<strong>Secretin</strong>-<strong>Enhanced</strong> <strong>MRCP</strong>TABLE 2: Description <strong>of</strong> Clinical Groups Used to Classify Chronic PancreatitisClinical Group Description <strong>of</strong> Group No. <strong>of</strong> PatientsNormalChronic abdominal pain <strong>and</strong> no risk factors for chronic pancreatitis. Risk factors include heavy31alcohol use, acute pancreatitis, pancreas divisum, very high triglycerides, <strong>and</strong> well-documentedsphincter <strong>of</strong> Oddi dysfunction. No early or late imaging findings <strong>of</strong> chronic pancreatitis. At least oneimaging test was performed (usually CT) with normal results.EquivocalChronic abdominal pain with at least one <strong>of</strong> the normal risk factors; endoscopic pancreatic function53test with normal results.Early chronic pancreatitis Pain, risk factors, <strong>and</strong> either mild imaging changes (e.g., ERCP Cambridge score <strong>of</strong> 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 than<strong>MRCP</strong> 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 <strong>of</strong> the cysts after secretin injectionsuggests ductal communication (Fig.13). Because the management <strong>of</strong> IPMNs <strong>and</strong>mucinous cystic neoplasms differs, visualization<strong>of</strong> ductal communication plays an importantrole in both the confirmation <strong>of</strong> thediagnosis <strong>and</strong> the management algorithm.There is very little literature on the use <strong>of</strong> secretin-enhanced<strong>MRCP</strong> in the evaluation <strong>of</strong>cystic neoplasms. The frequency with whichsecretin actually improves visualization <strong>of</strong>ductal communication is unknown.Status <strong>of</strong> <strong>Secretin</strong>-<strong>Enhanced</strong> <strong>MRCP</strong>That secretin-enhanced <strong>MRCP</strong> holdsgreat promise in the evaluation <strong>of</strong> chronicpancreatitis is not disputed. However, despitethe availability <strong>of</strong> <strong>MRCP</strong> 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 <strong>of</strong> complications,direct function test is cumbersome<strong>and</strong> limited to few centers, <strong>and</strong> EUSis highly operator dependent, <strong>and</strong> none <strong>of</strong>these can match the unique combined functional<strong>and</strong> morphologic perspective providedby secretin-enhanced <strong>MRCP</strong>. These limitationsaccentuate the advantages <strong>of</strong> secretinenhanced<strong>MRCP</strong>. Currently the use <strong>of</strong> secretin-enhanced<strong>MRCP</strong> is somewhat limited tolarge centers where it is <strong>of</strong>ten used in combinationwith other tests. Considering thehigh prevalence <strong>of</strong> chronic pancreatitis <strong>and</strong>the extensive use <strong>of</strong> invasive investigations toestablish this diagnosis, secretin-enhanced<strong>MRCP</strong> has been significantly underutilized.Even patients who undergo <strong>MRCP</strong> for suspectedchronic pancreatitis <strong>of</strong>ten do not havesecretin administered despite the clear incrementalvalue <strong>of</strong> secretin to the test. Lack<strong>of</strong> awareness, cost, <strong>and</strong> paucity <strong>of</strong> large trialsproving its effectiveness are all partly responsiblefor this. The shortage <strong>of</strong> secretinfaced a few years ago has now resolved <strong>and</strong>synthetic human secretin is easily available.Quantification <strong>of</strong> Duodenal SecretionA drawback <strong>of</strong> secretin-enhanced <strong>MRCP</strong>is the subjective nature <strong>of</strong> the reports [25].As a result, the reports do not harness thetrue potential <strong>of</strong> the test. The subjective assessment<strong>of</strong> duodenal filling used in practiceintroduces large interobserver variations becauseradiologists may differ in their interpretation<strong>of</strong> adequate secretion. Because oursecretin-enhanced <strong>MRCP</strong> reports <strong>of</strong>ten donot include objective data, gastroenterologistssometimes perceive them to be ambiguousor inconclusive, creating a need for thedevelopment <strong>of</strong> an objective parameter to establishthe diagnosis <strong>of</strong> pancreatitis.Despite several prior attempts to quantifythe volume <strong>of</strong> duodenal fluid as measure <strong>of</strong>exocrine function [12, 15, 26–28], a method<strong>of</strong> quantification that can reliably differentiatebetween normal, early, <strong>and</strong> 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,<strong>and</strong> grade 3, when it fills beyond the genu.A lower score on this grading scale was associatedwith a low bicarbonate concentration<strong>and</strong> impaired exocrine function [10, 15].The main attraction <strong>of</strong> this grading system isits extreme simplicity. However, Cappeliez etal. [15] found that this grading system had alow sensitivity <strong>of</strong> 72% for impaired pancreaticfunction, whereas Hellerh<strong>of</strong>f et al. [14]reported it to have a low positive predictivevalue <strong>of</strong> 58% for chronic pancreatitis. Furthermore,this grading system was not able todifferentiate between patients with mild <strong>and</strong>established chronic pancreatitis [15].Gillams <strong>and</strong> Lees [29] measured changes insmall intestine water volume to calculate thepancreatic flow rate as an indicator <strong>of</strong> the volume<strong>of</strong> secretion. This model was able to identifysevere pancreatitis from normal <strong>and</strong> moderatechronic pancreatitis but was unable to differentiatenormal from