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1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at M. Fatih Akisik, MD Alex M. Aisen, MD Kumar Sandrasegaran, MD S. Gregory Jennings, MD Chen Lin, PhD Stuart Sherman, MD John A. Lin Magnus Rydberg Assessment of Chronic Pancreatitis: Utility of Diffusionweighted MR Imaging with Secretin Enhancement 1 Purpose: Materials and Methods: To retrospectively measure and compare changes in pancreatic apparent diffusion coefficient (ADC) following secretin administration in patients with and those without chronic pancreatitis (CP) who underwent magnetic resonance (MR) cholangiopancreatography with diffusionweighted (DW) imaging. This retrospective HIPAA-compliant study was approved by the authors institutional review board, with waiver of informed consent. Eighty-nine patients were categorized by the referring gastroenterologist as having no CP (n 37), mild CP (n 33), or severe CP (n 19) on the basis of Cambridge criteria and/or clinical course. Mean age was 52.2 years (range, years) in women and 54.3 years (range, years) in men. Patients underwent 1.5-T MR cholangiopancreatography, including DW sequences (b 0, 100, and 400 sec/mm 2 ) performed serially for 10 minutes after secretin injection. Severity level of CP was analyzed for sex (Fisher exact test) and age (analysis of variance) differences. Pairwise comparisons of mean ADCs for each parameter (no CP vs mild CP, no CP vs severe CP, mild CP vs severe CP) were performed (Mann- Whitney test). Threshold values of non secretin-enhanced ADC for pancreatitis discrimination were calculated with receiver operating characteristic analysis. P.05 was considered to show a significant difference. ORIGINAL RESEARCH GASTROINTESTINAL IMAGING 1 From the Department of Radiology (M.F.A., A.M.A., K.S., S.G.J., C.L., J.A.L., M.R.) and Department of Medicine, Division of Gastroenterology/Hepatology (S.S.), Indiana University School of Medicine, 550 N University Blvd, Room 0279, Indianapolis, IN Received February 1, 2008; revision requested April 9; revision received May 13; accepted June 18; final version accepted July 1. Address correspondence to M.F.A. ( ). Results: Conclusion: Patients with severe CP were more likely to be men than were those without pancreatitis; there were no significant age differences between groups. Mean nonenhanced and maximum secretin-enhanced ADCs were higher in patients without CP than in those with mild or severe CP but did not vary between those with mild and severe CP. Percentage increase in ADC after secretin injection and time to peak ADC did not vary among groups. An ADC of less than mm 2 /sec was optimal for delineating normal pancreas from CP groups. In symptomatic patients, baseline pancreatic ADC obtained with DW imaging prior to secretin administration may aid in diagnosis of CP and assessment of its severity; ADC response to secretin administration may be less useful. RSNA, 2008 RSNA, 2008 Radiology: Volume 250: Number 1 January

2 The clinical evaluation of the pancreas typically involves assessment of its structure and endocrine and exocrine function. Assessment of pancreatic exocrine function is the most challenging. While direct measurement of pancreatic fluid and bicarbonate output can be made to quantify function, this assessment requires invasive and timeconsuming procedures and thus is rarely performed. Alternative methods that are less invasive and that do not use ionizing radiation have been introduced and are growing in popularity. Magnetic resonance (MR) cholangiopancreatography has become the noninvasive imaging modality of choice to assess both the structure and the function of the pancreas. Dynamic MR cholangiopancreatography is usually performed following the intravenous injection of secretin, a 27 amino acid peptide hormone that is excreted by the duodenum in response to food and that stimulates pancreatic exocrine secretion. By transiently increasing exocrine secretion, the use of secretin during MR cholangiopancreatography improves ductal visualization (1) and facilitates measurement of pancreatic duct caliber and shape and the quantity of exocrine secretion of fluid into the duodenum (2 4). The dynamic changes measured in response to a secretin challenge permit assessment of pancreatic function and thus the overall health of the exocrine pancreas. Advances in Knowledge Apparent diffusion coefficients (ADCs) in the pancreas are reduced in patients with chronic pancreatitis (mild, mm 2 /sec; severe, mm 2 /sec) compared