[show abstract][hide abstract] ABSTRACT: A key discovery in gastrointestinal motility has been the central role played by interstitial cells of Cajal (ICC) in generating electrical slow waves that coordinate contractions. Multielectrode mapping and multiscale modeling are two emerging interdisciplinary strategies now showing translational promise to investigate ICC function, electrophysiology, and contractions in the human gut.
[show abstract][hide abstract] ABSTRACT: The use of cutaneous recordings to non-invasively characterize gastric slow waves has had limited clinical acceptance, primarily due to the uncertainty in relating the recorded signal to the underlying gastric slow waves. In this study we aim to distinguish and quantitatively reconstruct different slow wave patterns using an inverse algorithm. Slow wave patterns corresponding to normal, retrograde and uncoupled activity at different frequencies were imposed on a stomach surface model. Gaussian noise (10% peak-to-peak) was added to cutaneous potentials and the Greensite-Tikhonov inverse method was used to reconstruct the potentials on the stomach. The effectiveness of the number or location of electrodes on the accuracy of the inverse solutions was investigated using four different electrode configurations. Results showed the reconstructed solutions were able to reliably distinguish the different slow wave patterns and waves with lower frequency were better correlated to the known solution than those with higher. The use of up to 228 electrodes improved the accuracy of the inverse solutions. However, the use of 120 electrodes concentrated around the stomach was able to achieve similar results. The most efficient electrode configuration for our model involved 120 electrodes with an inter-electrode distance of 32 mm.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Slow-waves modulate the pattern of small intestine contractions. However, the large-scale spatial organization of intestinal slow-wave pacesetting remains uncertain because most previous studies have had limited resolution. This study applied high-resolution (HR) mapping to evaluate intestinal pacesetting mechanisms and propagation patterns in vivo. METHODS: HR serosal mapping was performed in anesthetized pigs using flexible arrays (256 electrodes; 32 × 8; 4 mm spacing), applied along the jejunum. Slow-wave propagation patterns, frequencies, and velocities were calculated. Slow-wave initiation sources were identified and analyzed by animation and isochronal activation mapping. KEY RESULTS: Analysis comprised 32 recordings from nine pigs (mean duration 5.1 ± 3.9 min). Slow-wave propagation was analyzed, and a total of 26 sources of slow-wave initiation were observed and classified as focal pacemakers (31%), sites of functional re-entry (23%) and circumferential re-entry (35%), or indeterminate sources (11%). The mean frequencies of circumferential and functional re-entry were similar (17.0 ± 0.3 vs 17.2 ± 0.4 cycle min(-1) ; P = 0.5), and greater than that of focal pacemakers (12.7 ± 0.8 cycle min(-1) ; P < 0.001). Velocity was anisotropic (12.9 ± 0.7 mm s(-1) circumferential vs 9.0 ± 0.7 mm s(-1) longitudinal; P < 0.05), contributing to the onset and maintenance of re-entry. CONCLUSIONS & INFERENCES: This study has shown multiple patterns of slow-wave initiation in the jejunum of anesthetized pigs. These results constitute the first description and analysis of circumferential re-entry in the gastrointestinal tract and functional re-entry in the in vivo small intestine. Re-entry can control the direction, pattern, and frequency of slow-wave propagation, and its occurrence and functional significance merit further investigation.
