Measurement of fasted state gastric antral motility before and after a standard bioavailability and bioequivalence 240 mL drink of water: Validation of MRI method against concomitant perfused manometry in healthy participants

Abstract

Objective The gastrointestinal environment in which drug products need to disintegrate before the drug can dissolve and be absorbed has not been studied in detail due to limitations, especially invasiveness of existing techniques. Minimal in vivo data is available on undisturbed gastrointestinal motility to improve relevance of predictive dissolution models and in silico tools such as physiologically-based pharmacokinetic models. Recent advances in magnetic resonance imaging methods could provide novel data and insights that can be used as a reference to validate and, if necessary, optimize these models. The conventional method for measuring gastrointestinal motility is via a manometric technique involving intubation. Nevertheless, it is feasible to measure gastrointestinal motility with magnetic resonance imaging. The aim of this study was is to develop and validate a magnetic resonance imaging method using the most recent semi-automated analysis method against concomitant perfused manometry method. Material and methods Eighteen healthy fasted participants were recruited for this study. The participants were intubated with a water-perfused manometry catheter. Subsequently, stomach motility was assessed by cine-MRI acquired at intervals, of 3.5min sets, at coronal oblique planes through the abdomen and by simultaneous water perfused manometry, before and after administration of a standard bioavailability / bioequivalence 8 ounces (~240mL) drink of water. The magnetic resonance imaging motility images were analysed using Spatio-Temporal Motility analysis STMM techniques. The area under the curve of the gastric motility contractions was calculated for each set and compared between techniques. The study visit was then repeated one week later. Results Data from 15 participants was analysed. There was a good correlation between the MRI antral motility plots area under the curve and corresponding perfused manometry motility area under the curve (r = 0.860) during both antral contractions and quiescence. Conclusion Non-invasive dynamic magnetic resonance imaging of gastric antral motility coupled with recently developed, semi-automated magnetic resonance imaging data processing techniques correlated well with simultaneous, ‘gold standard’ water perfused manometry. This will be particularly helpful for research purposes related to oral absorption where the absorption of a drug is highly depending on the underlying gastrointestinal processes such as gastric emptying, gastrointestinal motility and availability of residual fluid volumes. Clinical trial This trial was registered at ClinicalTrials.gov as NCT03191045.

Quantification of the Regional Properties of Gastric Motility Using Dynamic Magnetic Resonance Images

“…Separating the lesser and greater curvature enabled individual contractions in the contraction maps to be distinguished and contraction properties to be quantified. Previous studies have combined the contractions of the lesser and greater curvature seen in the MRI slice (and therefore analyzed the variation in the diameter of the stomach) [21] , [23] , [24] , [32] . However, as the contraction points may not always align well, increased error can result.…”

“…Free-breathing MRI scans of gastric motility were also used to quantify contraction speed using an axis drawn through the center of the antrum [21] . Other studies have used manually prescribed lines as the reference for the propagation speed calculations of breath-hold images [12] , [22] , [23] , [24] . More recently, researchers have investigated the use of an automated method for analyzing dynamic 3-dimensional MRI data [25] , [26] , [27] .…”

Magnetic Resonance Imaging of the Gastrointestinal Tract: Current Role, Recent Advancements and Future Prospectives

“…Until now, gastric motility has not been extensively studied with MRI; there exist only a few articles focusing on it. The study by Heissam et al [59], based on fifteen healthy adults, compared the motility cine-MRI, performed with semi-automated techniques, with simultaneous water perfused manometry, using water as a contrast agent and demonstrating a strong correlation between the two methods. Another study, by Hosseini et al [60] performed cine-MRI on four healthy volunteers, using pineapple juice as contrast and demonstrating the possibility of using MRI to measure and quantify gastric motility in human participants, even quantifying different motility patterns in different gastric portions.…”

“Development of Fixed Dose Combination Products” Workshop Report: Considerations of Gastrointestinal Physiology and Overall Development Strategy

“…Besides telemetric capsules, magnetic resonance imaging (MRI) has been recently applied to the study the GI function and this technique offers some major advantages compared to other techniques: it is non-invasive, does not expose subjects to ionizing radiation, and does not require any contrast medium. It is a unique technique that offers the possibility of simultaneously measuring gastric, small intestinal and colonic volumes, the physicochemical characteristics of the luminal environment, transit rate and to quantify motility [14]. This technique has not yet been standardized across research centers and for the moment does not allow the evaluation of gastric function in an upright position [15].…”

“…For instance, one subject showed to have only 2 pockets with a total volume of 1.4 mL whereas another subject demonstrated to have 23 pockets with a total volume of 160 mL. A follow-up study aims to unravel a potential link between the appearance of fluid pockets and the present motility [14]. In the seventies, Vantrappen et al observed a higher secretion rate of bicarbonate shortly after an upper GI phase III contraction [3].…”