Magnetic resonance imaging of coeliac disease

Background Coeliac disease is an autoimmune disease affecting primarily the small bowel mucosa. Diagnosis is by blood test and duodenal biopsy, with the patient on a gluten-containing diet. The only treatment currently available is a gluten free diet (GFD). Further work is required to understand macroscopic gastrointestinal (GI) function and mechanisms of symptoms in coeliac disease. Magnetic Resonance Imaging (MRI) offers a unique tool to study GI fluid volumes, organ volumes and gut transit non-invasively. Objectives This study aimed to test the main hypotheses that: In adults newly diagnosed with coeliac disease, treatment with a GFD will reduce the water content of the fasting small bowel, the volume of the fasting colon and whole gut transit time (WGTT). This work also validated a new method for calibrating small bowel water content (SBWC) measurement on different MRI scanners. Methods 36 newly diagnosed patients and 36 healthy controls were recruited. They attended for an MRI visit having fasted overnight. SBWC, colonic volumes and WGTT were measured. Symptoms, expired breath hydrogen, stool diaries and stool samples were also collected. This was then repeated at 12 months follow-up. A validation study in healthy volunteers was carried out to calibrate and optimise the MRI scanner measurement of SBWC. Results No significant difference in SBWC was seen for the coeliac patients between baseline and 12 month follow up although there was significant difference in fluid volumes compared to the controls. Significant reductions were seen in the overall colonic volumes, and the ascending colon volumes in coeliac patients after treatment with a GFD. Ascending colon volumes and overall colonic volume were also larger in coeliac patients than in the controls both before and after treatment initiation with a GFD. A significant decrease in whole gut transit time was seen in coeliac patients between baseline and 12 month follow up. Transit time between coeliac patients and healthy controls was significantly slower both at baseline (44%) and at 12 month follow up (29%). Quality of life reported by the incident coeliacs was poorer than that in the healthy controls, even following GFD treatment. GI symptoms were significantly greater at baseline than at follow-up for the coeliac patients and although had improved following the GFD were still significantly higher than the controls at both time points. There was also a correlation seen between the severity of study day GI symptoms, and poorer PHQ_15 and overall HADS scores. Conclusion This study in patients with incident coeliac disease has shown for the first time that treatment with a gluten free diet for a year reduces the small bowel water, significantly reduces the overall colon volume and decreases the whole gut transit time. The coeliac patients also have greater SBWC than healthy controls at baseline and at follow up. Furthermore, the colon volumes are also larger at the time of diagnosis of coeliac disease and reduce over 12 month follow up on a gluten free diet. Finally, there is a significant reduction in whole gut transit time following a gluten free diet in the coeliac patients. The increased SBWC in coeliacs before and after treatment compared to healthy controls may represent an imbalance between absorption and secretion due to the damaged villi. These results support the underlying hypotheses of this work and show that MRI can be a useful non-invasive tool in evaluating coeliac patients and this work can add to our understanding of coeliac disease. This work provided also a new method to calibrate and standardise such small bowel water volume quantitation between scanners and laboratories

Distinct abnormalities of small bowel and regional colonic volumes in subtypes of irritable bowel syndrome revealed by MRI

OBJECTIVES: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes. METHODS: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC). RESULTS: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10–42), significantly less than HV at 44 ml (15–70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200–329) compared with HV, IBS-nonC whose values were 165 (117–255) and 198 (106–270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51–111), compared with HV at 34 (4–63) and IBS-D at 34 (17–78) h, P=0.03. Bloating score (VAS 0–10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04. CONCLUSIONS: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease

Corticotrophin releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomised control trial

