Pancreatic Perfusion Using Secretin and MRI
Study Details
Study Description
Brief Summary
The purpose of this study is to assess pancreatic perfusion in patients with chronic pancreatitis at rest and after secretin stimulation and compare this to published data on pancreatic perfusion in normal subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Pancreatic blood flow or perfusion is difficult to quantify due to the complex vascular supply to the organ and its retroperitoneal location, adjacent to the abdominal aorta. The pancreas is supplied by the superior gastroduodenal artery from the celiac plexus, branches from the hepatic and splenic arteries, which originate from the celiac plexus, and the inferior gastroduodenal artery, which originates from the superior mesenteric artery. Identifying changes in flow in all these vessels with good spatial and temporal resolution is challenging but important in understanding many of the chronic conditions of the pancreas.
Chronic pancreatitis (CP) is an inflammatory condition of the pancreas leading to irreversible damage to the tissue. It is increasing in incidence in all nations, and is related to rising alcohol consumption and improved diagnostic techniques. In Europe the incidence is approximately 6-7/100,000 population. 73-91% of patients affected are male with an average age of 49-60yrs. Patients affected by CP have a high morbidity, such as diabetes and chronic abdominal and/or post-prandial pain in 80-90%, which required frequent hospital admission, control-drug prescriptions and intervention by specialist hospital services. However the mechanisms of chronic and post-prandial pain for CP patients are not well understood, but tissue ischaemia, inflammation and neurological changes have been proposed. These mechanisms may be inter-related with pancreatic inflammation and neurochemical changes, such as an increase substance P, which can produce vasoconstriction, reducing pancreatic perfusion and worsening ischaemia of intra-pancreatic nerves(3). A greater understanding of the ischaemic and inflammatory mechanisms behind the pain in CP, would greatly enhance the development of treatment for this and other debilitating conditions.
There are a few studies of pancreatic tissue perfusion in humans, those studies which have assessed perfusion have used invasive techniques such as endoscopic or laparoscopic measurement and hydrogen gas clearance methods. Although these methods have demonstrated decreased resting blood flow and little response to secretin stimulation in CP patients compared to healthy controls, the techniques are highly invasive, time consuming and expensive and can cause the participant significant morbidity. This has led to several non-invasive techniques including infusion of oxygen-15 water and positron emission tomography (PET), contrast-material-enhanced trans-abdominal ultrasound (US) or contrast-enhanced dynamic computer tomography (CT). However these techniques involve infusion of an exogenous marker to detect the change in flow rate and often require a radiation exposure or are operator dependant and give poor spatial or temporal resolution, limiting the usefulness of the studies.
MRI is an attractive alternative for the assessment of pancreatic perfusion, providing good spatial and temporal resolution with no radiation exposure. Two methods can be used, Contrast-Enhanced (CE) MRI or Arterial Spin Labelling (ASL) techniques. ASL provides a tool for quantitative assessment of tissue perfusion without the need for contrast administration.
Contrast-enhanced MRI using gadodiamide has been used to explore the changes in pancreatic perfusion with secretin stimulation. This study in 10 healthy volunteers demonstrated that at rest there was a higher blood flow within the body and the tail of the pancreas, compared to the head. With secretin stimulation there was a significant increased perfusion in all regions of the pancreas. ASL techniques, do not require exogenous contrast agents, only two previous studies have measured pancreatic perfusion with ASL, one exploring pancreatic exocrine functions in type 1 diabetics. A recent study at the Nottingham Digestive Diseases Centre on pancreatic perfusion measurement using ASL at baseline and after intravenous secretin stimulation has standardised the MRI technique of measuring pancreatic perfusion.