mild or moderate pancreatitis.Subjects <strong>and</strong> MaterialsIn view <strong>of</strong> the scant data available on secretin-enhanced<strong>MRCP</strong> quantification, weperformed a study to quantify the volume <strong>of</strong>secretions on secretin-enhanced <strong>MRCP</strong> inpatients with suspected chronic pancreatitis<strong>and</strong> compared it with the clinical diagnosis<strong>of</strong> chronic pancreatitis.PatientsBetween March 2005 <strong>and</strong> September 2008, 166patients underwent secretin-enhanced <strong>MRCP</strong> atour institution. After exclusion <strong>of</strong> 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), <strong>and</strong> ERCP (n = 36), to diagnosechronic pancreatitis.Clinical GroupsAn experienced pancreatologist, who wasblinded to the secretin-enhanced <strong>MRCP</strong> results,classified the patients into four clinical groups(Table 2) on the basis <strong>of</strong> clinical risk factors <strong>and</strong>the findings <strong>of</strong> the investigations mentioned earlier.AJR:198, January 2012 129
Sanyal et al.Fig. 14—35-year-old woman with normal pancreaticfunction. Image shows region <strong>of</strong> interest drawnaround fluid in duodenum to obtain area. Obtainingsimilar measurements on all slices allows volume <strong>of</strong>secretion to be calculated.<strong>Secretin</strong>-<strong>Enhanced</strong> <strong>MRCP</strong> Quantification<strong>Technique</strong>Volume—In patients prepared with a negativeoral contrast agent, new high T2 signal areasin the duodenum after secretin administrationrepresent new pancreatic secretions. A region <strong>of</strong>interest (ROI) was drawn around the T2 brightduodenal <strong>and</strong> proximal jejunal fluid on each slice<strong>of</strong> the postsecretin coronal HASTE sequence (Fig.14). The area (in cm 2 ) <strong>of</strong> the ROI in each slicewas added <strong>and</strong> the total multiplied by the slicethickness (0.4 cm) to obtain the total volume fluid(in mL) secreted in response to secretin.Rate <strong>of</strong> secretion—Diminished pancreaticexocrine function may not only manifest asa decreased volume <strong>of</strong> secretion but also as adecreased rate <strong>of</strong> secretion in response to secretin.To assess this function, the maximal rate <strong>of</strong>secretion was measured in each patient. An ROIwas drawn on each <strong>of</strong> 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 calculation<strong>of</strong> maximum pancreatic flow rate. Region <strong>of</strong> interestis drawn around duodenum in each <strong>of</strong> 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 <strong>of</strong> the maximum rate <strong>of</strong>secretion in response to secretin for each patient.Endoscopic pancreatic function test—Sixtyfivepatients underwent secretin-stimulatedendoscopic PFT for measurement <strong>of</strong> pancreaticexocrine function. After injection <strong>of</strong> 0.2 μg/kg<strong>of</strong> 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 <strong>of</strong> variance was conducted tolook at the relationship between the clinical groups<strong>and</strong> the two parameters measured on secretinenhanced<strong>MRCP</strong>—that is, volume <strong>of</strong> secretin <strong>and</strong>maximum rate <strong>of</strong> secretion. When significancewas found, further exploration was conducted byexamining the mean differences between eachclinical group pairing. A Bonferroni correctionwas made to limit the probability <strong>of</strong> 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 <strong>and</strong>volume <strong>and</strong> rate was determined by the Kendallrank coefficient (Kendal tau). The Kendall tau wasalso used to calculate the correlation between thevolume measurements <strong>and</strong> 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 <strong>and</strong> volume measurements(p = 0.0003). Mean volumes becameprogressively smaller with increasingdegree <strong>of</strong> pancreatitis (Table 3). Significantvolume differences were found between thenormal group <strong>and</strong> established pancreatitisgroup as well as the equivocal group <strong>and</strong> establishedpancreatitis group. Marginally significantdifferences were also found betweenthe normal group <strong>and</strong> early pancreatitis groupas well as the early <strong>and</strong> established pancreatitisgroups (Table 4). Significant correlationwas found between the clinical groups <strong>and</strong> thevolume measurements on secretin-enhanced<strong>MRCP</strong> (τ = −0.324, p < 0.0001).Rate <strong>of</strong> SecretionThe mean values for the maximum rate<strong>of</strong> secretion in any 2-minute period tendedto decrease with higher degree or suspicion<strong>of</strong> 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 analysis<strong>of</strong> variance test. There was a weak butTABLE 4: Differences in Mean Volumes Between Various Clinical Groups <strong>and</strong>p Values Using Analysis <strong>of</strong> Variance TestTABLE 3: Mean Secretory Volumes<strong>of</strong> Various Clinical GroupsClinical GroupMean Volume (mL)Normal 57.3Equivocal 49.7Early pancreatitis 39.8Established pancreatitis 22.1Groups Mean Volume Difference (mL) pNormal <strong>and</strong> equivocal 7.6 0.2367Normal <strong>and</strong> early pancreatitis 17.5 0.0150 aNormal <strong>and</strong> established pancreatitis 35.2 < 0.0001 bEquivocal <strong>and</strong> early pancreatitis 9.9 0.1177Equivocal <strong>and</strong> established pancreatitis 27.6 0.0005 bEarly <strong>and</strong> 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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