Myotomy technique and esophageal contractility impact blown-out myotomy formation in achalasia: an in silico investigation.

We used in silico models to investigate the impact of the dimensions of myotomy, contraction pattern, the tone of the esophagogastric junction (EGJ), and musculature at the myotomy site on esophageal wall stresses potentially leading to the formation of a blown-out myotomy (BOM). We performed three sets of simulations with an in silico esophagus model, wherein the myotomy-influenced region was modeled as an elliptical section devoid of muscle fibers. These sets investigated the effects of the dimensions of myotomy, differing esophageal contraction types, and differing esophagogastric junction (EGJ) tone and wall stiffness at the myotomy affected region on esophageal wall stresses potentially leading to BOM. Longer myotomy was found to be accompanied by a higher bolus volume accumulated at the myotomy site. With respect to esophageal contractions, deformation at the myotomy site was greatest with propagated peristalsis, followed by combined peristalsis and spasm, and pan-esophageal pressurization. Stronger EGJ tone with respect to the wall stiffness at the myotomy site was found to aid in increasing deformation at the myotomy site. In addition, we found that an esophagus with a shorter myotomy performed better at emptying the bolus than that with a longer myotomy. Shorter myotomies decrease the chance of BOM formation. Propagated peristalsis with EGJ outflow obstruction has the highest chance of BOM formation. We also found that abnormal residual EGJ tone may be a co-factor in the development of BOM, whereas remnant muscle fibers at myotomy site reduce the risk of BOM formation.NEW & NOTEWORTHY Blown-out myotomy (BOM) is a complication observed after myotomy, which is performed to treat achalasia. In silico simulations were performed to identify the factors leading to BOM formation. We found that a short myotomy that is not transmural and has some structural architecture intact reduces the risk of BOM formation. In addition, we found that high esophagogastric junction tone due to fundoplication is found to increase the risk of BOM formation.

Estimation of mechanical work done to open the esophagogastric junction using functional lumen imaging probe panometry.

In this study, we quantify the work done by the esophagus to open the esophagogastric junction (EGJ) and create a passage for bolus flow into the stomach. Work done on the EGJ was computed using functional lumen imaging probe (FLIP) panometry. Eighty-five individuals underwent FLIP panometry with a 16-cm catheter during sedated endoscopy including asymptomatic controls (n = 14), 45 patients with achalasia (n = 15 each, three subtypes), those with gastroesophageal reflux disease (GERD; n = 13), those with eosinophilic esophagitis (EoE; n = 8), and those with systemic sclerosis (SSc; n = 5). Luminal cross-sectional area (CSA) and pressure were measured by the FLIP catheter positioned across the EGJ. Work done on the EGJ (EGJW) was computed (millijoules, mJ) at 40-mL distension. Additionally, a separate method was developed to estimate the "work required" to fully open the EGJ (EGJROW) when it did not open during the procedure. EGJW for controls had a median [interquartile range (IQR)] value of 75 (56-141) mJ. All achalasia subtypes showed low EGJW compared with controls (P < 0.001). Subjects with GERD and EoE had EGJW 54.1 (6.9-96.3) and 65.9 (10.8-102.3) mJ, similar to controls (P < 0.08 and P < 0.4, respectively). The scleroderma group showed low values of EGJW, 12 mJ (P < 0.001). For patients with achalasia, EGJROW was the greatest and had a value of 210.4 (115.2-375.4) mJ. Disease groups with minimal or absent EGJ opening showed low values of EGJW. For patients with achalasia, EGJROW significantly exceeded EGJW values of all other groups, highlighting its unique pathophysiology. Balancing the relationship between EGJW and EGJROW is potentially useful for calibrating achalasia treatments and evaluating treatment response.NEW & NOTEWORTHY Changes in pressure and diameter occur at the EGJ during esophageal emptying. Similar changes can be observed during FLIP panometry. Data from healthy and diseased individuals were used to estimate the mechanical work done on the EGJ during distension-induced relaxation or, in instances of failed opening, work required to open the EGJ. Quantifying these parameters is potentially valuable to calibrate treatments and gauge treatment efficacy for subjects with disorders of EGJ function, especially achalasia.

Assessment of esophageal body peristaltic work using functional lumen imaging probe panometry.

