dc.description.abstract |
The human gastrointestinal (GI) tract is a highly sophisticated organ system which controls the
majority of the body’s oral nutrient absorption, and excretion of waste. Key to the healthy
function of the GI system, is effective GI motility. GI motility is governed by the interstitial
cells of Cajal (ICC), which generate and propagate bioelectric events called slow waves,
responsible for the coordination of GI contractions.
A large body of research has recently focused on the propagation of slow waves in the stomach,
and studies have shown that patterns of propagation which differ from an established norm are
associated with several functional GI disorders, such as gastroparesis (GP), chronic nausea and
vomiting (CUNV), and functional dyspepsia (FD). These diseases affect a significant portion
of the global population, with FD alone estimated to afflict approximately 5-11% of the
community.
Tests used to diagnose these diseases have classically focused on evaluation of gastric
emptying (GE), which has recently been shown to be a poor metric. Treatment options, for the
most part, also fail to address the underlying cause of the disorders, instead focusing on
symptom relief. One promising treatment option currently being investigated is gastric
ablation, which seeks to target the underlying defective tissue possibly responsible for diseases
caused by abnormal slow wave activity. Gastric ablation is built on the technique of cardiac
ablation, which requires high-resolution (HR) mapping of electrical activation in the heart.
Gastric ablation also relies on detailed prior mapping of electrical activity to identify
appropriate locations to ablate.
Current methods for mapping gastric electrical activation carry a number of limitations, which
would preclude their use in a clinical setting. Some techniques, such as magnetogastrography
(MGG), are prohibitively expensive, and as such, restricted to research use. Others, such as
HR-Electrogastrography (HR-EGG), hold promise for non-invasive diagnosis of abnormal
slow wave conduction, but do not provide the accuracy required to guide therapy, like ablation.
Intra-operative HR slow wave recording techniques that have previously defined slow wave
abnormalities in diseased patients and can provide the necessary accuracy to guide ablation are far too invasive to routinely use in the clinic, requiring surgical access to the serosal surface of
the stomach.
In this thesis, a clinical trial was conducted, which validated the use of a novel, high-resolution,
endoscopic mapping device to record slow waves in a minimally invasive method, from the
mucosal surface of the stomach. By deploying the recording device in this fashion, the issues
associated with previous far-field, or invasive techniques, are addressed.
The trial involved 13 patients at Auckland City Hospital. Following ethical approval and
informed consent, the novel device was safely deployed and retrieved in all patients, with slow
waves able to be detected in 12 of the 13 patients. Slow wave events were recorded with an
average frequency of 2.84 ± 0.45 cycles per minute (cpm) and amplitude of 2.6 ±1.9 mV. Slow
wave events with electrode coverage greater than 33% were detected in 5 of the 13 patients,
allowing endoscopic spatiotemporal mapping of human slow wave data for the first time. The
average slow wave velocity in these 5 patients was 4.26 ± 1.42 mm/s. All of the values for
frequency, amplitude and velocity accorded with known physiological ranges from goldstandard
surgical mapping methods, thereby validating the new endoscopic device and the data
obtained from this pioneering clinical cohort.
The average signal to noise ratio across all recordings was -1.58 ± 3.13 dB. A statistically
significant difference (p=0.04) was seen in the SNRs of recordings that had maximum electrode
coverage of more than 33% of the device versus those which did not. Recordings with a
maximum electrode coverage greater than 33% had a mean SNR of 0.46 ± 0.78 dB. Recordings
with maximum electrode coverage of less than 33% had a mean SNR of -3.04 ± 3.35dB. The
difference in amplitude across the same samples was not significant (p=0.09), indicating that
increased noise may be the primary factor in reduced slow wave detection, and that with more
refined filtering, additional slow waves may be detected. The value of 33% electrode coverage
thereby appears to be a critical threshold for meaningful slow wave data, providing a
quantitative threshold for future study design and device application.
The clinical validation of minimally invasive, endoscopic HR slow wave recordings from the
mucosal surface of the stomach, carried out in this thesis, represents a substantial, first-inhumans
step towards a new diagnostic tool for patients with functional GI disorders. Integration
with gastric ablation techniques currently being developed could provide a uniquely effective clinical diagnosis and treatment pathway, significantly improving the lives of countless
individuals suffering these diseases. |
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