Khalaf, Asseel
(2018)
MRI and Molecular imaging studies of post-prandial gastrointestinal motility and peptide response in health and Crohn’s disease.
PhD thesis, University of Nottingham.
Abstract
Introduction: Crohn’s disease (CD) patients suffer postprandial symptoms such as chronic diarrhoea, abdominal pain, bloating, weight loss and nutritional abnormalities. The changes in the regulation of gut hormones and gut dysmotility are believed to play a role but these are rarely studied together in the postprandial state in an unprepared bowel. This project aimed to: (a) develop an MRI methodology to assess fasting and postprandial intestinal motility and gut peptides using a soup test meal intervention in healthy volunteers and (b) to use this methodology to investigate the pathophysiological fasting and postprandial responses in CD.
Methods: Sixteen CD patients with active disease (age 36±3 years, BMI 26±1 kg/m2) and 20 healthy volunteers (age 31±3 years, BMI 24±1 kg/m2) participated. They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling at intervals for 270 minutes following a 400 g soup meal (204 kcal). Gastric volume, gall bladder volume, small bowel water content, small bowel motility, whole gut transit, GLP-1, PYY, and CCK were measured. A new processing technique was developed and used to quantify small bowel motility from cine MRI data. A standard magnetic resonance enterography (MRE) test was also performed at the end of the feeding study to measure disease activity. An assessment of gastric emptying of the soup meal by MRI and gamma scintigraphy (GS) was also carried out.
Key results: (mean±SEM) The healthy volunteers had significantly higher fasting motility index (106±13 a.u.) compared to CD subjects (70±8 a.u., p<0.05). The average time to empty half of the stomach contents (T1/2) in healthy volunteers and CD subjects was 43±4 min, 63±7.5 min respectively. A significant difference was seen in the area under the curve of small bowel water content in CD subjects (19778±2119 mL/min) compared to healthy volunteers (14197±1249 mL/min, p<0.05). A significant increase was noted in fasting plasma measures of total GLP-1 in CD subjects compared to healthy volunteers (CD 50±8 µg/mL versus HV 13±3 µg/mL, p<0.0001) with a significantly higher postprandial GLP-1 (AUC CD: 12725 versus HV: 2400, p<0.0001). Fasting PYY levels increased significantly in CD subjects compared to the healthy volunteers (CD 236±16 pg/mL versus HV 118±12 pg/mL, p<0.0001) with a significant postprandial increase in levels in CD subjects compared to healthy volunteers (AUC CD 62782±4313 pg/mL versus HV: 34744±3169 pg/mL, p<0.0001). Fasting and postprandial CCK levels were not significantly different between CD subjects and healthy volunteers. CD subjects showed a significantly higher fasting fullness scores compared to healthy volunteers (CD 21±6 mm versus HV 5±3 mm, p<0.01). The meal challenge induced a significant postprandial increase in all symptoms scores in CD subjects compared to healthy volunteers (p<0.05). Gastric emptying carried out by MRI and GS correlated well (r=0.95, p<0.0001)
Conclusions: Multiple gastrointestinal motility, peptide and symptom responses were successfully measured in a single study session. The optimised MRI motility technique was sensitive to changes in motility induced by feeding. Small bowel motility and different physiological outcomes were successfully quantified in unprepared small bowel during fasting and after a nutrient soup meal in patients with CD and healthy volunteers. Gastric emptying of the soup meal can also be translated to gamma scintigraphy. These techniques will be useful for studying physiopathological pathways in different groups. The improved understanding of gastrointestinal pathophysiology will allow a better of understanding of the aetiology of symptoms in these patient groups with consequent identification of better therapeutic targets.
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