PROJECT SUMMARY
Swallowing difficulties are extremely common and result in substantial morbidity, reduction in the quality of life,
and mortality related to malnutrition and complications from regurgitation and aspiration. Unfortunately, our
understanding regarding the pathophysiology of dysphagia and GERD has been hampered by focusing
predominantly on circular muscle activity and ignoring the essential biomechanical properties of the esophageal
wall that promote normal emptying. Our initial work explored the relationship between intrabolus pressure (IBP)
and esophagogastric junction (EGJ) compliance as a metric for outflow resistance. This work highlighted the
direct relationship between IBP and EGJ opening and was the foundation for the development of the
classification scheme utilized around the world to diagnose esophageal motor disorders: “the Chicago
Classification” (CC). Despite this improved understanding focused on bolus transit dynamics, there are still
significant gaps in our scientific understanding centered on the lack of a true correlate for symptoms, reliable
predictive models and effective treatments for Functional dysphagia, IEM and EGJOO. Given these limitations,
we have developed novel approaches that combine assessments of primary and secondary peristalsis (a
NeuroMyogenic Model of esophageal function). These will leverage our recent findings supporting the
importance of the esophageal response to distension in bolus clearance, noting that this response of the
esophageal wall to bolus retention or reflux is one of the most essential functions of the esophagus in preventing
complications of aspiration, or reflux injury. We will also include an assessment of esophageal geometry and
wall biomechanics (elasticity/dilatation) as these carry essential interactions with esophageal function that are
overlooked in the current diagnostic paradigms.
In order to test our hypothesis that wall mechanics are a major determinant of esophageal diseases, we
had to develop new approaches and new technology to directly measure mechanical wall state, descending
inhibition and LES opening. Using impedance techniques combined with manometry, we are now capable of
assessing IBP and diameter changes across a space-time continuum (4D HRM). We also developed physics-
based hybrid diagnostics that include a FLIP technique to assess esophageal work and power during volumetric
distention (FLIP-MECH) and a fluoroscopy approach that simultaneously assesses esophageal diameter-
pressure relationships (Fluoro-MECH). We also developed a new approach, Interactive FLIP Panometry, which
facilitates an assessment of descending inhibition and the mechanism behind impaired LES opening. These
tools will allow us to expand our models to combine an assessment of neuromyogenic function simultaneously
with geometry. Our overarching goal will be to study well-defined patient populations (Functional Dysphagia,
IEM/GERD, EGJOO and Achalasia) before and after targeted interventions to test the NeuroMyogenic and
MechanoGeometric Model. This work will build upon the previous success of the CC and help advance the
evolution of the CC by defining new, relevant biomechanical physiomarkers of disease activity that can identify
new targets for therapeutic intervention and facilitate prediction of clinical outcomes.