Secretin-Enhanced MRCP: Review of Technique and Application With Proposal for Quantification of Exocrine Function

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1 Gastrointestinal Imaging Original Research Sanyal et al. Secretin-Enhanced MRCP Gastrointestinal Imaging Original Research Rupan Sanyal 1 Tyler Stevens 2 Eric Novak 3 Joseph C. Veniero 1 Sanyal R, Stevens T, Novak E, Veniero JC Keywords: chronic pancreatitis, MRCP, quantification, secretin DOI: /JR Received ugust 30, 2010; accepted after revision May 25, This work was a Silver Medal winner as an educational exhibit at the 2010 annual meeting of the merican Roentgen Ray Society. 1 Imaging Institute, Cleveland Clinic, H6, 9500 Euclid ve, Cleveland, OH ddress correspondence to R. Sanyal (sanyalr@ccf.org). 2 Digestive Disease Institute, Cleveland Clinic, Cleveland, OH. 3 Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH. JR 2012; 198: X/12/ merican Roentgen Ray Society Secretin-Enhanced MRCP: Review of Technique and pplication With Proposal for Quantification of Exocrine Function OJECTIVE. The purpose of this article is to present a proposal for quantification of exocrine function using secretin-enhanced MRCP for the diagnosis of chronic pancreatitis. The article also reviews the technique and application of secretin-enhanced MRCP in evaluating various pancreatic abnormalities. SUJECTS ND METHODS. One hundred thirty-four consecutive patients with chronic abdominal pain undergoing secretin-enhanced MRCP for suspected chronic pancreatitis were included. Patients were divided into four clinical groups (normal, equivocal, early chronic pancreatitis, established pancreatitis) on the basis of clinical symptoms and additional investigations, including CT (n = 98), endoscopic pancreatic function test (n = 65), endoscopic ultrasound (n = 84), and ERCP (n = 36). The volume of secretion was obtained by drawing a region of interest around T2 bright fluid secreted on postsecretin HSTE images. The maximal rate of secretion in response to secretin was obtained by plotting change in signal intensity on sequential postsecretin images. The analysis of variance test was used to compare the clinical groups with the volume and rate of secretion. RESULTS. Significant volume differences were found between the normal and established pancreatitis groups (p < ) as well as the equivocal and established pancreatitis groups (p < ). Marginally significant differences were found between the normal and early pancreatitis groups (p = ) as well as early and established pancreatitis groups (p = ). Differences in the maximal rate of secretion were not statistically significant. CONCLUSION. Secretory volume measurement of secretin-enhanced MRCP data is a simple method that brings out significant differences between normal, early, and established pancreatitis patients. T he diagnosis of chronic pancreatitis can be difficult and patients routinely undergo a battery of tests to confirm or refute it. Whereas CT, endorectal ultrasound (EUS), ERCP, and MRCP are used to evaluate the pancreas for morphologic changes of pancreatitis, several direct and indirect tests are available to measure the degree of pancreatic exocrine dysfunction that accompanies chronic pancreatitis. Indirect functional tests, including fecal elastase 1, are easy to perform but have low sensitivity [1]. Direct function tests involve serial collection of duodenal juices after stimulation of pancreatic secretion with IV cholecystokinin or secretin. The collected juices are measured for enzyme levels (cholecystokinin stimulation) or bicarbonate levels (secretin stimulation). Direct function tests provide an accurate assessment of exocrine function but are cumbersome and inva- sive, requiring either fluoroscopic oroduodenal placement of Dreiling tubes [2] or endoscopic fluid collection [3, 4]. Secretinenhanced MRCP is a noninvasive method of evaluating pancreatic function that involves stimulation of pancreatic exocrine function by IV secretin, similar to the direct function tests. However, un like the direct function tests, in secretin- enhanced MRCP, the exocrine function is evaluated by observing the T2 bright fluid secreted by the pancreas. Direct pancreatic function tests are limited to evaluating exocrine function in patients with suspected chronic pancreatitis. In secretin-enhanced MRCP, stimulation of pancreatic secretion allows not only estimation of exocrine function in chronic pancreatitis but also dynamic visualization of a host of changes in the pancreatic ductal system. This provides a unique insight into the functional and morphologic status of the pancreas, which en- 124 JR:198, January 2012

