in three (20%) of the 15 children with the following imaging parameters: repetition time msec/echo time msec, 500–600/14; 6-mm section thickness; a 1-mm intersection gap; a 256 x 192 matrix; one signal acquired; and a 30-cm field of view. A spoiled gradient-echo pulse sequence was performed in 12 (80%) of the 15 children with the following imaging parameters: 160/4.2, a 90° flip angle, 6-mm section thickness, 1-mm intersection gap, a 256 x 192 matrix, one signal acquired, and a 30-cm field of view.
A transverse T2-weighted half-Fourier single-shot rapid acquisition with relaxation enhancement (RARE) (ie, single-shot fast spin-echo) sequence was performed in all patients with the following parameters: 
/110, a 256 x 256 matrix, 0.5 signal acquired, 6-mm section thickness, a 1-mm intersection gap, and a 30-cm field of view.
Coronal T2-weighted half-Fourier single-shot RARE images were obtained of the pancreas in all patients with the following parameters: /110, a 256 x 256 matrix, 0.5 signal acquired, 6-mm section thickness, 1-mm intersection gap, and a 40-cm field of view. Transverse and coronal T2-weighted sequences were repeated with respiratory triggering in those patients who could not hold their breath for the total imaging time.
MR cholangiopancreatography was performed with a dynamic, breath-hold, two-dimensional, half-Fourier single-shot RARE heavily T2-weighted pulse sequence along the coronal or coronal oblique plane. The following parameters were used: />800, 21–35-mm section thickness, a 256 x 256 matrix, 0.5 signal acquired, and a 26–32-cm field of view for a total acquisition time of 2 seconds. No postprocessing was performed.
A negative contrast agent consisting of up to 200 mL of superparamagnetic iron oxide particles (ferumoxsil, Lumirem; Guerbet, Aulnay-sous-Bois, France) was administered orally before MR cholangiopancreatography to eliminate shadowing caused by overlapping fluid-containing organs.
A series of MR cholangiopancreatograms was acquired before secretin administration with a different degree of angulation to optimally position the image sections so that they included the entire pancreatic ducts and their emergence in the papillae. Once the optimal imaging plane was selected, secretin (Secrelux; Goldham-Bioglan, Zusmarhausen, Germany) was administered intravenously in a dose of 1 U per kilogram of body weight. Subsequently, MR cholangiopancreatography was repeated every 30 seconds for 10 minutes. No side effects were recorded.
Image Analysis
MR cholangiopancreatograms were analyzed by two radiologists experienced in biliopancreatic imaging (R.M., M.G.B.) who were blinded to other imaging information; any interpretation discrepancies were resolved by consensus.
Qualitative image analysis included classification of MR cholangiopancreatographic visualization of the common bile duct as good, fair, or poor. The criteria for these three categories were as follows: Visualization was considered good when the entire length of the duct could be visualized, it was considered fair when two-thirds of the duct could be visualized, and it was considered poor when only one segment of the duct could be visualized.
The number of main pancreatic duct segments (head, body, and tail of the gland) that could be visualized was assessed, as was visualization of the accessory duct of Santorini, visualization of side branches, morphology of the contour of the main pancreatic duct (ie, smooth or irregular), presence of ductal narrowing or endoluminal filling defects, presence of cavities, presence of acinar filling, and presence of pancreas divisum. The categorization of narrowed segments was based on the Cambridge classification (16); however, side-branch dilatation was diagnosed when the observer could visualize side branches on MR cholangiopancreatograms.
Quantitative image analysis included measurement of the caliber of the main pancreatic duct before and 3 minutes after administration of secretin and the degree of duodenal filling 10 minutes after administration of secretin. The degree of duodenal filling was classified according to the following scale: grade 0, no duodenal filling; grade 1, limited to the duodenal bulb; grade 2, up to the genu inferius; and grade 3, beyond the genu inferius. Measurements were performed with an electronic caliper in the head, body, and tail of the pancreatic duct by a radiologist (B.G.) who did not perform the qualitative analysis.