with patients without pancreatitis ( mm 2 /sec; P.01). Differences in ADC cannot be used to reliably differentiate the severity of chronic pancreatitis. ADCs in the pancreas may increase after secretin administration, but the degree of increase is not useful in the diagnosis of chronic pancreatitis. Implication for Patient Care ADCs may be useful in identification of chronic pancreatitis. In addition, diffusion-weighted (DW) imaging has been shown to provide information regarding pancreatic exocrine function, through measurement of the accumulation of tissue fluid in the pancreatic parenchyma itself before it is actually secreted into the ductal system (5). DW imaging is sensitive to the random motion of water molecules, which is restricted by cell membranes. For example, when extracellular fluid moves into cells, there is a reduction of diffusive motion and a consequent increase in DW signal intensity. This process occurs, for example, when brain tissue becomes ischemic, and as a result DW imaging has been shown to be sensitive for detecting early cerebral ischemia (6). DW imaging is performed by modifying MR pulse sequences to incorporate diffusion-sensitizing magnetic gradient pulses; the degree of diffusion weighting is determined by the strength, duration, and separation of these gradients, termed b values. If at least two images are acquired with different b values, it is possible to quantify the diffusion properties of tissue by calculating the apparent diffusion coefficient (ADC). The acquisition of additional images with different b values will increase the accuracy of calculating the ADC but requires longer imaging time. The use of DW imaging in secretinenhanced MR cholangiopancreatography was first described by Erturk et al (5). They concluded that there was a statistically significant difference in ADC peaks between patients with and those without chronic pancreatitis. However, to our knowledge, the change in ADC following secretin administration has not been quantified in a large group of patients. We have routinely performed secretin-enhanced MR cholangiopancreatography for several years, and we recently instituted routine performance of DW imaging in patients scheduled to undergo MR cholangiopancreatography for evaluation of suspected pancreatic disease. The purpose of our study was to retrospectively measure and compare changes in pancreatic ADC following secretin administration in patients with and those without chronic pancreatitis who underwent MR cholangiopancreatography with DW imaging. Materials and Methods M.F.A. and A.M.A. have been consultants for RepliGen (Waltham, Mass), a manufacturer of secretin; these authors did not control patient selection or data inclusion for this study. This retrospective Health Insurance Portability and Accountability Act compliant study was approved by our institutional review board, with waiver of informed consent. Since November 2006, our imaging protocol for MR cholangiopancreatography has included dynamic secretin-enhanced imaging performed for a 10-minute interval, with interleaved anatomic and DW imaging. From November 2006 to July 2007, we retrospectively identified 277 patients who underwent MR cholangiopancreatography for evaluation of known or suspected pancreatic disease. We excluded those patients in whom secretin was not used (n 6) or DW imaging was not performed (n 20). Patients were also excluded if there was a history of pan- Published online before print /radiol Radiology 2009; 250: Abbreviations: ADC apparent diffusion coefficient DW diffusion weighted ERCP endoscopic retrograde cholangiopancreatography RARE rapid acquisition with relaxation enhancement Author contributions: Guarantor of integrity of entire study, M.F.A.; study concepts/study design or data acquisition or data analysis/ interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, A.M.A., K.S., S.G.J., C.L.; clinical studies, M.F.A., K.S., S.G.J., C.L., S.S., J.A.L.; statistical analysis, M.F.A., K.S., S.G.J., M.R.; and manuscript editing, all authors See Materials and Methods for pertinent disclosures. 104 Radiology: Volume 250: Number 1 January 2009

