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).
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).
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 μM 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.
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).
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. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.
INVESTIGATIONS INTO THE MECHANISMS driving gastric emptying have allowed better understanding of pathophysiology of certain gastrointestinal disorders and consequences of surgical and/or pharmacological interventions. Particular attention has been devoted to gastric motility. Taken as the final expression of complex neurohormonal interactions, gastric motility is central to effective controlled delivery of ingested food and oral medications for subsequent duodenal absorption.
Liquid emptying has been largely attributed to tonic contraction of the gastric fundus, creating an overall pressure gradient across the pylorus, controlling liquid emptying during periods of pyloric opening (1–3). Recent studies have concluded that the primary purposes of phasic distal antral contraction waves (ACWs) are mixing of gastric content and triturating of solids (4–6). However, it has also been argued that ACWs contribute to the rate of liquid gastric emptying (4, 7, 8) and the generation of pulsatile emptying patterns (1, 3, 9, 10). Although ACWs may contribute to and modulate the emptying process, they may not be necessarily related to or required for gastric outflow (5, 6, 11). Prokinetic medications stimulating antral contractility, applied for treatment of gastroparesis, support this hypothesis. Their efficacy is modest and results of clinical studies are controversial (12). Hence, the contribution of ACWs to gastric emptying of liquids remains unclear.
Detailed quantification of propagation, geometry, and occlusive characteristics of ACWs in a normal physiological state, and modulation by drug or disease, may offer new insight into the relative contribution of peristaltic activity to gastric emptying. Accurate quantification, however, is difficult. MRI has progressed to allow noninvasive recording of antral motility with high spatiotemporal resolution (13, 14). Coupled with advanced computer-based image analysis, MRI can provide quantitative detail on gastric motor function. Such quantitative detail is lacking in the current literature. An in vivo quantification is necessary for complete understanding of the role of distal antral motility in gastric trituration, mixing, and emptying, as well as the consequences of the alteration of antral motility by nutrients, drugs, and disease, enhancement of future drug design, and clinical treatment, as well as for computer modeling of gastric function. Currently, the only modality available for precise quantification of ACW motility is state-of-the-art time-resolved MRI coupled with purpose-written image analysis requiring a combination of experimental and numerical expertise.
The aims of this study were 1) to quantify accurately distal ACW motility, specifically propagation, frequency, geometry, and extent of antral occlusion in the presence of a nutrient liquid, and 2) to quantify changes in ACW activity over the postprandial period in relationship to patterns of liquid gastric emptying in health.
Nine healthy subjects (four males, aged 23–42 years, body-mass index [BMI]: 19–29 kg/m2) participated in the study. All subjects gave written informed consent. The study protocol was approved by the local ethics committee.
Following an eight-hour fast, subjects ingested 500 mL of 10% liquid glucose (200 kcal), labeled with 0.5 mmol/liter Gd-DOTA (Dotarem; Laboratorie Guerbet, Aulnay-sous-Bois, France) in the right decubitus position. Postprandial stomach volume (total gastric volume; TGV), gastric contents (meal volume; MV), and distal antral peristaltic activity were assessed over 90 minutes with volunteers remaining in the right decubitus position.
Studies were performed using a 1.5-T whole body MRI system (1.5 T Intera, Philips Medical System, Best, The Netherlands). Two different types of scans were applied: 1) a “volume scan,” covering the complete stomach volume, to assess TGV and MV, and 2) a “motility scan,” dynamically imaging three longitudinal sections through the gastroduodenal region, to assess antropyloroduodenal luminal wall motion with a focus on distal ACWs. Six rectangular surface coils (height = 20 cm, width = 10 cm), fixed around the abdomen and connected to six independent receive channels were used for signal detection.
Gastric volumes were assessed using a balanced steady-state free precession (b-SSFP) imaging technique (TE/TR = 1.9/4.0 msec; flip angle = 35°). A total of 40 sagittal and 15 transverse image slices were acquired in 23 seconds with a slice thickness of 5 mm, field of view (FOV) = 400 mm, and matrix size = 256 × 205 pixels (spatial resolution: 1.56 × 1.95 × 5 mm3). To avoid motion artifact, volunteers were asked to hold their breath in expiration during the length of each volume measurement. Volume scans were performed every five minutes.
