Prospective Assessment of Normal Pancreatic Secretory Function Measured by MRI in a Cohort of Healthy Children.

OBJECTIVES: Magnetic resonance imaging (MRI) with secretin stimulation promises to allow non-invasive testing for exocrine pancreatic insufficiency but normal data do not exist for children. The purpose of this study was to define, in healthy children, normal pancreatic secreted fluid volume and secretion rate, measured by MRI, in response to secretin. METHODS: In this Institutional Review Board-approved, prospective, cross-sectional study, 50 healthy children ages 6 to <16 years underwent MRI with secretin stimulation. Images were obtained before and at 1, 5, 10 and 15 min after secretin administration to calculate total secreted fluid volume and secretion rate based on image segmentation. Regression was used to define the relationship between secretory function and participant size measures, and linear quantile regression was used to define normal secretory values based on size measures. RESULTS: Median total secreted fluid volume post secretin was 79 mL (range: 32-162 mL; 5th and 95th percentiles: 43 and 123 mL) and median secretion rate was 5.1 mL/min (range: 2-9.4 mL/min; 5th and 95th percentiles: 2.3 and 7.7 mL/min). Secreted volume and secretion rate had the strongest correlation with body surface area (BSA) (r = 0.54 and 0.59, respectively) and multiple regression defined BSA as the only significant predictor of secretory function. Each 1 m2 increase in BSA was associated with a 38 mL increase in secreted fluid volume. CONCLUSIONS: In children, pancreatic secretory response to secretin, measured by MRI, depends on participant size, particularly BSA. Secreted volume <43 mL or a secretion rate <2.3 mL/min (5th percentile values) can be considered abnormal for children.

The clinical value of secretin-enhanced MRCP in the functional and morphological assessment of pancreatic diseases.

Secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) provides a non-invasive way, with which, to evaluate pancreatic duct (PD) anatomy and exocrine pancreatic function. S-MRCP can be added to the routine pancreas MR examination in equivocal cases. Moreover, it can detect subtle PD involvement, allowing diagnosis of early, rather than end-stage, pancreatic diseases. Although S-MRCP is a valuable non-invasive diagnostic method, it is only performed in a few centres due to relative high cost. Furthermore, less familiarity with its indications, the examination technique, and image interpretation also contribute to its limited use. Thus, the purpose of this article is to explain secretin's mechanism of action, the examination technique, the clinically relevant indications, the advantages, and limitations. Finally, we will focus on image analysis and its role in achieving an early and accurate diagnosis of specific pancreatic and PD diseases.

Secretin-stimulated MRI assessment of exocrine pancreatic function in patients with cystic fibrosis and healthy controls.

PURPOSE: Secretin-stimulated magnetic resonance imaging (s-MRI) and pancreatic diffusion weighted imaging (DWI) are novel non-invasive imaging techniques for assessment of exocrine pancreatic insufficiency (EPI). The aim was to validate s-MRI assessed pancreatic secreted volume using novel semi-automatic quantification software, and to assess the ability of s-MRI with DWI to diagnose EPI in patients with cystic fibrosis (CF). METHODS: s-MRI and DWI was performed in 19 patients with CF (median age 21 years; range 16-56; eight men) and in 10 healthy controls (HC) (median age 46 years; range 20-65; four men). Sequential coronal T2-weighted images covering the duodenum and small bowel and axial DWI were acquired before and 1, 5, 9, and 13 min after secretin stimulation. A short endoscopic secretin test was used as reference method for EPI. RESULTS: CF patients with EPI had lower apparent diffusion coefficient before secretin in the pancreatic head (P < 0.001) and lower secreted bowel fluid volumes (P = 0.035) compared to HC and CF patients without EPI. ROC curve analyses identified that secreted fluid volume after 13 min yielded the highest diagnostic accuracy for diagnosing EPI (AUC 0.93; 95% CI [0.80-1.00]). CONCLUSION: Pancreatic s-MRI is useful for the assessment of exocrine pancreatic function with high diagnostic accuracy for the diagnosis of EPI in CF.