3 creatic surgery (n 37), known or suspected intraductal papillary mucinous neoplasm (n 21) or other pancreatic malignancy (n 9), acute or acute recurrent pancreatitis (n 16), ampullary adenoma (n 2), or pancreatic trauma (n 1). Twelve patients were excluded because they had evidence of chronic pancreatitis at MR cholangiopancreatography but had no clinical follow-up available. Thus, 153 patients were evaluated for ADC measurement. MR Protocol All MR studies were obtained with a 1.5-T imager (Avanto; Siemens Medical Solutions, Malvern, Pa) by using a surface phased-array body coil. All patients underwent the following: three-plane scout view acquisition, T1-weighted imaging through the pancreaticobiliary ductal system, and MR cholangiopancreatography sequences that included axial and coronal breath-hold twodimensional half-fourier rapid acquisition with relaxation enhancement (RARE) and a coronal respiratorytriggered three-dimensional turbo spinecho (prospective acquisition correction) T2-weighted sequence (Table 1). For DW imaging, a spin-echo echoplanar sequence was performed with b values of 0, 100, and 400 sec/mm 2, with parallel imaging (generalized autocalibrating partially parallel acquisition) acceleration factor of two. Six oblique sections of mm field of view, 10-mm section thickness, and 25% intersection gap were prescribed, using a graphic tool to cover the entire pancreas. The imaging time was 36 seconds in order to acquire three data sets for averaging, to improve the signal-tonoise ratio, and to reduce the potential artifacts from a non breath-hold acquisition. An ADC map was calculated for each section automatically by the imager software. After DW and MR cholangiopancreatographic thick-slab images were obtained at baseline, 16 g of secretin (Secreflo; RepliGen) was injected intravenously over the course of 1 minute. Imaging began immediately after the completion of injection. DW and MR cholangiopancreatographic thick-slab images were then acquired every minute for 10 minutes after injection. Table 1 Parameters for MR Cholangiopancreatography Sequence Figure 1 Repetition Time (msec) Echo Time (msec) Image Analysis For each of the 153 patients evaluated for ADC measurement, a research assistant (J.A.L.) with 6 years of experience in abdominal MR image analysis, blinded to diagnosis, identified the pancreas on each nonenhanced and secretin-enhanced image. The ADC in a single region of interest drawn in each segment (head, body, and tail) of the pancreas was measured (Figs 1, 2). The image that best represented each segment was used. A minimum area of 50 mm 2 of pancreatic parenchyma was required for ADC measurement, as that was the smallest region of interest available with our measurement software, and was the size used in our study. Patients with a smaller area in all three segments were excluded from analysis (n 9). Care was taken to avoid pancreatic ducts, cystic lesions, and artifacts within the regions of interest. If there was substantial artifact throughout the region of interest for a particular pancreatic segment, the ADC was not measured in that segment, and these patients were not included for analysis (n 15). Flip Angle (degree) Section Thickness (mm) Matrix Coronal three-dimensional turbo spin-echo respiratory triggered * Axial and coronal half-fourier RARE Coronal thick slab Axial DW spin-echo echo planar * Slab thickness, 40 mm. Performed with b values of 0, 100, and 400 sec/mm 2, with generalized autocalibrating partially parallel acquisition acceleration factor of two. Figure 1: (a) Axial non breath-hold spin-echo echo-planar DW image (b 400 sec/mm 2 ) in a patient with a normal pancreas. The visualized portion of the pancreas (arrow) is seen without parenchymal atrophy. Parallel imaging acceleration factor of two was used (repetition time msec/echo time msec, 1000/68; 90 flip angle; matrix, ). (b) Axial ADC map calculated from basis images obtained with b values of 0, 100, and 400 sec/mm 2 in the same patient. The region of interest is shown without interference from surrounding tissue (arrow). Radiology: Volume 250: Number 1 January

4 All regions of interest equivocal for artifact were evaluated for measurement suitability by a radiologist (M.F.A.) with 8 years of experience in body MR. Patients with only coronal images available (n 6) were also not included. Thus, 123 patients had ADCs measured. Pancreatitis Severity Classification Of the 123 patients with ADC measurements, we first identified those who underwent endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasonography (US) and who had no evidence of chronic pancreatitis at these examinations (n 71) and had clinical follow-up results available (ERCP, n 31; endoscopic US, n 6). These 37 patients comprised the normal pancreas group. We then identified those patients who had a diagnosis of equivocal (n 9), mild (n 24), moderate (n 