Transcutaneous intraluminal impedance measurement (TIIM) is a new method to cutaneously measure gastric contractions by assessing the attenuation dynamics of a small oscillating voltage emitted by a battery-powered ingestible capsule retained in the stomach. In the present study, we investigated whether TIIM can reliably assess gastric motility in acute canine models.
Distal postprandial gastric motility involves contractions that mechanically crush ingested food and mix it with secretions to prepare it for absorption, while maintaining an appropriate pressure gradient across the pyloric sphincter to regulate gastric emptying [
Gastric function studies that can identify delayed gastric emptying include scintigraphy, C13 breath tests, wireless motility capsule tests, and combinations thereof [
Transcutaneous intraluminal impedance measurement (TIIM) works by emitting a small high-frequency electrical signal from within the stomach, with parameters (50 kHz, 1.5 V peak-to-peak) chosen for their optimal transmission properties through smooth and abdominal muscles [
(a) The TIIM principle shown schematically: a small electrical signal is emitted from the TIIM transducer intraluminally from within the stomach after ingestion. The transducer is contained within an expandable pill that swells within the stomach, thus preventing it from being expelled through the pylorus for a prolonged amount of time (days). The attenuation dynamics of the electrical signal across the gastric and extraluminal tissue is measured from the skin via external cutaneous electrodes. The TIIM signals are measured using a standard multichannel bioelectric amplifier (electrogastrograph). After a predetermined amount of time (depending on the materials used), the long-term gastric-retentive enclosure disintegrates and the resulting smaller constituents of the pill individually exit the gastrointestinal tract via natural peristalsis. The TIIM components in the figure are deliberately zoomed in. (b) TIIM gastric-retentive pill design: (1) electronic oscillator circuit; (2) capsule body; (3) assembled capsule; (4) superabsorbent granules; (5) capsule and granules inside a liquid-permeable mesh; (6) dissolvable pill containing the meshed capsule; (7) TIIM gastric-retentive pill; (8) pill expanded in water; and (9) test dish. Horizontal and vertical 1 cm scales are depicted at the bottom left corner.
TIIM is a substantially different concept from standard electrogastrography (EGG), where cutaneous electrodes measure the intrinsic spontaneous electrical activity of the stomach. EGG has substantial drawbacks due to dynamic artifacts and lack of direct correlation with gastric muscular function, disease, or symptoms [
The aim of the present study was to evaluate the effectiveness of the minimally invasive, ingestible, gastric-retentive TIIM capsule for measuring gastric motility in comparison to a sham gastric-retentive, ingestible capsule, with both being referenced to force transducers attached to the serosa of the stomach in acute canine models [
For the present study, the TIIM miniature electronic oscillator was integrated into a gastric-retentive pill, which further lowers the already minimal impact of the catheter-based design [
This study was approved by the Life and Environmental Sciences Animal Care Committee, University of Calgary, Calgary, Alberta, Canada.
Experiments were performed on eight mongrel dogs (6 F) with a mean weight of 23.8 kg ± 3.3 kg, four of which were administered an active TIIM capsule, while the rest were given a deactivated (battery-removed) capsule. After 24 h fasting and 12 h water deprivation, each animal ingested transorally a single capsule as described above (TIIM or sham) with 500 cc of room-temperature water. The pill swelled to its maximum size in the stomach within 15 minutes after ingestion to dimensions exceeding 1.5 cm in any direction and subsequently was unable to pass the pyloric sphincter even when subjected to propulsive peristalsis. The animals then underwent induction with an intravenous injection of thiopental (Thiotal 15 mg kg−1 IV, Vetoquinol Canada, Lavaltrie, QC, Canada) and were continuously maintained on inhalant isoflurane and oxygen (Halocarbon Laboratories, River Edge, New Jersey, USA) with a vaporizer setting of 1%–3% until the end of the experiment, so that gastric motility was minimally affected. The anesthesia was chosen because it did not influence gastric neurotransmitters and as such would not affect gastric contractions [
After the incision the location of the ingested pill in the stomach was verified endoscopically using an EPK-700 veterinary endoscope (Pentax, Tokyo, Japan), and the serosa of the stomach was measured using an oscilloscope (Tektronix, Beaverton, OR, USA) to confirm the presence of an activated or deactivated pill. After this verification, two 90W24 force transducers (RB Products, Stillwater, MN, USA), specifically designed for gastric motility monitoring, were surgically sutured to the serosal side of the antral stomach along the gastric axis [
Position of the force transducers sutured to the serosa of the stomach (a) and the intraluminal position of the expanded gastric-retentive pill carrying the TIIM oscillator (b).
