Pancreatic Perfusion Using Secretin and MRI
Pancreatic Perfusion Using Secretin and MRI
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.
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.
Inclusion Criteria:

 -  Adults with chronic pancreatitis (as defined by the Cambridge criteria)

 Exclusion Criteria:

 1. Allergy to secretin

 2. Claustraphobia

 3. Refusal to consent for the study

 4. MRI contraindications e.g. pacemaker, artificial heart valve

 5. Previous abdominal surgery except appendectomy or hernia repair

 6. History of chronic abdominal pain from causes other than pancreatitis eg. inflammatory
 bowel or coeliac disease

 7. Pregnant women (safety concerns from injection of secretin)

 8. Patients younger than 18 years of age