8), or severe (n 11) chronic pancreatitis made by the gastroenterologist caring for them. These 52 patients comprised the chronic pancreatitis group. The diagnosis of chronic pancreatitis was based on findings at ERCP (n 26), endoscopic US (n 19), or computed tomography (CT) (n 5) or on clinical history (n 2). The Cambridge classification criteria were used for grading pancreatitis severity with ERCP (7). Equivocal chronic pancreatitis is based on this Figure 2 classification scheme and is generally accepted by gastroenterologists. Endoscopic US findings were classified as mild chronic pancreatitis if inhomogeneous echotexture or echogenic strands were seen in the gland. Presence of severe chronic pancreatitis was demonstrated by means of glandular atrophy, main pancreatic duct dilation or irregularity, or parenchymal or ductal calculi. CT findings of focal or diffuse fatty change were deemed to represent mild chronic pancreatitis, while ductal or parenchymal calcification or severe glandular atrophy was taken to indicate severe chronic pancreatitis. For patients without ERCP, endoscopic US, or CT results available, the presence of typical chronic deep gnawing abdominal pain necessitating daily use of analgesics, including narcotic medication, was deemed to indicate severe chronic pancreatitis. The presence of endocrine or exocrine dysfunction necessitating the use of antidiabetic or enzyme supplement therapy was also used to indicate severe chronic pancreatitis. Presence of at least three prior episodes of pancreatitis with intermittent pain, not sufficient to be classified as severe chronic pancreatitis, was classified as mild chronic pancreatitis. All data were entered into an electronic database program (Excel; Figure 2: (a) Axial T2-weighted half-fourier RARE image in a patient with severe chronic pancreatitis (twodimensional interleaved 4-mm sections with no gap; 1100/90, 130 flip angle, matrix). The main pancreatic duct is dilated and multiple abnormal side branches are seen. There is parenchymal atrophy (arrowhead pancreatic head, arrow body and tail). (b) Axial ADC map in the same patient. The pancreas parenchyma can be easily identified for reliable measurements (arrowhead pancreatic head; arrow body and tail). Spin-echo echo-planar imaging with b values of 0, 100, and 400 sec/mm 2 with a parallel imaging acceleration factor of two was used (1000/68, 90 flip angle, matrix). Microsoft, Redmond, Wash) for analysis. Data Analysis Patients with moderate or severe chronic pancreatitis were combined into one group, which was called the severe pancreatitis group for data analysis, owing to the low anticipated number of patients in these categories and the difficulty of measuring ADC in many patients with severe chronic pancreatitis because of the limited amount of remaining parenchyma. We also combined patients with equivocal or mild chronic pancreatitis into one group, which was called the mild pancreatitis group. We thus had three patient groups: no pancreatitis (n 37), mild chronic pancreatitis (n 33), and severe chronic pancreatitis (n 19). The severity of chronic pancreatitis was analyzed for differences in sex (Fisher exact test) and mean age (oneway analysis of variance). For each pancreatic segment, the ADC obtained before secretin injection ( nonenhanced ADC ), the peak secretin-enhanced ADC, the percentage increase over the nonenhanced ADC, and the postinjection time of ADC peak were documented. For all parameters, the mean for each segment was averaged for each patient and then compared between groups (Kruskal-Wallis test). Pairwise comparisons of the mean for each parameter (no pancreatitis vs mild disease, no pancreatitis vs severe disease, mild vs severe disease) were made by using the Mann-Whitney test. In addition, for the nonenhanced ADC only, the mean for each pancreatic segment was compared between groups (Kruskal- Wallis), as were pairwise comparisons (Mann-Whitney). To ensure that ADCs did not reflect sex differences, nonenhanced values were also compared between men and women without chronic pancreatitis in the head segment (Kruskal-Wallis). Finally, for each segment, the nonenhanced ADCs that most accurately helped discriminate between no pancreatitis and any degree of chronic pancreatitis were calculated by using receiver operating characteristic analysis (MedCalc version 9.2; MedCalc 106 Radiology: Volume 250: Number 1 January 2009

