A fully resolved active musculo-mechanical model for esophageal transport

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, which is modeled as an actively contracting, fiber-reinforced tube. A simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are then extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall due to the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function

A continuum mechanics-based musculo-mechanical model for esophageal transport

In this work, we extend our previous esophageal transport model using an immersed boundary (IB) method with discrete fiber-based structural model, to one using a continuum mechanics-based model that is approximated based on finite elements (IB-FE). To deal with the leakage of flow when the Lagrangian mesh becomes coarser than the fluid mesh, we employ adaptive interaction quadrature points to deal with Lagrangian-Eulerian interaction equations based on a previous work (Griffith and Luo [1]). In particular, we introduce a new anisotropic adaptive interaction quadrature rule. The new rule permits us to vary the interaction quadrature points not only at each time-step and element but also at different orientations per element. This helps to avoid the leakage issue without sacrificing the computational efficiency and accuracy in dealing with the interaction equations. For the material model, we extend our previous fiber-based model to a continuum-based model. We present formulations for general fiber-reinforced material models in the IB-FE framework. The new material model can handle non-linear elasticity and fiber-matrix interactions, and thus permits us to consider more realistic material behavior of biological tissues. To validate our method, we first study a case in which a three-dimensional short tube is dilated. Results on the pressure-displacement relationship and the stress distribution matches very well with those obtained from the implicit FE method. We remark that in our IB-FE case, the three-dimensional tube undergoes a very large deformation and the Lagrangian mesh-size becomes about 6 times of Eulerian mesh-size in the circumferential orientation. To validate the performance of the method in handling fiber-matrix material models, we perform a second study on dilating a long fiber-reinforced tube. Errors are small when we compare numerical solutions with analytical solutions. The technique is then applied to the problem of esophageal transport. We use two fiber-reinforced models for the esophageal tissue: a bi-linear model and an exponential model. We present three cases on esophageal transport that differ in the material model and the muscle fiber architecture. The overall transport features are consistent with those observed from the previous model. We remark that the continuum-based model can handle more realistic and complicated material behavior. This is demonstrated in our third case where a spatially varying fiber architecture is included based on experimental study. We find that this unique muscle fiber architecture could generate a so-called pressure transition zone, which is a luminal pressure pattern that is of clinical interest. This suggests an important role of muscle fiber architecture in esophageal transport

Development and validation of the brief esophageal dysphagia questionnaire

BackgroundEsophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy.Methods1638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split‐half reliability, ceiling and floor effects, and construct validity.Key ResultsThe BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split‐half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter‐item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant.Conclusions & InferencesThe BEDQ represents a rapid, reliable, and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction.Validated, rapid clinical assessment tools for esophageal dysphagia are lacking. The brief esophageal dysphagia questionnaire aims to gauge the severity and frequency of dysphagia with additional items to gauge food impaction. The BEDQ is a reliable and valid tool to assess esophageal dysphagia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135130/1/nmo12889.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135130/2/nmo12889_am.pd

Neurological disorders leading to mechanical dysfunction of the esophagus: an emergent behavior of a neuromechanical dynamical system

An understanding how neurological disorders lead to mechanical dysfunction of the esophagus requires knowledge of the neural circuit of the enteric nervous system. Historically, this has been elusive. Here, we present an empirically guided neural circuit for the esophagus. It has a chain of unidirectionally coupled relaxation oscillators, receiving excitatory signals from stretch receptors along the esophagus. The resulting neuromechanical model reveals complex patterns and behaviors that emerge from interacting components in the system. A wide variety of clinically observed normal and abnormal esophageal responses to distension are successfully predicted. Specifically, repetitive antegrade contractions (RACs) are conclusively shown to emerge from the coupled neuromechanical dynamics in response to sustained volumetric distension. Normal RACs are shown to have a robust balance between excitatory and inhibitory neuronal populations, and the mechanical input through stretch receptors. When this balance is affected, contraction patterns akin to motility disorders are observed. For example, clinically observed repetitive retrograde contractions emerge due to a hyper stretch sensitive wall. Such neuromechanical insights could be crucial to eventually develop targeted pharmacological interventions

Direct and retrograde signal propagation in unidirectionally coupled Wilson-Cowan oscillators

Certain biological systems exhibit both direct and retrograde propagating wave signals, despite unidirectional neural coupling. However, there is no model to explain this. Therefore, the underlying physics of reversing the signal's direction for one-way coupling remains unclear. Here, we resolve this issue using a Wilson-Cowan oscillators network. By analyzing the limit cycle period of various coupling configurations, we determine that intrinsic frequency differences among oscillators control wave directionality

A mechanics--based perspective on the function of human sphincters during functional luminal imaging probe manometry

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 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

A multi-stage machine learning model on diagnosis of esophageal manometry

High-resolution manometry (HRM) is the primary procedure used to diagnose esophageal motility disorders. Its interpretation and classification includes an initial evaluation of swallow-level outcomes and then derivation of a study-level diagnosis based on Chicago Classification (CC), using a tree-like algorithm. This diagnostic approach on motility disordered using HRM was mirrored using a multi-stage modeling framework developed using a combination of various machine learning approaches. Specifically, the framework includes deep-learning models at the swallow-level stage and feature-based machine learning models at the study-level stage. In the swallow-level stage, three models based on convolutional neural networks (CNNs) were developed to predict swallow type, swallow pressurization, and integrated relaxation pressure (IRP). At the study-level stage, model selection from families of the expert-knowledge-based rule models, xgboost models and artificial neural network(ANN) models were conducted, with the latter two model designed and augmented with motivation from the export knowledge. A simple model-agnostic strategy of model balancing motivated by Bayesian principles was utilized, which gave rise to model averaging weighted by precision scores. The averaged (blended) models and individual models were compared and evaluated, of which the best performance on test dataset is 0.81 in top-1 prediction, 0.92 in top-2 predictions. This is the first artificial-intelligence-style model to automatically predict CC diagnosis of HRM study from raw multi-swallow data. Moreover, the proposed modeling framework could be easily extended to multi-modal tasks, such as diagnosis of esophageal patients based on clinical data from both HRM and functional luminal imaging probe panometry (FLIP)

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe

© 2016 by the American College of Gastroenterology. Objectives:Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia.Methods:In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed up per endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was < 2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions.Results:HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI.Conclusions:FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.Link_to_subscribed_fulltex