Statistical Analysis
A two-way analysis of variance with a "sphericity assumed" correction was applied to analyze the differences in the size of the main pancreatic duct on MR cholangiopancreatograms obtained before and 1, 3, 5, and 10 minutes after administration of secretin. A P value less than .05 was considered to indicate a statistically significant increase in the size of the duct.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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The number of main pancreatic duct segments (head, body, and tail of the gland) visualized on MR cholangiopancreatograms was 24 (53%) of 45 before administration of secretin and 42 (93%) of 45 after administration of secretin. The accessory duct of Santorini was visualized in one (7%) of 15 patients before the administration of secretin and in eight (53%) of 15 patients after the administration of secretin.
Side branches were detected in three (20%) of 15 patients on MR cholangiopancreatograms obtained before the administration of secretin and in seven (47%) of 15 patients on images obtained after the administration of secretin (Fig 1). The agreement between MR cholangiopancreatography before secretin administration and ERCP in depicting dilatation of side branches is reported in Table 1; the agreement between MR cholangiopancreatography after secretin administration and ERCP is reported in Table 2.
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The agreement between findings at MR cholangiopancreatography performed before and after the administration of secretin, respectively, and findings at ERCP of ductal narrowing, endoluminal filling defects, presence of cavities, and pancreas divisum is reported in Table 1 and Table 2.
Compared with ERCP, MR cholangiopancreatography after secretin administration resulted in an overall increase in the number of true-positive findings (nine vs 16) compared with MR cholangiopancreatography before secretin administration. There was, however, also an increase in the number of false-positive findings at MR cholangiopancreatography after secretin administration (one false-positive finding of side branches and two false-positive instances of ductal narrowing were observed).
Quantitative Image Analysis
The mean diameters of the main pancreatic duct in the head, body, and tail of the gland are reported in Figure 5. The two-way analysis of variance demonstrated a significant increase in the size of the main pancreatic duct after secretin administration in each segment (head, body, and tail) of the pancreatic duct (P < .001). A higher degree of significance in the changes in duct size was reached 3 and 5 minutes after secretin administration in all three main pancreatic duct segments (Table 3).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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MR cholangiopancreatography permits the noninvasive assessment of pancreatic ducts in both adults (7–10) and children (17,18) with good image quality, especially when pulse sequences that necessitate breath holding are used. In our series, we also obtained good or fair visualization of the common bile duct in all patients; this represents an indirect assessment of overall image quality and indicates the reliability and reproducibility of the technique.
However, despite good image quality, MR cholangiopancreatography may result in a high number of false-negative findings in the assessment of the pancreatic ducts because of the small size of the main pancreatic duct (especially in the tail of the pancreas) and of the side branches (9).
Exogenous administration of secretin stimulates the exocrine pancreas in the production of fluid and bicarbonates that accumulate inside the pancreatic ducts and thus improves visualization of the pancreatic duct at MR cholangiopancreatography (11–13).
In our series, because of this improved visualization of the pancreatic duct, MR cholangiopancreatography after secretin administration enabled visualization of dilated side branches in all patients who had altered side branches at ERCP; in this manner, consequences of three false-negative findings at MR cholangiopancreatography before secretin administration were avoided. However, there was also a false-positive finding of dilation of side branches on an MR cholangiopancreatogram obtained after secretin administration. This is most likely due to the difficulty in discriminating between normal and altered side branches at MR cholangiopancreatography after secretin administration, owing to the lower spatial resolution of MR cholangiopancreatography both before and after secretin administration compared with ERCP.
In our series, administration of secretin did improve the detection of ductal narrowing but at the same time increased the number of false-positive findings compared with ERCP. This discrepancy might be explained by the different way of imaging the pancreatic ducts between the two procedures: At MR cholangiopancreatography, the ducts are visualized in their normal physiologic condition, whereas at ERCP they are imaged under pressure. This may cause an overestimation of narrowing on MR cholangiopancreatograms obtained after secretin administration.
