P Gowland

Field strength dependence of R1 and R2* relaxivities of human whole blood to ProHance, Vasovist, and deoxyhemoglobin.

This study has measured the longitudinal and transverse (T  2* ) relaxivity curves for ProHance (Gadoteridol), Vasovist (Gadofosveset) and deoxyhemoglobin at 1.5, 3.0, and 7.0 Tesla. The plots of R1 versus both contrast agent and deoxyhemoglobin concentration were linear. The plots of R  2* versus deoxyhemoglobin concentration showed a quadratic dependence. R  2* versus contrast agent concentration showed a parabolic dependence with a minimum occurring at contrast agent concentrations of approximately 1.5 mM, corresponding to an accessible concentration in vivo. Monte Carlo simulations were performed to support the hypothesis that the minimum results from the susceptibility of the red blood cells being matched to the susceptibility of the plasma. Relaxivity values (s−1mM−1) for R  2* and R1 for all agents and all three field strengths are given. Magn Reson Med 60:1313–1320, 2008.

A study of T1 relaxation time as a measure of liver fibrosis and the influence of confounding histological factors

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. Copyright

In vivo perfusion, T1, and T2 measurements in the female pelvis during the normal menstrual cycle: A feasibility study

To quantify T1, T2, and regional tissue perfusion in uterine tissues, with MR imaging in clinically feasible imaging times, using echo planar imaging (EPI) techniques over a single menstrual cycle.

Comparing GABA-dependent physiological measures of inhibition with proton magnetic resonance spectroscopy measurement of GABA using ultra-high-field MRI

ABSTRACT Imbalances in glutamatergic (excitatory) and GABA (inhibitory) signalling within key brain networks are thought to underlie many brain and mental health disorders, and for this reason there is considerable interest in investigating how individual variability in localised concentrations of these molecules relate to brain disorders. Magnetic resonance spectroscopy (MRS) provides a reliable means of measuring, in vivo, concentrations of neurometabolites such as GABA, glutamate and glutamine that can be correlated with brain function and dysfunction. However, an issue of much debate is whether the GABA observed and measured using MRS represents the entire pool of GABA available for measurement (i.e., metabolic, intracellular, and extracellular) or is instead limited to only some portion of it. GABA function can also be investigated indirectly in humans through the use of non‐invasive transcranial magnetic stimulation (TMS) techniques that can be used to measure cortical excitability and GABA‐mediated physiological inhibition. To investigate this issue further we collected in a single session both types of measurement, i.e., TMS measures of cortical excitability and physiological inhibition and ultra‐high‐field (7 T) MRS measures of GABA, glutamate and glutamine, from the left sensorimotor cortex of the same group of right‐handed individuals. We found that TMS and MRS measures were largely uncorrelated with one another, save for the plateau of the TMS IO curve that was negatively correlated with MRS‐Glutamate (Glu) and intra‐cortical facilitation (10ms ISI) that was positively associated with MRS‐Glutamate concentration. These findings are consistent with the view that the GABA concentrations measured using the MRS largely represent pools of GABA that are linked to tonic rather than phasic inhibition and thus contribute to the inhibitory tone of a brain area rather than GABAergic synaptic transmission. Highlightsultra‐high‐field (7 Tesla) MRS used to measure of GABA concentration.TMS used to measure cortical excitability and GABA‐mediated physiological inhibition.Both TMS and MRS measures obtained from primary motor cortex in the same individuals.TMS measures of physiological inhibition uncorrelated with MRS measures of GABA.MRS may represent pools of GABA linked to tonic rather than phasic inhibition.

Development and validation of a large, modular test meal with liquid and solid components for assessment of gastric motor and sensory function by non‐invasive imaging

Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study introduces the large ‘Nottingham Test Meal’ (NTM) for assessment of gastric motor and sensory function by non‐invasive imaging.

OC-070 Dietary Supplementation With Fodmaps Increases Fasting Colonic Volume And Breath Hydrogen In Healthy Volunteers: A Mechanistic Study Using Mri