2 Secretin-Enhanced MRCP ables a more thorough evaluation of chronic pancreatitis and expands the horizon of this test to other pancreatic abnormalities. This improves on ERCP and EUS, which evaluate only the morphologic changes. In this article, we will discuss the technique and indications of secretin-enhanced MRCP and present the results of a study performed for the quantification of pancreatic exocrine function with secretin-enhanced MRCP in patients with suspected chronic pancreatitis. Secretin-Enhanced MRCP: Technique, pplications, and Quantification Secretin Secretin is a gastrointestinal peptide that stimulates pancreatic duct epithelial cells to produce a bicarbonate-rich fluid. Physiologic gastrointestinal actions of secretin include inhibition of gastric acid secretion and decreasing intestinal motility [5]. Production of biologically derived porcine secretin, which was used for pancreatic stimulation tests, ceased in Synthetic forms of both porcine and human secretin (ChiRho- Stim, ChiRhoClin and SecreFlo, Repligen) are now available. ll three forms that is, biologic, synthetic porcine, and synthetic human secretin have been shown to be equivalent and can be used interchangeably [6]. The adverse effects of secretin are mainly nausea, flushing, abdominal pain, and vomiting and can be seen in up to 5% of patients. cute pancreatitis is listed as a contraindication to secretin administration (package insert, ChiRhoClin). However, some institutions inject secretin before resolution of acute episodes without reported major adverse effects [7, 8]. Secretin-Enhanced MRCP Technique The MRI protocol used for secretinenhanced MRCP, which is the functional evaluation of the pancreas, can be performed alone or in combination with a standard pancreas protocol. t our institution, patients referred for their first secretin-enhanced MRCP who have never had a pancreatic MR evaluation usually undergo an examination in which the standard pancreas protocol is combined with the secretin-enhanced MRCP protocol to evaluate both pancreatic morphology and function. In this article, we describe the sequences used only for the secretin-enhanced MRCP portion of the protocol. Patient Preparation superparamagnetic iron oxide containing oral MR contrast agent (such as ferumox- Fig year-old woman imaged without administration of oral ferumoxsil. MR image shows preexisting T2 bright natural duodenal secretions (arrows). sil, [Gastromark, Covidien]) is administered orally before the examination. Two bottles, 300 ml each, are administered 30 minutes and just before the examination. This T2-shortening negative enteric contrast agent mixes with the preexisting T2 bright gastric and duodenal fluid, essentially eliminating its T2 signal. T2 bright pancreatic fluid subsequently secreted in response to secretin can be easily identified on this T2 dark background (Figs. 1 and 2). Naturally occurring negative oral contrast can be obtained from blueberry and pineapple juices and may be used as a lower cost alternative to ferumoxsil for qualitative evaluation [9]. These juices have a natural high manganese content that makes them paramagnetic and therefore dark on T2 imaging. Sequences Secretin-enhanced MRCP were performed using 1.5-T systems at our institute. fter obtaining scout images, axial and coronal T2- weighted HSTE images through the abdo- TLE 1: Typical Sequence Parameters Fig year-old woman imaged with oral ferumoxsil administration. MR image shows T2 dark fluid (ferumoxsil) in stomach and duodenum (arrows). men are obtained. Table 1 contains typical secretin-enhanced MRCP parameters. n initial breath-hold thick oblique coronal fat-suppressed heavily T2-weighted long- TE HSTE image encompassing the pancreas and duodenum is acquired and assessed for position. fter an IV test dose of 0.2 μg of human secretin (ChiRhoStim), 0.2 μg/kg of the same is administered over 1 minute with the patient in the gantry and the breath-hold oblique coronal heavily T2-weighted fatsuppressed long-te HSTE sequence (thick slab MRCP sequence) is repeated every 30 seconds for 10 minutes. slice thickness of 60 mm is used so that the entire pancreas and duodenum are included. When these 20 images are viewed sequentially, they provide a dynamic assessment of pancreatic exocrine function in response to secretin (Fig. 3). t the end of the 10-minute dynamic assessment, another set of axial and coronal HSTE images is obtained through the abdomen. This set of images allows estimation of the total Sequence HSTE Long TE HSTE TR (ms) Infinite 3000 Time between slice acquisition (ms) TE (ms) Matrix 256 x 176 (axial) 256 x x 256 (coronal) Slice thickness (mm) 4 60 cquisition 2D 2D Flip angle Slices Multislice Thick slab FOV (mm) 350 x 240 (axial) 200 x x 350 (coronal) Pixel bandwidth (Hz) JR:198, January

