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Abstract BackgroundEsophageal motility disorders can be diagnosed by either high‐resolution manometry (HRM) or the functional lumen imaging probe (FLIP) but there is no systematic approach to synergize the measurements of these modalities or to improve the diagnostic metrics that have been developed to analyze them. This work aimed to devise a formal approach to bridge the gap between diagnoses inferred from HRM and FLIP measurements using deep learning and mechanics. MethodsThe “mechanical health” of the esophagus was analyzed in 740 subjects including a spectrum of motility disorder patients and normal subjects. The mechanical health was quantified through a set of parameters including wall stiffness, active relaxation, and contraction pattern. These parameters were used by a variational autoencoder to generate a parameter space called virtual disease landscape (VDL). Finally, probabilities were assigned to each point (subject) on the VDL through linear discriminant analysis (LDA), which in turn was used to compare with FLIP and HRM diagnoses. ResultsSubjects clustered into different regions of the VDL with their location relative to each other (and normal) defined by the type and severity of dysfunction. The two major categories that separated best on the VDL were subjects with normal esophagogastric junction (EGJ) opening and those with EGJ obstruction. Both HRM and FLIP diagnoses correlated well within these two groups. ConclusionMechanics‐based parameters effectively estimated esophageal health using FLIP measurements to position subjects in a 3‐D VDL that segregated subjects in good alignment with motility diagnoses gleaned from HRM and FLIP studies. 

Abstract Functional luminal imaging probe (FLIP) is used to measure cross-sectional area (CSA) and pressure at sphincters. It consists of a catheter surrounded by a fluid filled cylindrical bag, closed on both ends. Plotting the pressure-CSA hysteresis of a sphincter during a contraction cycle, which is available through FLIP testing, offers information on its functionality, and can provide diagnostic insights. However, limited work has been done to explain the mechanics of these pressure-CSA loops. This work presents a consolidated picture of pressure-CSA loops of different sphincters. Clinical data reveal that although sphincters have a similar purpose (controlling the flow of liquids and solids by opening and closing), two different pressure-CSA loop patterns emerge: negative slope loop (NSL) and positive slope loop (PSL). We show that the loop type is the result of an interplay between (or lack thereof) two mechanical modes: (i) neurogenic mediated relaxation of the sphincter muscle or pulling applied by external forces, and (ii) muscle contraction proximal to the sphincter which causes mechanical distention. We conclude that sphincters which only function through mechanism (i) exhibition NSL whereas sphincters which open as a result of both (i) and (ii) display a PSL. This work provides a fundamental mechanical understanding of human sphincters. This can be used to identify normal and abnormal phenotypes for the different sphincters and help in creating physiomarkers based on work calculation. 

Abstract Balloon dilation catheters are often used to quantify the physiological state of peristaltic activity in tubular organs and comment on their ability to propel fluid which is important for healthy human function. To fully understand this system's behavior, we analyzed the effect of a solitary peristaltic wave on a fluid-filled elastic tube with closed ends. A reduced order model that predicts the resulting tube wall deformations, flow velocities, and pressure variations is presented. This simplified model is compared with detailed fluid–structure three-dimensional (3D) immersed boundary (IB) simulations of peristaltic pumping in tube walls made of hyperelastic material. The major dynamics observed in the 3D simulations were also displayed by our one-dimensional (1D) model under laminar flow conditions. Using the 1D model, several pumping regimes were investigated and presented in the form of a regime map that summarizes the system's response for a range of physiological conditions. Finally, the amount of work done during a peristaltic event in this configuration was defined and quantified. The variation of elastic energy and work done during pumping was found to have a unique signature for each regime. An extension of the 1D model is applied to enhance patient data collected by the device and find the work done for a typical esophageal peristaltic wave. This detailed characterization of the system's behavior aids in better interpreting the clinical data obtained from dilation catheters. Additionally, the pumping capacity of the esophagus can be quantified for comparative studies between disease groups. 

