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.

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.

Propagation Characteristics of Fasting Duodeno-Jejunal Contractions in Healthy Controls Measured by Clustered Closely-spaced Manometric Sensors.

BACKGROUND/AIMS: High-resolution methods have advanced esophageal and anorectal manometry interpretation but are incompletely established for intestinal manometry. We characterized normal fasting duodeno-jejunal manometry parameters not measurable by standard techniques using clustered closely-spaced recordings. METHODS: Ten fasting recordings were performed in 8 healthy controls using catheters with 3-4 gastrointestinal manometry clusters with 1-2 cm channel spacing. Migrating motor complex phase III characteristics were quantified. Spatial-temporal contour plots measured propagation direction and velocity of individual contractions. Coupling was defined by pressure peak continuity within clusters. RESULTS: Twenty-three phase III complexes (11 antral, 12 intestinal origin) with 157 (95% CI, 104-211) minute periodicities, 6.99 (6.25-7.74) minute durations, 10.92 (10.68-11.16) cycle/minute frequencies, 73.6 (67.7-79.5) mmHg maximal amplitudes, and 4.20 (3.18-5.22) cm/minute propagation velocities were recorded. Coupling of individual contractions was 39.1% (32.1-46.1); 63.0% (54.4-71.6) of contractions were antegrade and 32.8% (24.1-41.5) were retrograde. Individual phase III contractions propagated > 35 fold faster (2.48 cm/sec; 95% CI, 2.25-2.71) than complexes themselves. Phase III complexes beyond the proximal jejunum were longer in duration (P = 0.025) and had poorer contractile coupling (P = 0.025) than proximal complexes. Coupling was greater with 1 cm channel spacing vs 2 cm (P ＜ 0.001). CONCLUSIONS: Intestinal manometry using clustered closely-spaced pressure ports characterizes novel antegrade and retrograde propagation and coupling properties which degrade in more distal jejunal segments. Coupling is greater with more closely-spaced recordings. Applying similar methods to dysmotility syndromes will define the relevance of these methods.

Formulation predictive dissolution (fPD) testing to advance oral drug product development: An introduction to the US FDA funded '21st Century BA/BE' project.

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions.

Three-dimensional mechanisms of macro-to-micro-scale transport and absorption enhancement by gut villi motions.

We evaluate the potential for physiological control of intestinal absorption by the generation of "micromixing layers" (MMLs) induced by coordinated motions of mucosal villi coupled with lumen-scale "macro" eddying motions generated by gut motility. To this end, we apply a three-dimensional (3D) multigrid lattice-Boltzmann model of a lid-driven macroscale cavity flow with microscale fingerlike protuberances at the lower surface. Integrated with a previous 2D study of leaflike villi, we generalize to 3D the 2D mechanisms found there to enhance nutrient absorption by controlled villi motility. In three dimensions, increased lateral spacing within villi within groups that move axially with the macroeddy reduces MML strength and absorptive enhancement relative to two dimensions. However, lateral villi motions create helical 3D particle trajectories that enhance absorption rate to the level of axially moving 2D leaflike villi. The 3D enhancements are associated with interesting fundamental adjustments to 2D micro-macro-motility coordination mechanisms and imply a refined potential for physiological or pharmaceutical control of intestinal absorption.

Non-steady wind turbine response to daytime atmospheric turbulence.

Relevant to drivetrain bearing fatigue failures, we analyse non-steady wind turbine responses from interactions between energy-dominant daytime atmospheric turbulence eddies and the rotating blades of a GE 1.5 MW wind turbine using a unique dataset from a GE field experiment and computer simulation. Time-resolved local velocity data were collected at the leading and trailing edges of an instrumented blade together with generator power, revolutions per minute, pitch and yaw. Wind velocity and temperature were measured upwind on a meteorological tower. The stability state and other atmospheric conditions during the field experiment were replicated with a large-eddy simulation in which was embedded a GE 1.5 MW wind turbine rotor modelled with an advanced actuator line method. Both datasets identify three important response time scales: advective passage of energy-dominant eddies (≈25-50 s), blade rotation (once per revolution (1P), ≈3 s) and sub-1P scale (<1 s) response to internal eddy structure. Large-amplitude short-time ramp-like and oscillatory load fluctuations result in response to temporal changes in velocity vector inclination in the aerofoil plane, modulated by eddy passage at longer time scales. Generator power responds strongly to large-eddy wind modulations. We show that internal dynamics of the blade boundary layer near the trailing edge is temporally modulated by the non-steady external flow that was measured at the leading edge, as well as blade-generated turbulence motions.This article is part of the themed issue 'Wind energy in complex terrains'.