3 Sanyal et al. Fig year-old woman with normal pancreatic function. Three selected images after secretin injection of 20 sequential heavily T2-weighted long TE HSTE images obtained over 10 minutes show normal filling of duodenum, which progresses past genu. amount of T2 bright fluid secreted into the duodenum in response to secretin (Fig. 4) as well as assessment of changes in duct morphology. Fig year-old man with normal pancreatic function., Presecretin coronal HSTE image shows collapsed duodenum with minimal T2 dark ferumoxsil (arrows)., Postsecretin coronal HSTE image shows duodenum distended with new T2 bright fluid (arrows), indicating normal exocrine function. Chronic Pancreatitis and Secretin- Enhanced MRCP In chronic pancreatitis, fibrous tissue gradually replaces the glandular elements in the pancreas. This process is reflected in secretinenhanced MRCP by characteristic changes in the main pancreatic duct (MPD), side branches, and volume of pancreatic secretion [10]. Fig year-old man with established chronic pancreatitis. MR image obtained 5 minutes after secretin injection shows dilated irregular main pancreatic duct with loss of normal tapering. Side branch ectasia is present. Fig year-old man with chronic pancreatitis and transient side branch dilation. Image obtained 30 seconds after secretin injection (left) does not show significant side branch dilation. Image obtained at 3 minutes (center) shows transient filling of dilated side branches with T2 bright fluid (arrow), which becomes much less apparent on 5-minute image (right). Note volume of secretion is also reduced with only partial filling of bulb. Ductal Changes ERCP has been considered a radiologic reference standard because of its ability to detect mild ductal changes of chronic pancreatitis. During ERCP, injection of contrast material under pressure causes overdistention of the ductal system [11]. In comparison with this technique, administration of secretin in secretin-enhanced MRCP creates a more physiologic ductal distention. ecause of lower spatial resolution and lack of overdistention, secretin-enhanced MRCP cannot match the subtle ductal abnormalities identified on ERCP. However, ductal distention by T2 bright fluid after 126 JR:198, January 2012

4 Secretin-Enhanced MRCP secretin administration allows more complete visualization of the MPD, including the duct of Santorini and side branches, compared with MRCP without secretin [12 14]. In healthy patients, the MPD is smooth, measures less than 3 mm, and tapers in the tail. The normal MPD distends about 66% in response to secretin and returns to baseline within 10 minutes [15]. aseline MPD Fig year-old woman with chronic pancreatitis. Mid ductal stricture (arrow) is causing upstream main pancreatic duct and side branch dilation. Fig year-old man with pancreas divisum. Pancreatic duct drains through minor papilla (arrow). dilation, irregularity, and loss of tapering indicate chronic pancreatitis (Fig. 5). In chronic pancreatitis, the MPD does not adequately distend in response to secretin [15]. Inadequate distention may be secondary to reduced volume of secretion, but fibrosis along the duct also results in reduced compliance. Reduced MPD distention is considered a good indicator of chronic pancreatitis by some authors [10], whereas others have disputed this [13, 16]. In addition, distal ductal obstruction (by papillary stenosis, stricture, or stone) can potentially cause increased ductal distention in response to secretin in patients with chronic pancreatitis, and this distention should not be used to exclude pancreatitis. Side branch dilation is an important marker of chronic pancreatitis and visualization of more than three dilated side branches establishes the diagnosis of chronic pancreatitis by the Cambridge criteria [17]. fter secretin stimulation, significantly better visualization of side branches is obtained compared with presecretin images [14, 18]. Transient filling of dilated side branches with T2 bright fluid is often seen (Fig. 6). Volume of Secretion The morphologic changes of chronic pancreatitis do not necessarily correlate with exocrine dysfunction, and to establish the diagnosis of chronic pancreatitis, both morphologic and functional evaluation can be helpful [19]. During secretin-enhanced MRCP, Fig year-old woman with Santorinicele., Presecretin image does not reveal Santorinicele., Postsecretin image reveals Santorinicele (arrow). Fig year-old man with necrotizing pancreatitis resulting in disconnected duct., Contrast-enhanced CT image shows large collection replacing pancreatic body with pancreatic duct leading to collection., fter 5 months with pancreatic fistula, secretin-enhanced MRCP image obtained at 4 minutes shows dilation of upstream pancreatic duct in body and tail, nonvisualization of main pancreatic duct (MPD) at neck (large arrow), and normal caliber duct in head. Fistula tract (small arrows) extends from pancreatic duct to peripancreatic fluid collection (arrowhead). Small collection is present at neck. Contrast material injected during ERCP opacified only MPD in head. ttempt to cross disconnected segment of MPD during ERCP failed. C, MRCP image obtained at 8 minutes in same secretin-enhanced study shows secretions in duodenum separate from peripancreatic fluid. Fistula is no longer well visualized. C JR:198, January

