Gemma Chaddock

Novel MRI tests of orocecal transit time and whole gut transit time: studies in normal subjects.

Colonic 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.

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose

Most 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.

Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation

Functional 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.

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.

Effect of bread gluten content on gastrointestinal function: a crossover MRI study on healthy humans

Gluten is a crucial functional component of bread, but the effect of increasing gluten content on gastrointestinal (GI) function remains uncertain. Our aim was to investigate the effect of increasing gluten content on GI function and symptoms in healthy participants using the unique capabilities of MRI. A total of twelve healthy participants completed this randomised, mechanistic, open-label, three-way crossover study. On days 1 and 2 they consumed either gluten-free bread (GFB), or normal gluten content bread (NGCB) or added gluten content bread (AGCB). The same bread was consumed on day 3, and MRI scans were performed every 60 min from fasting baseline up to 360 min after eating. The appearance of the gastric chime in the images was assessed using a visual heterogeneity score. Gastric volumes, the small bowel water content (SBWC), colonic volumes and colonic gas content and GI symptoms were measured. Fasting transverse colonic volume after the 2-d preload was significantly higher after GFB compared with NGCB and AGCB with a dose-dependent response (289 (SEM 96) v. 212 (SEM 74) v. 179 (SEM 87) ml, respectively; P=0·02). The intragastric chyme heterogeneity score was higher for the bread with increased gluten (AGCB 6 (interquartile range (IQR) 0·5) compared with GFB 3 (IQR 0·5); P=0·003). However, gastric half-emptying time was not different between breads nor were study day GI symptoms, postprandial SBWC, colonic volume and gas content. This MRI study showed novel mechanistic insights in the GI responses to different breads, which are poorly understood notwithstanding the importance of this staple food.

PWE-161 The Macrogol Drink Test To Distinguish Functional Constipation (fc) And Constipation Predominant Irritable Bowel Syndrome (ibs-c): Underlying Mechanisms Demonstrated Using Mri

Introduction Patients with constipation may have either FC or IBS-C which require different treatments. They are often dissatisfied with their treatment because diagnosis relies on symptoms which frequently overlap. Methods 46 CC patients (24 FC and 22 IBS-C), age 18–68 years, unresponsive to simple laxatives, were compared with 11 healthy volunteers (HV). Whole gut transit (WGT) was assessed using a MRI scan 24 h following ingestion of 5 marker pills as previously validated. Patients then consumed 1 litre of macrogol (MCG) followed by hourly MRI scans for 4 h and scored bowel symptoms from 0–10 (none-severe). Colonic movements were assessed using a motility index (MI) based on colonic wall movement and hypersensitivity index (HI) was calculated as bloating symptom/ascending colon (AC) volume. Results Mean (SD) See Table 1. FC and IBS-C have slower WGT and higher HI than HV. FC showed significantly greater fasting SBWC, AC volume and reduced MI following ingestion of MCG compared to HV and IBS-C. Moreover, FC showed impaired response to MCG with longer time to first bowel movement and reduced stool frequency on the study day when compared with HV and IBS-C. Time to 1st bowel movement correlated significantly with AC volume 2h post MCG, r = 0.44, p = 0.004 and fasting SBWC,r = 0.34,p = 0.035. Using a cut-off >230 min distinguishes FC from IBS-C with sensitivity 55% and specificity 95%; this needs validation in a repeat study. Abstract PWE-161 Table 1 Mean (SD) HV (n = 11) FC (n = 23) IBS-C (n = 20) P value WGT (h) 30.4 108.2*,** 71.4* <0.0001 Fasting small bowel water content (SBWC) (ml) 83 (64) 114 (97) ** 57 (61) 0.0383 Fasting AC (ml) 193 (84) 314 (100) *,** 219 (66) 0.0002 AC volume 2h post ingestion of MCG (ml) 357 (153) 597 (170) 376 (163) <0.0001 MI 2h post ingestion of MCG (s) 80.2 (48.1) 28.3 (35.1) *,** 56.4 (42.9) 0.0044 Time to first bowel movement (min) 117.3 (62.4) 588 (1034) *,** 97.3 (72) 0.0001 Bowel frequency on study day 7.8 (2.7) 3.9 (4.1) *,** 7.8 (3.0) <0.0001 Hypersensitivy Index (l-1) 5.7 (4.9) 12.3 (6.6) * 16.6 (14) * 0.0133 * p < 0.05 compared to HV ** p < 0.05 compared to IBS-C. Conclusion Time to first bowel movement >230 min makes IBS unlikely and should help target treatments. Our MI studies show this is dueto greater motility response to distension in IBS-C who has lower fasting SBWC and AC volumes versus FC. IBS-C showed similar features to HV but can be distinguished by greater HI following distension which suggest hypersensitivity. This inexpensive test done without MRI could help clinicians to distinguish these 2 conditions. Disclosure of Interest C. Lam: None Declared, G. Chaddock: None Declared, C. Hoad: None Declared, C. Costigan: None Declared, E. Cox: None Declared, S. Pritchard: None Declared, K. Garsed: None Declared, L. Marciani: None Declared, P. Gowland Consultant for: Merck, Ironwood, Unilever, R. Spiller Grant/research support from: Lessaffre, Ironwood, Consultant for: Almirall, Astellas, Danone and Sanofi, Conflict with: Free drug for clinical trial from Norgine.