The Esophagiome: concept, status, and future perspectives.

The term "Esophagiome" is meant to imply a holistic, multiscale treatment of esophageal function from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. The development and application of multiscale mathematical models of esophageal function are central to the Esophagiome concept. These model elements underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease by quantitatively contrasting normal and pathophysiological function. Functional models incorporate anatomical details with sensory-motor properties and functional responses, especially related to biomechanical functions, such as bolus transport and gastrointestinal fluid mixing. This brief review provides insight into Esophagiome research. Future advanced models can provide predictive evaluations of the therapeutic consequences of surgical and endoscopic treatments and will aim to facilitate clinical diagnostics and treatment.

Analysis of Diffusion-Controlled Dissolution from Polydisperse Collections of Drug Particles with an Assessed Mathematical Model.

We introduce a "hierarchical" modeling strategy designed to be systematically extensible to increase the detail of dissolution predictions from polydisperse collections of drug particles and to be placed on firm mathematical and physical foundations with diffusion-dominated dissolution at its core to predict dissolution and the evolution of particle size distribution. We assess the model with experimental data and demonstrate higher accuracy by treating the polydisperse nature of dissolution. A level in the hierarchy is applied to study elements of diffusion-driven dissolution, in particular the role of particle-size distribution width with varying dose level and the influences of "confinement" on the process of dissolution. Confinement influences surface molecular flux, directly by the increase in bulk concentration and indirectly by the relative volume of particles to container. We find that the dissolution process can be broadly categorized within three "regimes" defined by the ratio of total concentration Ctot to solubility CS . Sink conditions apply in the first regime, when C tot /CS<∼0.1. When C tot /CS>∼5 (regime 3) dissolution is dominated by confinement and normalized saturation time follows a simple power law relationship. Regime 2 is characterized by a "saturation singularity" where dissolution is sensitive to both initial particle size distribution and confinement.

Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine-A Study with Felodipine as a Model Drug.

The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low-solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the in vitro tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at in vivo relevant surface tension levels is thus critical for in vivo predictive in vitro dissolution testing.

The invalidity of the Laplace law for biological vessels and of estimating elastic modulus from total stress vs. strain: a new practical method.

There are strong medical motivations to measure changes in material properties of tubular organs, in vivo and in vitro. The current approach estimates hoop stress from intraluminal pressure using the Laplace law and identifies 'elastic modulus' as the slope of a curve fitted hoop stress plotted against strain data. We show that this procedure is fundamentally flawed because muscle and other soft tissue are closely incompressible, so that the total stress includes a volume-preserving material-dependent hydrostatic response that invalidates the method. Furthermore, we show that the Laplace law incorrectly estimates total stress in biological vessels. However, the great need to estimate elastic modulus leads us to develop an alternative practical method, based on shear stress-strain, i.e. insensitive to nonelastic response from incompressibility, but that uses the same measurement data as the current (incorrect) method. The individual material parameters in the underlying (unknown) constitutive relation combine into an effective shear modulus that is a true measure of elastic response, unaffected by incompressibility and without reference to the Laplace law. Furthermore, our effective shear modulus is determined directly as a function of deformation, rather than as the slope of a fitted curve. We validate our method by comparing effective shear moduli against exact shear moduli for four theoretical materials with different degrees of nonlinearity and numbers of material parameters. To further demonstrate applicability, we reanalyse an in vivo study with our new method and show that it resolves an inconsistent change in modulus with the current method.

Comparison and analysis of theoretical models for diffusion-controlled dissolution.