5 Sanyal et al. Fig year-old woman who underwent postsurgical evaluation with secretin-enhanced MRCP. Patient had reimplantation of dorsal and ventral ducts after pancreas-sparing duodenectomy for familial adenomatous polyposis. Secretinenhanced MRCP showed overall reduced pancreatic function, with reimplanted dorsal duct contributing all pancreatic secretions. the volume of fluid secreted into the duodenum serves as a proxy for bicarbonate levels; thus, reduction in the volume of fluid correlates with exocrine dysfunction. In patients with normal exocrine function, fluid appears rapidly in the periampullary duodenum after secretin administration, then fills and distends the duodenal bulb and progresses past the genu. In patients with chronic pancreatitis, the appearance of fluid in the duodenum is often delayed and duodenal filling and distention are reduced. Role of Secretin-Enhanced MRCP in Evaluation of Recurrent Pancreatitis Secretin-enhanced MRCP helps in the evaluation of patients with recurrent episodes of pancreatitis. Pancreatic ductal strictures can cause recurrent attacks of pancreatitis. Distention of the MPD in secretin-enhanced MRCP Fig year-old man with side branch intraductal papillary mucinous neoplasm (IPMN)., Presecretin image shows lobulated cyst adjacent to main pancreatic duct in pancreatic body. No communication is noted., Image obtained at 4 minutes after secretin injection shows communication (arrowhead), confirming diagnosis of side branch IPMN. helps delineate MPD strictures better, which can guide further treatment [13, 18] (Fig. 7). Collapsed segments of the duct that may be mistaken for strictures on presecretin images distend after secretin administration. Secretinenhanced MRCP has an advantage over ERCP because of the inability of ERCP to delineate the duct proximal to very severe stenosis. Pancreas divisum has been associated with recurrent pancreatitis because of the presumed inadequate pancreatic drainage through the accessory duct. The distention of the ductal system in secretin-enhanced MRCP improves the diagnosis of pancreas divisum [14, 20, 21] (Fig. 8). Focal cystic dilation of the accessory duct or Santorinicele has been considered as a possible cause of relative stenosis of the accessory duct. Secretin-enhanced MRCP also improves the diagnosis of Santorinicele [13] (Fig. 9). Secretin-enhanced MRCP has also been used to show pancreatic ductal disconnection resulting from pancreatic necrosis or trauma [22]. This condition leads to disconnection of viable pancreatic tissue from the gastrointestinal tract and recurrent episodes of inflammation or fistula formation (Fig. 10). However, the frequent presence of adjacent fluid collections and suboptimal response of the inflamed pancreas make detecting small leaks challenging [8]. Secretin-enhanced MRCP can also be used to evaluate the pancreatic ductal system in postsurgical patients. Cannulation of the pancreatic duct by ERCP is often difficult in such patients because of the altered postsurgical anatomy (Fig. 11). Pancreatic Cystic Neoplasms and Secretin- Enhanced MRCP There has been a recent surge in interest in cystic pancreatic lesions, particularly intraductal pancreatic mucinous neoplasms. Secretin-enhanced MRCP is being increasingly used to evaluate these neoplasms [23]. The basis of performing secretin-enhanced MRCP for cystic pancreatic lesions is that the ductal distention after secretin injection Fig year-old man with multiple side branch intraductal papillary mucinous neoplasms (IPMNs)., Image obtained 1 minute after secretin injection shows multiple small pancreatic cysts., Image obtained 10 minutes after secretin injection shows cysts become brighter, suggesting ductal communication and confirming diagnosis of side branch IPMNs. 128 JR:198, January 2012

6 Secretin-Enhanced MRCP TLE 2: Description of Clinical Groups Used to Classify Chronic Pancreatitis Clinical Group Description of Group No. of Patients Normal Chronic abdominal pain and no risk factors for chronic pancreatitis. Risk factors include heavy 31 alcohol use, acute pancreatitis, pancreas divisum, very high triglycerides, and well-documented sphincter of Oddi dysfunction. No early or late imaging findings of chronic pancreatitis. t least one imaging test was performed (usually CT) with normal results. Equivocal Chronic abdominal pain with at least one of the normal risk factors; endoscopic pancreatic function 53 test with normal results. Early chronic pancreatitis Pain, risk factors, and either mild imaging changes (e.g., ERCP Cambridge score of 2, endorectal 32 ultrasound 5), or abnormal endoscopic pancreatic function test (peak bicarbonate < 80 meq/l). Established chronic pancreatitis Diagnostic imaging changes (CT with calcifications or ERCP Cambridge score 3 4). 