Enhancing Chicago Classification diagnoses with functional lumen imaging probe-mechanics (FLIP-MECH).

BACKGROUND: Esophageal 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. METHODS: The "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. RESULTS: Subjects 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. CONCLUSION: Mechanics-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.

Four-dimensional impedance manometry volume metrics for predicting abnormal bolus retention.

BACKGROUND: The objective measurement for esophageal bolus volume and bolus clearance could classify abnormal high-resolution manometry (HRM) beyond the current Chicago classification. We aimed to compare the novel four-dimensional impedance manometry (4D HRM) volume metrics with timed barium esophagram (TBE). METHODS: Adults with esophageal symptoms undergoing HRM and TBE were included. A custom-built program for 4D HRM analysis measured esophageal luminal cross-sectional area (CSA) from impedance and subsequently derived esophageal bolus volume and clearance. 4D HRM volume metrics included pre-swallow residual volume, maximal volume, retention volume, and clearance ratio defined as 1.0-retention volume divided by the maximal volume. An abnormal TBE was defined as a column height >5 cm at 1 min or 5 min. KEY RESULTS: A total of 95 patients (normal motility: 33%; ineffective esophageal motility: 12%; absent contractility: 10%; esophagogastric junction outflow obstruction: 30%; type I achalasia: 5%; type II achalasia: 12%) were categorized into normal TBE (58%), abnormal TBE at 1 min (17%), and abnormal TBE at 5 min (25%). The AUROC demonstrated that, among all 4D HRM volume metrics, the clearance ratio had the best performance in predicting abnormal TBE at 5 min (AUROC, 95% confidence interval: 0.89, 0.82-0.96), and exhibited a strong negative correlation with TBE at 5 min (r = -0.65; p < 0.001). CONCLUSIONS & INFERENCES: Novel 4D HRM volume metrics provide objective measurement of esophageal bolus volume and bolus clearance. The clearance ratio has a strong correlation with TBE and could potentially serve as a substitute for TBE to measure esophageal retention.

An Investigation of the Energy Harvesting Capabilities of a Novel Three-Dimensional Super-Cell Phononic Crystal with a Local Resonance Structure.

Using the piezoelectric (PZT) effect, energy-harvesting has become possible for phononic crystal (PnC). Low-frequency vibration energy harvesting is more of a challenge, which can be solved by local resonance phononic crystals (LRPnCs). A novel three-dimensional (3D) energy harvesting LRPnC is proposed and further analyzed using the finite element method (FEM) software COMSOL. The 3D LRPnC with spiral unit-cell structures is constructed with a low initial frequency and wide band gaps (BGs). According to the large vibration deformation of the elastic beam near the scatterer, a PZT sheet is mounted in the surface of that beam, to harvest the energy of elastic waves using the PZT effect. To further improve the energy-harvesting performance, a 5 × 5 super-cell is numerically constructed. Numerical simulations show that the present 3D super-cell PnC structure can make full use of the advantages of the large vibration deformation and the PZT effect, i.e., the BGs with a frequency range from 28.47 Hz to 194.21 Hz with a bandwidth of 142.7 Hz, and the maximum voltage output is about 29.3 V under effective sound pressure with a peak power of 11.5 µW. The present super-cell phononic crystal structure provides better support for low-frequency vibration energy harvesting, when designing PnCs, than that of the traditional Prague type.

The Severity of Reduced Esophageal Distensibility Parallels Eosinophilic Esophagitis Disease Duration.

