Secretin-Enhanced MRCP: Review of Technique and Application ...

Secretin-Enhanced MRCPables a more thorough evaluation of chronicpancreatitis and expands the horizon of thistest to other pancreatic abnormalities. Thisimproves on ERCP and EUS, which evaluateonly the morphologic changes. In this article,we will discuss the technique and indicationsof secretin-enhanced MRCP and present theresults of a study performed for the quantificationof pancreatic exocrine function withsecretin-enhanced MRCP in patients withsuspected chronic pancreatitis.Secretin-Enhanced MRCP: Technique,Applications, and QuantificationSecretinSecretin is a gastrointestinal peptide thatstimulates pancreatic duct epithelial cellsto produce a bicarbonate-rich fluid. Physiologicgastrointestinal actions of secretin includeinhibition of gastric acid secretion anddecreasing intestinal motility [5]. Productionof biologically derived porcine secretin,which was used for pancreatic stimulationtests, ceased in 1999. Synthetic forms ofboth porcine and human secretin (ChiRho-Stim, ChiRhoClin and SecreFlo, Repligen)are now available. All three forms—that is,biologic, synthetic porcine, and synthetic humansecretin—have been shown to be equivalentand can be used interchangeably [6].The adverse effects of secretin are mainlynausea, flushing, abdominal pain, and vomitingand can be seen in up to 5% of patients.Acute pancreatitis is listed as a contraindicationto secretin administration (package insert,ChiRhoClin). However, some institutions injectsecretin before resolution of acute episodeswithout reported major adverse effects [7, 8].Secretin-Enhanced MRCP TechniqueThe MRI protocol used for secretinenhancedMRCP, which is the functionalevaluation of the pancreas, can be performedalone or in combination with a standard pancreasprotocol. At our institution, patients referredfor their first secretin-enhanced MRCPwho have never had a pancreatic MR evaluationusually undergo an examination in whichthe standard pancreas protocol is combinedwith the secretin-enhanced MRCP protocolto evaluate both pancreatic morphology andfunction. In this article, we describe the sequencesused only for the secretin-enhancedMRCP portion of the protocol.Patient PreparationA superparamagnetic iron oxide–containingoral MR contrast agent (such as ferumox-Fig. 1—32-year-old woman imaged withoutadministration of oral ferumoxsil. MR image showspreexisting T2 bright natural duodenal secretions(arrows).sil, [Gastromark, Covidien]) is administeredorally before the examination. Two bottles,300 mL each, are administered 30 minutes andjust before the examination. This T2-shorteningnegative enteric contrast agent mixes withthe preexisting T2 bright gastric and duodenalfluid, essentially eliminating its T2 signal. T2bright pancreatic fluid subsequently secreted inresponse to secretin can be easily identified onthis T2 dark background (Figs. 1 and 2). Naturallyoccurring negative oral contrast can beobtained from blueberry and pineapple juicesand may be used as a lower cost alternative toferumoxsil for qualitative evaluation [9]. Thesejuices have a natural high manganese contentthat makes them paramagnetic and thereforedark on T2 imaging.SequencesSecretin-enhanced MRCP were performedusing 1.5-T systems at our institute. After obtainingscout images, axial and coronal T2-weighted HASTE images through the abdo-TABLE 1: Typical Sequence ParametersFig. 2—50-year-old woman imaged with oralferumoxsil administration. MR image shows T2 darkfluid (ferumoxsil) in stomach and duodenum (arrows).men are obtained. Table 1 contains typicalsecretin-enhanced MRCP parameters.An initial breath-hold thick oblique coronalfat-suppressed heavily T2-weighted long-TE HASTE image encompassing the pancreasand duodenum is acquired and assessedfor position. After an IV test dose of 0.2 μg ofhuman secretin (ChiRhoStim), 0.2 μg/kg ofthe same is administered over 1 minute withthe patient in the gantry and the breath-holdoblique coronal heavily T2-weighted fatsuppressedlong-TE HASTE sequence (thickslab MRCP sequence) is repeated every 30seconds for 10 minutes. A slice thickness of60 