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

   https://doi.org/10.1007/s10237-023-01688-4  

   Elisha, Guy; Halder, Sourav; Acharya, Shashank; Carlson, Dustin A.; Kou, Wenjun; Kahrilas, Peter J.; Pandolfino, John E.; Patankar, Neelesh A. (June 2023, Biomechanics and Modeling in Mechanobiology)

   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. 

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2. Enhancing Chicago Classification diagnoses with functional lumen imaging probe—mechanics (FLIP‐MECH)

   https://doi.org/10.1111/nmo.14841  

   Halder, Sourav; Yamasaki, Jun; Liu, Xinyi; Carlson, Dustin_A; Kou, Wenjun; Kahrilas, Peter_J; Pandolfino, John_E; Patankar, Neelesh_A (June 2024, Neurogastroenterology & Motility)

   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. 

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

   https://doi.org/10.1152/ajpgi.00032.2021  

   Acharya, Shashank; Halder, Sourav; Carlson, Dustin A.; Kou, Wenjun; Kahrilas, Peter J.; Pandolfino, John E.; Patankar, Neelesh A. (May 2021, American Journal of Physiology-Gastrointestinal and Liver Physiology)

   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. 

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

   https://doi.org/10.1152/ajpgi.00324.2020  

   Acharya, Shashank; Halder, Sourav; Carlson, Dustin A.; Kou, Wenjun; Kahrilas, Peter J.; Pandolfino, John E.; Patankar, Neelesh A. (February 2021, American Journal of Physiology-Gastrointestinal and Liver Physiology)

   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. 

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5. A mechanics-based perspective on the pressure-cross-sectional area loop within the esophageal body

   https://doi.org/10.3389/fphys.2022.1066351  

   Elisha, Guy; Halder, Sourav; Carlson, Dustin A.; Kahrilas, Peter J.; Pandolfino, John E.; Patankar, Neelesh A. (January 2023, Frontiers in Physiology)

   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. 

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