Progress Towards Bringing the Gap Between Noninvasive Bioelectromagnetic Physiological Measurements and Microphysiological Systems to Detect, Characterize, and Treat Functional Gastrointestinal Disorders

Abstract

The electrical gastric slow wave mediates neuromuscular interactions in the gastrointestinal syncytium, thus determining the functional status of peristalsis and digestion. It is regulated by interstitial cells of Cajal (ICC) and the enteric nervous system, which influences gastrointestinal motility and is affected by the gut-brain axis. Dysrhythmias of the gastric syncytium have been linked to functional GI motility disorders, which are characterized by overlapping symptomologies relating to dysfunction of the gastrointestinal system and lacking a physical, histological abnormality. There is a critical need for the development of diagnostic criteria that provide objective quantification of functional gastrointestinal abnormalities and dysrhythmia in order to improve patient outcomes. The central hypothesis for this work is that High-Resolution Electrogastrogram (HR-EGG) and Magnetogastrogram (MGG) can noninvasively distinguish the dysrhythmic slow wave patterns of pediatric functional nausea patients from the homeostatic slow wave of healthy pediatric controls. The overall objective is to utilize these tools to develop noninvasive objective markers of disease and severity to direct and inform clinical decision-making. Determining the optimal definition of normogastria that amplifies and does not inhibit the spatiotemporal characterization of slow wave propagation could lead to an enhanced characterization of gastrointestinal propagation dynamics, thus leading to greater clinical applicability of noninvasive bioelectromagnetic techniques. My research combines traditional approaches of measuring whole-body physiology with cell biology to create a multi-modal approach to understanding pathological processes of functional gastric activity. Our clinical investigations have identified spatial and temporal clinical features crucial for diagnosing dysrhythmias in diseased states by assessing frequency and its power distribution. As revealed by power spectral analysis, patients exhibit significantly decreased normogastria, alongside notable differences in propagation velocities and directions. My results indicate that HR-EGG shows sufficient sensitivity and may represent an effective, low-cost, and portable tool for the noninvasive clinical detection of key pathological signatures of pediatric functional nausea. Future investigations encompassing the proposed microphysiological systems coupled to patient-derived duodenal organoid development could ascertain personalized treatment options in vitro by recapitulating the complex structure and function of the patient’s disordered environment, allowing an opportunity to explore the potential impact of myriad therapeutic interventions simultaneously.