Dissolution models require, at their core, an accurate diffusion model. The accuracy of the model for diffusion-dominated dissolution is particularly important with the trend toward micro- and nanoscale drug particles. Often such models are based on the concept of a "diffusion layer." Here a framework is developed for diffusion-dominated dissolution models, and we discuss the inadequacy of classical models that are based on an unphysical constant diffusion layer thickness assumption, or do not correctly modify dissolution rate due to "confinement effects": (1) the increase in bulk concentration from confinement of the dissolution process, (2) the modification of the flux model (the Sherwood number) by confinement. We derive the exact mathematical solution for a spherical particle in a confined fluid with impermeable boundaries. Using this solution, we analyze the accuracy of a time-dependent "infinite domain model" (IDM) and "quasi steady-state model" (QSM), both formally derived for infinite domains but which can be applied in approximate fashion to confined dissolution with proper adjustment of a concentration parameter. We show that dissolution rate is sensitive to the degree of confinement or, equivalently, to the total concentration C(tot). The most practical model, the QSM, is shown to be very accurate for most applications and, consequently, can be used with confidence in design-level dissolution models so long as confinement is accurately treated. The QSM predicts the ratio of diffusion layer thickness to particle radius (the Sherwood number) as a constant plus a correction that depends on the degree of confinement. The QSM also predicts that the time required for complete saturation or dissolution in diffusion-controlled dissolution experiments is singular (i.e., infinite) when total concentration equals the solubility. Using the QSM, we show that measured differences in dissolution rate in a diffusion-controlled dissolution experiment are a result of differences in the degree of confinement on the increase in bulk concentration independent of container geometry and polydisperse vs single particle dissolution. We conclude that the constant diffusion-layer thickness assumption is incorrect in principle and should be replaced by the QSM with accurate treatment of confinement in models of diffusion-controlled dissolution.

The esophagogastric junction.

The following discussion of the esophagogastric junctions includes commentaries on the three component structures of the sphincteric segment between the stomach and the esophagus; the pressure contributions from the three sphincteric components in normal subjects and in gastroesophageal reflux (GERD) patients; the mechanism of action of endoscopic plication to determine the underlying pathophysiology of GERD; and in vitro muscle strip studies of defects within the gastroesophageal sphincteric segment potentially leading to GERD.

A multiscale lattice Boltzmann model of macro- to micro-scale transport, with applications to gut function.

Nutrient absorption in the small intestine cannot occur until molecules are presented to the epithelial cells that line intestinal villi, finger-like protrusions under enteric control. Using a two-dimensional multiscale lattice Boltzmann model of a lid-driven cavity flow with 'villi' at the lower surface, we analyse the hypothesis that muscle-induced oscillatory motions of the villi generate a controlled 'micro-mixing layer' (MML) that couples with the macro-scale flow to enhance absorption. Nutrient molecules are modelled as passive scalar concentrations at high Schmidt number. Molecular concentration supplied at the cavity lid is advected to the lower surface by a lid-driven macro-scale eddy. We find that micro-scale eddying motions enhance the macro-scale advective flux by creating an MML that couples with the macro-scale flow to increase absorption rate. We show that the MML is modulated by its interactions with the outer flow through a diffusion-dominated layer that separates advection-dominated macro-scale and micro-scale mixed layers. The structure and strength of the MML is sensitive to villus length and oscillation frequency. Our model suggests that the classical explanation for the existence of villi--increased absorptive surface area--is probably incorrect. The model provides support for the potential importance of villus motility in the absorptive function of the small intestine.

Quantitative analysis of peristaltic and segmental motion in vivo in the rat small intestine using dynamic MRI.

Conventional methods of quantifying segmental and peristaltic motion in animal models are highly invasive; involving, for example, the external isolation of segments of the gastrointestinal (GI) tract either from dead or anesthetized animals. The present study was undertaken to determine the utility of MRI to quantitatively analyze these motions in the jejunum region of anesthetized rats (N = 6) noninvasively. Dynamic images of the GI tract after oral gavage with a Gd contrast agent were acquired at a rate of six frames per second, followed by image segmentation based on a combination of three-dimensional live wire (3D LW) and directional dynamic gradient vector flow snakes (DDGVFS). Quantitative analysis of the variation in diameter at a fixed constricting location showed clear indications of both segmental and peristaltic motions. Quantitative analysis of the frequency response gave results in good agreement with those acquired in previous studies using invasive measurement techniques. Principal component analysis (PCA) of the segmented data using active shape models resulted in three major modes. The individual modes revealed unique spatial patterns for peristaltic and segmental motility.

Liquid in the gastroesophageal segment promotes reflux, but compliance does not: a mathematical modeling study.