mm is used so that the entire pancreas andduodenum are included. When these 20 imagesare viewed sequentially, they provide adynamic assessment of pancreatic exocrinefunction in response to secretin (Fig. 3).At the end of the 10-minute dynamic assessment,another set of axial and coronal HASTEimages is obtained through the abdomen. Thisset of images allows estimation of the totalSequence HASTE Long TE HASTETR (ms) Infinite 3000Time between slice acquisition (ms) 1050 3000TE (ms) 72 972Matrix256 x 176 (axial)256 x 256256 x 256 (coronal)Slice thickness (mm) 4 60Acquisition 2D 2DFlip angle 180° 150°Slices Multislice Thick slabFOV (mm)350 x 240 (axial)200 x 200350 x 350 (coronal)Pixel bandwidth (Hz) 780 130AJR:198, January 2012 125

Sanyal et al.Fig. 3—35-year-old woman with normal pancreatic function. Three selected images after secretin injection of 20 sequential heavily T2-weighted long TE HASTE imagesobtained over 10 minutes show normal filling of duodenum, which progresses past genu.AFig. 4—43-year-old man with normal pancreatic function.A, Presecretin coronal HASTE image shows collapsed duodenum with minimal T2 dark ferumoxsil (arrows).B, Postsecretin coronal HASTE image shows duodenum distended with new T2 bright fluid (arrows), indicatingnormal exocrine function.BFig. 5—55-year-old man with established chronicpancreatitis. MR image obtained 5 minutes aftersecretin injection shows dilated irregular mainpancreatic duct with loss of normal tapering. Sidebranch ectasia is present.Fig. 6—52-year-old man with chronic pancreatitis and transient side branch dilation. Image obtained 30 seconds after secretin injection (left) does not show significantside 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 on5-minute image (right). Note volume of secretion is also reduced with only partial filling of bulb.amount of T2 bright fluid secreted into the duodenumin response to secretin (Fig. 4) as wellas assessment of changes in duct morphology.Chronic Pancreatitis and Secretin-Enhanced MRCPIn chronic pancreatitis, fibrous tissue graduallyreplaces the glandular elements in thepancreas. This process is reflected in secretinenhancedMRCP by characteristic changes inthe main pancreatic duct (MPD), side branches,and volume of pancreatic secretion [10].Ductal ChangesERCP has been considered a radiologic referencestandard because of its ability to detectmild ductal changes of chronic pancreatitis.During ERCP, injection of contrast materialunder pressure causes overdistention of theductal system [11]. In comparison with thistechnique, administration of secretin in secretin-enhancedMRCP creates a more physiologicductal distention. Because of lower spatialresolution and lack of overdistention, secretin-enhancedMRCP cannot match the subtleductal abnormalities identified on ERCP. However,ductal distention by T2 bright fluid after126 AJR:198, January 2012

Secretin-Enhanced MRCPsecretin administration allows more completevisualization of the MPD, including the ductof Santorini and side branches, compared withMRCP without secretin [12–14].In healthy patients, the MPD is smooth,measures less than 3 mm, and tapers in thetail. The normal MPD distends about 66%in response to secretin and returns to baselinewithin 10 minutes [15]. Baseline MPDFig. 7—48-year-old woman with chronic pancreatitis.Mid ductal stricture (arrow) is causing upstream mainpancreatic duct and side branch dilation.Fig. 8—39-year-old man with pancreas divisum.Pancreatic duct drains through minor papilla (arrow).dilation, irregularity, and loss of taperingindicate chronic pancreatitis (Fig. 5). Inchronic pancreatitis, the MPD does not adequatelydistend in response to secretin [15].Inadequate distention may be secondary toreduced volume of secretion, but fibrosisalong the duct also results in reduced compliance.Reduced MPD distention is considereda good indicator of chronic pancreatitisby some authors [10], whereas othershave disputed this [13, 16]. In addition, distalductal obstruction (by papillary stenosis,stricture, or stone) can potentially cause increasedductal distention in response to secretinin patients with chronic