18 may show ductal communication better than MRCP without secretin [24]. Intraductal papillary mucinous neoplasms (IPMNs) communicate with the ductal system whereas ovarian stroma-containing mucinous cystic neoplasms do not. If ductal communication is seen, then these cystic neoplasms can be classified as intraductal papillary mucinous neoplasms (Fig. 12). Sometimes direct communication is not seen, but an increase in signal intensity of the cysts after secretin injection suggests ductal communication (Fig. 13). ecause the management of IPMNs and mucinous cystic neoplasms differs, visualization of ductal communication plays an important role in both the confirmation of the diagnosis and the management algorithm. There is very little literature on the use of secretin-enhanced MRCP in the evaluation of cystic neoplasms. The frequency with which secretin actually improves visualization of ductal communication is unknown. Status of Secretin-Enhanced MRCP That secretin-enhanced MRCP holds great promise in the evaluation of chronic pancreatitis is not disputed. However, despite the availability of MRCP for about a decade, the medical community has yet to exploit its full potential. There are limitations to the other diagnostic tests used to evaluate chronic pancreatitis. ERCP has a high rate of complications, direct function test is cumbersome and limited to few centers, and EUS is highly operator dependent, and none of these can match the unique combined functional and morphologic perspective provided by secretin-enhanced MRCP. These limitations accentuate the advantages of secretinenhanced MRCP. Currently the use of secretin-enhanced MRCP is somewhat limited to large centers where it is often used in combination with other tests. Considering the high prevalence of chronic pancreatitis and the extensive use of invasive investigations to establish this diagnosis, secretin-enhanced MRCP has been significantly underutilized. Even patients who undergo MRCP for suspected chronic pancreatitis often do not have secretin administered despite the clear incremental value of secretin to the test. Lack of awareness, cost, and paucity of large trials proving its effectiveness are all partly responsible for this. The shortage of secretin faced a few years ago has now resolved and synthetic human secretin is easily available. Quantification of Duodenal Secretion drawback of secretin-enhanced MRCP is the subjective nature of the reports [25]. s a result, the reports do not harness the true potential of the test. The subjective assessment of duodenal filling used in practice introduces large interobserver variations because radiologists may differ in their interpretation of adequate secretion. ecause our secretin-enhanced MRCP reports often do not include objective data, gastroenterologists sometimes perceive them to be ambiguous or inconclusive, creating a need for the development of an objective parameter to establish the diagnosis of pancreatitis. Despite several prior attempts to quantify the volume of duodenal fluid as measure of exocrine function [12, 15, 26 28], a method of quantification that can reliably differentiate between normal, early, and established chronic pancreatitis has been elusive. Matos et al. [12] suggested a grading system in which duodenal filling is defined as grade 0 when no fluid is observed, grade 1 when fluid is limited to the duodenal bulb, grade 2 when it partially fills the duodenum up to the genu, and grade 3, when it fills beyond the genu. lower score on this grading scale was associated with a low bicarbonate concentration and impaired exocrine function [10, 15]. The main attraction of this grading system is its extreme simplicity. However, Cappeliez et al. [15] found that this grading system had a low sensitivity of 72% for impaired pancreatic function, whereas Hellerhoff et al. [14] reported it to have a low positive predictive value of 58% for chronic pancreatitis. Furthermore, this grading system was not able to differentiate between patients with mild and established chronic pancreatitis [15]. Gillams and Lees [29] measured changes in small intestine water volume to calculate the pancreatic flow rate as an indicator of the volume of secretion. This model was able to identify severe pancreatitis from normal and moderate chronic pancreatitis but was unable to differentiate normal from mild or moderate pancreatitis. Subjects and Materials In view of the scant data available on secretin-enhanced MRCP quantification, we performed a study to quantify the volume of secretions on secretin-enhanced MRCP in patients with suspected chronic pancreatitis