Secretin-Stimulated Magnetic Resonance Imaging Assessment of the Benign Pancreatic Disorders: Systematic Review and Proposal for a Standardized Protocol.

This systemic review summarizes the current literature and general consensus on secretin-stimulated magnetic resonance imaging (s-MRI) of the benign pancreatic disorders and discusses important aspects on how s-MRI is optimally performed. The aim is to provide an overview, for clinicians and radiologist, of the s-MRI protocols and the range of clinical applications. Furthermore, the review will summarize the criteria for evaluation of pancreatic morphology and function based on s-MRI.The literature search indentified 69 original articles and 15 reviews. Chronic pancreatitis was the disease that was most frequently assessed by s-MRI (33%), followed by acute pancreatitis (9%). Dynamic thick-slab 2-dimensional magnetic resonance cholangiopancreatography was the most used imaging sequence (86%). The diameter of the main pancreatic duct (75%) and pancreatic exocrine function based on visual grading of duodenal filling (67%) were the most evaluated pancreatic features. Sufficient similarities between studies were identified to propose the most agreeable standardized s-MRI protocol for morphological and functional assessment of the pancreas. In the future, more research and increased collaboration between centers is necessary to achieve more consensus and optimization of s-MRI protocols.

Temporal assessment of pancreatic blood flow and perfusion following secretin stimulation using noninvasive MRI.

PURPOSE: To dynamically quantify pancreatic perfusion and flow within the arteries supplying the pancreas in response to secretin stimulation. MATERIALS AND METHODS: Twelve healthy male subjects were scanned at 1.5T with arterial spin labeling to measure tissue perfusion and phase contrast magnetic resonance imaging (MRI) to measure vessel flow. Superior mesenteric (SMA), gastroduodenal (GDA), common hepatic (HA), and splenic (SA) arterial flow and pancreatic perfusion were serially measured for 50 minutes following 1 IU/kg intravenous secretin. The significance of differences between timepoints was tested using a repeated measures one-way analysis of variance (ANOVA). RESULTS: Baseline blood flow (mean ± SEM or median [IQR]) for SMA, HA, SA, and GDA was 7.6 ± 1.3, 4.0 ± 0.5, 8.2 ± 0.8, and 0.9 (0.8-1.4) ml/s, respectively. Baseline pancreatic perfusion was 200 ± 25 ml/100g/min. Blood flow increased in the SMA (234%, P < 0.0001) and GDA (155%, P = 0.015) immediately after secretin injection. Reduced HA blood flow was observed after 10 minutes (P = 0.066) with no change in SA flow (P = 0.533). Increased pancreatic perfusion was maintained for 40 minutes after injection with a maximal increase at 5 minutes (16.8%, P = 0.025). CONCLUSION: Intravenous secretin resulted in significant temporal changes in pancreatic perfusion and arterial blood flow.

Assessment of exocrine pancreatic function by secretin-stimulated magnetic resonance cholangiopancreaticography and diffusion-weighted imaging in healthy controls.

PURPOSE: To characterize and quantify exocrine pancreatic function by secretin-stimulated magnetic resonance cholangiopancreaticography (s-MRCP) and diffusion-weighted imaging (DWI) in healthy subjects and compare these findings to morphological features, ie, pancreatic volume and secretin-stimulated peak bicarbonate concentration measured in pancreatic juice. MATERIALS AND METHODS: Pancreatic magnetic resonance imaging (MRI) (1.5 T) was performed in 20 healthy volunteers among which 10 underwent gastroscopy with duodenal intubation. MRI included T2-weighted imaging and DWI acquired before and 1, 5, 9, and 13 minutes after secretin administration. Secreted pancreatic juice volumes were calculated based on the sequential T2-weighted images and pancreatic volumes and apparent diffusion coefficient (ADC) values were estimated. RESULTS: The mean pancreatic secretion rate declined from 9.5 mL/min at 1-5 minutes (postsecretin) to 2.9 mL/min at 9-13 minutes. Pancreatic head ADC values significantly increased from baseline (1.29 × 10(-3) mm(2) /s) to 1 minute postsecretin (1.48 × 10(-3) mm(2) /s) (P = 0.003). Secreted pancreatic juice volume at 1 minute after secretin correlated positively with peak bicarbonate concentration (n = 10, P = 0.05). CONCLUSION: Secretin-stimulated MRCP and DWI can characterize and quantify exocrine pancreatic function in healthy subjects. These imaging methods may prove relevant for patients with exocrine pancreatic dysfunction.