5 Table 2 Comparison of Non Secretin-enhanced ADCs in Head, Body, and Tail of Pancreas according to Pancreatitis Severity Pancreatitis Severity Head Body Tail ADC* No. of Measurements ADC* No. of Measurements ADC* No. of Measurements P Value None Mild Severe * Data are mean ( 10 5 mm 2 /sec) standard deviation. Kruskal-Wallis test. Table 3 ADC Response to Secretin according to Severity of Pancreatitis Parameter P Value No Disease* Mild Disease* Severe Disease* All Groups vs Mild No Disease No Disease vs Severe Mild vs Severe Nonenhanced ADC ( 10 5 mm 2 /sec) Maximum secretin-enhanced ADC ( 10 5 mm 2 /sec) Increase in ADC after secretin injection (%) Time to peak ADC (min) * Data are mean standard deviation. Kruskal-Wallis test. Mann-Whitney test. Number of measurements used in each severity group: no disease, 36; mild disease, 32, severe disease, 19. Number of measurements used in each severity group: no disease, 36; mild disease, 33, severe disease, 19. Software, Mariakerke, Belgium). P.05 was considered to indicate a significant difference. Results The sex distribution was as follows: no disease, 29 women and eight men; mild disease, 22 women and 11 men; and severe disease, 12 women and seven men. Mean age was 52.2 years (range, years) for women and 54.3 years (range, years) for men. Patients with severe chronic pancreatitis were more likely to be men than were those without pancreatitis (P.01). Mean age was 50.7 years for no disease, 54.2 years for mild disease, and 54.8 years for severe disease; there was no association between patient age and the presence or severity of chronic pancreatitis (P.37). For each pancreatitis severity group, nonenhanced ADCs were not significantly different between pancreatic segments (Table 2). Thus, for each patient, the mean ADC among the three segments was used for all calculations and statistical comparisons. ADC changes after secretin administration are listed in Table 3; plots of mean nonenhanced ADC and ADC at various time points after secretin administration are given in Figure 3. Mean nonenhanced and maximum secretinenhanced ADCs varied significantly among the three groups as a whole, between no pancreatitis and mild chronic pancreatitis groups, and between no pancreatitis and severe chronic pancreatitis groups, but not between mild and severe chronic pancreatitis groups. The percentage increase in secretin-enhanced ADC and the time to peak ADC did not differ among groups. An ADC of less than mm 2 /sec was found to be optimal for differentiating patients with no pancreatitis from those with any degree of pancreatitis and yielded 74% sensitivity and 66% specificity (Table 4). All patients with a head segment ADC of less than mm 2 /sec before secretin injection had chronic pancreatitis. For 36 of 37 patients with no pancreatitis where head segments were available for ADC measurement, there was no significant difference between men (n 8) and women (n 28) in mean nonenhanced ADC (respectively, Radiology: Volume 250: Number 1 January

6 188.9 and mm 2 /sec, P.62), peak secretin-enhanced ADC (237.0 and mm 2 /sec, P.89), percentage increase in ADC (26.9% and 19.9%, P.89), or postinjection mean time to ADC peak (4.1 minutes and 3.8 minutes, P.49). Discussion Figure 3 Chronic pancreatitis is a common problem worldwide. While alcohol abuse is the most common cause, idiopathic, genetic, tropical-related, and drug-induced causes are also contributing factors (8). The incidence of the disease is slowly rising, perhaps owing to both the increase of alcoholism in some countries and the greater availability of diagnostic tools such as ERCP and MR cholangiopancreatography to detect the disease (9). Chronic pancreatitis is a progressive disease of inflammation and fibrosis that may cause severe intractable pain, requiring the use of narcotic analgesics, and endocrine insufficiency (diabetes mellitus). In some patients, surgery is Figure 3: Graph of ADC results. The normal pancreas group demonstrates higher ADC values than the pancreatitis groups, both before and after secretin administration. Table 4 Most Accurate Non Secretin-enhanced ADC Threshold Levels for Pancreatitis versus No Pancreatitis Parameter No. of Measurements Area under the Curve Best Cutoff ADC* Sensitivity (%) Specificity (%) P Value Pancreatitis vs no pancreatitis Nonenhanced MR Secretin-enhanced MR Mild pancreatitis vs severe pancreatitis Nonenhanced MR Secretin-enhanced MR * Measurements are 10 5 mm 2 /sec. Nonenhanced vs secretin-enhanced MR findings. unavoidable. While definitive proof of chronic pancreatitis requires pathologic sampling, the results from imaging