Serosal view
Internal view
The signals from the force transducers were amplified using a custom-designed multichannel bridge amplifier and digitized using a PCMCIA DAQ Card-AL-16XE-50 (National Instruments, Austin, TX, USA). The force transducer (FT) signals were monitored and analyzed with custom-designed signal processing and visualization software (GAS-6.2, Biomedical Instrumentation Laboratory, University of Calgary, Calgary, Alberta, Canada). Once the force transducers were in place, their functionality was verified mechanically by manual palpation of variable strength, and the offsets and gains were calibrated accordingly for maximal sensitivity. The intragastric position of the pill was then verified mechanically by palpating it to ensure that it had not been compromised during surgery.
Following the FT implantation the abdomen was closed, and after appropriate skin cleaning and preparation, three pediatric ECG electrodes (Conmed, Utica, NY, USA) were placed cutaneously over the stomach along the abdominal projection of the gastric axis, with a ground electrode positioned closer to the left hip of the animal [
The cutaneous electrodes were connected to a custom-designed multichannel electrogastrograph (EGG, James Long Company, Caroga Lake, NY, USA), which measured the surface electrical activity relative to ground. The cut-off frequencies of the bandpass filter of the EGG amplifier were set to the commonly used 0.03–0.1 Hz following the hypothesis that gastric motility signals in the animals will not exceed 6 cycles per minute (cpm) [
Immediately after the experimental setup was completed [
At the end of the experiments the animals were sacrificed by an IV injection of Euthanyl, 480 mg/4.5 kg (Bimeda-MTC Animal Health Inc., Cambridge, ON, Canada). Subsequent retrieval of the expanded pill was performed in order to verify its retention within the stomach and confirm the presence of the signal in the active TIIM pills or the lack thereof in the inactive sham pills using an oscilloscope. The postadministration volume of each gastric-retentive pill was measured to quantify expansion dimensions.
Since the cutaneous and the force transducer measurements were relativistic in nature, all measurements (2 cutaneous and 2 FT channels) were normalized with the maximal amplitude in 1-minute intervals becoming unity and the minimal set to zero. Thirty one-minute gastric motility indices [
In addition, the frequency spectra of the signals were computed at 3.4-minute intervals with 64% overlap (2048-point fast Fourier transform, 10 Hz sampling frequency), and the frequencies of the dominant peaks per spectrum per modality (FT, TIIM, or sham-based EGG) were recorded and averaged utilizing the custom-designed software package GAS 6.2.
Furthermore, the dominant peaks of the frequency spectra for each measuring modality (basal and post-neostigmine) were subjected to a comprehensive statistical analysis using the paired Student’s
Prior to the force transducer implantation, the electrical activity or lack thereof of the ingested pill was verified with an oscilloscope. Figure
An oscilloscope reading from the gastric serosa prior to the force transducer implantation verified the presence of an activated TIIM pill (a). The sham pills did not have any signal (b).
In each animal the expanded pill was retrieved from the stomach at the end of the experiment, with an average postretrieval volume of 12.1 ± 0.4 mL and dimensions exceeding 1.5 cm in all directions, indicating that even the neostigmine-invoked contractions had not been able to propel the expanded gastric-retentive capsule beyond the pyloric sphincter.
A typical example of simultaneous FT and TIIM recordings for an activated pill, as well as their one-minute motility indices, is shown in Figure
Averaged Pearson correlation coefficients (PCCs) of the one-minute gastric motility indices (GMIs) per state per capsule type [
Modality | State | PCCs proximal FT-proximal |
|
PCCs distal FT-distal |
|
---|---|---|---|---|---|
Cutaneous GMIs | Cutaneous GMIs | ||||
TIIM capsule | Baseline |
|
<.01 |
|
<.01 |
After neostigmine |
|
<.01 |
|
<.01 | |
|
|||||
Sham capsule | Baseline |
|
>.1 |
|
>.1 |
After neostigmine |
|
>.1 |
|
>.1 |
Combined plot of the raw signals and the 1-minute motility indices for an active pill in the baseline state (seconds 0–1800) and after the administration of neostigmine (seconds 1800–3600). The 1-minute duration for the administration of neostigmine is denoted by a thick vertical line.
