Real-time gastric motility monitoring using transcutaneous intraluminal impedance measurements (TIIM).

The stomach plays a critical role in digestion, processing ingested food mechanically and breaking it up into particles, which can be effectively and efficiently processed by the intestines. When the motility of the stomach is compromised, digestion is adversely affected. This can lead to a variety of disorders. Current diagnostic techniques for gastric motility disorders are seriously lacking, and are based more on eliminating other possibilities rather than on specific tests. Presently, gastric motility can be assessed by monitoring gastric emptying, food transit, intragastric pressures, etc. The associated tests are usually stationary and of relatively short duration. The present study proposes a new method of measuring gastric motility, utilizing the attenuation of an oscillator-induced electrical signal across the gastric tissue, which is modulated by gastric contractions. The induced high-frequency oscillator signal is generated within the stomach, and is picked up transluminally by cutaneous electrodes positioned on the abdominal area connected to a custom-designed data acquisition instrument. The proposed method was implemented in two different designs: first a transoral catheter was modified to emit the signal inside the stomach; and second, a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs (25.50 kg and 25.75 kg). Gastric contractions were registered and quantitatively compared to recordings from force transducers sutured onto the serosa of the stomach. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers showing statistically significant (p < 0.05) Pearson correlation coefficients (0.65 ± 0.08 for the catheter-based design and 0.77 ± 0.03 for the gastric retentive pill design). These results show that transcutaneous intraluminal impedance measurement has the potential with further research and development to become a useful diagnostic technique.

Intraluminal ultrasonic probe for volumetric monitoring of liquid gastroesophageal reflux.

Methods for volumetric monitoring of liquid gastroesophageal reflux (GER) are still lacking. The aim of this study was to develop an automated intraluminal measurement technique which allows ambulatory volumetric quantification of liquid GER utilizing a minimum-cost intraluminal ultrasonic probe. This probe consists of two 2 MHz ultrasonic crystals longitudinally assembled along a multi-channel intraluminal impedance (MII) catheter. The proposed probe was initially tested with tubular phantoms of different diameters. Measurements of the cross-sectional areas of the phantoms showed high correlation with the actual areas (R(2) = 0.99). Subsequently, two in-vivo human tests were performed. For each human test the catheter assembly was inserted transnasally and the ultrasonic probe was placed in the area of the lower esophageal sphincter. Multiple liquid swallows of different volumes were invoked using electrolyte drinks. Sectional luminal volume (SLV) in the esophagus between the two ultrasonic crystals was obtained. Results of the swallows demonstrated that measured SLVs correlated with the actual swallowed liquid volume. The ultrasonic probe was combined with a MII catheter to discriminate between antegrade and retrograde bolus transit. Increases of SLVs during liquid GER episodes could be utilized to evaluate GER volume in the vicinity of the ultrasonic probe.

Design, implementation and testing of an implantable impedance-based feedback-controlled neural gastric stimulator.

Functional neural gastrointestinal electrical stimulation (NGES) is a methodology of gastric electrical stimulation that can be applied as a possible treatment for disorders such as obesity and gastroparesis. NGES is capable of generating strong lumen-occluding local contractions that can produce retrograde or antegrade movement of gastric content. A feedback-controlled implantable NGES system has been designed, implemented and tested both in laboratory conditions and in an acute animal setting. The feedback system, based on gastric tissue impedance change, is aimed at reducing battery energy requirements and managing the phenomenon of gastric tissue accommodation. Acute animal testing was undertaken in four mongrel dogs (2 M, 2 F, weight 25.53 ± 7.3 kg) that underwent subserosal two-channel electrode implantation. Three force transducers sutured serosally along the gastric axis and a wireless signal acquisition system were utilized to record stimulation-generated contractions and tissue impedance variations respectively. Mechanically induced contractions in the stomach were utilized to indirectly generate a tissue impedance change that was detected by the feedback system. Results showed that increasing or decreasing impedance changes were detected by the implantable stimulator and that therapy can be triggered as a result. The implantable feedback system brings NGES one step closer to long term treatment of burdening gastric motility disorders in humans.

Comparative gastric motility study of Enterra ™ Therapy and neural gastric electrical stimulation in an acute canine model.

