Noninvasive markers of functional nausea in children

项目总结

Project Summary The gastric electrical slow wave mediates neuromuscular interactions in the gastrointestinal syncytium that determine the functional status of peristalsis and digestion. Millions of patients present to gastroenterologists each year with functional GI disorders which are associated with gastric slow wave dysrhythmia. However, noninvasive methods for assessing this activity quantitatively remain elusive. Structural imaging provided by CT and ultrasound can be useful when functional disorders are associated with anatomical changes, but frequently, gastric disorders occur with no concomitant structural abnormality. Functional nausea (FN) is a GI disorder that affects millions of Americans, particularly adolescents, but diagnoses remain largely exclusionary relying on symptomology with an otherwise normal diagnostic workup. FN is important to study in adolescents because it is ubiquitous, chronic, tracks into adulthood and adversely affects the quality of life in patients, yet understanding the pathophysiology might allow interventions at a time of therapeutic plasticity. The ability to study FN is limited by the lack of an objective clinical test to characterize or measure nausea or to predict its response to treatment or exacerbating factors. Electrogastrography (EGG) is as a possible approach, but signal quality and limitations of volume conduction in the abdomen have previously limited its utility to the characterization of temporal dynamics. Our preliminary data show that blind source separation applied to the multichannel electrogastrogram (EGG) can characterize propagation of the gastric slow wave, and that the magnetogastrogram (MGG), which measures spatiotemporal properties of magnetic fields from the gastric slow wave, also allows characterization of the propagation of the gastric slow wave in addition to evaluation of its frequency and power distribution. Furthermore, these spatiotemporal characteristics change during hyperglycemia and functional disorders like gastroparesis. We propose to study how functional nausea in adolescents may be characterized noninvasively by the use of multichannel EGG and MGG recordings. Our main aims in this proposal are to develop a mathematical model of FN, correlate functional differences in slow waves with nausea in patients with FN using modeling and experimental approaches, and to characterize biophysical, clinical and psychosocial phenotypes of FN using EGG/MGG. We will investigate differences between standard four-channel EGG and multichannel EGG/MGG, assess changes in slow wave rhythm and propagation pattern from EGG and MGG with disease in FN patients, examine differences between EGG and MGG signatures of severe nausea in FN patients, and will determine how MGG/EGG slow wave rhythm and pattern abnormalities relate to psychological functioning and pharmacological intervention. The analysis of slow wave activity represents the first physiologically-quantifiable noninvasive assessment method for pathological processes associated with functional nausea in adolescents.