pancreatitis,and this distention should not be used to excludepancreatitis.Side branch dilation is an important markerof chronic pancreatitis and visualizationof more than three dilated side branches establishesthe diagnosis of chronic pancreatitisby the Cambridge criteria [17]. Aftersecretin stimulation, significantly better visualizationof side branches is obtained comparedwith presecretin images [14, 18]. Transientfilling of dilated side branches with T2bright fluid is often seen (Fig. 6).Volume of SecretionThe morphologic changes of chronic pancreatitisdo not necessarily correlate withexocrine dysfunction, and to establish the diagnosisof chronic pancreatitis, both morphologicand functional evaluation can be helpful[19]. During secretin-enhanced MRCP,ABFig. 9—37-year-old woman with Santorinicele.A, Presecretin image does not reveal Santorinicele.B, Postsecretin image reveals Santorinicele (arrow).AFig. 10—45-year-old man with necrotizing pancreatitis resulting in disconnected duct.A, Contrast-enhanced CT image shows large collection replacing pancreatic body with pancreatic duct leading to collection.B, After 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 toperipancreatic fluid collection (arrowhead). Small collection is present at neck. Contrast material injected during ERCP opacified only MPD in head. Attempt to crossdisconnected 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 wellvisualized.BCAJR:198, January 2012 127

Sanyal et al.Fig. 11—42-year-old woman who underwentpostsurgical evaluation with secretin-enhancedMRCP. Patient had reimplantation of dorsal andventral ducts after pancreas-sparing duodenectomyfor familial adenomatous polyposis. SecretinenhancedMRCP showed overall reduced pancreaticfunction, with reimplanted dorsal duct contributingall pancreatic secretions.the volume of fluid secreted into the duodenumserves as a proxy for bicarbonate levels;thus, reduction in the volume of fluid correlateswith exocrine dysfunction. In patientswith normal exocrine function, fluid appearsrapidly in the periampullary duodenum aftersecretin administration, then fills and distendsthe duodenal bulb and progresses pastthe genu. In patients with chronic pancreatitis,the appearance of fluid in the duodenumis often delayed and duodenal filling and distentionare reduced.Role of Secretin-Enhanced MRCP in Evaluationof Recurrent PancreatitisSecretin-enhanced MRCP helps in the evaluationof patients with recurrent episodes ofpancreatitis. Pancreatic ductal strictures cancause recurrent attacks of pancreatitis. Distentionof the MPD in secretin-enhanced MRCPhelps delineate MPD strictures better, whichcan guide further treatment [13, 18] (Fig. 7).Collapsed segments of the duct that may bemistaken for strictures on presecretin imagesdistend after secretin administration. SecretinenhancedMRCP has an advantage over ERCPbecause of the inability of ERCP to delineatethe duct proximal to very severe stenosis.Pancreas divisum has been associatedwith recurrent pancreatitis because of thepresumed inadequate pancreatic drainagethrough the accessory duct. The distentionof the ductal system in secretin-enhancedMRCP improves the diagnosis of pancreasdivisum [14, 20, 21] (Fig. 8). Focal cystic dilationof the accessory duct or Santorinicelehas been considered as a possible cause ofrelative stenosis of the accessory duct. Secretin-enhancedMRCP also improves the diagnosisof Santorinicele [13] (Fig. 9).Secretin-enhanced MRCP has also beenused to show pancreatic ductal disconnectionresulting from pancreatic necrosis or trauma[22]. This condition leads to disconnectionof viable pancreatic tissue from the gastrointestinaltract and recurrent episodes of inflammationor fistula formation (Fig. 10).However, the frequent presence of adjacentfluid collections and suboptimal response ofthe inflamed pancreas make detecting smallleaks challenging [8]. Secretin-enhancedMRCP can also be used to evaluate the pancreaticductal system in postsurgical patients.Cannulation of the pancreatic duct by ERCPis often difficult in such patients because ofthe altered postsurgical anatomy (Fig. 11).Fig. 