Secretin-stimulated MRCP in volunteers: assessment of safety, duct visualization, and pancreatic exocrine function.

OBJECTIVE: The objective of our study was to investigate secretin-stimulated MRCP in terms of the safety of secretin, improvement of duct visualization, and assessment of pancreatic exocrine function. MATERIALS AND METHODS: Eight hundred sixteen volunteers (370 women and 446 men; mean age, 49.7 ± 13.1 [SD] years) underwent 3D MRCP before and after secretin stimulation (1 U/kg of body weight) at 1.5 T. For the first 2 hours after secretin injection, subjects were evaluated for adverse reactions. Improvement of duct visualization after secretin stimulation was subjectively evaluated by two readers and was quantified by duct diameter measurements. Pancreatic exocrine function was evaluated subjectively by two readers according to the duodenal filling and was quantified using calibrated volumetric measurements of total excreted volume and pancreatic flow output. RESULTS: Two subjects (0.2%) showed flushing (minor adverse reaction). Duct visualization after secretin injection was improved for reader 1 in 468 (57.4%) and for reader 2 in 478 (58.6%) subjects, was unchanged for reader 1 in 324 (39.7%) and for reader 2 in 315 (38.6%) subjects, and was worse for reader 1 in 24 (2.9%) and reader 2 in 23 (2.8%) subjects (interrater agreement, κ = 0.925). Main pancreatic duct diameters increased significantly after secretin stimulation: pancreatic head, 10.5% (mean); body, 12.5%; and tail, 7.7%. Pancreatic exocrine function evaluated according to assessment of duodenal filling was as follows: grade 0 (restricted function) in 0.7% of subjects by both readers, grade 1 (reduced function) in 4.8% of subjects by reader 1 and 4.5% of subjects by reader 2, grade 2 (low-grade reduced function) in 31.1% of subjects by reader 1 and 26.5% of subjects by reader 2, and grade 3 (physiologic function) in 63.4% of subjects by reader 1 and 68.3% of subjects by reader 2 (interrater agreement, κ = 0.838). The mean total excreted volume was 111.8 ± 49.8 (SD) mL, and the mean pancreatic flow output was 9.6 ± 4.2 mL/min. CONCLUSION: Secretin-stimulated MRCP moderately improves main pancreatic duct visualization and allows noninvasive quantification of pancreatic exocrine function with a negligible risk of side effects.

Quantitative MRCP assessment of pancreatic exocrine reserve and its correlation with faecal elastase-1 in patients with chronic pancreatitis.

PURPOSE: This retrospective study was done to correlate a quantitative assessment of the pancreatic exocrine reserve by dynamic secretin magnetic resonance cholangiopancreatography (MRCPQ) with the faecal elastase-1 (FE-1) test in patients with chronic pancreatitis. MATERIALS AND METHODS: Thirty-five patients with a clinical diagnosis of chronic (CP) or acute recurrent (ARP) pancreatitis were enrolled. FE-1 was indicative of the pancreatic exocrine reserve. Subsequently, the patient population was subdivided into two groups according to a clinical threshold value of 200 µg/g. All patients underwent MRCP examination during secretin administration. Duodenal filling volume was calculated on T2-weigthed rapid acquisition with relaxation enhancement (RARE) MRCP images obtained 10 min after secretin injection. Duodenal filling volumes were compared with FE-1 values. Scatter plots, Pearson correlation coefficient and the Mann-Whitney U test were performed. RESULTS: Thirty-five paired MRCPQ-FE1 data sets were analysed. MRCPQ was significantly different (p=0.007) between patients with impaired and preserved pancreatic function; median and interquartile range (IQR) were 150.7 ml (137.3-205.5 ml; n=9) and 332.4 ml (190.6-506.9 ml; n=26). Both Pearson correlation coefficient (p<0.001) and the Mann-Whitney U test (p=0.007) were significant. CONCLUSIONS: MRCPQ significantly correlates with FE-1 values. It is possible to discriminate impaired and preserved pancreatic exocrine function using MRCPQ.