Introduction Indigestible fermentable carbohydrates, grouped as FODMAPs, have been proposed to induce gastrointestinal symptoms. Some, such as oligofructose (OF), are prebiotics and modify the microbiota. The metabolic activity of the microbiota affected transit time in a mouse model.1 This study hypothesised that dietary supplementation with OF would shorten whole gut transit time (WGTT) and improve the capacity of the microbiota to metabolise a FODMAP challenge. Methods The study was an open-label case series. 16 healthy volunteers underwent fasting MRI to assess colonic volume [2] and the position of 5 transit markers ingested 24 h earlier from which WGTT could be calculated.3 Breath hydrogen (H2) and methane (CH4) were also measured. Subjects then consumed an inulin challenge drink (ICD): 500 ml water containing 40 g inulin. Inulin is fermented in the colon and known to increase H2 and colonic volume.4 After ICD subjects could sip water and were given a low FODMAP lunch but no other food was allowed. 8 h post-ICD MRI was repeated. Breath measurements were repeated 4 and 8 h post-ICD. Subjects then supplemented their usual diet with OF (gift from BENEO, Germany), 5 g twice daily, for a week. Fasting and post-ICD measurements were then repeated. Dietary questionnaires were completed for the weeks preceding MRIs to assess dietary fructan intake. Abstract OC-070 Figure 1 Results Median [IQR] given unless stated as mean [95% CI]. Fasting colonic volumes (510 ml [400–710]) increased by mean 94 ml [12 – 177, p = 0.03] after OF. Fasting H2 (33 ppm [9–87]) increased by mean 39 ppm [6 – 71, p = 0.02]. WGTT (34 h [10 – 45]) increased by 19 h [-9 – 42] but this increase did not reach significance (p = 0.09, Wilcoxon). Colonic volumes post-ICD were similar across weeks (mean 726 ml [667–785]). The change from baseline was significant in week 1 but not week 2 due to the difference in fasting volumes. There was no difference between weeks 1 and 2 in H2 at 4 or 8 h after ICD. CH4 did not change. Dietary fructan intake was similar in both weeks (mean < 8 g/ day). Conclusion OF increased fasting colonic volumes by 18%. H2 also rose. This may reflect increased bacterial mass with increased capacity for fermentation. The suggestion that OF slows WGTT is surprising and warrants further investigation. MRI can complement research on the microbiota to describe its impact on gut physiology. References 1 Kashyap P et al. Gastroenterology 2013;144(5):967–77 2 Chaddock G et al. Neurogastroenterology and Motility 2013 3 Pritchard S et al. Neurogastroenterol Motil 2013 4 Murray K et al. Am J Gastroenterol 2013 Disclosure of Interest None Declared.

PTH-045 Effects of an osmotic laxative on the distribution of water between the small and large intestine in humans

Introduction Understanding of the water distribution within the ascending colon (AC) is limited though this is important to study mechanisms of both functional and organic colonic diseases. We have developed novel MRI techniques which allow us to monitor undisturbed colonic function in health and diseases. Methods To use these new techniques to study the colonic response to two contrasting test meals: a readily absorbable glucose drink and a non-absorbable mannitol drink that stimulates small intestinal secretion and can be used as a model of acute diarrhoeal disease. Eight fasted healthy volunteers (HVs) underwent serial MRI on two occasions to visualise the free water content of the bowel using a previously described method.1 After a baseline scan, they were given a 350 ml 5% mannitol or 5% glucose drink, randomised. HVs were scanned at hourly intervals for 5 h after the drink and were also fed a large 1000 kcal solid/liquid test meal at 3 h to elicit the colonic response to feeding. Results (mean±SEM) Following the glucose drink the volume of free mobile water in the whole bowel ml did not vary significantly from the fasting baseline being 124±24 vs 112±27 ml at 90 min, p<0.9. Conversely, after the mannitol drink, the water in the whole bowel rose from baseline 109±36 ml to 590±73 ml at 90 min, p<0.008. The difference in the amount of free water that reached the AC at 90 min was particularly marked being 2±1 ml after the glucose drink and 73±20 ml after the mannitol drink, p<0.008. The water that arrived in the AC readily mixed with the colonic contents and caused distension of the AC. Its total (geometric) volume at 90 min rose from 146±17 ml for glucose to 230±18 ml for mannitol, p<0.0004. At later times a bright, homogeneous signal was observed inside the AC, while the for the glucose drink this was heterogeneous and low signal. The second larger meal was followed by a significant fall in total bowel water content from 396±58 ml at time 150 min to 198±37 ml at time 210 min with the mannitol drink (p<0.0011), while no corresponding change was observed for the glucose drink (p<0.7). Conclusion These images clearly show that the unabsorbable, osmotically active mannitol solution causes secretion in the small bowel. The change in total AC volume with mannitol can largely be explained by the arrival of free mobile water from the small bowel. These methods will be useful in future studies to evaluate mechanisms of diarrhoea and drug intervention and in clinical studies of diarrhoeal disease.

Techniques for assessing the functional response to food of the stomach and small and large intestine

Abstract: Functional foods are foods designed to have properties which enhance health. However, the key link between the design of the foods and the measurement of outcomes such as satiety and blood parameters, namely the digestive processes, are often neglected. In order to relate appropriately food properties to health outcomes, the physiological impact of the meal on the gastrointestinal tract needs to be assessed. Magnetic resonance imaging provides an ideal tool for such assessment without disturbing normal physiology. This chapter presents the evolution of different methods used to study these processes focusing particularly on our work with magnetic resonance imaging over the last decade.

