Delayed gastric emptying and reduced postprandial small bowel water content of equicaloric whole meal bread versus rice meals in healthy subjects: novel MRI insights

BACKGROUND/OBJECTIVES: Postprandial bloating is a common symptom in patients with functional gastrointestinal (GI) diseases. Whole meal bread (WMB) often aggravates such symptoms though the mechanisms are unclear. We used magnetic resonance imaging (MRI) to monitor the intragastric fate of a WMB meal (11% bran) compared to a rice pudding (RP) meal. SUBJECTS/METHODS: 12 healthy volunteers completed this randomised crossover study. They fasted overnight and after an initial MRI scan consumed a glass of orange juice with a 2267 kJ WMB or an equicaloric RP meal. Subjects underwent serial MRI scans every 45 min up to 270 min to assess gastric volumes and small bowel water content and completed a GI symptom questionnaire. RESULTS: The MRI intragastric appearance of the two meals was markedly different. The WMB meal formed a homogeneous dark bolus with brighter liquid signal surrounding it. The RP meal separated into an upper, liquid layer and a lower particulate layer allowing more rapid emptying of the liquid compared to solid phase (sieving). The WMB meal had longer gastric half emptying times (132±8 min) compared to the RP meal (104±7 min), P<0.008. The WMB meal was associated with markedly reduced MRI-visible small bowel free mobile water content compared to the RP meal, P<0.0001. CONCLUSIONS: WMB bread forms a homogeneous bolus in the stomach which inhibits gastric sieving and hence empties slower than the equicaloric rice meal. These properties may explain why wheat causes postprandial bloating and could be exploited to design foods which prolong satiation

Quantification of gastrointestinal liquid volumes and distribution following a 240 mL dose of water in the fasted state

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

Characterization of gastric volume responses and liquid emptying in functional dyspepsia and health by MRI or barostat and simultaneous 13C-acetate breath test

The assessment of gastric accommodation and emptying by different methodologies provides inconsistent results. We aimed to compare magnetic resonance imaging (MRI), barostat and 13C-acetate breath test (BT) for the assessment of gastric volume responses and emptying in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent: (i) continuous BT with simultaneous MRI in the upright position after ingestion of isocaloric, 300 kcal, 200 and 800 mL meals, both labelled with 100 mg of (13)C-acetate; and (ii) BT with gastric barostat after ingestion of the 200 mL meal. MRI measured total gastric volume and gastric content volume (GCV) at baseline, after filling and during emptying. Meal emptying half-times (T(1/2)) for MRI and BT were calculated (mean +/- SD). We found: (i) Initial GCV was lower in FD than in HC (762 +/- 22 vs 810 +/- 52 mL, P < 0.04) after the 800 mL meal but not the 200 mL meal. T(1/2)(MRI) was shorter for the 800 mL than the 200 mL meal (P < 0.001), but similar in HC and FD (200 mL: HC 117 +/- 30 min vs FD 138 +/- 42 min, ns; 800 mL: HC 71 +/- 16 min vs FD 78 +/- 27 min, ns). In contrast, T(1/2)(BT) was similar between meals and groups (200 mL: HC 111 +/- 11 min vs FD 116 +/- 19 min; 800 mL: HC 114 +/- 14 min vs FD: 113 +/- 17 min). (ii) Barostat measurements showed similar postprandial volume increases between groups. We conclude that direct measurements by MRI provide a sensitive, non-invasive assessment of gastric accommodation and emptying after a meal. In contrast to MRI, BT did not detect faster emptying of high-volume compared to low-volume liquid nutrient meals in HC or FD

Visualization and quantification of intestinal transit and motor function by real-time tracking of 19F labeled capsules in humans

A combined (19)F and (1)H MRI framework for the assessment of human intestinal transit and motor function is presented. This framework consists of silicone coated polychlorotrifluoroethylene capsules filled with perfluoro-[15]-crown-5-ether as (19)F marker, a flexible (19)F surface coil and a (19)F projection imaging sequence, allowing for real-time tracking of a single or multiple capsules. The capsules (length 11.5 mm, Ø 7.2 mm) contain 140 μL perfluoro-[15]-crown-5-ether and were tested for cytotoxicity and leakage prior to oral administration. A balanced SSFP projection sequence was implemented, yielding a temporal resolution of 133 ms. Optional multi-frequency excitation, allowing for interleaved tracking of differently labeled (19)F capsules, was incorporated. The passage of the (19)F capsules through intestinal sections was monitored in two healthy volunteers. Capsule coordinates were successfully coregistered with anatomical reference scans. Intestinal motility, residence times, lengths and forward velocities were determined. Simultaneous tracking of two capsules allowed for the assessment of peristaltic patterns with correction for respiratory motion. By providing the means for real-time multiple capsule tracking and high resolution anatomical imaging, the presented multinuclear imaging framework has the potential to provide important supplemental information for physiological and pharmaceutical research

