Non-invasive MRI to Quantify the Effect of Secretin on Pancreatic Blood Flow and Perfusion in Healthy Volunteers
Condition: Chronic Pancreatitis
MeSH terms: Pancreatitis; Pancreatitis, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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:

        1. Pancreatic perfusion

        2. Superior mesenteric artery blood flow

        3. Gastroduodenal artery blood flow

        4. Hepatic artery blood flow

        5. Splenic artery blood flow
    

Intervention name(s): Secretin
Intervention type(s): Drug
Intervention description(s): Secretin 1 IU/kg over 3 min
Intervention MeSH terms: Secretin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Pancreas; Chronic pancreatitis; Perfusion; Blood flow; Magnetic resonance imaging