This paper summarises work undertaken to visualise and characterise alginate gel beads, in vivo, in the human gastro-intestinal tract using magnetic resonance imaging (MRI). Two types of alginate beads were investigated: "strong" (strongly gelled) and "weak" (weakly gelled) beads, each prepared by long and short exposures to a calcium chloride gelling bath, respectively. Ten volunteers attended the study centre, on two different occasions, and consumed a different bead type on each visit. Before consuming the bead meal, the volunteers consumed 50 ml of Calogen® (a fatty preload) which converted gastric motility to a fed pattern and delayed the emptying of the non-nutrient model bead meal from the stomach. Gastric emptying of the bead meal was dominated by the fatty preload, with the median half-emptying time 48 min for both bead types. Gastric sieving of the strong beads occurred with the percentage of the meal remaining at 60 min significantly higher for the strong bead meal compared to the weak bead meal. Both types of gelled beads were clearly visualised by MRI in both the stomach and the small intestine, with beads being more visible in the ileum compared to the jejunum and duodenum. The water proton transverse relaxation time, T2, of the beads was measured in the stomach. After an initial increase, T2 decreased slightly over time from the initial in vivo measurement. In the first paper of this series, we correlate in vitro T2 shortening with formation of a more dense gel network. These in vivo investigations suggest that changes in the gel beads, within the GI tract, could be monitored using T2.

This paper summarises the work undertaken to characterise the physico-chemical properties of alginate gel beads in simulated gastro-intestinal (GI) conditions. Two types of alginate beads were investigated: "strong" (strongly gelled) and "weak" (weakly gelled) beads prepared by long and short exposure to a calcium chloride gelling bath, respectively. The beads were found to shrink in gastric conditions and swell in intestinal conditions due to changes in electrostatic forces in the gel matrix at the different pH and ionic strength conditions. We found a good correlation between the NMR transverse relaxation time (T2) of the water protons within the gel and alginate concentration which was dependant on environmental conditions. T2 shortening was observed in gastric conditions reflecting the formation of a more dense gel network on shrinking. In intestinal conditions, T2 increased reflecting the formation of a more open, porous gel network on swelling. This was corroborated by electron microscopy which clearly depicted the changes in gel density in simulated GI conditions. The mechanical properties of the beads similarly reflected the changes in the gel microstructure with the beads becoming stronger in gastric conditions and weaker in intestinal conditions, respectively. The beads were shown to eventually disintegrate towards the end of the intestinal phase which may make these alginate gel beads an attractive option as controlled delivery devices in the gastro-intestinal tract. The in vivo behaviour of the beads within the GI tract is investigated using non-invasive magnetic resonance imaging in the second paper of this series.

The inhomogeneity of alginate gel beads prepared by an external diffusion method has been characterised using spatially resolved nuclear magnetic resonance or “magnetic resonance imaging” (MRI) and transmission electron microscopy (TEM). The beads exhibited various degrees of inhomogeneity although reducing the length of exposure to the gelling bath and the presence of non-gelling ions decreased gel inhomogeneity. In order to gain information regarding the gastro-intestinal functionality of these beads for in vivo applications, they were exposed to simulated gastro-intestinal conditions. The increased polymer concentration at the edge of the beads was shown to persist throughout our gastro-intestinal model despite the centre of the bead becoming progressively more porous in nature. The porosity of the alginate gels has been quantified by image analysis of transmission electron micrographs and shown to depend on both location within the bead and gastro-intestinal conditions. We suggest that such changes in porosity of these alginate beads during simulated gastro-intestinal conditions may make these an attractive option for controlled delivery applications in vivo.

Purpose: To assess for the first time the potential of echo-planar magnetic resonance imaging (EPI) for measuring simultaneously both gallbladder and gastric emptying.Materials and Methods: Eight healthy subjects ingested 500 mL of an acid-stable liquid test meal containing 15% olive oil and flavoring. Every 20 minutes for three hours thereafter, a rapid EPI multislice set was acquired across the whole abdomen, using a dedicated whole-body 0.5-T EPI scanner.Results: The bile in the gallbladder and the test meal in the stomach appeared bright in the EPI images, aiding localization and region of interest analysis. We measured the gallbladder emptying curve and fitted the data to a simple analytical model. The mean fasted gallbladder volume was 25 +/- 4 mL, comparable to previously published MRI and ultrasound values. Gastric emptying data fitted well to a linear model linear (R-2 = 0.99), and we observed an exponential (R-2 = 0.98) relationship between gallbladder and gastric volumes for the first 90 minutes.Conclusion: This study shows the potential of EPI to monitor simultaneously and noninvasively the emptying of the gallbladder and of the gastric lumen. No contrast enhancing agents are needed. This method could overcome the limitations of previous gamma scintigraphy and ultrasound techniques.