Neurogastroenterology and Motility 03/2013; · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background Extracellular recordings are used to define gastric slow wave propagation. Signal filtering is a key step in the analysis and interpretation of extracellular slow wave data; however, there is controversy and uncertainty regarding the appropriate filtering settings. This study investigated the effect of various standard filters on the morphology and measurement of extracellular gastric slow waves. Methods Experimental extracellular gastric slow waves were recorded from the serosal surface of the stomach from pigs and humans. Four digital filters: finite impulse response filter (0.05-1 Hz); Savitzky-Golay filter (0-1.98 Hz); Bessel filter (2-100 Hz); and Butterworth filter (5-100 Hz); were applied on extracellular gastric slow wave signals to compare the changes temporally (morphology of the signal) and spectrally (signals in the frequency domain). Key Results The extracellular slow wave activity is represented in the frequency domain by a dominant frequency and its associated harmonics in diminishing power. Optimal filters apply cutoff frequencies consistent with the dominant slow wave frequency (3-5 cpm) and main harmonics (up to ∼2 Hz). Applying filters with cutoff frequencies above or below the dominant and harmonic frequencies was found to distort or eliminate slow wave signal content. Conclusions & Inferences Investigators must be cognizant of these optimal filtering practices when detecting, analyzing, and interpreting extracellular slow wave recordings. The use of frequency domain analysis is important for identifying the dominant and harmonics of the signal of interest. Capturing the dominant frequency and major harmonics of slow wave is crucial for accurate representation of slow wave activity in the time domain. Standardized filter settings should be determined.
Neurogastroenterology and Motility 09/2012; · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: One approach for non-invasively characterizing gastric electrical activity, commonly used in the field of electrocardiography, involves solving an inverse problem whereby electrical potentials on the stomach surface are directly reconstructed from dense potential measurements on the skin surface. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on stomach and skin surfaces arising from normal gastric electrical activity. The effectiveness of the Greensite-Tikhonov or the Tikhonov inverse methods were compared under the presence of 10% Gaussian noise with either 84 or 204 body surface electrodes. The stability and accuracy of the Greensite-Tikhonov method were further investigated by introducing varying levels of Gaussian signal noise or by increasing or decreasing the size of the stomach by 10%. Results showed that the reconstructed solutions were able to represent the presence of propagating multiple wave fronts and the Greensite-Tikhonov method with 204 electrodes performed best (correlation coefficients of activation time: 90%; pacemaker localization error: 3 cm). The Greensite-Tikhonov method was stable with Gaussian noise levels up to 20% and 10% change in stomach size. The use of 204 rather than 84 body surface electrodes improved the performance; however, for all investigated cases, the Greensite-Tikhonov method outperformed the Tikhonov method.
Physics in Medicine and Biology 07/2012; 57(16):5205-19. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastric slow waves propagate aborally as rings of excitation. Circumferential propagation does not normally occur, except at the pacemaker region. We hypothesized that (i) the unexplained high-velocity, high-amplitude activity associated with the pacemaker region is a consequence of circumferential propagation; (ii) rapid, high-amplitude circumferential propagation emerges during gastric dysrhythmias; (iii) the driving network conductance might switch between interstitial cells of Cajal myenteric plexus (ICC-MP) and circular interstitial cells of Cajal intramuscular (ICC-IM) during circumferential propagation; and (iv) extracellular amplitudes and velocities are correlated.
An experimental-theoretical study was performed. High-resolution gastric mapping was performed in pigs during normal activation, pacing, and dysrhythmia. Activation profiles, velocities, and amplitudes were quantified. ICC pathways were theoretically evaluated in a bidomain model. Extracellular potentials were modeled as a function of membrane potentials.
High-velocity, high-amplitude activation was only recorded in the pacemaker region when circumferential conduction occurred. Circumferential propagation accompanied dysrhythmia in 8/8 experiments was faster than longitudinal propagation (8.9 vs 6.9 mm s(-1) ; P = 0.004) and of higher amplitude (739 vs 528 μV; P = 0.007). Simulations predicted that ICC-MP could be the driving network during longitudinal propagation, whereas during ectopic pacemaking, ICC-IM could outpace and activate ICC-MP in the circumferential axis. Experimental and modeling data demonstrated a linear relationship between velocities and amplitudes (P < 0.001).
The high-velocity and high-amplitude profile of the normal pacemaker region is due to localized circumferential propagation. Rapid circumferential propagation also emerges during a range of gastric dysrhythmias, elevating extracellular amplitudes and organizing transverse wavefronts. One possible explanation for these findings is bidirectional coupling between ICC-MP and circular ICC-IM networks.