Background: Poorly absorbed, fermentable carbohydrates can provoke irritable bowel syndrome (IBS) symptoms by escaping absorption in the small bowel and being rapidly fermented in the colon in some susceptible subjects. IBS patients are often anxious and stressed and stress accelerates small bowel transit which may exacerbate malabsorption. Objective: In this study we investigated the effect of intravenous injection of corticotrophin releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomised, placebo controlled, cross-over study of CRF versus saline injection in 11 male and 10 female healthy subjects, examining the effect on the malabsorption of a 40 g fructose test meal and its transit through the gut which was assessed by serial Magnetic Resonance imaging (MRI) and breath hydrogen measurement. Orocaecal transit was assessed using the lactose-ureide C13 breath test and the adrenal response to CRF assessed by serial salivary cortisol measurements. Results: (Mean ± SD) CRF injection caused a significant rise in salivary cortisol which lasted 135 minutes. Small bowel water content (SBWC) rose from baseline, peaking at 45 minutes after fructose ingestion while breath hydrogen peaked later at 75 minutes. The area under the curve (AUC) for SBWC from -15 - 135 minutes was significantly lower after CRF versus saline (mean difference [95% CI] 7433 [275, 14591] mL.min, P = 0.04). Ascending colon volume rose after CRF, significantly more for male volunteers than female (P = 0.025). Conclusions: CRF constricts the small bowel and increases fructose malabsorption as shown by increased ascending colon volumes. This mechanism may help to explain the increased sensitivity of some stressed individuals to fructose malabsorption. This trial was registered at ClinicalTrials.gov as NCT0176328

Gastric motor and sensory function in health assessed by magnetic resonance imaging: Establishment of reference intervals for the Nottingham test meal in healthy subjects

BACKGROUND Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham test meal" (NTM) in healthy volunteers (HVs). METHODS The NTM comprises (a) 400 mL liquid nutrient (0.75 kcal/mL) labeled with Gadolinium-DOTA and (b) an optional solid component (12 agar-beads [0 kcal]). Filling sensations were documented. MRI measurements of gastric volume, emptying, contraction wave frequency, and secretion were obtained using validated methods. KEY RESULTS Gastric function was measured in a population of 73 HVs stratified for age and sex. NTM induced moderate satiety and fullness. Labeled fluid was observed in the small bowel in all subjects after meal ingestion ("early-phase" GE). Secretion was rapid such that postprandial gastric content volume was often greater than meal volume (GCV0 > 400 mL), and there was increasing dilution of the meal during the study (P < 0.001). Gastric half-time was median 66-minutes (95% reference interval 35 to 161-minutes ["late-phase" GE]). The number of intact agar beads in the stomach was 7/12 (58%) at 60-minutes and 1/12 (8%) at 120-minutes. Age, bodyweight and sex had measurable effects on gastric function; however, these were small compared to inter-individual variation for most metrics. CONCLUSIONS AND INFERENCES Reference intervals are presented for MRI measurements of gastric function assessed for the mixed liquid/solid NTM. Studies in patients will determine which metrics are of clinical value and also whether the reference intervals presented here offer optimal diagnostic sensitivity and specificity

Effects of Bolus and Continuous Nasogastric Feeding on Gastric Emptying, Small Bowel Water Content, Superior Mesenteric Artery Blood Flow, and Plasma Hormone Concentrations in Healthy Adults: A Randomized Crossover Study

Objective: We aimed to demonstrate the effect of continuous or bolus nasogastric feeding on gastric emptying, small bowel water content, and splanchnic blood flow measured by magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal hormone secretion.Background: Nasogastric/nasoenteral tube feeding is often complicated by diarrhea but the contribution of feeding strategy to the etiology is unclear.Methods: Twelve healthy adult male participants who underwent nasogastric intubation before a baseline MRI scan, received 400 mL of Resource Energy (Nestle) as a bolus over 5 minutes or continuously over 4 hours via pump in this randomized crossover study. Changes in gastric volume, small bowel water content, and superior mesenteric artery blood flow and velocity were measured over 4 hours using MRI and blood glucose and plasma concentrations of insulin, peptide YY, and ghrelin were assayed every 30 minutes.Results: Bolus nasogastric feeding led to significant elevations in gastric volume (P < 0.0001), superior mesenteric artery blood flow (P < 0.0001), and velocity (P = 0.0011) compared with continuous feeding. Both types of feeding reduced small bowel water content, although there was an increase in small bowel water content with bolus feeding after 90 minutes (P < 0.0068). Similarly, both types of feeding led to a fall in plasma ghrelin concentration although this fall was greater with bolus feeding (P < 0.0001). Bolus feeding also led to an increase in concentrations of insulin (P = 0.0024) and peptide YY (P < 0.0001), not seen with continuous feeding.Conclusion: Continuous nasogastric feeding does not increase small bowel water content, thus fluid flux within the small bowel is not a major contributor to the etiology of tube feeding-related diarrhea