12—51-year-old man with side branch intraductal papillary mucinous neoplasm (IPMN).A, Presecretin image shows lobulated cyst adjacent to main pancreatic duct in pancreatic body. Nocommunication is noted.B, Image obtained at 4 minutes after secretin injection shows communication (arrowhead), confirmingdiagnosis of side branch IPMN.ABPancreatic Cystic Neoplasms and Secretin-Enhanced MRCPThere has been a recent surge in interestin cystic pancreatic lesions, particularly intraductalpancreatic mucinous neoplasms.Secretin-enhanced MRCP is being increasinglyused to evaluate these neoplasms [23].The basis of performing secretin-enhancedMRCP for cystic pancreatic lesions is thatthe ductal distention after secretin injectionABFig. 13—46-year-old man with multiple side branchintraductal papillary mucinous neoplasms (IPMNs).A, Image obtained 1 minute after secretin injectionshows multiple small pancreatic cysts.B, Image obtained 10 minutes after secretin injectionshows cysts become brighter, suggesting ductalcommunication and confirming diagnosis of sidebranch IPMNs.128 AJR:198, January 2012

Secretin-Enhanced MRCPTABLE 2: Description of Clinical Groups Used to Classify Chronic PancreatitisClinical Group Description of Group No. of PatientsNormalChronic abdominal pain and no risk factors for chronic pancreatitis. Risk factors include heavy31alcohol use, acute pancreatitis, pancreas divisum, very high triglycerides, and well-documentedsphincter of Oddi dysfunction. No early or late imaging findings of chronic pancreatitis. At least oneimaging test was performed (usually CT) with normal results.EquivocalChronic abdominal pain with at least one of the normal risk factors; endoscopic pancreatic function53test with normal results.Early chronic pancreatitis Pain, risk factors, and either mild imaging changes (e.g., ERCP Cambridge score of 2, endorectal32ultrasound ≥ 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). 18may show ductal communication better thanMRCP without secretin [24]. Intraductal papillarymucinous neoplasms (IPMNs) communicatewith the ductal system whereasovarian stroma-containing mucinous cysticneoplasms do not. If ductal communicationis seen, then these cystic neoplasms can beclassified as intraductal papillary mucinousneoplasms (Fig. 12). Sometimes direct communicationis not seen, but an increase insignal intensity of the cysts after secretin injectionsuggests ductal communication (Fig.13). Because the management of IPMNs andmucinous cystic neoplasms differs, visualizationof ductal communication plays an importantrole in both the confirmation of thediagnosis and the management algorithm.There is very little literature on the use of secretin-enhancedMRCP in the evaluation ofcystic neoplasms. The frequency with whichsecretin actually improves visualization ofductal communication is unknown.Status of Secretin-Enhanced MRCPThat secretin-enhanced MRCP holdsgreat promise in the evaluation of chronicpancreatitis is not disputed. However, despitethe availability of MRCP for about a decade,the medical community has yet to exploit itsfull potential. There are limitations to theother diagnostic tests used to evaluate chronicpancreatitis. ERCP has a high rate of complications,direct function test is cumbersomeand limited to few centers, and EUSis highly operator dependent, and none ofthese can match the unique combined functionaland morphologic perspective providedby secretin-enhanced MRCP. These limitationsaccentuate the advantages of secretinenhancedMRCP. Currently the use of secretin-enhancedMRCP is somewhat limited tolarge centers where it is often used in combinationwith other tests. Considering thehigh prevalence of chronic pancreatitis andthe extensive use of invasive investigations toestablish this diagnosis, secretin-enhancedMRCP has been significantly underutilized.Even patients who undergo MRCP for suspectedchronic pancreatitis often do not havesecretin administered despite the clear incrementalvalue of secretin to the test. Lackof awareness, cost, and paucity of large trialsproving its effectiveness are all partly responsiblefor this. The shortage of