The goal of this study was to conceptualize and compute measures of "mechanical work" done by the esophagus using data generated during functional lumen imaging probe (FLIP) panometry and compare work done during secondary peristalsis among patients and controls. Eighty-five individuals were evaluated with a 16-cm FLIP during sedated endoscopy, including asymptomatic controls (n = 14) and those with achalasia subtypes I, II, and III (n = 15, each); gastroesophageal reflux disease (GERD; n = 13); eosinophilic esophagitis (EoE; n = 9); and systemic sclerosis (SSc; n = 5). The FLIP catheter was positioned to have its distal segment straddling the esophagogastric junction (EGJ) during stepwise distension. Two metrics of work were assessed: "active work" (during bag volumes ≤ 40 mL where contractility generates substantial changes in lumen area) and "work capacity" (for bag volumes ≥ 60 mL when contractility cannot substantially alter the lumen area). Controls showed median [interquartile range (IQR)] of 7.3 (3.6-9.2) mJ of active work and 268.6 (225.2-332.3) mJ of work capacity. Patients with all achalasia subtypes, GERD, and SSc showed lower active work done than controls (P ≤ 0.003). Patients with achalasia subtypes I and II, GERD, and SSc had lower work capacity compared with controls (P < 0.001, 0.004, 0.04, and 0.001, respectively). Work capacity was similar between controls and patients with achalasia type III and EoE. Mechanical work of the esophagus differs between healthy controls and patient groups with achalasia, EoE, SSc, and GERD. Further studies are needed to fully explore the utility of this approach, but these work metrics would be valuable for device design (artificial esophagus), to measure the efficacy of peristalsis, to gauge the physiological state of the esophagus, and to comment on its pumping effectiveness.NEW & NOTEWORTHY Functional lumen imaging probe (FLIP) panometry assesses esophageal response to distension and provides a simultaneous assessment of pressure and dimension during contractility. This enables an objective assessment of "mechanical work" done by the esophagus. Eighty-five individuals were evaluated, and two work metrics were computed for each subject. Controls showed greater values of work compared with individuals with achalasia, gastroesophageal reflux disease (GERD), and systemic sclerosis (SSc). These values can quantify the mechanical behavior of the distal esophagus and assist in the estimation of muscular integrity.

Pumping Patterns and Work Done During Peristalsis in Finite-Length Elastic Tubes.

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.

Repetitive Antegrade Contractions: A novel response to sustained esophageal distension is modulated by cholinergic influence.

BACKGROUND & AIMS: A unique motor response to sustained esophageal distension, repetitive antegrade contractions (RACs), is observed using functional luminal imaging probe (FLIP) panometry. However, physiologic mechanisms related to this response are unexplored. This study aimed to evaluate the impact of cholinergic inhibition with atropine on the esophageal contractile response to sustained distention, including RACs, among healthy volunteers. METHODS: 8 asymptomatic volunteers (ages 22-45) were evaluated in a crossover study design with 16-cm FLIP positioned across the esophagogastric junction and distal esophagus during sedated upper endoscopy. The FLIP study involving stepwise volumetric distension was performed twice in each subject, at baseline and again after atropine (15 mcg/kg) was administered intravenously. FLIP panometry was analyzed to assess the contractile response to distension. RESULTS: Antegrade contractions, lumen-occluding contractions, and a RAC pattern were observed in 8/8, 8/8, and 7/8(88%) subjects, respectively, at baseline and in 5/8 (63%), 2/8 (25%) and 2/8 (25%) subjects after atropine. The rate of contractions in the RAC pattern was similar (6-7 contractions per minute) before and after atropine. Compared with the baseline study, distension-induced contractility was triggered at higher fill volumes after atropine. FLIP pressures were lower in response to volumetric filling after atropine than at baseline. CONCLUSIONS: The vigor and triggering of the esophageal contractile response to distension is reduced by cholinergic inhibition in asymptomatic controls. The observation that the rate of contractions did not change when patients developed repetitive contractile responses suggests that this rate is not modified by cholinergic inhibition once contractility is triggered.

Stabilization approaches for the hyperelastic immersed boundary method for problems of large-deformation incompressible elasticity.

The immersed boundary method is a mathematical framework for modeling fluid-structure interaction. This formulation describes the momentum, viscosity, and incompressibility of the fluid-structure system in Eulerian form, and it uses Lagrangian coordinates to describe the structural deformations, stresses, and resultant forces. Integral transforms with Dirac delta function kernels connect the Eulerian and Lagrangian frames. The fluid and the structure are both typically treated as incompressible materials. Upon discretization, however, the incompressibility of the structure is only maintained approximately. To obtain an immersed method for incompressible hyperelastic structures that is robust under large structural deformations, we introduce a volumetric energy in the solid region that stabilizes the formulation and improves the accuracy of the numerical scheme. This formulation augments the discrete Lagrange multiplier for the incompressibility constraint, thereby improving the original method's accuracy. This volumetric energy is incorporated by decomposing the strain energy into isochoric and dilatational components, as in standard solid mechanics formulations of nearly incompressible elasticity. We study the performance of the stabilized method using several quasi-static solid mechanics benchmarks, a dynamic fluid-structure interaction benchmark, and a detailed three-dimensional model of esophageal transport. The accuracy achieved by the stabilized immersed formulation is comparable to that of a stabilized finite element method for incompressible elasticity using similar numbers of structural degrees of freedom.