Neurogastroenterology and Motility 07/2012; 24(7):e299-312. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Electrogastrograms (EGG) and magnetogastrograms (MGG) provide two complementary methods for non-invasively recording electric or magnetic fields resulting from gastric electrical slow wave activity. It is known that EGG signals are relatively weak and difficult to reliably record while magnetic fields are, in theory, less attenuated by the low-conductivity fat layers present in the body. In this paper, we quantified the effects of fat thickness and conductivity values on resultant magnetic and electric fields using anatomically realistic torso models and trains of dipole sources reflecting recent experimental results. The results showed that when the fat conductivity was increased, there was minimal change in both potential and magnetic fields. However, when the fat conductivity was reduced, the magnetic fields were largely unchanged, but electric potentials had a significant change in patterns and amplitudes. When the thickness of the fat layer was increased by 30 mm, the amplitude of the magnetic fields decreased 10% more than potentials but magnetic field patterns were changed about four times less than potentials. The ability to localize the underlying sources from the magnetic fields using a surface current density measure was altered by less than 2 mm when the fat layer was increased by 30 mm. In summary, results confirm that MGG provides a favorable method over EGG when there are uncertain levels of fat thickness or conductivity.
[show abstract][hide abstract] ABSTRACT: The significance of gastric dysrhythmias remains uncertain. Progress requires a better understanding of dysrhythmic behaviors, including the slow wave patterns that accompany or promote them. The aim of this study was to use high-resolution spatiotemporal mapping to characterize and quantify the initiation and conduction of porcine gastric dysrhythmias.
High-resolution mapping was performed on healthy fasted weaner pigs under general anesthesia. Recordings were made from the gastric serosa using flexible arrays (160-192 electrodes; 7.6mm spacing). Dysrhythmias were observed to occur in 14 of 97 individual recordings (from 8 of 16 pigs), and these events were characterized, quantified and classified using isochronal mapping and animation.
All observed dysrhythmias originated in the corpus and fundus. The range of dysrhythmias included incomplete conduction block (n=3 pigs; 3.9±0.5cpm; normal range: 3.2±0.2cpm) complete conduction block (n=3; 3.7±0.4cpm), escape rhythm (n=5; 2.0±0.3cpm), competing ectopic pacemakers (n=5, 3.7±0.1cpm) and functional re-entry (n=3, 4.1±0.4cpm). Incomplete conduction block was observed to self-perpetuate due to retrograde propagation of wave fragments. Functional re-entry occurred in the corpus around a line of unidirectional block. 'Double potentials' were observed in electrograms at sites of re-entry and at wave collisions.
Intraoperative multi-electrode mapping of fasted weaner healthy pigs detected dysrhythmias in 15% of recordings (from 50% of animals), including patterns not previously reported. The techniques and findings described here offer new opportunities to understand the nature of human gastric dysrhythmias.
Neurogastroenterology and Motility 06/2011; 23(9):e345-55. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Stomach contractions are initiated and coordinated by electrical events termed slow waves, and slow wave abnormalities contribute to gastric motility disorders. Recently, flexible printed circuit board (PCB) multi-electrode arrays were introduced, facilitating high-resolution mapping of slow wave activity in humans. However PCBs with gold contacts have shown a moderately inferior signal quality to previous custom-built silver-wire platforms, potentially limiting analyses. This study determined if using silver instead of gold contacts improved flexible PCB performance. In a salt-bath test, modestly higher stimulus amplitudes were recorded from silver PCBs (mean 312, s.d. 89 µV) than those from gold (mean 281, s.d. 85 µV) (p < 0.001); however, the signal-to-noise ratio (SNR) was similar (p = 0.26). In eight in vivo experimental studies, involving gastric serosal recordings from five pigs, no silver versus gold differences were found in terms of slow wave amplitudes (mean 677 versus 682 µV; p = 0.91), SNR (mean 8.8 versus 8.8 dB; p = 0.94) or baseline drift (NRMS; mean 12.0 versus 12.1; p = 0.97). Under the prescribed conditions, flexible PCBs with silver or gold contacts provide comparable results in vivo, and contact material difference does not explain the performance difference between current-generation slow wave mapping platforms. Alternative explanations for this difference and the implications for electrode design are discussed.