Dynamic magnetic resonance imaging (MRI) is a popular medical imaging technique that generates image sequences of the flow of a contrast material inside tissues and organs. However, its application to imaging bolus movement through the esophagus has only been demonstrated in few feasibility studies and is relatively unexplored. In this work, we present a computational framework called mechanics-informed MRI (MRI-MECH) that enhances that capability, thereby increasing the applicability of dynamic MRI for diagnosing esophageal disorders. Pineapple juice was used as the swallowed contrast material for the dynamic MRI, and the MRI image sequence was used as input to the MRI-MECH. The MRI-MECH modeled the esophagus as a flexible one-dimensional tube, and the elastic tube walls followed a linear tube law. Flow through the esophagus was governed by one-dimensional mass and momentum conservation equations. These equations were solved using a physics-informed neural network. The physics-informed neural network minimized the difference between the measurements from the MRI and model predictions and ensured that the physics of the fluid flow problem was always followed. MRI-MECH calculated the fluid velocity and pressure during esophageal transit and estimated the mechanical health of the esophagus by calculating wall stiffness and active relaxation. Additionally, MRI-MECH predicted missing information about the lower esophageal sphincter during the emptying process, demonstrating its applicability to scenarios with missing data or poor image resolution. In addition to potentially improving clinical decisions based on quantitative estimates of the mechanical health of the esophagus, MRI-MECH can also be adapted for application to other medical imaging modalities to enhance their functionality. 

The esophagogastric junction (EGJ) is located at the distal end of the esophagus and acts as a valve allowing swallowed food to enter the stomach and preventing acid reflux. Irregular weakening or stiffening of the EGJ muscles results in changes to its opening and closing patterns which can progress into esophageal disorders. Therefore, understanding the physics of the opening and closing cycle of the EGJ can provide mechanistic insights into its function and can help identify the underlying conditions that cause its dysfunction. Using clinical functional lumen imaging probe (FLIP) data, we plotted the pressure-cross-sectional area loops at the EGJ location and distinguished two major loop types—a pressure dominant loop and a tone dominant loop. In this study, we aimed to identify the key characteristics that define each loop type and determine what causes the inversion from one loop to another. To do so, the clinical observations are reproduced using 1D simulations of flow inside a FLIP device located in the esophagus, and the work done by the EGJ wall over time is calculated. This work is decomposed into active and passive components, which reveal the competing mechanisms that dictate the loop type. These mechanisms are esophageal stiffness, fluid viscosity, and the EGJ relaxation pattern. 

A FLIP device gives cross-sectional area along the length of the esophagus and one pressure measurement, both as a function of time. Deducing mechanical properties of the esophagus including wall material properties, contraction strength, and wall relaxation from these data are a challenging inverse problem. Knowing mechanical properties can change how clinical decisions are made because of its potential for in-vivo mechanistic insights. To obtain such information, we conducted a parametric study to identify peristaltic regimes by using a 1D model of peristaltic flow through an elastic tube closed on both ends and also applied it to interpret clinical data. The results gave insightful information about the effect of tube stiffness, fluid/bolus density and contraction strength on the resulting esophagus shape through quantitive representations of the peristaltic regimes. Our analysis also revealed the mechanics of the opening of the contraction area as a function of bolus flow resistance. Lastly, we concluded that peristaltic driven flow displays three modes of peristaltic geometries, but all physiologically relevant flows fall into two peristaltic regimes characterized by a tight contraction. 

Introduction:Plotting the pressure-cross-sectional area (P-CSA) hysteresis loops within the esophagus during a contraction cycle can provide mechanistic insights into esophageal motor function. Pressure and cross-sectional area during secondary peristalsis can be obtained from the functional lumen imaging probe (FLIP). The pressure-cross-sectional area plots at a location within the esophageal body (but away from the sphincter) reveal a horizontal loop shape. The horizontal loop shape has phases that appear similar to those in cardiovascular analyses, whichinclude isometric and isotonic contractions followed by isometric and isotonic relaxations. The aim of this study is to explain the various phases of the pressurecross-sectional area hysteresis loops within the esophageal body. Materials and Methods:We simulate flow inside a FLIP device placed inside the esophagus lumen. We focus on three scenarios: long functional lumen imaging probe bag placed insidethe esophagus but not passing through the lower esophageal sphincter, long functional lumen imaging probe bag that crosses the lower esophageal sphincter, and a short functional lumen imaging probe bag placed in the esophagus body that does not pass through the lower esophageal sphincter. Results and Discussion:Horizontal P-CSA area loop pattern is robust and is reproduced in all three cases with only small differences. The results indicate that the horizontal loop pattern is primarily a product of mechanical conditions rather than any inherently different function of the muscle itself. Thus, the distinct phases of the loop can be explained solely based on mechanics.