BACKGROUND: Gastric electrical stimulation (GES) is an avenue for treating gastroparesis and obesity by controlling gastric motility using electrically mediated gastric contractions. Neural gastrointestinal electrical stimulation (NGES) is a GES modality capable of producing strong lumen-occluding local gastric contractions. Conversely, Enterra ™ Therapy, a commercial implantable gastric electrical stimulator, has been utilized to treat symptoms of gastroparesis, but its nominal electrical parameters are not capable of generating lumen-occluding contractions. However, comparative studies between these two stimulation modalities are lacking. METHODS: Strain gauge transducers complemented by endoscopic monitoring have been utilized to register gastric contractions invoked with NGES and Enterra neurostimulators in four acute dogs. Mucosal and serosal electrode implantations, 'nominal' and 'maximum' electrical parameters, and longitudinal and transverse electrode placements have been tested with each neurostimulator type. KEY RESULTS: Strong lumen-occluding, circumferential contractions were induced with a wide variety of NGES parameters utilizing both transverse and longitudinal electrode configurations from the serosal side of the stomach. Similarly, local gastric contractions were observed with the Enterra neurostimulator programmed at its 'maximum' electrical parameters but only when utilizing transverse serosal electrode implantation. Under 'maximum' electrical parameters Enterra was not capable of producing registerable gastric contractions with longitudinally implanted serosal electrodes. Mucosal electrode implantations did not result in GES-invoked gastric contractions in both stimulation modalities. CONCLUSIONS & INFERENCES: Enterra Therapy is capable of producing gastric contractions under 'maximum' parameters and transverse electrode configuration. Neural gastrointestinal electrical stimulation produces stronger, lumen-occluding contractions under a wider range of electrode configurations and parameters.

Implantable functional gastrointestinal neurostimulation.

Neural Gastrointestinal Electrical Stimulation (NGES) is a new microprocessor-based method for invoking gastric or colonic contractions by generating multi-channel, high energy, high frequency waveforms. It has been shown that when applied to the lower stomach, NGES offers the possibility for enhancing propulsive peristalsis for the treatment of gastric motor dysfunctions, or for producing retrograde peristalsis for the treatment of obesity. When applied to the colon, NGES can be utilized either for propulsive control in severe constipation or for invoked retrograde contractility. This paper briefly discusses the implementation of an implantable neurostimulator and summarizes the performance of the NGES technique in acute tests on experimental animals and humans, and in chronic tests on animals. These experimental tests indicate that NGES is successful in accelerating gastric emptying of both liquids and solids, and in producing strong, externally-controlled, retrograde contractions.

Pilot acute study of feedback-controlled retrograde peristalsis invoked by neural gastric electrical stimulation.

Neural gastric electrical stimulation (NGES) is a new method for invoking gastric contractions under microprocessor control. However, optimization of this technique using feedback mechanisms to minimize power consumption and maximize effectiveness has been lacking. The present pilot study proposes a prototype feedback-controlled neural gastric electric stimulator for the treatment of obesity. Both force-based and inter-electrode impedance-based feedback neurostimulators were implemented and tested. Four mongrel dogs (2 M, 2 F, weight 14.9 +/- 2.3 kg) underwent subserosal implantation of two-channel, 1 cm, bipolar electrode leads and two force transducers in the distal antrum. Two of the dogs were stimulated with a force feedback system utilizing the force transducers, and the other two animals were stimulated utilizing an inter-electrode impedance-based feedback system utilizing the proximal electrode leads. Both feedback systems were able to recognize erythromycin-driven contractions of the stomach and were capable of overriding them with NGES-invoked retrograde contractions which exceeded the magnitudes of the erythromycin-driven contractions by an average of 100.6 +/- 33.5% in all animals. The NGES-invoked contractions blocked the erythromycin-driven contractions past the proximal electrode pair and induced temporary gastroparesis in the vicinity of the distal force transducer despite the continuing erythromycin infusion. The amplitudes of the erythromycin-invoked contractions in the vicinity of the proximal force transducer decreased abruptly by an average of 47.9 +/- 6.3% in all four dogs after triggering-invoked retrograde contractions, regardless of the specific feedback-controlled mechanism. The proposed technique could be helpful for retaining food longer in the stomach, thus inducing early satiety and diminishing food intake.

Manipulation of food intake and weight dynamics using retrograde neural gastric electrical stimulation in a chronic canine model.

Neural gastric electrical stimulation (NGES) could be a new technique for treating obesity. However, chronic animal experimentation exploring the efficacy of this therapy is lacking. In this study we investigated the utility of retrograde NGES in a chronic canine model. Nine mongrel dogs (26.8 +/- 5.2 kg) underwent laparoscopic implantation of 2-channel neurostimulator leads in the distal antrum. Five dogs formed a control group and four dogs underwent stimulation. Food intake and weight dynamics were regularly monitored during two separate research protocols, each comprising 2-week baseline, stimulation and washout periods. The stimulation voltage was constant in the first protocol and was ramped in the second. In the first protocol three out of the four stimulated dogs demonstrated significant decrease in food intake (P < 0.05). However, this materialized in a significant weight reduction in one dog only. In the second protocol, all stimulated dogs exhibited significant food intake and weight reduction (P < 0.05) compared to controls. Necropsies and histopathological analysis did not reveal any abnormalities in the stomach, the adjacent organs or around the implant. NGES could be a safe new technique for reducing food intake and weight and, therefore, it might be helpful for treating obesity.