modalities such as radiography, CT, ERCP, and endoscopic US are often used to make the diagnosis. The major limitations of these techniques are that they are often unable to help detect mild pancreatitis or differentiate mild from moderate disease. Moreover, the clinical presentation and imaging results sometimes indicate the presence of mild chronic pancreatitis despite a lack of obvious morphologic changes in the duct and gland when sampled (10). ERCP has been considered to be the best available test for making the diagnosis of chronic pancreatitis. However, ERCP is invasive, requires patient sedation, and can itself result in acute pancreatitis. A recent study demonstrated that the incidence of post-ercp pancreatitis is directly proportional to the extent of pancreatic duct filling during the examination (11). Moreover, there is substantial interobserver variability in interpreting pancreatographic findings, particularly in mild disease. Because of its invasive nature and its lack of specificity for diagnosis of early stage disease, ERCP has largely been abandoned for diagnosis of chronic pancreatitis. Identification of a noninvasive sensitive and specific test to diagnose mild chronic pancreatitis would be a major advance. With technologic advances in the resolution and speed of MR imaging, MR cholangiopancreatography was developed as an alternative imaging method that would be safer than ERCP and also allow anatomic imaging of the surrounding pancreatic parenchyma and other nearby vessels and organs, as well as dynamic functional imaging of the pancreas with the use of secretin. While MR cholangiopancreatography is growing in popularity for evaluation of suspected pancreatic disease, including for chronic pancreatitis (12) and response to therapy (13,14), the lack of an ERCP-like classification scheme and the inability to accurately diagnose mild chronic pancreatitis has hindered its wider use. In our study we found that, in gen- 108 Radiology: Volume 250: Number 1 January 2009

7 eral, patients with chronic pancreatitis had lower ADCs before secretin administration than did patients without pancreatitis. Non secretin-enhanced ADCs did not vary between the mild and severe chronic pancreatitis groups. The ADC response to secretin did not vary among groups. DW imaging measures changes in the microscopic diffusion of water. In the liver, fibrosis and cirrhosis have been shown to reduce diffusion (8). In chronic pancreatitis, fibrosis and chronic inflammation are associated with destruction and permanent loss of exocrine pancreatic tissue (15), with permanent loss of exocrine and endocrine pancreatic function (16,17). Limited knowledge exists regarding the underlying biophysical phenomena that determine ADC in vivo. Thus, we can only speculate about the possible underlying basis of changes in ADCs that may occur in chronic pancreatitis. It is possible that replacement of normal pancreatic parenchyma with fibrous tissue and/or reduced exocrine function may reduce diffusible tissue water and result in decreased measured ADCs. Erturk et al (5) demonstrated that the application of DW sequences to secretin-enhanced MR cholangiopancreatography can be used to diagnose chronic pancreatitis. However, only patients with severe disease and patients without any disease were classified as such (many at-risk patients without a specific diagnosis were included), and only the change in ADC following secretin administration was analyzed in that study. In our study, while we found that ADCs increased with secretin, we did not find the ADC response to secretin to be useful for grading chronic pancreatitis; this may reflect differences in the patient populations in the two studies or limitations imposed by sample size in one or both of the studies. In our study, with a larger group of patients, we examined whether nonenhanced ADCs or the ADC response to secretin could be used to predict disease status and whether we could differentiate patients without chronic pancreatitis from those with mild disease. Our results show that the baseline ADC is lower in patients with chronic pancreatitis than in those without pancreatitis and is not significantly different between mild and severe chronic pancreatitis. Secretin-enhanced ADCs showed a tendency toward differentiating mild from severe chronic pancreatitis (P.10), but the difference was not statistically significant. In this series, we did not find that changes in ADC following secretin administration were helpful for diagnosis. Our