MRI assessment of chronic pancreatitis.

Magnetic resonance imaging (MRI) plays an important role in the assessment of chronic pancreatitis. By standard MRI techniques, decreased parenchymal signal on T1-weighted fat-suppressed images and delayed gradual enhancement on serial contrast enhanced images represent fibrotic changes caused by chronic inflammation. Magnetic resonance cholangiopancreaticography (MRCP) can reveal ductal changes, including side branch ectasias, that are related to tissue fibrosis and destruction. The exocrine function of the gland and an increased number of side branch ectasias can be evaluated with secretin-stimulated MRCP. Diffusion weighted imaging is an emerging technology that can complement standard MRI to assess the parenchymal changes associated with chronic pancreatitis. The same technique can also quantify the parenchymal response to secretin stimulation. This article reviews standard imaging techniques and new advancements in MRI technology as they relate to the assessment of chronic pancreatitis.

Whole-body magnetic resonance imaging of healthy volunteers: pilot study results from the population-based SHIP study.

PURPOSE: Approximately 4000 volunteers will undergo whole-body magnetic resonance imaging (WB-MRI) within the next 3 years in the population-based Study of Health in Pomerania (SHIP). Here we present a pilot study conducted (a) to determine the feasibility of adding a WB-MRI protocol to a large-scale population-based study, (b) to evaluate the reliability of standardized MRI interpretation, and (c) to establish an approach for handling pathological findings. MATERIALS AND METHODS: The institutional review board approved the study, and oral and written informed consent was obtained from each participant. Two hundred healthy volunteers (99 women, 101 men; mean age 48.3 years) underwent a standardized WB-MRI protocol. The protocol was supplemented by contrast-enhanced cardiac MRI and magnetic resonance (MR) angiography in 61 men (60.4%) and cardiac MRI and MR mammography in 44 women (44.4%). MR scans were evaluated independently by two readers. Abnormalities were discussed by an advisory board and classified according to the need for further clinical work-up. RESULTS: One hundred ninety-four (97.0%) WB-MRI examinations were successfully completed in a mean scan time per subject of 90 minutes. There were 431 pathological findings in 176 (88%) of the participants. Of those 45 (10.4%) required further clinical work-up and 386 (89.6%) characterized as benign lesions did not. The interobserver agreement for the detection of pathological findings was excellent (kappa = 0.799). CONCLUSION: The preliminary results presented here indicate that a large prospective, population-based study using WB-MRI is feasible and that the results of image analysis are reproducible. A variety of positive findings provide valuable information regarding disease prevalence in a general adult population.

Assessment of chronic pancreatitis: utility of diffusion-weighted MR imaging with secretin enhancement.

PURPOSE: 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 diffusion-weighted (DW) imaging. MATERIALS AND METHODS: 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, 21-82 years) in women and 54.3 years (range, 32-81 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. RESULTS: 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 179 x 10(-5) mm(2)/sec was optimal for delineating normal pancreas from CP groups. CONCLUSION: 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.

Pancreatic perfusion: noninvasive quantitative assessment with dynamic contrast-enhanced MR imaging without and with secretin stimulation in healthy volunteers--initial results.