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging

Conventional measurement of gastric secretion is invasive and cannot assess the intra-gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T(1) mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium-DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double-blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T(1) mapping. Data was described by the kappa-coefficient (volume change after meal ingestion), by GE half time (T(50)) and maximal GE rate (GER(max)) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [kappa(GCV):1.6 +/- 0.1 vs 0.6 +/- 0.1; kappa(TGV): 1.6 +/- 0.1 vs 0.7 +/- 0.1; P < 0.001]. T(1) maps revealed a secretion layer above the meal, the volume of which was associated with kappa (R(2) = 83%, P < 0.001). TGV and GCV change were similar in both conditions (kappa; P = ns). T(50) was higher for pentagastrin than for placebo (84 +/- 7 vs 56 +/- 4min, P < 0.001); however, GER(max) was similar (5.9 +/- 0.6 vs 4.9 +/- 0.4 mL min(-1), P = ns). This study shows volume and distribution of gastric secretion can be quantified in-vivo by non-invasive MRI T(1) mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T(50); however, GE rate is unchanged

Fast and optimized T1 mapping technique for the noninvasive quantification of gastric secretion

Purpose To evaluate the noninvasive quantification of gastric secretion volume after administration of a labeled viscous glucose solution by fast T1 mapping. Materials and Methods T1 values of a series of labeled and diluted glucose solutions were measured in vitro to characterize the interrelationship between T1 and contrast agent concentration (CGd) as well as the dependency of relaxivity and reference T1 (T10) on the macromolecular concentration. Abdominal T1 mapping in five healthy volunteers of different body mass index was performed after filling an intragastric balloon with a labeled and diluted glucose solution. In additional ex vivo experiments, T1 values of gastric (GJ) and duodenal juice (DJ) and 0.1 N HCl solution were determined. Results A linear relationship between relaxivity and macromolecular concentration and between T10 and macromolecular concentration was found. The in vitro T1-CGd calibration curve was successfully validated in all volunteers. T1 values of GJ, DJ, and HCl (2939 msec vs. 2858 msec vs. 2760 msec) were close to the T1 of water (3000 msec). Conclusion The presented method allows one to noninvasively quantify the spatial distribution of gastric secretory products in the human stomach and provides a valuable tool for evaluating the efficacy of drugs to stimulate/inhibit gastric secretion

Intersubject and intrasubject variability of gastric volumes in response to isocaloric liquid meals in functional dyspepsia and health

Gastric emptying (GE) has a considerable variability, but data on reproducibility of gastric volume measurements are sparse. We aimed to study the reproducibility of postprandial gastric volume responses and GE using magnetic resonance imaging (MRI) in healthy controls (HC) and patients with functional dyspepsia (FD). Eight HC and eight FD patients underwent a MRI study on two occasions. MR images were acquired in seated position before and up to 120 min after liquid meal administration (200 mL, 300 kcal). Fasting (V0), initial postprandial stomach volumes (V1), volume changes (V1 - V0) and meal emptying half-times (T 1/2) were determined. Intersubject and intrasubject coefficients of variation (CV(inter), CV(intra)) and Pearson's correlation coefficients (r) were calculated. T 1/2 on both occasions were (mean +/- SD) 113 +/- 28 and 121 +/- 30 min in HC (ns) and 127 +/- 31 and 128 +/- 37 min in FD (ns), respectively. In HC, CV(inter), CV(intra), r were 31%, 23%, 0.49 for V0; 13%, 7%, 0.68 for V1; 10%, 4%, 0.71 for V1 - V0 and 25%, 7%, 0.90 for T 1/2. In FD these parameters were for V0: 42%, 41%, -0.06; for V1: 18%, 10%, 0.40; for V1 - V0: 20%, 14%, 0.74 and for T 1/2: 26%, 10%, 0.84. The stomach accommodates to a given meal volume, resulting in similar and reproducible postprandial volumes within- and between-subjects. MRI provides reproducible measurements of gastric volume responses in health and disease