Combined plot of the raw signals and the 1-minute motility indices for an inactive pill in the baseline state (seconds 0–1800) and after the administration of neostigmine (seconds 1800–3600). The 1-minute duration for the administration of neostigmine is denoted by a thick vertical line.
Table
Averaged cycles per minute (CPM) of the raw force transducer (FT) and the cutaneous recordings per state per capsule type.
Modality | State | Channel | CPM |
---|---|---|---|
TIIM capsule | Baseline | FT |
|
TIIM |
|
||
After neostigmine | FT |
|
|
TIIM |
|
||
|
|||
Sham capsule | Baseline | FT |
|
EGG |
|
||
After neostigmine | FT |
|
|
EGG |
|
Statistical comparison between the dominant frequency peaks of the FT and TIIM/EGG recordings using paired Student’s
Modality | State |
|
---|---|---|
TIIM capsule | Baseline |
.048* |
After neostigmine |
.049* | |
|
||
Sham capsule | Baseline |
.92 |
After neostigmine |
.33 |
The clinical utility of gastric electrical measurements (EGG or bioimpedance) for assessing gastric motility has been previously shown to be limited [
It is worth noting that although the aim of the present study was to further validate the TIIM technique, the sham pill study was fundamentally a direct comparison between gastric motility indices obtained via routine EGG and force transducers, since standard EGG bandpass filtering parameters (0.03–0.1 Hz) were used. In four animals no statistically significant correlation was observed in the motility indices between any of the channel pairs (FT-EGG) examined, further supporting our understanding that EGG cannot reliably monitor gastric motility due to its important and, in our opinion, unsurpassable limitation; the relatively low average electric-power of extracellular ERA-I and ERA-II preceding mechanically relevant gastric contractions dissipates intraluminally in an inconsistent and nonlinear fashion before reaching the abdominal skin surface and thus cannot be reliably recorded by traditional cutaneous EGG. With the electrically isolated, gastric-retentive pill-based design presented in this study, it is possible that environmental electrical phenomena such as capsule tumbling due to motion not associated with gastric contractions, static electricity, and external electromagnetic signals may affect the measurements in an ambulatory setting, particularly if the patient is mobile in an electromagnetically dynamic environment. In addition, in an ambulatory setting it is possible that abdominal muscle contractions and motion artifacts might also be registered. In such cases, adaptive filtering procedures [
It should be noted that in the case of the inactive sham study small noise artifacts appear dramatic since there is no 50 kHz carrier signal as a reference. In fact, these noise artifacts were much lower (10–100 times) than the measurements from the active TIIM study. However, since the signals were normalized (the highest peaks were equated to unity and the lowest were equated to zero) before visualization and subsequent presentation, electrostatic noises affected the cutaneous recordings of the sham TIIM signals, and they appeared as enlarged white noise. Unfortunately, we cannot avoid normalization, because there is no exact way to determine the basal impedance the TIIM electrical oscillator faces, which can also be dynamically changing, particularly in chronic studies of longer duration. Regardless, it should be noted that if the sham TIIM tracings were displayed on the same scale as the active TIIM figure, they would appear as virtually flat lines. In future long-term (e.g., 24 h) chronic gastric motility studies utilizing TIIM, we do not perceive the normalization of the TIIM data to pose a significant problem, since the interdigestive motor complex and postprandial contractility would be clearly seen, particularly if a data logger marks the meal periods while recording the TIIM data.
The next steps for TIIM involve the development of a portable data-logger to enable ambulatory measurements in long-term chronic tests, which can examine the effectiveness of the method in more clinically relevant settings, in dynamic, noise-ridden environments and during meals. Further long-term chronic animal studies (>24 h) should be considered, potentially evaluating gastric motility and gastric emptying using TIIM, before moving to chronic human trials.
Transcutaneous intraluminal impedance measurement (TIIM) is a minimally invasive gastric motility monitoring technique which has now been validated in a sham-comparative study. Acute canine models confirmed that TIIM was able to measure gastric motility with comparable precision to force transducers implanted invasively to the serosa of the stomach.
There are no financial arrangements to disclose at this time.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This paper was supported in part by the Natural Sciences and Engineering Research Council of Canada.