[show abstract][hide abstract] ABSTRACT: The pig is a popular model for gastric electrophysiology studies. However, its normal baseline gastric activity has not been well characterized. High-resolution (HR) mapping has recently enabled an accurate description of human and canine gastric slow wave activity, and was employed here to define porcine gastric slow wave activity.
Fasted pigs underwent HR mapping following anesthesia and laparotomy. Flexible printed-circuit-board arrays were used (160-192 electrodes; spacing 7.62 mm). Anterior and posterior surfaces were mapped simultaneously. Activation times, velocities, amplitudes and frequencies were calculated, and regional differences evaluated.
Mean slow wave frequency was 3.22 ± 0.23 cpm. Slow waves propagated isotropically from the pacemaker site (greater curvature, mid-fundus). Pacemaker activity was of higher velocity (13.3 ± 1.0 mm s(-1)) and greater amplitude (1.3 ± 0.2 mV) than distal fundal activity (9.0 ± 0.6 mm s(-1), 0.9 ± 0.1 mV; P < 0.05). Velocities and amplitudes were similar in the distal fundus, proximal corpus (8.4 ± 0.8 mm s(-1), 1.0 ± 0.1 mV), distal corpus (8.3 ± 0.8 mm s(-1), 0.9 ± 0.2 mV) and antrum (6.8 ± 0.6 mm s(-1), 1.1 ± 0.2 mV). Activity was continuous across the anterior and posterior gastric surfaces.
This study has quantified normal porcine gastric slow wave activity at HR during anesthesia and laparotomy. The pacemaker region was associated with high-amplitude, high-velocity slow wave activity compared to the activity in the rest of the stomach. The increase in distal antral slow wave velocity and amplitude previously described in canines and humans is not observed in the pig. Investigators should be aware of these inter-species differences.
Neurogastroenterology and Motility 10/2010; 22(10):e292-300. · 2.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to obtain detailed information regarding the three-dimensional structure of the gastro-oesophageal region, and, in particular, the fiber orientation of the different muscle layers of the junction. This was achieved by a study of an en bloc resection of the gastro-oesophageal junction (GOJ) harvested from a human cadaver. The excised tissue block was suspended in a cage to preserve anatomical relationships, fixed in formalin and embedded in wax. The tissue block was then processed by a custom-built extended-volume imaging system to obtain the microstructural information using a digital camera which acquires images at a resolution of 8.2 microm/pixel. The top surface of the tissue block was sequentially stained and imaged. At each step, the imaged surface was milled off at a depth of 50 microm. The processing of the tissue block resulted in 650 images covering a length of 32.25 mm of the GOJ. Structures, including the different muscle and fascial layers, were then traced out from the cross-sectional images using color thresholding. The traced regions were then aligned and assembled to provide a three-dimensional representation of the GOJ. The result is the detailed three-dimensional microstructural anatomy of the GOJ represented in a new way. The next stage will be to integrate key physiological events, including peristalsis and relaxation, into this model using mathematical modeling to allow accurate visual tools for training health professionals and patients.
[show abstract][hide abstract] ABSTRACT: Gastric pacing is used to modulate normal or abnormal gastric slow-wave activity for therapeutic purposes. New protocols are required that are optimized for motility outcomes and energy efficiency. A computational tissue model was developed, incorporating smooth muscle and interstitial cell of Cajal layers, to enable predictive simulations of slow-wave entrainment efficacy under different pacing frequencies. Concurrent experimental validation was performed via high-resolution entrainment mapping in a porcine model (bipolar pacing protocol: 2 mA amplitude; 400 ms pulsewidth; 17-s period; midcorpus). Entrained gastric slow-wave activity was found to be anisotropic (circular direction: 8.51 mmmiddots<sup>-1</sup>; longitudinal: 4.58 mmmiddots <sup>-1</sup>), and the simulation velocities were specified accordingly. Simulated and experimental slow-wave activities demonstrated satisfactory agreement, showing similar propagation patterns and frequencies (3.5-3.6 cycles per minute), and comparable zones of entrainment (ZOEs; 64 cm <sup>2</sup>). The area of ZOE achieved was found to depend on the phase interactions between the native and entrained activities. This model allows the predictions of phase interactions between native and entrained activities, and will be useful for determining optimal frequencies for gastric pacing, including multichannel pacing studies. The model provides a framework for the development of more sophisticated predictive gastric pacing simulations in future.