Response to Uno

in all studies of transit times and refl ects the very many, usually un controlled, factors which determine this parameter, including diet, activity, and emotion. Th e author’s reference to Bernoulli’s principle is, we believe, of uncertain value. Th e principle, which essentially is a statement of the conservation of energy states that in an incompressible fl uid fl owing down a tube any change in velocity is associated with a proportionate change in pressure such that potential energy is unchanged. Th us, if a fl uid is forced through a constriction resulting in an increase in fl ow the intraluminal pressure will fall or conversely if it enters a wider part of the tube its pressure will rise. However, as we indicated above, the colon is not readily modeled by a tube with a constant fl ow. Colonic movement is typically erratic, with long periods of no movement alternating with periods of to and fro movements. We doubt that Bernoulli’s principle can be applied to such a system. Nevertheless, the concept that alteration in the proportion of gas to chyme will alter pressure-fl ow relationships is of interest and prompted us to reexamine more closely the distribution of gas in the diff erent regions of the colon. We found, surprisingly, little gas in the colon, transverse or other regions in our subjects, which did not diff er between patients and healthy controls. However, as Table 1 shows there was a tendency for there to be less gas in the ascending colon in the postprandial period and more in the transverse and descending colon in both healthy controls, and signifi cantly so for irritable bowel syndrome with diarrhoea (IBS-D) subgroup. Our method particularly the transverse colon. Most of this increase was due to chyme, with only around 3% due to gas. Th e transit through the whole colon was variably prolonged in the IBS patients with constipation. Th e author quotes Laplace’s law to argue that as the radius of colon increases the wall tension is likely to be reduced if the intraluminal pressure is constant. While we have not measured the intraluminal pressure, studies that have, show frequent pressures with wide variability in intraluminal pressure. Our recent imaging of colonic volumes during stimulation with an osmotic laxative show that the luminal diameter also changes frequently ( 3 ) giving a complexity which is rather diff erent to the situations Laplace’s law was designed to illuminate. We found a weak but signifi cant correlation with bloating and transverse colon volumes at the time of peak bloating symptoms and peak transverse colonic volumes aft er the subjects consumed the large test meal (600 ml Fortisip providing 960 kcal) 405 min aft er eating. Th e relationship was weak and only signifi cant if we maximized numbers by including all the subjects. Th e correlation was nonsignifi cant in the irritable bowel syndrome with constipation (IBS-C) subgroup, so plainly there are many other infl uences on this very subjective experience which is related as much to visceral sensitivity as it is to any objective distension. Th e author refers to the wide variability we observed in colonic transit in IBS-C patients. However, we cannot agree that this distinguishes IBS-C as it was a feature in both groups. Th is is a common observation study by Lam. In addition, in IBS-C, excessive gas can increase in the small intestine ( 2 ). Although the incidence of such cases may be small, such cases may also have long WGTT due to the low density of the gas.

OC-067 Different Mechanisms of Disease in Subtypes of Irritable Bowel Syndrome as Demonstrated by MRI

