Non-invasive MRI to Quantify the Effect of Secretin on Pancreatic Blood Flow and Perfusion in Healthy Volunteers

Non-invasive MRI to Quantify the Effect of Secretin on Pancreatic Blood Flow and Perfusion in Healthy Volunteers

The Use of Non-invasive MRI to Quantify the Effect of Secretin on Pancreatic Blood Flow and Perfusion in Healthy Volunteers

Alterations in pancreatic blood have been implicated in pancreatic inflammation and pain. Several modalities have been used to assess pancreatic blood flow although some of these methods are invasive, use ionising radiation or intravenous contrast media. This is the first study to utilise non-invasive magnetic resonance imaging to quantify flow within arteries supplying the pancreas and pancreatic perfusion is response to secretin stimulation.

Background An alteration in pancreatic blood flow may be important in a number of clinical conditions. Reduction of blood flow is seen in patients with acute and chronic pancreatitis and the quantification of perfusion may be useful in the management of pancreatic malignancy and assessment of pancreatic transplants. Unfortunately, the measurement of pancreatic blood flow is technically difficult due to the anatomical location of the organ and complex blood supply. The pancreas receives its blood supply from a rich plexus of arteries but the foremost arterial supply arises from the splenic and pancreaticoduodenal arteries, both superior and inferior. Various methods have been used in an attempt to quantify the blood flow but all have potential drawbacks. The use of endoscopic and laparoscopic methods are invasive as is the use of intravenous contrast media. Furthermore, the use of computed tomography exposes patients to ionising radiation. As the arterial supply to the pancreas is complex, measuring single artery flow does not provide an accurate measure of perfusion. Furthermore, as some of the named branches supplying the arteries are secondary or tertiary branches of more major vessels, narrow arterial diameter precludes accurate radiological measurement. Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI), on the other hand is a validated technique allowing accurate measurement of visceral perfusion. Transient physiological changes occur in pancreatic blood flow secondary to increased demands such as eating. Changes can also be induced pharmacologically using pancreatic stimulating agents, such as secretin. This naturally occuring peptide is produced within the S cells of the proximal small bowel mucosa. It causes an increase in bicarbonate secretion by the duct cells of the pancreas and biliary tract via an oxygen dependant cyclic AMP mediated pathway. Secretin has been used previously to assess alterations in blood flow and is used clinically in the assessment of sphincter of Oddi dysfunction in conjunction with magnetic resonance cholangiopancreatography. Aims and Hypothesis This pilot study aims to evaluate the MRI techniques of measuring pancreatic perfusion and blood flow at rest and during secretin stimulation in healthy volunteers, prior to an evaluation in the chronic pancreatitis patient group. Experimental protocol and methods Volunteers will be recruited from advertisements placed on designated University of Nottingham notice boards. All volunteers will complete a questionnaire of abdominal symptoms, Hospital anxiety and depression scale (HAD) and the patient health questionnaire 15 (PhQ15). Each volunteers will attend the 1.5T Brain and Body Imaging centre on the University of Nottingham Campus for all study evaluations. Following an overnight fast a baseline MRI scan will be undertaken. Volunteers will then receive 1 IU/kg of secretin (Sanochemia Pharmazeutika AG, Wien, Germany) via the intravenous route over 3 minutes. The volunteers will then be scanned again at 5, 10, 20, 30 and 40 min following the stimulus. MRI scanning will be carried out on the Philips 1.5T Achieva MRI scanner located in the Brain and Body Imaging Centre University of Nottingham. The volunteers will be placed supine in the scanner with a receiver body coil wrapped around the abdomen. All image analysis will be carried out using commercial and/or in house packages. Outcome measures at baseline and following secretin stimulation: Pancreatic perfusion Superior mesenteric artery blood flow Gastroduodenal artery blood flow Hepatic artery blood flow Splenic artery blood flow

Inclusion Criteria: Male Healthy Able to give informed consent Exclusion Criteria: Current illness Contraindications to magnetic resonance imaging

Delrue L, Blanckaert P, Mertens D, Van Meerbeeck S, Ceelen W, Duyck P. Tissue perfusion in pathologies of the pancreas: assessment using 128-slice computed tomography. Abdom Imaging. 2012 Aug;37(4):595-601. doi: 10.1007/s00261-011-9783-0.

Tsushima Y, Kusano S. Age-dependent decline in parenchymal perfusion in the normal human pancreas: measurement by dynamic computed tomography. Pancreas. 1998 Aug;17(2):148-52. doi: 10.1097/00006676-199808000-00006.

Ishida H, Makino T, Kobayashi M, Tsuneoka K. Laparoscopic measurement of pancreatic blood flow. Endoscopy. 1983 May;15(3):107-10. doi: 10.1055/s-2007-1021480.

Lewis MP, Lo SK, Reber PU, Patel A, Gloor B, Todd KE, Toyama MT, Sherman S, Ashley SW, Reber HA. Endoscopic measurement of pancreatic tissue perfusion in patients with chronic pancreatitis and control patients. Gastrointest Endosc. 2000 Feb;51(2):195-9. doi: 10.1016/s0016-5107(00)70417-2.

Bali MA, Metens T, Denolin V, De Maertelaer V, Deviere J, Matos C. Pancreatic perfusion: noninvasive quantitative assessment with dynamic contrast-enhanced MR imaging without and with secretin stimulation in healthy volunteers--initial results. Radiology. 2008 Apr;247(1):115-21. doi: 10.1148/radiol.2471070685. Epub 2008 Feb 21.

Bize PE, Platon A, Becker CD, Poletti PA. Perfusion measurement in acute pancreatitis using dynamic perfusion MDCT. AJR Am J Roentgenol. 2006 Jan;186(1):114-8. doi: 10.2214/AJR.04.1416.

Hirota M, Tsuda M, Tsuji Y, Kanno A, Kikuta K, Kume K, Hamada S, Unno J, Ito H, Ariga H, Chiba T, Masamune A, Satoh K, Shimosegawa T. Perfusion computed tomography findings of autoimmune pancreatitis. Pancreas. 2011 Nov;40(8):1295-301. doi: 10.1097/MPA.0b013e31821fcc4f.

Cuthbertson CM, Christophi C. Disturbances of the microcirculation in acute pancreatitis. Br J Surg. 2006 May;93(5):518-30. doi: 10.1002/bjs.5316.

Foitzik T, Eibl G, Hotz HG, Faulhaber J, Kirchengast M, Buhr HJ. Endothelin receptor blockade in severe acute pancreatitis leads to systemic enhancement of microcirculation, stabilization of capillary permeability, and improved survival rates. Surgery. 2000 Sep;128(3):399-407. doi: 10.1067/msy.2000.107104.

Drewes AM, Krarup AL, Detlefsen S, Malmstrom ML, Dimcevski G, Funch-Jensen P. Pain in chronic pancreatitis: the role of neuropathic pain mechanisms. Gut. 2008 Nov;57(11):1616-27. doi: 10.1136/gut.2007.146621. Epub 2008 Jun 19.

Terrace JD, Paterson HM, Garden OJ, Parks RW, Madhavan KK. Results of decompression surgery for pain in chronic pancreatitis. HPB (Oxford). 2007;9(4):308-11. doi: 10.1080/13651820701481497.

Heverhagen JT, Wagner HJ, Ebel H, Levine AL, Klose KJ, Hellinger A. Pancreatic transplants: noninvasive evaluation with secretin-augmented mr pancreatography and MR perfusion measurements--preliminary results. Radiology. 2004 Oct;233(1):273-80. doi: 10.1148/radiol.2331031188.