IEEE Transactions on Biomedical Engineering 01/2010; · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gastric electrical stimulation (GES) involves the delivery of electrical impulses to the stomach for therapeutic purposes. New GES protocols are needed that are optimized for improved motility outcomes and energy efficiency. In this study, a biophysically based smooth muscle cell (SMC) model was modified on the basis of experimental data and employed in conjunction with experimental studies to define the effects of a large range of GES protocols on individual SMCs. For the validation studies, rat gastric SMCs were isolated and subjected to patch-clamp analysis during stimulation. Experimental results were in satisfactory agreement with simulation results. The results define the effects of a wide range of GES parameters (pulse width, amplitude, and pulse-train frequency) on isolated SMCs. The minimum pulse width required to invoke a supramechanical threshold response from SMCs (defined at -30 mV) was 65 ms (at 250-pA amplitude). The minimum amplitude required to invoke this threshold was 75 pA (at 1,000-ms pulse width). The amplitude of the invoked response beyond this threshold was proportional to the stimulation amplitude. A high-frequency train of stimuli (40 Hz; 10 ms, 150 pA) could invoke and maintain the SMC plateau phase while requiring 60% less power and accruing approximately 30% less intracellular Ca(2+) concentration during the plateau phase than a comparable single-pulse protocol could in a demonstrated example. Validated computational simulations are an effective strategy for efficiently identifying effective minimum-energy GES protocols, and pulse-train protocols may also help to reduce the power consumption of future GES devices.
[show abstract][hide abstract] ABSTRACT: Gastric disorders are often associated with abnormal propagation of gastric electrical activity (GEA). The identification of clinically relevant parameters of GEA using noninvasive measures would therefore be highly beneficial for clinical diagnosis. While magnetogastrograms (MGG) are known to provide a noninvasive representation of GEA, standard methods for their analysis are limited. It has previously been shown in simplistic conditions that the surface current density (SCD) calculated from multichannel MGG measurements provides an estimate of the gastric source location and propagation velocity. We examine the accuracy of this technique using more realistic source models and an anatomically realistic volume conductor model. The results showed that the SCD method was able to resolve the GEA parameters more reliably when the dipole source was located within 100 mm of the sensor. Therefore, the theoretical accuracy of SCD method would be relatively diminished for patients with a larger body habitus, and particularly in those patients with significant truncal obesity. However, many patients with gastric motility disorders are relatively thin due to food intolerance, meaning that the majority of the population of gastric motility patients could benefit from the methods developed here. Large errors resulted when the source was located deep within the body due to the distorting effects of the secondary sources on the magnetic fields. Larger errors also resulted when the dipole was oriented normal to the sensor plane. This was believed to be due to the relatively small contribution of the dipole source when compared to the field produced by the volume conductor. The use of three orthogonal magnetic field components rather than just one component to calculate the SCD yielded marginally more accurate results when using a realistic dipole source. However, this slight increase in accuracy may not warrant the use of more complex vector channels in future superconducting quantum interference device designs. When multiple slow waves were present in the stomach, the SCD map contained only one maximum point corresponding to the more dominant source located in the distal stomach. Parameters corresponding to the slow wave in the proximal stomach were obtained once the dominant slow terminated at the antrum. Additional validation studies are warranted to address the utility of the SCD method to resolve parameters related to gastric slow waves in a clinical setting.