In our series, secretin did not improve the visualization of endoluminal filling defects; this is probably due to the fact that endoluminal filling defects are a sign of severe chronic pancreatitis in which the main pancreatic duct is already dilated, with a larger amount of fluid inside surrounding the entire circumference of the protein plug. However, the visualization of cavities, a typical finding in moderate and severe chronic pancreatitis, was improved at MR cholangiopancreatography after secretin administration because of the communication between the cavity and the duct system.
Irregularity of the contour of the main pancreatic duct is a sign of chronic pancreatitis (16). In our series, administration of secretin improved the visualization of an irregular ductal contour that was not detected on MR cholangiopancreatograms in one patient. The irregularity of the contour is an expression of the chronic inflammatory process of the pancreatic duct; therefore, detection of this irregular contour may help in recognizing chronic pancreatitis in its early phase. The detection of pancreas divisum was improved on MR cholangiopancreatograms obtained after secretin administration compared with those obtained before secretin administration.
One patient in our series had progressive hydrographic enhancement of the pancreatic parenchyma ("acinar filling") after secretin administration. This patient did not have any other ductal alteration at MR cholangiopancreatography before or after secretin administration; at ERCP, however, there were ductal alterations typical of mild chronic pancreatitis. Therefore, acinar filling may represent an early sign of chronic pancreatitis—leakage of fluid caused by increased ductal and tissue pressure in a pancreas that has lost its elasticity—that has been described in human and animal models (19).
In our series, five (33%) of 15 patients had normal morphology of the pancreatic ducts at both MR cholangiopancreatography and ERCP, despite clinical symptoms; recurrent episodes of idiopathic acute pancreatitis were diagnosed in these patients. In these patients it is unclear whether the inflammatory process had not had enough time to result in the morphologic changes of the pancreatic ducts that occur in early chronic pancreatitis (considering that the patients were children) or if it will eventually regress.
According to the quantitative image evaluation in our study, the size of the main pancreatic duct significantly increased after the administration of secretin, reaching a peak 3 minutes after injection. These data are in agreement with those obtained in adults with MR cholangiopancreatography (13) and US (20,21); however, they are particularly important in children, in whom the pancreatic ducts are physiologically smaller.
The assessment of duodenal filling on MR cholangiopancreatograms after secretin stimulation can be used to semiquantitatively evaluate pancreatic secretion (14). Pancreatic secretion represents an indirect index of the pancreatic exocrine reserve, which is typically reduced with chronic pancreatitis in adults (22). In children we found that duodenal filling was normal in 14 (93%) of 15 patients; only one (7%) had a minor reduction in duodenal filling. This discrepancy is most likely explained by the fact that, in children, chronic inflammation of the pancreas has not as yet caused destruction of the parenchyma; this process is responsible for the pancreatic insufficiency typical of chronic pancreatitis in adulthood.
One of the limitations of the present study was the relatively long interval between ERCP and MR cholangiopancreatography in two patients. The reason for this delay in these patients was that they had negative results at MR cholangiopancreatography before and after secretin administration, so the ERCP procedure was delayed until the children experienced the next acute episode. In conclusion, we believe MR cholangiopancreatography represents a valid, noninvasive alternative to ERCP in the diagnosis of early-onset ICP in children. Furthermore, the administration of secretin improves the accuracy of MR cholangiopancreatography, especially in assessing the early phase of the disease. The ability to noninvasively diagnose and follow up pediatric patients with recurrent episodes of acute pancreatitis and early-onset ICP may improve their treatment, and early diagnoses may also help researchers better understand the natural history of the disease.
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FOOTNOTES |
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Author contributions: Guarantor of integrity of entire study, P.M.; study concepts, R.M., V.L., G.C.; study design, R.M., G.C.; literature research, B.G.; clinical studies, G.C., R.M., L.D.; data acquisition and analysis/ interpretation, R.M., B.G.; manuscript preparation, R.M.; manuscript definition of intellectual content, R.M., V.L., G.C.; manuscript editing, R.M., B.G.; manuscript revision/review, A.V., G.M., M.G.B.; manuscript final version approval, P.M.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSIONREFERENCES |
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), body (
), and tail (
) of the pancreas at 0, 1, 3, 5, and 10 minutes after secretin administration.