secretinfaced a few years ago has now resolved andsynthetic human secretin is easily available.Quantification of Duodenal SecretionA drawback of secretin-enhanced MRCPis the subjective nature of the reports [25].As a result, the reports do not harness thetrue potential of the test. The subjective assessmentof duodenal filling used in practiceintroduces large interobserver variations becauseradiologists may differ in their interpretationof adequate secretion. Because oursecretin-enhanced MRCP reports often donot include objective data, gastroenterologistssometimes perceive them to be ambiguousor inconclusive, creating a need for thedevelopment of an objective parameter to establishthe diagnosis of pancreatitis.Despite several prior attempts to quantifythe volume of duodenal fluid as measure ofexocrine function [12, 15, 26–28], a methodof quantification that can reliably differentiatebetween normal, early, and establishedchronic pancreatitis has been elusive. Matoset al. [12] suggested a grading system inwhich duodenal filling is defined as grade 0when no fluid is observed, grade 1 when fluidis limited to the duodenal bulb, grade 2 whenit partially fills the duodenum up to the genu,and grade 3, when it fills beyond the genu.A lower score on this grading scale was associatedwith a low bicarbonate concentrationand impaired exocrine function [10, 15].The main attraction of this grading system isits extreme simplicity. However, Cappeliez etal. [15] found that this grading system had alow sensitivity of 72% for impaired pancreaticfunction, whereas Hellerhoff et al. [14]reported it to have a low positive predictivevalue of 58% for chronic pancreatitis. Furthermore,this grading system was not able todifferentiate between patients with mild andestablished chronic pancreatitis [15].Gillams and Lees [29] measured changes insmall intestine water volume to calculate thepancreatic flow rate as an indicator of the volumeof secretion. This model was able to identifysevere pancreatitis from normal and moderatechronic pancreatitis but was unable to differentiatenormal from mild or moderate pancreatitis.Subjects and MaterialsIn view of the scant data available on secretin-enhancedMRCP quantification, weperformed a study to quantify the volume ofsecretions on secretin-enhanced MRCP inpatients with suspected chronic pancreatitisand compared it with the clinical diagnosisof chronic pancreatitis.PatientsBetween March 2005 and September 2008, 166patients underwent secretin-enhanced MRCP atour institution. After exclusion of 32 patients whohad either prior pancreatic surgery, a pancreaticneoplasm greater than 3 cm, or a technicallyinadequate study, 134 consecutive patients (45men, 89 women; mean age, 51 ± 14.1 years)with chronic abdominal pain were included inthis study. These patients underwent variousadditional investigations, including CT (n = 98),endoscopic pancreatic function tests (PFTs) (n =65), EUS (n = 84), and ERCP (n = 36), to diagnosechronic pancreatitis.Clinical GroupsAn experienced pancreatologist, who wasblinded to the secretin-enhanced MRCP results,classified the patients into four clinical groups(Table 2) on the basis of clinical risk factors andthe findings of the investigations mentioned earlier.AJR:198, January 2012 129

Sanyal et al.Fig. 14—35-year-old woman with normal pancreaticfunction. Image shows region of interest drawnaround fluid in duodenum to obtain area. Obtainingsimilar measurements on all slices allows volume ofsecretion to be calculated.Secretin-Enhanced MRCP QuantificationTechniqueVolume—In patients prepared with a negativeoral contrast agent, new high T2 signal areasin the duodenum after secretin administrationrepresent new pancreatic secretions. A region ofinterest (ROI) was drawn around the T2 brightduodenal and proximal jejunal fluid on each sliceof the postsecretin coronal HASTE sequence (Fig.14). The area (in cm 2 ) of the ROI in each slicewas added and the total multiplied by the slicethickness (0.4 cm) to obtain the total volume fluid(in mL) secreted in response to secretin.Rate of secretion—Diminished pancreaticexocrine function may not only manifest asa decreased volume of secretion but also as adecreased rate of secretion in response to secretin.To assess this function, the maximal rate ofsecretion was measured in each patient. An ROIwas drawn on each of the heavily T2-weightedimages obtained during the dynamic phase toinclude all the secreted fluid (Fig. 15). This ROI wasconstant for all 20 sequential images obtained overthe 10 minutes after secretin administration. Thetotal signal intensity within the ROI in each imagewas calculated by multiplying the mean intensityFig. 