OBJECTIVES:The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. METHODS: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan.RESULTS:Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0–5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11–132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17–106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121–12,300) p.p.m./min relative to fructose alone (P<0.01, n=13).CONCLUSIONS:Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non-breath-holding, fast scanning protocol was used to acquire MR relaxation time data (T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) for the training cohort were 0.81 (0.65-0.96) and 0.92 (0.81-1.0) respectively (p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy.

BackgroundColonic transit tests are used to manage patients with Functional Gastrointestinal Disorders. Some tests used expose patients to ionizing radiation. The aim of this study was to compare novel magnetic resonance imaging (MRI) tests for measuring orocecal transit time (OCTT) and whole gut transit time (WGT), which also provide data on colonic volumes.Methods21 healthy volunteers participated. Study 1: OCTT was determined from the arrival of the head of a meal into the cecum using MRI and the Lactose Ureide breath test (LUBT), performed concurrently. Study 2: WGT was assessed using novel MRI marker capsules and radio-opaque markers (ROMs), taken on the same morning. Studies were repeated 1 week later.Key ResultsOCTT measured using MRI and LUBT was 225 min (IQR 180–270) and 225 min (IQR 165–278), respectively, correlation rs = 0.28 (ns). WGT measured using MRI marker capsules and ROMs was 28 h (IQR 4–50) and 31 h ± 3 (SEM), respectively, correlation rs = 0.85 (p < 0.0001). Repeatability assessed using the intraclass correlation coefficient (ICC) was 0.45 (p = 0.017) and 0.35 (p = 0.058) for MRI and LUBT OCTT tests. Better repeatability was observed for the WGT tests, ICC being 0.61 for the MRI marker capsules (p = 0.001) and 0.69 for the ROM method (p < 0.001) respectively.Conclusions & InferencesThe MRI WGT method is simple, convenient, does not use X-ray and compares well with the widely used ROM method. Both OCTT measurements showed modest reproducibility and the MRI method showed modest inter-observer agreement.

BackgroundMost methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing.MethodsTwelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes.Key ResultsSmall bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103).Conclusions & InferencesIngestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies.

BackgroundFunctional constipation (FC) and irritable bowel syndrome with constipation (IBS‐C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep®. We aim to use these biomarkers to study the pathophysiology in IBS‐C and FC.MethodsTwenty‐four FC and 24 IBS‐C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep® followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h.Key ResultsWeighted average position score for FC was 3.6 (2.5–4.2), significantly greater than IBS‐C at 2.0 (1.5–3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63–142) mL vs 39 (15–70) mL in IBS‐C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS‐C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS‐C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep® was greater for FC, being 295 (116–526) min, compared to IBS‐C at 84 (49–111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep®, r = 0.44, p < 0.01. Using a cut‐off >230 min distinguishes FC from IBS‐C with low sensitivity of 55% but high specificity of 95%.Conclusion & InferencesOur objective MRI biomarkers allow a distinction between FC and IBS‐C.