and compared it with the clinical diagnosis of chronic pancreatitis. Patients etween March 2005 and September 2008, 166 patients underwent secretin-enhanced MRCP at our institution. fter exclusion of 32 patients who had either prior pancreatic surgery, a pancreatic neoplasm greater than 3 cm, or a technically inadequate study, 134 consecutive patients (45 men, 89 women; mean age, 51 ± 14.1 years) with chronic abdominal pain were included in this study. These patients underwent various additional investigations, including CT (n = 98), endoscopic pancreatic function tests (PFTs) (n = 65), EUS (n = 84), and ERCP (n = 36), to diagnose chronic pancreatitis. Clinical Groups n experienced pancreatologist, who was blinded to the secretin-enhanced MRCP results, classified the patients into four clinical groups (Table 2) on the basis of clinical risk factors and the findings of the investigations mentioned earlier. JR:198, January

7 Sanyal et al. Fig year-old woman with normal pancreatic function. Image shows region of interest drawn around fluid in duodenum to obtain area. Obtaining similar measurements on all slices allows volume of secretion to be calculated. Secretin-Enhanced MRCP Quantification Technique Volume In patients prepared with a negative oral contrast agent, new high T2 signal areas in the duodenum after secretin administration represent new pancreatic secretions. region of interest (ROI) was drawn around the T2 bright duodenal and proximal jejunal fluid on each slice of the postsecretin coronal HSTE sequence (Fig. 14). The area (in cm 2 ) of the ROI in each slice was added and the total multiplied by the slice thickness (0.4 cm) to obtain the total volume fluid (in ml) secreted in response to secretin. Rate of secretion Diminished pancreatic exocrine function may not only manifest as a decreased volume of secretion but also as a decreased rate of secretion in response to secretin. To assess this function, the maximal rate of secretion was measured in each patient. n ROI was drawn on each of the heavily T2-weighted images obtained during the dynamic phase to include all the secreted fluid (Fig. 15). This ROI was constant for all 20 sequential images obtained over the 10 minutes after secretin administration. The total signal intensity within the ROI in each image was calculated by multiplying the mean intensity TLE 3: Mean Secretory Volumes of Various Clinical Groups Clinical Group Mean Volume (ml) Normal 57.3 Equivocal 49.7 Early pancreatitis 39.8 Established pancreatitis 22.1 Fig year-old woman evaluated for calculation of maximum pancreatic flow rate. Region of interest is drawn around duodenum in each of 20 images. by the pixel count. The total signal intensity within the ROI for each image was charted sequentially. The 2-minute segment (four sequential time points) showing the maximal change in signal intensity was recorded for each patient. This maximum change in signal intensity within any 2-minute segment was considered a measure of the maximum rate of secretion in response to secretin for each patient. Endoscopic pancreatic function test Sixtyfive patients underwent secretin-stimulated endoscopic PFT for measurement of pancreatic exocrine function. fter injection of 0.2 μg/kg of IV secretin, intermittent duodenal aspirates were obtained at 15-minute intervals for 60 minutes. The endoscopic fluid specimens were analyzed for bicarbonate concentration. maximum bicarbonate concentration < 80mEq/L is considered abnormal [3]. Statistical nalysis one-way analysis of variance was conducted to look at the relationship between the clinical groups and the two parameters measured on secretinenhanced MRCP that is, volume of secretin and maximum rate of secretion. When significance was found, further exploration was conducted by examining the mean differences between each clinical group pairing. onferroni correction was made to limit the probability of obtaining a significant result by chance. result that would have been significant before the correction but not after was referred to as marginally significant. The correlation between clinical groups and volume and rate was determined by the Kendall rank coefficient (Kendal tau). The Kendall tau was also used to calculate the correlation between the volume measurements and maximum bicarbonate levels on endoscopic PFT, which were available for 65 patients. Results Volume Quantification mong the 134 patients included in the study, a significant association was observed between the clinical groups and volume measurements (p = ). Mean volumes became progressively smaller with increasing degree of pancreatitis (Table 3). Significant volume differences were found between the normal group and established pancreatitis group as well as the equivocal group and established pancreatitis group. Marginally significant differences were also