There are no studies using MRI ASL to measure pancreatic perfusion in patients with chronic pancreatitis after secretin stimulation. This pilot study aims to test the feasibility of using MRI ASL to measure pancreatic perfusion in patients with chronic pancreatitis with a view to perfecting the technique. This will allow future studies comparing pancreatic perfusion in healthy adult controls to patients with chronic pancreatitis thus improving the investigators understanding of the pathophysiology of pain in patients with chronic pancreatitis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Secretin Secretin 1 IU/kg over 3 min |
Drug: Secretin
Secretin 1 IU/kg over 3 min
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Blood flow to pancreas as measured by arterial spin labelling MRI [1.5 hours]
Secondary Outcome Measures
- Change in blood flow to pancreas after intravenous secretin [1.5 hours]
- Pancreatic diffusion [T 0, 5, 10, 20, 30, 40]
- Pancreatic volume [T 0, 5, 20, 40]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Adults with chronic pancreatitis (as defined by the Cambridge criteria)
Exclusion Criteria:
-
Allergy to secretin
-
Claustraphobia
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Refusal to consent for the study
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MRI contraindications e.g. pacemaker, artificial heart valve
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Previous abdominal surgery except appendectomy or hernia repair
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History of chronic abdominal pain from causes other than pancreatitis eg. inflammatory bowel or coeliac disease
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Pregnant women (safety concerns from injection of secretin)
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Patients younger than 18 years of age
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 1.5T Brain and Body Imaging centre, University of Nottingham Campus | Nottingham | Nottinghamshire | United Kingdom | NG7 2RD |
Sponsors and Collaborators
- University of Nottingham
Investigators
- Principal Investigator: John Simpson, University of Nottingham
Study Documents (Full-Text)
None provided.More Information
Publications
- Andrén-Sandberg A, Hoem D, Gislason H. Pain management in chronic pancreatitis. Eur J Gastroenterol Hepatol. 2002 Sep;14(9):957-70. Review.
- Bali MA, Metens T, Denolin V, De Maertelaer V, Devière 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.
- Ceyhan GO, Demir IE, Maak M, Friess H. Fate of nerves in chronic pancreatitis: Neural remodeling and pancreatic neuropathy. Best Pract Res Clin Gastroenterol. 2010 Jun;24(3):311-22. doi: 10.1016/j.bpg.2010.03.001. Review.
- D'Onofrio M, Gallotti A, Principe F, Mucelli RP. Contrast-enhanced ultrasound of the pancreas. World J Radiol. 2010 Mar 28;2(3):97-102. doi: 10.4329/wjr.v2.i3.97.
- Drewes AM, Krarup AL, Detlefsen S, Malmstrøm 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. Review.
- Hirshberg B, Qiu M, Cali AM, Sherwin R, Constable T, Calle RA, Tal MG. Pancreatic perfusion of healthy individuals and type 1 diabetic patients as assessed by magnetic resonance perfusion imaging. Diabetologia. 2009 Aug;52(8):1561-5. doi: 10.1007/s00125-009-1406-8. Epub 2009 Jun 3.
- Ishida H, Makino T, Kobayashi M, Tsuneoka K. Laparoscopic measurement of pancreatic blood flow. Endoscopy. 1983 May;15(3):107-10.
- Jupp J, Fine D, Johnson CD. The epidemiology and socioeconomic impact of chronic pancreatitis. Best Pract Res Clin Gastroenterol. 2010 Jun;24(3):219-31. doi: 10.1016/j.bpg.2010.03.005. Review.
- Kubo S, Yamamoto K, Magata Y, Iwasaki Y, Tamaki N, Yonekura Y, Konishi J. Assessment of pancreatic blood flow with positron emission tomography and oxygen-15 water. Ann Nucl Med. 1991 Nov;5(4):133-8.
- 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.
- Miles KA, Hayball MP, Dixon AK. Measurement of human pancreatic perfusion using dynamic computed tomography with perfusion imaging. Br J Radiol. 1995 May;68(809):471-5.
- Schraml C, Schwenzer NF, Martirosian P, Claussen CD, Schick F. Perfusion imaging of the pancreas using an arterial spin labeling technique. J Magn Reson Imaging. 2008 Dec;28(6):1459-65. doi: 10.1002/jmri.21564.
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