PURPOSE: To prospectively quantify pancreatic regional perfusion with dynamic contrast material-enhanced magnetic resonance (MR) imaging by using a one-compartment model and to assess perfusion changes during secretin stimulation in healthy volunteers. MATERIALS AND METHODS: The study had institutional review board approval, and written informed consent was obtained. Ten healthy volunteers (five men, five women; mean age, 24.7 years +/- 1.9 [standard deviation]; range, 22-29 years) underwent MR imaging pancreatic perfusion studies performed twice without secretin and twice during secretin stimulation. Dynamic contrast-enhanced MR imaging consisted of saturation-recovery T1-weighted turbo-field-echo imaging with peripheral pulse triggering and respiratory tracking. A dose of 0.05 mmol gadodiamide per kilogram of body weight was injected at a rate of 3.5 mL/sec. Regional perfusion parameters were fitted with a one-compartment model. The analysis of variance test for repeated measurements was used to assess differences in pancreatic perfusion without and that with secretin administration. RESULTS: Significant differences in perfusion parameters between the three pancreatic regions were observed (P < .05). During secretin stimulation, a significant difference was observed only between the body and the tail of the pancreas (P = .02). A significant increase (P = .003) in pancreatic perfusion was observed after secretin administration. Mean pancreatic perfusion was 184 mL/min/100 g of tissue +/- 71, 207 mL/min/100 g +/- 77, and 230 mL/min/100 g +/- 87 without secretin and 342 mL/min/100 g +/- 154, 338 mL/min/100 g +/- 156, and 373 mL/min/100 g +/- 176 after secretin stimulation in the head, body, and tail of the pancreas, respectively. Intraindividual variability was 21% without secretin stimulation and 46% with secretin stimulation. CONCLUSION: Dynamic contrast-enhanced MR imaging enables noninvasive quantification of regional pancreatic perfusion in resting conditions and demonstrates the increase in pancreatic perfusion during secretin stimulation in healthy subjects.

Diagnosis of duct disruption and assessment of pancreatic leak with dynamic secretin-stimulated MR cholangiopancreatography.

OBJECTIVE: The management of pancreatic duct disruption is complex and depends on several factors including the cause, morphology, and degree of disruption. ERCP can show duct disruption in as many as 75% of patients but is invasive and cannot detect disruption beyond an obstruction. We studied the role of secretin MR cholangiopancreatography in patients with suspected pancreatic duct disruption. CONCLUSION: Secretin MR cholangiopancreatography is a safe, noninvasive test that can provide additional useful information about duct integrity and facilitate management.

Use of capillary electrophoresis in drug quality assessment of synthetic porcine secretin.

The purity profile for porcine secretin attributable to contamination by equilibrium products such as aspartoyl(3) secretin has been shown to be dependent on the pH of the analytical system. Capillary zone electrophoresis (CZE) methods have been developed for the efficient separation of synthetic porcine secretin, its equilibrium products and other impurities in aqueous solutions at both acidic and alkaline pH. These conditions are more representative of those used for the reconstitution and administration of porcine secretin, and good results cannot be achieved using HPLC due to poor peak shape above pH 5.8. The influence of various CZE operational parameters was systematically examined. The methods were validated for accuracy, precision, linearity, LOD and LOQ. A comparative evaluation of the stability of test solutions was determined using CZE and HPLC over a range of pH values. HPLC and CZE methods produced similar results at low pH.

Computed tomography and magnetic resonance imaging in the assessment of acute pancreatitis.