study has limitations. This is a retrospective study and relies on clinical evaluation for the diagnosis of chronic pancreatitis and the grading of its severity. Such evaluation is known to be subjective, as the assessment of patients may differ from physician to physician. In addition, ADC measurements are unavoidably subject to error, particularly in body imaging applications, owing to both low signal-to-noise ratio and artifacts caused by physiologic motion and magnetic susceptibility. Therefore, ADC measurement could not be performed in some patients or pancreatic regions, and this missing data could have affected the results. In particular, measurements often could not be made in patients with severe chronic pancreatitis, who were more likely to have atrophy. This may introduce a bias toward less significance in the results. The practical importance of this is mitigated since the diagnosis of severe chronic pancreatitis is usually relatively easy, based on imaging criteria, and is not likely to require quantitative measurement of ADCs. Measurement of ADC is technically difficult in the abdomen; we used a multiple signal acquisition rather than a breath-hold technique, to improve patient tolerance of the complex protocol. With improvements in MR imaging technology, and as further investigations better define which measurements are most important, it is likely that technique and accuracy will improve. We conclude that, in symptomatic patients, the measurement of ADCs from DW images prior to secretin administration may aid in the diagnosis of chronic pancreatitis, while assessment of the ADC response to secretin administration is less useful. References 1. Manfredi R, Costamagna G, Brizi MG, et al. Severe chronic pancreatitis versus suspected pancreatic disease: dynamic MR cholangiopancreatography after secretin stimulation. Radiology 2000;214: Heverhagen JT, Muller D, Battmann A, et al. MR hydrometry to assess exocrine function of the pancreas: initial results of noninvasive quantification of secretion. Radiology 2001;218: Matos C, Metens T, Deviere J, et al. Pancreatic duct: morphological and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997;203: Punwani S, Gillams AR, Lees WR. Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP. Eur Radiol 2003;13: Erturk SM, Ichikawa T, Motosugi U, Sou H, Araki T. Diffusion-weighted MR imaging in the evaluation of pancreatic exocrine function before and after secretin stimulation. Am J Gastroenterol 2006;101: Moseley ME, Cohen Y, Mintorovitch J, et al. Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy. Magn Reson Med 1990;14: Axon AT, Classen M, Cotton PB, Cremer M, Freeny PC, Lees WR. Pancreaticography in chronic pancreatitis: international definitions. Gut 1984;25: Taouli B, Tolia AJ, Losada M, et al. Diffusion-weighted MRI for quantification of liver fibrosis: preliminary experience. AJR Am J Roentgenol 2007;189: Andersen BN, Pedersen NT, Scheel J, Worning H. Incidence of alcoholic chronic pancreatitis in Copenhagen. Scand J Gastroenterol 1982;17: Stevens T, Conwell DL. Chronic pancreatitis. In: Ginsburg GG, Ahmad NA, eds. The clinician s guide to pancreaticobiliary disorders. Thorofare, NJ: Slack, 2006; Cheon YK, Cho KB, Watkins JL, et al. Frequency and severity of post-ercp pancreatitis correlated with extent of pancreatic ductal opacification. Gastrointest Endosc 2007;65: Hellerhoff KJ, Helmberger H, Rosch T, Settles MR, Link TM, Rummeny EJ. Dynamic MR pancreatography after secretin administration: image quality and diagnostic accuracy. AJR Am J Roentgenol 2002;179: Bali MA, Sztantics A, Metens T, et al. Quantification of pancreatic exocrine function with secretin-enhanced magnetic resonance cholangiopancreatography: normal values and short-term effects of pancreatic duct drainage procedures in chronic pancreatitis initial results. Eur Radiol 2005;15: Monill J, Pernas J, Clavero J, et al. Pancreatic duct after pancreatoduodenectomy: morphologic and functional evaluation with secretin-stimulated MR pancreatography. AJR Am J Roentgenol 2004;183: Go VLM, Everhart JE. Pancreatitis. In: Everhart JE, ed. Digestive disease in the United States: epidemiology and impact. Washington, DC: U.S. Government Printing Office, 1994; Hayakawa T, Kondo T, Shibata T, et al. Relationship between pancreatic exocrine function and histological changes in chronic pancreatitis. Am J Gastroenterol 1992;87: Sarles H, Bernard JP, Gullo L. Pathogenesis of chronic pancreatitis. Gut 1990;31: Radiology: Volume 250: Number 1 January