MRI and Molecular imaging studies of post-prandial gastrointestinal motility and peptide response in health and Crohn’s disease

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

Magnetic resonance imaging biomarkers of gastrointestinal motor function and fluid distribution

Magnetic resonance imaging (MRI) is a well established technique that has revolutionized diagnostic radiology. Until recently, the impact that MRI has had in the assessment of gastrointestinal motor function and bowel fluid distribution in health and in disease has been more limited, despite the novel insights that MRI can provide along the entire gastrointestinal tract. MRI biomarkers include intestinal motility indices, small bowel water content and whole gut transit time. The present review discusses new developments and applications of MRI in the upper gastrointestinal tract, the small bowel and the colon reported in the literature in the last 5 years

Simultaneous measurement of gastric emptying of a soup test meal using MRI and gamma scintigraphy

Measurement of gastric emptying is of clinical value for a range of conditions. Gamma scintigraphy (GS) has an established role, but the use of magnetic resonance imaging (MRI) has recently increased. Previous comparison studies between MRI and GS showed good correlation, but were performed on separate study days. In this study, the modalities were alternated rapidly allowing direct comparison with no intra-individual variability confounds. Twelve healthy participants consumed 400 g of Technetium-99m (99mTc)-labelled soup test meal (204 kcal) and were imaged at intervals for 150 min, alternating between MRI and GS. The time to empty half of the stomach contents (T1/2) and retention rate (RR) were calculated and data correlated. The average T1/2 was similar for MRI (44 ± 6 min) and GS (35 ± 4 min) with a moderate but significant difference between the two modalities (p ≤0.004). The individual T1/2 values were measured, and MRI and GS showed a good positive correlation (r = 0.95, p ≤ 0.0001), as well as all the RRs at each time point up to 120 min. Gastric emptying was measured for the first time by MRI and GS on the same day. This may help with translating the use of this simple meal, known to elicit reliable, physiological, and pathological gastrointestinal motor, peptide, and appetite response

Gastrointestinal peptides and small bowel hypomotility are possible causes for fasting and postprandial symptoms in active Crohn’s disease

BackgroundCrohn's disease (CD) patients suffer postprandial aversive symptoms, which can lead to anorexia and malnutrition. Changes in the regulation of gut hormones and gut dysmotility are believed to play a role.ObjectivesThis study aimed to investigate small-bowel motility and gut peptide responses to a standard test meal in CD by using MRI.MethodsWe studied 15 CD patients with active disease (age 36 ± 3 y; BMI 26 ± 1 kg/m 2) and 20 healthy volunteers (HVs; age 31 ± 3 years; BMI 24 ± 1 kg/m 2). They underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling following a 400-g soup meal (204 kcal). Small-bowel motility, other MRI parameters, and glucagon-like peptide-1 (GLP-1), polypeptide YY (PYY), and cholecystokinin peptides were measured. Data are presented as means ± SEMs.ResultsHVs had significantly higher fasting motility indexes [106 ± 13 arbitrary units (a.u.)], compared with CD participants (70 ± 8 a.u.; P ≤ 0.05). Postprandial small-bowel water content showed a significant time by group interaction (P < 0.05), with CD participants showing higher levels from 210 min postprandially. Fasting concentrations of GLP-1 and PYY were significantly greater in CD participants, compared with HVs [GLP-1, CD 50 ± 8 µg/mL versus HV 13 ± 3 µg/mL (P ≤ 0.0001); PYY, CD 236 ± 16 pg/mL versus HV 118 ± 12 pg/mL (P ≤ 0.0001)]. The meal challenge induced a significant postprandial increase in aversive symptom scores (fullness, distention, bloating, abdominal pain, and sickness) in CD participants compared with HVs (P ≤ 0.05).ConclusionsThe decrease in fasting small-bowel motility noted in CD participants can be ascribed to the increased fasting gut peptides. A better understanding of the etiology of aversive symptoms in CD will facilitate identification of better therapeutic targets to improve nutritional status. This trial was registered at clinicaltrials.gov as NCT03052465

MRI and Molecular imaging studies of post-prandial gastrointestinal motility and peptide response in health and Crohn’s disease

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

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans

Background: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort. Methods: Fifteen healthy volunteers (29.3±2.7years and BMI 20.1±1.2Kg/m2) underwent baseline and postprandial MRI scans, symptom questionnaires and blood sampling (for subsequent GI peptide analysis, Glucagon-like peptide-1 (GLP-1), Polypeptide YY (PYY), Cholecystokinin (CCK)) at intervals for 270min following a 400g soup meal (204kcal, Heinz, UK). Gastric volume, gall bladder volume, small bowel water content, small bowel motility and whole gut transit were measured from the MRI scans. Key Results: (mean±SEM) Small bowel motility index increased from fasting 39±3 arbitrary units (a.u.) to a maximum of 87±7a.u. immediately after feeding. PYY increased from fasting 98±10pg/ml to 149±14pg/ml at 30min and GLP-1 from fasting 15±3µg/ml to 22±4µg/ml. CCK increased from fasting 0.40±0.06pmol/ml to 0.94±0.1pmol/ml. Gastric volumes declined with a T1/2 of 46±5min and the gallbladder contracted from a fasting volume of 19±2ml to 12±2ml. Small bowel water content increased from 39±2ml to 51±2ml postprandial. Fullness VAS score increased from 9±5mm to 41±6mm at 30min postprandial. Conclusions and Inferences: The test meal challenge was effective in inducing a change in MRI motility end-points which will improve understanding of the pathophysiological postprandial GI response