ACWs were assessed using a dynamic b-SSFP imaging technique accelerated with the sensitivity encoding (SENSE) parallel imaging technique (15) (TE/TR = 1.8/4.0 msec; flip angle = 35°; SENSE reduction factor = 1.6). A total of 120 consecutive scans were acquired over a period of 2.78 minutes (167 seconds). Each scan imaged three oblique coronal or sagittal image planes (depending on the volunteer's anatomy) of slice thickness = 8 mm, FOV = 400 mm, and matrix size = 256 × 205 (spatial resolution = 1.56 × 1.95 × 8.0 mm3). Dynamic imaging was performed during normal breathing. Motility scans were performed one minute (preparation time) after each completed volume scan.
TGV was evaluated by semiautomatically outlining the contour of the gastric wall within each slice using the “Spline_p” procedure within the IDL 5.5 library (Research Systems Inc., Boulder, CO, USA), which performs a parametric cubic spline interpolation between user-defined points. The segmented area within each slice was multiplied by the slice thickness and all “slice volumes” were added to calculate the stomach volume. Since intragastric air (black) and labeled liquid meal (bright signal) had a distinct contrast, a manually selected intensity threshold was used to determine and compute MV. Volume analysis was performed using an in-house-written software package implemented in IDL 5.5 (14).
Details of gastric motility were computed using custom designed image analysis software based on Matlab 6.5 (Mathworks Inc., Natick, MA, USA). Each dynamic MRI motility sequence was analyzed frame by frame to follow propagating indentations on the walls of the distal antrum, which denoted ACWs. The image analysis described below is illustrated in Fig. 1.
From the three slices of every MRI motility scan, an image plane was chosen that best displayed the antropyloroduodenal axis and the propagating ACWs (Fig. 1a). The pylorus was located and marked on the appropriate image plane and tracked through the dynamic image sequence by finding the maximum correlation between two consecutive images calculated over an area of 20 × 20 pixels around the marked location. A long axis was drawn through the center of the visible portion of the antrum (Fig. 1b). The position of the pylorus was the anchoring point for the central axis. The propagation periodicity (second) and speed (cm/second) of ACWs were computed as a function of time and distance from the pylorus (XCW in cm; Figs. 1b and 2a). The tips and bases of the ACWs were selected within every frame of the image sequence (Fig. 1c). These selected points were used to calculate the “occlusion diameter” (the distance between the tips in centimeters) and “antral diameter” at the location of the ACW (the average distance between base points of the ACWs across the antrum in centimeters) (Fig. 1d). The distance from the tip to the middle of the base provided the amplitude of the ACW (cm) and the distance between base points along the antral wall provided the width of the ACW (cm) (Fig. 1c).
For ACWs propagating along the inner and outer curvature of the antral wall, data from both indentations were averaged to calculate amplitude and width of each ACW. In frames where the ACW was visible only on one curvature, amplitude and width of the ACW was calculated using this data only. The distance of the ACW from the pylorus (XCW in cm) was calculated along the antral axis from the mean location of the ACW tips.
A P-value < 0.05 was considered statistically significant. All values are shown as mean ± standard error of mean (SEM).
Postprandial (t0–90) TGV and MV were plotted against time to create volume curves. Gastric and meal volume curves were least-squares fit to the following linear exponential model (LinExp),
designed to capture a potential initial increase in gastric volume before subsequent emptying using a data analysis package R with a non-linear mixed effect model library (R, lib. nlme, Vers 2.0.1.© 2004). In this expression, V0 is the initial postprandial volume at time t0 [mL], κ parameterizes the rate of initial increase in volume from V0, and tempt is an emptying time constant [minutes]) (16). This model has advantages over the often used power exponential model, F(t)=2 (F(t), fraction of stomach or meal volume; t50, half emptying time; β, rate parameter), proposed by Elashoff et al (17), in that it captures any initial increases in volume due to secretion and/or accommodation. V0 is determined by a least square from all data points, hence the first data point in not given greater weighting.
Student's t-test was used to assess differences between the fitted parameters for TGV and MV, specifically V0, κ, tempt, t50, maximal volume detected Vmax, changes in volumes detected ΔV, and the time period from initial to maximal volume Δt.
Nonmodeled MV changes within five-minute intervals (mL/5 minutes) were correlated with characteristics of ACWs (percent occlusion, amplitude, and width) described below.
Student's t-test and correlations were assessed using GraphPad Prism version 4.00 for Windows statistical package (GraphPad Software, San Diego, CA, USA; www.graphpad.com).
