Secretin Enhanced Imaging of the Pancreas



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Secretin Enhanced Imaging of the Pancreas Pablo R. Ros, MD University Hospitals Case Medical Center Case Western Reserve University SCBT-MR Boston, MA October, 2012 Pablo.Ros@UHhospitals.org

Disclosures Consultant, Repligen Corporation Member, Radiology Medical Advisory Network, Philips

Acknowledgment Raj Paspulati, MD

ERCP Traditional Gold Standard for visualizing pancreatic and biliary ducts 500,000 cases /year for diagnosis & therapy Issues Technically difficult Cost: >$2,000 + cost of complications Safety Radiation exposure & sedation Morbidity: ~10% = 50,000/yr Mortality: ~0.5% = 2,500 deaths/yr NIH Consensus Statement (2002): ERCP NOT for diagnostic purposes Litigation Confidential

MRCP MRCP almost completely replaced ERCP for imaging diagnosis of the pancreatic duct Pancreatic duct diameter challenges the resolution of MRCP Benefit from increased pancreatic secretion Confidential

Secretin Hormone produced by duodenal epithelial cells under the stimulus of gastric acid Produces secretion of fluid and bicarbonate by the exocrine pancreas Increases the tone of the sphincter of Oddi Matos C, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997, 203:435-441

Secretin - Historical Perspective 1902: GI tract extract stimulates pancreas secretions; Secretin: first hormone discovered (Starling) 1940: Use in pancreatic exocrine function testing 1981: Extracted porcine secretin approved in US 2002: Synthetic porcine secretin approved US (SecreFlo) 2004: Synthetic human secretin approved US (Chirostim) 1979: Specific binding in brain (Taylor) 1998: Potential use in CNS disorders (Horvath) Confidential

Secretin Safety No deaths or drug-related SAEs No anti-secretin antibody formation (allergic reactions unusual) Most common side effects: Transient increase in heart rate Flushing Transient, mild abdominal discomfort Confidential

Secretin MRCP (S-MRCP) Secretin increases release of pancreatic juice into ducts Secretin acts as a natural imaging agent during MRCP Pre-secretin Post-secretin Liver Liver Gall Bladder Gall Bladder Pancreas Pancreas Intestine Narrow pancreatic duct Intestine Wider pancreatic duct Confidential

S-MRCP: Literature Review S-MRCP well documented (off label) Over 100 articles; 40+ safety; 20+ efficacy analyses Safety meta-analysis Extent of exposure: 1,320 patients / 1,468 exposures AE s: only 9 reported, none serious (transient, mild) Efficacy meta-analysis Duct segments, accessory and branch ducts (p<0.001; 11 studies, 874 patients) Duct diameters (p<0.001; 9 studies, 756 patients) Image quality (p=0.01; 6 studies, 572 patients) Diagnostic sensitivity (94% vs 53%) Confidential http://www.smrcp.com/

S-MRCP: Patient Preparation Fasting Minimum 6hrs Avoid gastric contents overlapping PD Negative oral contrast agents Gastromark [Ferumoxil] Pineapple juice Suppress high signal of gastric contents Patient education and cooperation, key Matos C, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997, 203:435-441

S-MRCP: Technique MR pancreatography pres-secretin (20 min): Breath-hold HASTE/SSFSE localizer + MIP Axial & coronal [3-5 mm] T2-weighted images Thick slab breath-hold RARE Oblique coronal T2-slab, entire PD selected Navigator controlled 3D images Secretin MRCP (S-MRP) Post IV administration of Secretin (0.2 mg/kg body weight) Dynamic imaging for 15 min (15-30 secs) Test dose (?) 1. Soto JA, Barish MA, Yucel EK, et al. Pancreatic duct: MR cholangiopancreatography with a three-dimensional fast spin-echo technique. Radiology 1995; 196:459-464 2. Matos C et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997, 203:435-441

S-MRCP: Technique Technique of T2 TSE Coronal slabs Imaging plane- Coronal Breath hold Slab thickness 20-50mm No of signals acquired 1 FOV- 250mm(Rectangular) Acquisition matrix- 256 Flip angle 150 degrees TR - 2800 Echo time - 1100 Matos C, et al. Pancreatic duct: morphologic and functional evaluation with dynamic MR pancreatography after secretin stimulation. Radiology 1997-2009

S-MRCP: Interpretation Pre-secretin MRCP: Ductal morphology Post-secretin MRCP: Ductal morphology and distension Characterization of filling defects Duodenal distension, index of function

S-MRCP : Clinical Applications Congenital anomalies: Pancreas Divisum Annular Pancreas Ductal anatomical variations Acute Pancreatitis: Ductal stricture, causing recurrent pancreatitis Ductal involvement in pancreatic necrosis Communicating vs noncommunicating pseudocyts Planning interventional ERCP Chronic pancreatitis: Staging, severity chronic Number, length of strictures for possible intervention Focal pancreatic mass evaluation Assessment of exocrine function

S-MRCP : Clinical Applications Congenital anomalies: Pancreas Divisum Annular Pancreas Ductal anatomical variations

S-MRCP : Clinical Applications Acute Pancreatitis: Ductal stricture, causing recurrent pancreatitis Ductal involvement in pancreatic necrosis Communicating v noncommunicating pseudocyts Planning interventional ERCP

S-MRCP : Clinical Applications Chronic pancreatitis: Staging, severity Number, length of strictures for possible intervention Focal pancreatic mass evaluation Assessment of exocrine function

S-MRCP : Clinical Applications Pancreatic focal lesions: Differentiating side branch dilatation from cystic neoplasm Differentiating side branch IPMT from nonductal cystic neoplasm Differentiating pancreatic adenocarcinoma from chronic pancreatitis Possible better delineation

S-MRCP : Clinical Applications Post surgical follow up: Post sphincterectomy Post stent placement Post Whipple pancreatectomy

Pancreatic MRI - Functional Imaging Parameters Exocrine function Sphincter of Oddi function Pancreatic Fibrosis Methodology Dynamic S-MRCP Diffusion-weighted MR (DW-MR) MR spectroscopy (MRS) Pre 5 min 10 min Confidential

Functional Imaging: Diffusion-weighted Secretin MR as a Proxy for Fibrosis 3.5 Time of Peak ADC Value ADC in mm 2 /sec (x10-3 ) 3 2.5 2 1.5 1 0.5 Normals At Risk (Alcohol Abuse) 0 0 1 2 3 4 5 6 7 8 9 10 Time after Secretin, in minutes Confidential Erturk SM, Ichikawa T, Motosugi U, et al: Diffusion-weighted MR imaging in the evaluation of pancreatic exocrine function before and after secretin stimulation. Am J Gastroenterol. 2006 ;101(1):133-6.

S-MRCP : Summary Detailed evaluation of the pancreatic ductal morphology Pancreatic exocrine function (functional pancreatic MRI) Patient education & cooperation, key to good images Radiologist supervision mandatory

Summary: Including secretin augmented MRCP in selected cases of pancreatic MR imaging provides more detailed evaluation of the pancreatic ductal morphology and also of pancreatic exocrine function Patient education & cooperation is the key to good images Radiologist supervision is mandatory