The mechanical force relationships that distinguish normal from chronic reflux at sphincter opening are poorly understood and difficult to measure in vivo. Our aim was to apply physics-based computer simulations to determine mechanical pathogenesis of gastroesophageal reflux. A mathematical model of the gastroesophageal segment (GES) was developed, incorporating the primary anatomical and physiomechanical elements that drive GES opening and reflux. In vivo data were used to quantify muscle stiffness, sphincter tone, and gastric pressure. The liquid lining the mucosa was modeled as an "effective liquid film" between the mucosa and a manometric catheter. Newton's second law was solved mathematically, and the space-time details of opening and reflux were predicted for systematic variations in gastric pressure increase, film thickness, muscle stiffness, and tone. "Reflux" was defined as "2 ml of refluxate entering the esophagus within 1 s." GES opening and reflux were different events. Both were sensitive to changes in gastric pressure and sphincter tone. Reflux initiation was extremely sensitive to the liquid film thickness; the protective function of the sphincter was destroyed with only 0.4 mm of liquid in the GES. Compliance had no effect on reflux initiation, but affected reflux volume. The presence of abnormal levels of liquid within the collapsed GES can greatly increase the probability for reflux, suggesting a mechanical mechanism that may differentiate normal reflux from gastroesophageal reflux disease. Compliance does not affect the probability for reflux, but affects reflux volume once it occurs. Opening without reflux suggests the existence of "gastroesophageal pooling" in the distal esophagus, with clinical implications.

New observations on the gastroesophageal antireflux barrier.

The use of high-frequency ultrasound transducers combined with manometry in the gastrointestinal (GI) tract has yielded important findings concerning the anatomy, physiology, and pathophysiology of the high-pressure zone of the gastroesophageal junction and the sphincteric muscles within. These transducers have made previously invisible portions of the GI tract accessible to investigation. Three distinct high-pressure zones have been identified and correlated with anatomic structures: the extrinsic sphincter (crural diaphragm) and the two components of the intrinsic sphincter (an upper LES and a lower LES [the gastric sling fiber/clasp fiber complex]). This article discusses the possible underlying pathophysiology of gastroesophageal reflux disease; the biomechanics of the gastroesophageal junction high-pressure zone; and the mechanism of action of standard surgical and newer endoscopic therapies for gastroesophageal reflux disease.

Function of longitudinal vs circular muscle fibers in esophageal peristalsis, deduced with mathematical modeling.

We summarize from previous works the functions of circular vs. longitudinal muscle in esophageal peristaltic bolus transport using a mix of experimental data, the conservation laws of mechanics and mathematical modeling. Whereas circular muscle tone generates radial closure pressure to create a local peristaltic closure wave, longitudinal muscle tone has two functions, one physiological with mechanical implications, and one purely mechanical. Each of these functions independently reduces the tension of individual circular muscle fibers to maintain closure as a consequence of shortening of longitudinal muscle locally coordinated with increasing circular muscle tone. The physiological function is deduced by combining basic laws of mechanics with concurrent measurements of intraluminal pressure from manometry, and changes in cross sectional muscle area from endoluminal ultrasound from which local longitudinal shortening (LLS) can be accurately obtained. The purely mechanical function of LLS was discovered from mathematical modeling of peristaltic esophageal transport with the axial wall motion generated by LLS. Physiologically, LLS concentrates circular muscle fibers where closure pressure is highest. However, the mechanical function of LLS is to reduce the level of pressure required to maintain closure. The combined physiological and mechanical consequences of LLS are to reduce circular muscle fiber tension and power by as much as 1/10 what would be required for peristalsis without the longitudinal muscle layer, a tremendous benefit that may explain the existence of longitudinal muscle fiber in the gut. We also review what is understood of the role of longitudinal muscle in esophageal emptying, reflux and pathology.

Pharmacological dissection of the human gastro-oesophageal segment into three sphincteric components.