A mechanics-based perspective on the function of the esophagogastric junction during functional luminal imaging probe manometry.

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.

Peristaltic regimes in esophageal transport.

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.

A fully resolved multiphysics model of gastric peristalsis and bolus emptying in the upper gastrointestinal tract.

Over the past few decades, in silico modeling of organ systems has significantly furthered our understanding of their physiology and biomechanical function. In spite of the relative importance of the digestive system in normal functioning of the human body, there is a scarcity of high-fidelity models for the upper gastrointestinal tract including the esophagus and the stomach. In this work, we present a detailed numerical model of the upper gastrointestinal tract that not only accounts for the fiber architecture of the muscle walls, but also the multiphasic components they help transport during normal digestive function. Construction details for 3D models of representative stomach geometry are presented along with a simple strategy for assigning circular and longitudinal muscle fiber orientations for each layer. We developed a fully resolved model of the stomach to simulate gastric peristalsis by systematically activating muscle fibers embedded in the stomach. Following this, for the first time, we simulate gravity-driven bolus emptying into the stomach due to density differences between ingested contents and fluid contents of the stomach. Finally, we present a case of retrograde flow of fluid from the stomach into the esophagus, resembling the phenomenon of acid reflux. This detailed computational model of the upper gastrointestinal tract provides a foundation for future models to investigate the biomechanics of acid reflux and probe various strategies for gastric bypass surgeries to address the growing problem of obesity.

Virtual disease landscape using mechanics-informed machine learning: Application to esophageal disorders.

Esophageal disorders are related to the mechanical properties and function of the esophageal wall. Therefore, to understand the underlying fundamental mechanisms behind various esophageal disorders, it is crucial to map mechanical behavior of the esophageal wall in terms of mechanics-based parameters corresponding to altered bolus transit and increased intrabolus pressure. We present a hybrid framework that combines fluid mechanics and machine learning to identify the underlying physics of various esophageal disorders (motility disorders, eosinophilic esophagitis, reflux disease, scleroderma esophagus) and maps them onto a parameter space which we call the virtual disease landscape (VDL). A one-dimensional inverse model processes the output from an esophageal diagnostic device called the functional lumen imaging probe (FLIP) to estimate the mechanical "health" of the esophagus by predicting a set of mechanics-based parameters such as esophageal wall stiffness, muscle contraction pattern and active relaxation of esophageal wall. The mechanics-based parameters were then used to train a neural network that consists of a variational autoencoder that generated a latent space and a side network that predicted mechanical work metrics for estimating esophagogastric junction motility. The latent vectors along with a set of discrete mechanics-based parameters define the VDL and formed clusters corresponding to specific esophageal disorders. The VDL not only distinguishes among disorders but also displayed disease progression over time. Finally, we demonstrated the clinical applicability of this framework for estimating the effectiveness of a treatment and tracking patients' condition after a treatment.

Mechanics informed fluoroscopy of esophageal transport.

Fluoroscopy is a radiographic procedure for evaluating esophageal disorders such as achalasia, dysphasia and gastroesophageal reflux disease. It performs dynamic imaging of the swallowing process and provides anatomical detail and a qualitative idea of how well swallowed fluid is transported through the esophagus. In this work, we present a method called mechanics informed fluoroscopy (FluoroMech) that derives patient-specific quantitative information about esophageal function. FluoroMech uses a convolutional neural network to perform segmentation of image sequences generated from the fluoroscopy, and the segmented images become input to a one-dimensional model that predicts the flow rate and pressure distribution in fluid transported through the esophagus. We have extended this model to identify and estimate potential physiomarkers such as esophageal wall stiffness and active relaxation ahead of the peristaltic wave in the esophageal musculature. FluoroMech requires minimal computational time and hence can potentially be applied clinically in the diagnosis of esophageal disorders.

Powder Metallurgical Processing and Characterization of Molybdenum Addition to Tungsten Heavy Alloys by Spark Plasma Sintering.

The effect of adding molybdenum to the heavy tungsten alloy of W-Ni-Fe on its material characteristics was examined in the current study. The elemental powders of tungsten, iron, nickel, and molybdenum, with a composition analogous to W-3Fe-7Ni-xMo (x = 0, 22.5, 45, 67.5 wt.%), were fabricated using the spark plasma sintering (SPS) technique at a sintering temperature of 1400 °C and under pressure of 50 MPa. The sintered samples were subjected to microstructural characterization and tested for mechanical strength. The smallest grain size of 9.99 microns was observed for the 45W-45Mo alloy. This alloy also gave the highest tensile and yield strengths of 1140 MPa and 763 MPa, respectively. The hardness increased with the increased addition of molybdenum. The high level of hardness was observed for 67.5Mo with a 10.8% increase in the base alloy's hardness. The investigation resulted in the alloy of 45W-7Ni-3Fe-45Mo, observed to provide optimum mechanical properties among all the analyzed samples.