Propagating ACWs were defined as: (condition i) ACWs that propagated over a distance d > 1.5 cm and (condition ii) ACWs that had a linear least squares regression trajectory R2 > 0.8 (Fig. 2a). Condition i was based on definitions used for analysis of antral pressure waves detectable by intraluminal manometry (18–20). Condition ii was based on strength criteria used in statistics, where goodness-of-fit R2 is considered strong when > 0.8 (21).
The periodicity of propagating ACWs was calculated as the time difference between consecutive contractions that fulfill criteria above during each motility scan period (2.78 minutes). The slope of least squares regression trajectory denoted the speed of each ACW (Fig. 2a). Mean periodicity and speed were computed for every volunteer at each postprandial time point. Analysis of variance (ANOVA) with time as a factor was used to assess postprandial changes (GraphPad Prism version 4.00 for Windows, GraphPad Software).
Mean percent occlusion ([1 – occlusion “diameter”/antral “diameter”] × 100), amplitude, and width of ACWs were determined for every volunteer, at each postprandial time point and at four sections of XCW: 1) XCW1, 0–1 cm; 2) XCW2, >1–2 cm; 3) XCW3, >2–3 cm; and 4) XCW4, >3–4 cm. The dependency of geometric characteristics of ACWs on XCW and postprandial time was assessed with a linear mixed-effects model using a data analysis package R with a non-linear mixed effect model library (R, lib. lme, Vers 2.0.1, © 2004) with a reference point at t0 and XCW1.
Modeled postprandial TGV and MV are shown in Fig. 3 with key parameters detailed in Table 1. Ingestion of the test meal resulted in greater initial postprandial TGV than MV (ΔV: Vpreingestion → V0 and V0). The dynamics of subsequent increase to maximal volume were comparable (ΔV: V0 → Vmax and κ), but the time required for TGV to reach maximal volume (Δt: V0 → Vmax) was significantly longer than for the meal. Greater V0 and delayed rise to Vmax translated into longer t50 and tempt for TGV than for MV. The mean emptying rate was 24 ± 3 mL/5 minutes (approximate equivalent of 2 kcal/minute).
|Total gastric volume (TGV)||Meal volume (MV)||P value|
|ΔV: Vpre-ingestion→V0||738 ± 38||500 ± 13||0.0009*|
|V0 (mL)||890 ± 45||528 ± 13||0.0002*|
|Vmax (mL)||941 ± 46||564 ± 21||0.0001*|
|κ||1.4 ± 0.1||1.4 ± 0.1||0.67|
|ΔV: V0→Vmax (mL)||51 ± 21||36 ± 15||0.25|
|Δt: V0→Vmax (minutes)||14 ± 4||8 ± 3||0.02*|
|t50 (minutes)||119 ± 12||71 ± 6||0.0005*|
|tempt (minute−1)||60 ± 6||35 ± 3||0.0006*|
Of 900 ACWs detected over a total of ∼349 minutes, 82% propagated over d > 1.5 cm (Fig. 2b), 88% had a linear least squares regression trajectory of R2 > 0.8 (Fig. 2c), and 77% satisfied both criteria for propagating ACWs.
There was a decrease in the periodicity of consecutive propagating ACWs from 40 ± 2 seconds at t0, to 23 ± 2 seconds at t35 (P = 0.0004; Fig. 4a; top), reflected by the histogram of periodicities being skewed to the right (Fig. 4a; bottom). This change was not complemented by a change in propagation speed of ACWs (P = 0.33; Fig. 4b; top), despite the broad range of speeds recorded during the analysis (Fig. 4b bottom). The overall mean speed was 0.27 ± 0.01 cm/second. On average, ACWs terminated 1.17 ± 0.02 cm before reaching the pylorus; 43% and 50% of analyzed ACWs stopped at XCW1 and XCW2, respectively.
ACWs were largely nonlumen occlusive (Fig. 5a; right). The modeled percent of occlusion was greatest closer to the pylorus (XCW1); at proximal XCW, percentage of occlusion increased during emptying, resulting in the greatest divergence of modeled results at t0, from 58.1 ± 5.9% at XCW1 by 8.4 ± 1.5%/cm (Fig. 5a; left). Statistically, the percent of occlusion depended on both the distance from the pylorus (XCW) and the postprandial time (P = 0.04), but the distance from the pylorus (XCW) was the main modulating factor (P < 0.001).