Quantifications of gastro-oesophageal anatomy in cadavers have led some to identify the lower oesophageal sphincter (LOS) with the anatomical gastric sling-clasp fibres at the oesophago-cardiac junction (OCJ). However, in vivo studies have led others to argue for two overlapping components proximally displaced from the OCJ: an extrinsic crural sphincter of skeletal muscle and an intrinsic physiological sphincter of circular smooth-muscle fibres within the abdominal oesophagus. Our aims were to separate and quantify in vivo the skeletal and smooth muscle sphincteric components pharmacologically and clarify the description of the LOS. In two protocols an endoluminal ultrasound-manometry assembly was drawn through the human gastro-oesophageal segment to correlate sphincteric pressure with the anatomic crus. In protocol I, fifteen normal subjects maintained the costal diaphragm at inferior/superior positions by full inspiration/expiration (FI/FE) during pull-throughs. These were repeated after administering atropine to suppress the cholinergic smooth-muscle sphincter. The cholinergic component was reconstructed by subtracting the atropine-resistant pressures from the full pressures, referenced to the anatomic crus. To evaluate the extent to which the cholinergic contribution approximated the full smooth-muscle sphincter, in protocol II seven patients undergoing general anaesthesia for non-oesophageal pathology were administered cisatracurium to paralyse the crus. The smooth-muscle sphincter pressures were measured after lung inflation to approximate FI. The cholinergic smooth-muscle pressure profile in protocol I (FI) matched closely the post-cisatracurium smooth-muscle pressure profile in protocol II, and the atropine-resistant pressure profiles correlated spatially with the crural sling during diaphragmatic displacement. Thus, the atropine-resistant and cholinergic pressure contributions in protocol I approximated the skeletal and smooth muscle sphincteric components. The smooth-muscle pressures had well-defined upper and lower peaks. The upper peak overlapped and displaced rigidly with the crural sling, while the distal peak separated from the crus/upper-peak by 1.1 cm between FI and FE. These results suggest the existence of separate upper and lower intrinsic smooth-muscle components. The 'upper LOS' overlaps and displaces with the crural sling consistent with a physiological LOS. The distal smooth-muscle pressure peak defines a 'lower LOS' that likely reflects the gastric sling/clasp muscle fibres at the OCJ. The distinct physiology of these three components may underlie aspects of normal sphincteric function, and complexity of sphincter dysfunction.

A stomach road or "Magenstrasse" for gastric emptying.

Gastric muscle contractions grind and mix solid/liquid meal within the stomach, and move it into the bowels at a controlled rate. Contractions are of two types: slow volume-reducing contractions of the proximal stomach (the fundus), and peristaltic contraction waves in the distal stomach (the antrum). Fundic squeeze maintains gastro-duodenal pressure difference to drive gastric emptying. Emptying is generally assumed to proceed from the antrum to the fundus, so that ingested drugs can take hours to enter the small intestines and activate. Antral contraction waves (ACW), in contrast, generate fluid motions that break down and mix gastric content. Using a computer model of the human stomach, we discover a new function of these contraction waves apart from grinding and mixing. In coordination with fundic contraction, antral contraction waves move liquid content from the fundus along a very narrow path to the duodenum through the center of the antrum. Using physiological data, we show that this gastric emptying "Magenstrasse" (stomach road) can funnel liquid gastric content from the farthest reaches of the fundus directly to the intestines within 10 min. Consequently, whereas drugs (tablets, capsules, liquid) released off the Magenstrasse may require hours to enter the duodenum, at low concentration, when released on the Magenstrasse the drug can enter the duodenum and activate within 10 min-at high concentration. This discovery might explain observed high variability in drug initiation time, and may have important implications to both drug delivery and digestion, as well as to other wall-driven emptying of elastic containers.

Quantification of distal antral contractile motility in healthy human stomach with magnetic resonance imaging.

PURPOSE: To quantify healthy postprandial: 1) propagation, periodicity, geometry, and percentage occlusion by distal antral contraction waves (ACWs); and 2) changes in ACW activity in relationship to gastric emptying (GE). MATERIALS AND METHODS: Using 1.5-T MR scanner, nine healthy fasted volunteers were examined in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) with 500 microM Gd-DOTA. Total gastric (TGV) and meal volumes (MV) were assessed every five minutes for 90 minutes, in and interspersed with dynamic scan sequences (duration: 2.78 minutes) providing detailed images of distal ACWs. RESULTS: TGV increased by 738+/-38 mL after ingestion (t0), subsequently decreasing in parallel to GE. The mean GE rate and half-emptying time were 24+/-3 mL/5 minutes and 71+/-6 minutes, respectively. Accompanying ACWs reached a periodicity of 23+/-2 seconds at t35 and propagated at an unvarying speed of 0.27+/-0.01 cm/second. Their amplitude of 0.70+/-0.08 cm was constant, but the width decreased along the antral wall by 6+/-2%/cm (P=0.003). ACWs were nonocclusive (percentage occlusion 58.1+/-5.9%, t0 at the pylorus) with a reduction in occlusion away from the pylorus (P<0.001). No propagation and geometry characteristics of ACWs correlated with the changes of MV (mL/5 minutes; R2<0.05). CONCLUSION: Our results indicate that ACWs are not imperative for emptying of liquids. This study provides a detailed quantitative reference for MRI inquiries into pharmacologically- and pathologically-altered gastric motility.