OC-090 Different effects of FODMAP (fermentable oligo-, di-, and mono-saccharides, and polyols) components on small bowel water content: an MRI study

Introduction A randomised placebo controlled trial (RCT) has shown that FODMAPs exacerbate irritable bowel syndrome (IBS) symptoms in selected patients. FODMAPs are heterogeneous chemically, the major components being fructose and fructans. Both are poorly absorbed in the small bowel but fructose exerts a much greater osmotic effect than fructans which are fructose polymers. Whether this alters the overall impact is unknown. This study aims to test the hypotheses that (a) fructose will increase small bowel water content (SBWC) more than fructans; (b) adding glucose to fructose will reduce its effect, and (c) fructans will exert most of their effect as a result of colonic fermentation. Methods 4-way, randomised, single blind, crossover study. 16 healthy volunteers underwent abdominal scans in a 1.5T MRI scanner after an overnight fast. They were then fed 500 ml of water containing 40 g glucose, fructose, fructan or 40 g glucose plus 40 g fructose and underwent scanning and breath H2 measurement and completed bowel symptom questionnaires at hourly intervals for 5 h. SBWC was measured from heavily T2 weighted magnetic resonance scans. 1-way analysis of variance was used. Results (Mean±SEM) All drinks were well tolerated with only minor symptoms of gas, bloating, abdominal pain and diarrhoea reported. Relative to glucose, fructose increased SBWC significantly (184±35 ml vs 118±24 ml glucose, p=0.001), while fructans had little effect (SBWC=119±23 ml, p=0.7 vs glucose). Adding 40 g glucose to 40 g fructose decreased SBWC (145±27 ml, but the difference was not significant, p=0.08 vs fructose). Breath H2 was initially higher for fructose than the other three solutions. (AUC was 8959±1880 ppm.min) with fructans having the largest AUC at 14 987±2568 ppm.min). Values returned to baseline for fructose over the 5 h study, but increased to a maximum for fructan after 300 min. Glucose had no effect on breath H2 concentration, but adding an equivalent amount to fructose significantly reduced breath H2 relative to fructose alone (p=0.0006). Conclusion FODMAPs exert a variety of GI responses. Fructose but not fructans increases SBWC relative to glucose. Both fructose and fructans are malabsorbed as confirmed by breath H2 measurements. Fructose malabsorption is significantly reduced by addition of glucose. These different gastrointestinal responses can be readily identified using our non-invasive MRI techniques. Competing interests None declared.

OC-068 Measuring the Effect of Ispaghula on Gut Content and Function Using MRI

Introduction Ispaghula husk (IS) is believed to modulate functional gastrointestinal symptoms by drawing water into the bowel to soften stool and accelerate transit, and by adding bulk. It is not thought to be readily fermented. Magnetic Resonance Imaging (MRI) can assess gastrointestinal content and function. The aim of the study was to assess whether MRI could detect and quantify the effects of IS in patients with chronic constipation. Methods A double-blind crossover study in adults with functional constipation or constipation-predominant irritable bowel syndrome. Intervention: Metamucil Original Coarse Fibre® (P&G, USA) 14 g tds – daily IS dose 21 g. Placebo: Maltodextrin(MD) 14 g tds. On day 5 subjects swallowed 5 gadolinium filled capsules. On day 6 MRI scans were taken fasting and hourly for 7 hours while subjects ingested a rice pudding meal and treatment (IS or MD). Whole gut transit was assessed by the weighted average position score of the capsules 24 hours after ingestion (WAPS). Free water in the small bowel (SBWC) and ascending colon (ACWC) was measured as were T1 and T2 relaxation times in the ascending and descending colon (AC & DC), colonic volume and gas.Abstract OC-068 Figure 1 Results 16 subjects completed both treatments. Transit was faster after IS with a mean decrease in WAPS of 24% (p = 0.05, 1 tailed). Postprandial SBWC was markedly higher on IS (p < 0.001) with smaller increases seen in ACWC (p < 0.05). Fasting T1 was significantly higher after IS in both AC and DC. T2 fasting values were also higher. A postprandial rise was seen in both T1AC and T2AC after IS but not MD. Fasting colonic volume increased on PS by mean 332 mL or 48%. Exploratory analysis of colonic gas found that after IS significantly more was detectable both fasting (p < 0.05) and postprandially (p < 0.05). AC gas did not increase until 240 min after PS while transverse colon gas increased steadily through the day.Abstract OC-068 Table 1 Maltodextrin Ispaghula Mean difference(95% confidence interval) WAPS 3.4 (1.6–4.8) 2.2 (1.5–3.0) 0.8 (-0.2–1.7) Colonic Volume (mL) 690 (±55) 1022 (±60) 332 (213–451) T1AC (ms) 596 (±61) 829 (±98) 234 (15–453) T1DC (ms) 366 (±67) 613 (±94) 247 (82–411) Conclusion MRI parameters demonstrated accelerated in transit, increased intestinal water content and increasedcolonic volume with IS. Fasting T1 appears to discriminate constipation from health and responded to treatment. More colonic gas was detected with IS. This may reflect fermentation of IS or interference with small bowel absorption leading to malabsorption of carbohydrate in the rice meal. These novel findings illustrate the potential for MRI to provide insights into the in vivo effects and mechanisms of action of gut modulators. Disclosure of Interest None Declared