found between the normal group and early pancreatitis group as well as the early and established pancreatitis groups (Table 4). Significant correlation was found between the clinical groups and the volume measurements on secretin-enhanced MRCP (τ = 0.324, p < ). Rate of Secretion The mean values for the maximum rate of secretion in any 2-minute period tended to decrease with higher degree or suspicion of pancreatitis (normal group mean, 10.7; equivocal group, 8.1; early chronic pancreatitis, 8.1; established chronic pancreatitis, 5.5). However, these values were not found to be statistically significant using the analysis of variance test. There was a weak but TLE 4: Differences in Mean Volumes etween Various Clinical Groups and p Values Using nalysis of Variance Test Groups Mean Volume Difference (ml) p Normal and equivocal Normal and early pancreatitis a Normal and established pancreatitis 35.2 < b Equivocal and early pancreatitis Equivocal and established pancreatitis b Early and established pancreatitis a a Marginally significant at the 95% CI level. b Significant at the 95% CI level. 130 JR:198, January 2012

8 Secretin-Enhanced MRCP statistically significant correlation between the maximum rate of secretion and the clinical groups (τ = 0.187, p = ). Endoscopic Pancreatic Function Test icarbonate Levels The maximum bicarbonate levels obtained on secretin-stimulated endoscopic PFT showed a statistically significant correlation with the volume measurements on secretinenhanced MRCP (τ = 0.270, p = ). Discussion No single investigation can currently serve as a reference standard for the diagnosis of chronic pancreatitis a fact that limits any study design used to evaluate the accuracy of a diagnostic tool. It has been established that functional and morphologic tests measure different parameters, and the complementary use of these tests leads to better diagnostic accuracy [30]. In our study, a pancreatologist used the results of a gamut of investigations along with the clinical presentation to divide patients into normal, equivocal, early, and established pancreatitis groups. Our results show that patients with established chronic pancreatitis had significantly lower secretory volumes after secretin stimulation compared with the normal and equivocal groups. Patients with early chronic pancreatitis had higher secretory volumes than healthy patients and lower secretory volumes than patients with established chronic pancreatitis (marginally significant). These results indicate that the secretory volume measurements on secretin-enhanced MRCP reflect the extent of pancreatic exocrine function. That quantification of secretin-enhanced MRCP may help in diagnosing early chronic pancreatitis is very encouraging. In this study, the measurements were made by manually calculating the volume of fluid secreted. However, this step can be done automatically by either adapting existing software or developing new software for this purpose. With a larger patient population and the use of standardized software, it may be possible to establish volume measurement criteria for diagnosing chronic pancreatitis. In endoscopic PFT, the concentration of bicarbonate in the fluid obtained is used as an indicator of pancreatic exocrine function, whereas secretin-enhanced MRCP uses secretory volume for this purpose. The volume of secretion on secretin-enhanced MRCP is theoretically a different parameter from bicarbonate secretion. However, both volume and bicarbonate concentration reflect exocrine function and should be suitable for pancreatic evaluation. This is borne out by the significant correlation obtained between these two measurements among the 65 patients who had also undergone endoscopic PFT in this study. We did not find a significant association between the maximal rate of secretion and the clinical groups. Nevertheless, there is a trend toward lower mean rates of secretion on secretin-enhanced MRCP as we go from the normal to established pancreatitis groups. Continued investigation with larger study populations may be able to establish this trend. Secretory volume measurement of secretin-enhanced MRCP data provides a simple quantitative method that brings out significant differences in exocrine function between healthy patients, patients with early chronic pancreatitis, and patients with established chronic pancreatitis. Incorporating and reporting objective volume data on routine secretin-enhanced MRCP reports will help resolve some of the ambiguity in our clinical results. Development of automated software and validation of volume measurements in larger studies will enable more widespread use of quantitative secretin- enhanced MRCP functional data and will help in realizing its true potential in the diagnosis and management of chronic pancreatitis. 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