The relationship between the intragastric distribution, dilution, and emptying of meals and satiety was studied using noninvasive magnetic resonance imaging techniques in 12 healthy subjects with four polysaccharide test meals of varying viscosity and nutrient content as follows: 1) low-viscosity nonnutrient, 2) low-viscosity nutrient, 3) high-viscosity nonnutrient, and 4) high-viscosity nutrient. Increasing the nutrient content of the high-viscosity meal delayed gastric emptying from 46 +/- 9 to 76 +/- 6 min (P < 0.004), whereas increasing viscosity had a smaller effect. The volume of secretions within the stomach 60 min after ingestion was higher for the high-viscosity nutrient meal (P < 0.04). A simple model to calculate the total volume of secretion added to the test meal is presented. Color-coded dilution map images showed the heterogeneous process of progressive gastric dilution of high-viscosity meals, whereas low-viscosity meals were uniformly diluted. Fullness was found to be linearly related to total gastric volumes for the nutrient meals (R(2) = 0.98) and logarithmically related for the nonnutrient meals (R(2) = 0.96). Fullness was higher for high- compared with low-viscosity meals (P < 0.02), and with the nutrient meals this was associated with greater antral volumes (P < 0.05).

The rate and extent of drug dissolution and absorption from solid oral dosage forms is highly dependent upon the volumes and distribution of gastric and small intestinal water. However, little is known about the time courses and distribution of water volumes in vivo in an undisturbed gut. Previous imaging studies offered a snapshot of water distribution in fasted humans and showed that water in the small intestine is distributed in small pockets. This study aimed to quantify the volume and number of water pockets in the upper gut of fasted healthy humans following ingestion of a glass of water (240 mL, as recommended for bioavailability/bioequivalence (BA/BE) studies), using recently validated noninvasive magnetic resonance imaging (MRI) methods. Twelve healthy volunteers underwent upper and lower abdominal MRI scans before drinking 240 mL (8 fluid ounces) of water. After ingesting the water, they were scanned at intervals for 2 h. The drink volume, inclusion criteria, and fasting conditions matched the international standards for BA/BE testing in healthy volunteers. The images were processed for gastric and intestinal total water volumes and for the number and volume of separate intestinal water pockets larger than 0.5 mL. The fasted stomach contained 35 ± 7 mL (mean ± SEM) of resting water. Upon drinking, the gastric fluid rose to 242 ± 9 mL. The gastric water volume declined rapidly after that with a half emptying time (T50%) of 13 ± 1 min. The mean gastric volume returned back to baseline 45 min after the drink. The fasted small bowel contained a total volume of 43 ± 14 mL of resting water. Twelve minutes after ingestion of water, small bowel water content rose to a maximum value of 94 ± 24 mL contained within 15 ± 2 pockets of 6 ± 2 mL each. At 45 min, when the glass of water had emptied completely from the stomach, total intestinal water volume was 77 ± 15 mL distributed into 16 ± 3 pockets of 5 ± 1 mL each. MRI provided unprecedented insights into the time course, number, volume, and location of water pockets in the stomach and small intestine under conditions that represent standard BA/BE studies using validated techniques. These data add to our current understanding of gastrointestinal physiology and will help improve physiological relevance of in vitro testing methods and in silico transport analyses for prediction of bioperformance of oral solid dosage forms, particularly for low solubility Biopharmaceutics Classification System (BCS) Class 2 and Class 4 compounds.

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.

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Normal meals are highly viscous, and viscosity is a key factor in influencing gastric emptying of food. However, the process of meal dilution and mixing is difficult to assess with the use of conventional methods. The aim of this study was to validate an in vivo, novel, noninvasive, echo-planar magnetic resonance imaging (EPI) technique, capable of monitoring the viscosity of a model meal, and to use this to investigate the effects of viscosity on gastric emptying, meal dilution and satiety. Healthy volunteers (n = 8) ingested 500 mL of locust bean gum (0.25, 0.5, 1.0 or 1.5 g/100 g), nonnutrient, liquid meals of varying viscosities, and labeled with a nonabsorbable marker, phenol red. Meal viscosity was calibrated against the water proton transverse relaxation rate (T(2)(-1)) in vitro before ingestion, thus viscosity was measured in vivo via EPI measurements of T(2)(-1). Viscosity and dilution were also measured directly using nasogastric aspirates. Gastric volumes as measured by EPI, fullness, appetite and hunger were also assessed serially. Before ingestion, the log of initial meal viscosity was linearly related to T(2)(-1) (n = 8, r(2) = 0.95). Similarly, T(2)(-1) measured in vivo was also linearly related to the viscosity of the aspirates (r(2) = 0.88). All meals underwent rapid dilution, leading to a reduction in viscosity, which was greatest for the most viscous meal (P < 0.01). Surprisingly, despite the fact that the initial meal viscosity varied 1000-fold, there was only a small delay in gastric emptying (P for trend < 0.05). The area under the curve for satiety increased with initial meal viscosity, whereas that for hunger decreased (P < 0.05). In conclusion, the viscosity of a meal in vivo can be measured noninvasively using EPI. The stomach responds to meal ingestion by rapid intragastric dilution, causing a reduction of meal viscosity, and gastric emptying is minimally delayed. However, increased viscosity is associated with more prolonged satiety.