BACKGROUND & AIMS: This study aimed to compare the accuracy of magnetic resonance imaging (MRI) with computed tomography (CT) in assessing acute pancreatitis (AP) and to explore the correlation between MRI findings and clinical outcome. METHODS: Patients with AP were investigated by contrast-enhanced CT and MRI on admission and 7 and 30 days thereafter. MRI was performed with intravenous secretin and contrast medium. Balthazar's grading system was used to measure CT and MRI severity indices (CTSI and MRSI, respectively). RESULTS: Thirty-nine patients (median age, 47 years; range, 15-86) were studied. AP was of biliary etiology in 19 patients (49%). On admission, AP was assessed clinically as severe in 7 patients (18%). A strong correlation was demonstrated between CTSI and MRSI on admission and 7 days later. MRSI on admission correlated with the following: the Ranson score, C-reactive protein levels 48 hours after admission, duration of hospitalization, and clinical outcome regarding morbidity, including local and systemic complications. Considering the Ranson score as the gold standard, MRI detected severe AP with 83% (58-96, 95% CI) sensitivity, 91% (68-98) specificity vs. 78% (52-93) and 86% (63-96) for CT. Magnetic resonance cholangiopancreatography after i.v. secretin injection showed pancreatic duct leakage in 3 patients (8%). CONCLUSIONS: MRI is a reliable method of staging AP severity, has predictive value for the prognosis of the disease, and has fewer contraindications than CT. It can also detect pancreatic duct disruption, which may occur early in the course of AP.

Pancreas divisum and santorinicele: assessment by dynamic magnetic resonance cholangiopancreatography during secretin stimulation.

PURPOSE: To evaluate the usefulness of MRCP, before and after secretin administration, in diagnosing Santoriniceles in patients with pancreas divisum. MATERIAL AND METHODS: One hundred and eight patients with suspected pancreatic disease, underwent dynamic magnetic resonance cholangiopancreatography (MRCP) before and after secretin administration (S-MRCP). S-MRCP images were evaluated for presence/absence of pancreas divisum, Santorinicele; size of the main pancreatic duct and of the Santorinicele. The onset of duodenal filling was calculated on dynamic S-MRCP images. S-MRCP findings were compared to endoscopic retrograde cholangiopancreatography (ERCP) ones (39/108). RESULTS: Pancreas divisum (PD) was detected in 6/108 patients (6%) at MRCP, and in 16/108 patients (14%) at S-MRCP. ERCP confirmed the diagnosis in 12/16 patients, with 1 false positive. 3 patients did not undergo ERCP. Santorinicele was detected in 4/108 (3%) patients at MRCP and in additional 4/108 (3%) patients at S-RMCP, only in patients with PD. Santoriniceles were confirmed in 7/8 patients at ERCP; in 1/8 patient CPRE was unsuccessful. The duct of Santorini was significantly larger (p< 0.05), in the pancreatic head, in patients with PD and Santorinicele (3.6 mm) compared to those with PD only (2.2 mm). A significant reduction in size of the pancreatic duct (26%) and of the Santorinicele (63%) was observed after sphincterotomy. The onset of duodenal filling was significantly delayed in patients with Santorinicele (2.1 vs 1.3 minutes)(p<0.05). CONCLUSIONS: S-MRCP helps to identify patients with pancreas divisum and Santorinicele, a known cause of impeded pancreatic outflow which benefits from endoscopic treatment.

Functional assessment of pancreatic parenchyma after secretin administration using serial T2-weighted echo-planar magnetic resonance imaging.

Signal intensity (SI) changes of pancreatic parenchyma were evaluated after intravenous administration of secretin using T2-weighted single-shot spin-echo echo-planar imaging (EPI) to assess this method as a magnetic resonance (MR) test of pancreatic exocrine function. Nine volunteers were studied with serial single-shot EPI of the pancreas for 15 minutes after the injection of secretin or saline. The normal pattern of pancreatic SI change was demonstrated after intravenous injection of secretin, a single peak at 3-4 minutes in the head, body, and tail, followed by a gradual decrease in SI. Saline injection did not induce a significant SI change. There was no statistical difference in the peak contrast ratios (first mean, 1.21-1.25, vs. second mean, 1.18-1.22) and peak times (first mean, 3.2-3.7 minutes, vs. second mean, 3.1-3.6) in a repeat study. By evaluating the pattern of time-response curves obtained from serial T2-weighted EPI after secretin injection, pancreatic exocrine function may be directly assessed at the level of the head, body, and tail.