15—51-year-old woman evaluated for calculationof maximum pancreatic flow rate. Region of interestis drawn around duodenum in each of 20 images.by the pixel count. The total signal intensity withinthe ROI for each image was charted sequentially.The 2-minute segment (four sequential time points)showing the maximal change in signal intensity wasrecorded for each patient. This maximum changein signal intensity within any 2-minute segmentwas considered a measure of the maximum rate ofsecretion in response to secretin for each patient.Endoscopic pancreatic function test—Sixtyfivepatients underwent secretin-stimulatedendoscopic PFT for measurement of pancreaticexocrine function. After injection of 0.2 μg/kgof IV secretin, intermittent duodenal aspirateswere obtained at 15-minute intervals for 60minutes. The endoscopic fluid specimens wereanalyzed for bicarbonate concentration. Amaximum bicarbonate concentration < 80mEq/Lis considered abnormal [3].Statistical AnalysisA one-way analysis of variance was conducted tolook at the relationship between the clinical groupsand the two parameters measured on secretinenhancedMRCP—that is, volume of secretin andmaximum rate of secretion. When significancewas found, further exploration was conducted byexamining the mean differences between eachclinical group pairing. A Bonferroni correctionwas made to limit the probability of obtaining asignificant result by chance. A result that wouldhave been significant before the correction but notafter was referred to as marginally significant.The correlation between clinical groups andvolume and rate was determined by the Kendallrank coefficient (Kendal tau). The Kendall tau wasalso used to calculate the correlation between thevolume measurements and maximum bicarbonatelevels on endoscopic PFT, which were availablefor 65 patients.ResultsVolume QuantificationAmong the 134 patients included in thestudy, a significant association was observedbetween the clinical groups and volume measurements(p = 0.0003). Mean volumes becameprogressively smaller with increasingdegree of pancreatitis (Table 3). Significantvolume differences were found between thenormal group and established pancreatitisgroup as well as the equivocal group and establishedpancreatitis group. Marginally significantdifferences were also found betweenthe normal group and early pancreatitis groupas well as the early and established pancreatitisgroups (Table 4). Significant correlationwas found between the clinical groups and thevolume measurements on secretin-enhancedMRCP (τ = −0.324, p < 0.0001).Rate of SecretionThe mean values for the maximum rateof secretion in any 2-minute period tendedto decrease with higher degree or suspicionof 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 foundto be statistically significant using the analysisof variance test. There was a weak butTABLE 4: Differences in Mean Volumes Between Various Clinical Groups andp Values Using Analysis of Variance TestTABLE 3: Mean Secretory Volumesof Various Clinical GroupsClinical GroupMean Volume (mL)Normal 57.3Equivocal 49.7Early pancreatitis 39.8Established pancreatitis 22.1Groups Mean Volume Difference (mL) pNormal and equivocal 7.6 0.2367Normal and early pancreatitis 17.5 0.0150 aNormal and established pancreatitis 35.2 < 0.0001 bEquivocal and early pancreatitis 9.9 0.1177Equivocal and established pancreatitis 27.6 0.0005 bEarly and established pancreatitis 17.7 0.0351 aa Marginally significant at the 95% CI level.b Significant at the 95% CI level.130 AJR:198, January 2012

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