Introduction The study of irritable bowel syndrome (IBS) has been hampered by the absence of biomarkers to accurately categorise subgroups of this heterogeneous condition. Our aim was to assess gut transit, small bowel water content and colonic regional volumes of different clinically defined IBS subtypes both fasted and post-prandially using MRI scans. Methods 91 subjects were recruited (34 healthy volunteers (HV), 30 IBS with diarrhoea (IBS-D), 16 IBS with constipation (IBS-C) and 11 IBS with mixed bowel habit (IBS-M). Subjects underwent MRI scans every 45 min on the study day. Whole gut transit times (WGTT), small bowel water content (SBWC) and regional colonic volumes were assessed as previously described1,2,3. Abdominal symptoms were scored using visual analogue score questionnaires after each set of MRI scans. Breakfast was given before t = 0 and lunch after t = 360 min. Postprandial assessment is timed between t = 0 to t = 360 min. Results (See Table 1). Fasting and postprandial SBWC area under the curve (AUC) in IBS-D and IBS-M were significantly less than HV, p = 0.02 & p < 0.01 (1 way ANOVA) respectively. The fasting transverse colon volume in IBS-C was significantly larger compared to HV, IBS-D and IBS-M p = 0.02 (Kruskal-Wallis). The AUC postprandial total colonic volume for IBS-C was significantly larger than HV and IBS-D, p = 0.03(Kruskal-Wallis). The WGTT for IBS-C was significantly longer than HV and IBS-D, p = 0.02(Kruskal-Wallis). There was significant correlation between bloating score (VAS 0–10 cm) and transverse colon volume after lunch (t = 405 min) with spearman r = 0.21, p = 0.04.Abstract OC-067 Table 1 HV IBS-C IBS-D IBS-M P value Fasting SWBC (mL)Mean(SD) 63 (67) 62 (44) 29 (25)a 22 (17)a 0.03 (Anova) AUC postprandial SBWC (L*min)Mean(SD) 23 (10) 19 (12) 14 (8) a 14 (6) a <0.01 (Anova) Fasting transverse colon volume (mL) [median, IQR] 165 (117–255) 253 (200–329)a 212 (103–274)b 169 (119–227)b 0.02 (Kruskal-Wallis) Area under the curve for postprandial total colonic volume (t = 0 to t = 360 min) L*min (median, IQR) 180 (137–231)b 224 (190–251) 173 (139–232)b 171 (146–217) p = 0.06Kruskal-wallis WGTT (h)(median, IQR) 34 (4–63) 69 (51–111)a 34 (10–77)b 34 (19–81) 0.06 (Kruskal-Wallis) ap ≤ 0.05 versus HV; bp ≤ 0.05 versus IBS-C Conclusion The constricted small bowel in IBS-D & IBS-M and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease in these IBS subtypes. References 1 Chaddock G, et al. Neurogastroenterol Motil 2014;26:205–214. 2 Pritchard SE, et al. Neurogastroenterol Motil 2014;26:124–30. 3 Hoad CL, et al. Phys Med Biol 2007;52:6909–22. Disclosure of Interest C. Lam: None Declared, G. Chaddock: None Declared, L. Marciani: None Declared, C. Costigan: None Declared, E. Cox: None Declared, C. Hoad: None Declared, S. Pritchard: None Declared, P. Gowland: None Declared, R. Spiller Grant/research support from: Lessafre and Ironwood, Consultant for: Almirall, Yuhan Corporation,Ibsen and Danone, Speaker bureau with: Menarini

OC-032 A New Validated whole Gut Transit Time (WGTT) Measurement using Magnetic Resonance Imaging (Mri-Wgtt) Technique

Introduction Disorders of gut transit are very common in gastroenterology clinics. Objective assessment may be useful for targeting and monitoring treatment. Current scintigraphic or radio-opaque marker techniques involve undesirable ionising radiation. Aims To validate a new MRI method for measuring WGTT against the current gold standard in which 20 radio-opaque markers (ROMs) are ingested per day on 3 consecutive days and the number retained assessed from a single abdominal x-ray on day 4. To assess reproducibility of MRI-WGTT. Methods 20 healthy volunteers (HV) ages 21–70 (12 males and 8 females) participated in the study involving 2 visits a week apart (test-retest). On each visit, each HV underwent 2 tests: (A) MRI-WGTT test for which HV swallow 5 pills, each filled with a MRI contrast agent diluted with water, 24 hours before undergoing MRI scans which precisely locate the pills in the colon. Transit of the markers was assessed by scoring each pill from its position in the colon (7 = small bowel, 6 = lower ascending 5 = upper AC, 4 = right transverse (TC), 3 = left TC, 2 = descending, 1 = rectosigmoid, 0 = expelled) and calculating an average score (Transit score TS) using an algorithm which gives a weighting inversely related to the distance from the median. (B) ROM test: the number of ROM was counted and multiplied by 1.2 to give a WGTT in hours. Spearman’s correlation was used to assess the correlation between the two measurements and intra-class correlation coefficient (ICC) was used to assess the variability of each test when repeated twice. Results The MRI images provided excellent 3D spatial resolution, allowing the gut to be viewed from all angles, hence allowing accurate location of the pills within the colon especially the sigmoid region (Figure 1). WGTT using ROM was median (SD), 27.6 (20.8) and TS was 0.9 (0.8). WGTT using ROM and TS were well correlated, Spearman’s r = 0.85, p < 0.01. Using this we converted TS to MRI-WGTT in hours. Mean calculated MRI-WGTT was 27.6 (24.7) hours. The mean absolute difference in the MRI-WGTT on 2 separate visits was 15.3 hours (SD, 15.8) with an ICC of 0.62 (p < 0.01). The mean absolute difference in the WGTT for ROMS on 2 separate visits was 11.3 hours (SD, 9.7) with and ICC of 0.69 (p < 0.01). Abstract OC-032 Figure 1 Maximum intensity projection, T1 weighted MRI image showing the MRI transit pills in descending and sigmoid colon. Conclusion MRI-WGTT correlated well with the gold standard ROM WGTT but was more convenient, involving only one day of marker ingestion and no exposure to ionising radiation. This technique could be implemented easily in most NHS hospitals. Funded by: Medical Research Council and NIHR UK. Disclosure of Interest None Declared