Neural gastrointestinal electrical stimulation enhances colonic motility in a chronic canine model of delayed colonic transit.

Neural gastrointestinal electrical stimulation (NGES) induces sequential contractions and enhances emptying in acute canine gastric and colonic models. This study was set to determine (i) the effect of NGES in a chronic canine model of delayed colonic transit and (ii) possible mechanism of action. Four pairs of electrodes were implanted in the distal colon of nine mongrel dogs. Delayed colonic transit was induced by diphenoxylate/atropine and alosetron. Transit was fluoroscopically determined by the rate of evacuation of radiopaque markers, and was tested twice in each dog, in random order, on and off stimulation. Two stimulation sequences, separated by 1 min, were delivered twice a day via exteriorized electrodes. Colonic manometry during stimulation was performed before and after intravenous (i.v.) injection of 1 mg of atropine. Complete evacuation of all markers was significantly shortened by NGES, from 4 days to 2 days, interquartile range 3-4 days vs 2-3 days, respectively, P = 0.016. NGES induced strong sequential contractions that were significantly diminished by atropine: 190.0 +/- 14.0 mmHg vs 48.7 +/- 19.4 mmHg, respectively (P < 0.001). NGES induces strong sequential colonic contractions and significantly accelerates movement of content in a canine model of delayed colonic transit. The effect is atropine sensitive.

Centre-specific multichannel electrogastrographic testing utilizing wavelet-based decomposition.

Although the principles of electrogastrography (EGG) have been known for years, the clinical utility of EGG has not been clearly demonstrated, and EGG recording and analysis techniques have not been fully standardized. The aim of this study was to develop a multichannel EGG technique for detecting abnormal gastric motility using an EGG database specifically designed for a particular testing centre, maximizing the sensitivity and the specificity of the test. Eight healthy volunteers formed a reference group to which 4 study groups (17 gastro-oesophageal reflux disease (GORD) patients, 7 functional dyspepsia patients, 8 post-fundoplication patients and 12 healthy volunteers) were compared. Eight-channel EGG was recorded in the postprandial and fasting states for 30 min each. The recorded signals were wavelet compressed and the resulting error (per cent root mean square difference (PRD)) after the compression was utilized to compare the study groups to the reference group. A threshold in the number of channels with significantly different PRD values was introduced. Sensitivity (SE), specificity (SP) and correct classification rate (CC) of the test in recognizing each clinical condition in the study groups for several channel thresholds and compressions were calculated, and were maximized. Increasing the compression and channel threshold levels improved the specificity, but decreased the sensitivity of the multichannel EGG test. An optimal combination region was identified based on a centre-specific adjustment of the channel threshold and the wavelet compression. The achieved maximum sensitivity, specificity and correct classification for this region in our test centre were as follows: GORD--SE 82.4%, SP 83.3%, CC 82.8%; functional dyspepsia--SE 100%, SP 75%, CC 84.2%; post-fundoplication--SE 75.0%, SP 83.3%, CC 80.0%. The utilization of a wavelet-based decomposition technique to process multichannel EGG signals can be a very effective method for enhancing the clinical utility of EGG, provided it is specifically developed for a given testing centre.

Friction-assisted magnetic holding of an ingestible capsule for esophageal pH and impedance monitoring.

24-hour catheter-based ambulatory pH and impedance monitoring is an essential tool for diagnosing esophageal disorders. However, catheter-based monitoring systems are uncomfortable and interfere with normal activities of the patient. To overcome these disadvantages, different wireless monitoring systems have been proposed. However, efficient ways to position and hold wireless capsules are lacking. Currently there is a need to develop safe and reliable methods to hold an esophageal wireless monitoring system in position for 24 hours. Friction-assisted magnetic holding is proposed as an alternative to conventional holding techniques. Permanent magnet and electromagnet designs with the required characteristics to achieve this task were computer-designed and simulated. The size and power requirements of the magnets were considered. Simulation results were verified using laboratory experiments. Permanent neodymium magnets offered the best performance for the intended application. The obtained results show the feasibility of friction-assisted magnetic holding for esophageal monitoring. Improvements to the thread design, friction enhancing pins, magnetic shielding and encapsulation methods are necessary for in vivo testing.