The amplitude of ACW indentations was 0.70 ± 0.08 cm, at the reference point of t0 and XCW1 (Fig. 5b; left) with constant range of values across distances from pylorus (Fig. 5b; right). The amplitude did not alter over XCW and the entire postprandial time (P = 0.65).
The width of ACWs was greater that their amplitude (P < 0.0001; 0.97 ± 0.06 cm at t0 and XCW1). The width of ACWs decreased on approach to the pylorus (P = 0.003) by approximately 6 ± 2%/cm (Fig. 5c; left) with a broadening spread of values at XCW3 and XCW4 (Fig. 5c; right), but not over postprandial time.
Although the association between the rate of emptying (mL/5 minutes) and percent occlusion was significant (P = 0.02), its magnitude was negligible (R2 = 0.04). The magnitude of association between the rate of emptying and amplitude or width of ACWs was also minor (R2 < 0.001 or R2 = 0.001, respectively), but in contrast to percent occlusion, it was insignificant (P = 0.83 or P = 0.65, respectively).
In this study, we utilized the current advances in MR imaging and analysis technology for comprehensive assessment of postprandial gastric motor function over a prolonged period. Fast acquisition of images with high spatiotemporal resolution allowed virtually simultaneous assessment of postprandial gastric volume responses and distal ACWs. For the first time, using purpose-written software, characteristics such as the propagation and geometry of ACWs were quantified in detail. Following ingestion of a liquid meal (10% glucose), the periodicity of ACWs was initially high, subsequently reaching a constant periodicity approximating pacesetter frequency (∼20 seconds = 3 ACWs/minute) without significant alteration in the propagation speed. ACWs were largely nonlumen occlusive (percent occlusion < 70%). The increasing occlusion of ACWs on approach to the pylorus and over postprandial time may be attributed to narrowing of the antrum closer to the pylorus, rather than amplification of their amplitude. None of the characteristics of ACWs correlated with the rate of gastric emptying, while the gastric volume responses and patterns of emptying paralleled each other, indicating that ACWs are not essential for liquid emptying.
The “gold standards” for assessing motility of the stomach are gastric barostat and intraluminal manometry. These techniques are limited to either the proximal (barostat measures of compliance and tonicity) or distal stomach (manometry measures of antral contractility) and are incapable of simultaneous estimation of gastric emptying. Barostat is invasive, uncomfortable, and difficult to use in the presence of a meal, hence, it not only affects normal mechanosensory physiology (22, 23), but repeated measurements are poorly tolerated. Manometry is also invasive and has reduced sensitivity for detection of nonlumen occlusive contractions in the gastric antrum (3, 5, 6, 24). Imaging methods provide a noninvasive alternative. Scintigraphy estimates patterns of gastric emptying and antral motility (24); single photon emission computed tomography (SPECT) has been validated against the barostat for measuring volume responses of the stomach wall (25–27); the rate of emptying can be estimated based on gastric volume or antral cross-section measurement done by ultrasound (US) (28–30) which is also used to evaluate antral motility (9, 11, 31, 32). MRI has the advantage of a large FOV, allowing instantaneous and concurrent assessment of gastric volume responses and emptying, as well as related antral motility with good spatial resolution. Similarly to US, which has comparable image quality, MRI is still limited to a two-dimensional acquisition approach to preserve the required temporal resolution of approximately one second per measurement. However, with the advent of multiple coil arrays and the ongoing optimization of parallel imaging techniques, faster image acquisition and larger volume coverage without significant loss in image quality will soon be feasible on most MRI systems. Moreover, the recently introduced k-t BLAST or k-t SENSE dynamic acquisition schemes promise the possibility of three-dimensional dynamic imaging of the abdominal region, adding to the advantages of using MRI for the study of gastrointestinal physiology in humans (33).
The periodicity and propagation speed of ACWs have previously been assessed using MR images (5, 6, 13, 34–37). Likewise, percent occlusion was estimated at a single spatial point (37) or along a visible gastric wall (5, 36). In contrast to previous publications, first, we have extended the quantification of ACWs to their geometry characteristics such as amplitude and width, and second, we have measured changes in geometry (percent occlusion, amplitude, and width) in relation to both postprandial time and the position of ACWs along the wall of the distal antrum. However, the detailed assessment was limited to the terminal 4 cm of the gastric antrum. Whole-body MRI systems restrict imaging of human physiology to reclined positions. Although supine and left decubitus positions delay gastric emptying (38–41), gastric volumetric responses and volumetric emptying in right decubitus are comparable to a seated position (14, 42). Hence, the right decubitus position, as used here, is to a large extent representative of the typical postprandial habitus. The tradeoff is a pronounced curvature between the proximal and distal stomach compared to the seated position, which further hinders capturing a cross-section including the fundus, incisura, and pyloric sphincter for complete quantification of motility. We have optimized image acquisition to visualize the pylorus, as the least mobile gastrointestinal structure (43). Hence, we could localize distal ACWs during propagation and their point of termination with reference to the pylorus, but were consequently unable to see their origin.