Annals of biomedical engineering 09/2009; 38(1):177-86. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The magnetogastrogram (MGG) records clinically relevant parameters of the electrical slow wave of the stomach noninvasively. Besides slow wave frequency, gastric slow wave propagation velocity is a potentially useful clinical indicator of the state of health of gastric tissue, but it is a difficult parameter to determine from noninvasive bioelectric or biomagnetic measurements. We present a method for computing the surface current density from multichannel MGG recordings that allows computation of the propagation velocity of the gastric slow wave. A moving dipole source model with hypothetical as well as realistic biomagnetometer parameters demonstrates that while a relatively sparse array of magnetometer sensors is sufficient to compute a single average propagation velocity, more detailed information about spatial variations in propagation velocity requires higher density magnetometer arrays. Finally, the method is validated with simultaneous MGG and serosal electromyography measurements in a porcine subject.
IEEE Transactions on Biomedical Engineering 09/2009; · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to combine the anatomy and physiology of the human gastroesophageal junction (the junction between the esophagus and the stomach) into a unified computer model. A three-dimensional (3D) computer model of the gastroesophageal junction was created using cross-sectional images from a human cadaver. The governing equations of finite deformation elasticity were incorporated into the 3D model. The model was used to predict the intraluminal pressure values (pressure inside the junction) due to the muscle contraction of the gastroesophageal junction and the effects of the surrounding structures. The intraluminal pressure results obtained from the 3D model were consistent with experimental values available in the literature. The model was also used to examine the independent roles of each muscle layer (circular and longitudinal) of the gastroesophageal junction by contracting them separately. Results showed that the intraluminal pressure values predicted by the model were primarily due to the contraction of the circular muscle layer. If the circular muscle layer was quiescent, the contraction of the longitudinal muscle layer resulted in an expansion of the junction. In conclusion, the model provided reliable predictions of the intraluminal pressure values during the contraction of a normal gastroesophageal junction. The model also provided a framework to examine the role of each muscle layer during the contraction of the gastroesophageal junction.
Journal of biomechanics 06/2009; 42(11):1604-9. · 2.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: High-resolution, multi-electrode mapping is providing valuable new insights into the origin, propagation, and abnormalities of gastrointestinal (GI) slow wave activity. Construction of high-resolution mapping arrays has previously been a costly and time-consuming endeavor, and existing arrays are not well suited for human research as they cannot be reliably and repeatedly sterilized. The design and fabrication of a new flexible printed circuit board (PCB) multi-electrode array that is suitable for GI mapping is presented, together with its in vivo validation in a porcine model. A modified methodology for characterizing slow waves and forming spatiotemporal activation maps showing slow waves propagation is also demonstrated. The validation study found that flexible PCB electrode arrays are able to reliably record gastric slow wave activity with signal quality near that achieved by traditional epoxy resin-embedded silver electrode arrays. Flexible PCB electrode arrays provide a clinically viable alternative to previously published devices for the high-resolution mapping of GI slow wave activity. PCBs may be mass-produced at low cost, and are easily sterilized and potentially disposable, making them ideally suited to intra-operative human use.
Annals of biomedical engineering 03/2009; 37(4):839-46. · 2.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Many functional pathologies of the small intestine are difficult to diagnose clinically without an invasive surgical intervention. Often such conditions are associated with a disruption of the normal electrical activity occurring within the musculature of the small intestine. The far field electrical signals on the torso surface arising from the electrical activity within the small intestine cannot be reliably measured. However, it has been shown that abnormal electrical activity in the small intestine can be distinguished by recording the magnetic fields of intestinal origin immediately outside the torso surface. We have developed an anatomically-based computational model to simulate slow wave propagation in the small intestine, the resulting cutaneous electrical field and the magnetic field outside the torso. Using both a one-dimensional and a three-dimensional model of the duodenum we investigate the degree of detail that is required to realistically simulate this far field activity. Our results indicate that some of the qualitative behavior in the far field activity can be replicated using a one-dimensional model, although there are clear situations where the greater level modeling detail is required.
Annals of Biomedical Engineering 09/2006; 34(8):1322-31. · 2.58 Impact Factor