Previous combined findings of semi- and quantitative analysis of MRI and scintigraphy after intraduodenal nutrient infusion (2.1 kcal/minute) and ingestion of liquid or even solids were that ACWs occurred at mean periodicity and speed approximating 20 seconds and 0.3 cm/second, respectively, with occlusion magnitude remaining below 70%, which was inversely related to the distance of an ACW from the pylorus and antral filling (5, 6, 14, 24, 36, 37). However, none of the studies presented all the above features at once and in detail, including dynamics over extended postprandial time. With our current methodology, we were able to address these issues, broaden the scope of analyzable characteristics of distal ACWs, and relate them to gastric emptying.
The initial decrease in periodicity of ACWs suggests a regulation phase in the emptying process and has also been observed in other MRI studies using liquids and semisolid meals (13, 37, 44). This finding coincides with the increase in meal and stomach volume. The relationship between these two phenomena and the effect of different initial emptying patterns or gastric secretion were not examined and remain speculative. Further specifically designed studies are needed to examine this interrelation. However, the majority of the postprandial time, the propagation periodicity and speed of ACWs remained constant, while the geometric characteristics were unrelated to the volume of the 10% glucose liquid emptying during five-minute intervals. This contrasts with the initial conclusions of animal studies, in which an electromagnetic flowmeter was used to measure volumes of gastric outflow. After intragastric infusion of saline, events of outflow usually coincided with antral contractions (1, 8, 45). This has often been taken as an association between phasic motility of the distal stomach and gastric emptying, as well as an explanation of the pulsatile nature of gastric outflow. However, outflow and antral contractions were not necessarily initiated together (8, 46), although antral contractions augmented the volume of each saline pulse (8, 45–47). In humans, most US studies consistently provide results indicative of varied association between antral contractions and transpyloric flow. Gastric outflow occurs both prior to or after occlusive antral contractions, as well as during their absence or lack of termination at the pylorus, with episodes of reflux from the duodenum appearing during times of antral activity (31, 32, 48–50). In fact, the fluctuations across the pylorus, of gastric outflow and reflux, are greater than the frequency of antral contractions (11). Hence, our findings from statistical analysis of MRI data support the above indications that distal ACWs are not central to the emptying of liquids, although they may still play a role in a complex interaction between gastric and duodenal motility to effect emptying—a conclusion also reached with statistical analysis of high-resolution manometry data of the antropyloric region (6). Moreover, our volumetric data showed parallels in the dynamics of TGV and MV, indicating involvement of other motility mechanisms (i.e., tonic motility and/or pyloric resistance). Concurrent intraluminal and pyloric pressure readings in further studies may assist in differentiating whether the emptying process is controlled by tonic pressurization (i.e., stomach drives emptying) or by pyloric modulation (i.e., stomach follows meal).
In conclusion, distal antral contraction waves are not imperative for gastric emptying of liquids. The main control is provided by gastric pressurization and/or pyloric resistance. For 10% glucose, distal ACWs are exclusively nonoccluding with initially long periodicity, but have constant speed and amplitude along with decreasing width when propagating to the pylorus. The constant amplitude indicates that observed changes in percent occlusion are affected by morphology of antral diameter. Improvements in MRI allow detailed quantitative computer analysis of propagation and geometry characteristics of ACWs with relation to volumetric gastric responses and emptying in healthy patients. The study established a reference for future studies analyzing altered gastric motility under pharmacological modulation, with either prokinetic medications or in relation to formulations affecting gastric relaxation, or in patients with disturbed gastric motility, such as subgroups of patients with functional dyspepsia or gastroparesis. Further studies establishing the proposed technology and additional automation of image analysis will be necessary to establish the method in the diagnostic setting.
We thank Mrs. Bernadette Stutz, Dr. Heiko Fruehauf, Dr. Oliver Goetze, and Mr. Reto Treier for their clinical and technical assistance.