BACKGROUND & AIMS: Chronic inflammation of eosinophilic esophagitis (EoE) results in progressive, fibrostenotic remodeling of the esophageal wall. This study aimed to demonstrate objective changes in esophageal distensibility relative to duration of EoE disease using a functional lumen imaging probe (FLIP). METHODS: Adult patients with EoE who completed a 16-cm FLIP protocol during endoscopy were evaluated in a cross-sectional study. FLIP analysis focused on distensibility plateau (DP) of the esophageal body. The time from onset of symptoms to time of endoscopy with FLIP was assessed, as was time from symptom onset to EoE diagnosis (ie, diagnostic delay). RESULTS: A total of 171 patients (mean age 38 ± 12 years; 31% female) were included; the median symptom duration was 8 (interquartile range, 3-15) years and diagnostic delay was 4 (interquartile range, 1-12) years. At the time of endoscopy with FLIP, there were 54 patients (39%) in histologic remission (<15 eosinophils per high-power field [eos/hpf]). Symptom duration and diagnostic delay were negatively correlated with DP (rho = -0.326 and -0.309; P values < .001). Abnormal esophageal distensibility (DP ≤17 mm) was more prevalent with increased duration of symptoms (P < .004): 23% at <5 years to 64% at ≥25 years. When stratifying the cohort based on mucosal eosinophil density, patients with ≥15 eos/hpf had significantly lower DP with greater symptom duration (P = .004), while there was not a significant difference among patients with <15 eos/hpf (P = .060). CONCLUSIONS: Esophageal distensibility objectively measured with FLIP was reduced in EoE patients with greater symptom duration and diagnostic delay. This supports that EoE is a progressive, fibrostenotic disease and that FLIP may be a useful tool to monitor disease progression in EoE.

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 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.

Assessing mechanical function of peristalsis with functional lumen imaging probe panometry: Contraction power and displaced volume.

BACKGROUND AND AIMS: The distal contractile integral (DCI) quantifies the contractile vigor of primary peristalsis on high-resolution manometry (HRM), whereas no such metric exists for secondary peristalsis on functional lumen imaging probe (FLIP) panometry. This study aimed to evaluate novel FLIP metrics of contraction power and displaced volume in asymptomatic controls and a patient cohort. METHODS: Thirty-five asymptomatic controls and adult patients (with normal esophagogastric junction outflow/opening and without spasm) who completed HRM and FLIP panometry were included. The patient group also completed timed barium esophagram (TBE). Contraction power (estimate of esophageal work over time) and displaced volume (estimate of contraction-associated fluid flow) were computed from FLIP. HRM was analyzed per Chicago Classification v4.0. KEY RESULTS: In controls, median (5th-95th percentile) contraction power was 27 mW (10-44) and displaced volume was 43 mL (17-66). 95 patients were included: 72% with normal motility on HRM, 17% with ineffective esophageal motility (IEM), and 12% with absent contractility. Among patients, DCI was significantly correlated with both contraction power (rho = 0.499) and displaced volume (rho = 0.342); p values < 0.001. Both contraction power and displaced volume were greater in patients with normal motility versus IEM or absent contractility, complete versus incomplete bolus transit, and normal versus abnormal retention on TBE; p values < 0.02. CONCLUSIONS: FLIP panometry metrics of contraction power and displaced volume appeared to effectively quantify peristaltic vigor. These novel metrics may enhance evaluation of esophageal motility with FLIP panometry and provide a reliable surrogate to DCI on HRM.

Relaxation of the lower esophageal sphincter in response to reduced volume distension during FLIP Panometry.

BACKGROUND: The esophageal response to stepwise distension during the functional lumen imaging probe (FLIP) Panometry study often parallels high-resolution manometry (HRM) motility diagnoses. This study aimed to describe the changes in FLIP metrics during FLIP emptying, that is, reduced volume distension. METHODS: Adult patients who completed FLIP and HRM for esophageal motility evaluation were included. Esophagogastric junction (EGJ) opening parameters were assessed during stepwise FLIP filling to volumes of 60 mL ("filling 60 mL"), then 70 mL, and then back to 60 mL ("emptying 60 mL"). HRM studies were analyzed per Chicago classification version 4.0 (CCv4.0). KEY RESULTS: Among 265 patients included, HRM/CCv4.0 diagnoses included achalasia in 80 patients (30%), normal motility in 70 (26%), and ineffective esophageal motility (IEM) in 43 (16%). EGJ-distensibility index (DI) and EGJ diameter were greater during emptying 60 mL than filling 60 mL in achalasia, normal motility, and IEM (p values <0.002). If applying the emptying 60 mL EGJ-DI (vs. filling 60 mL EGJ-DI), EGJ opening classification changed from reduced EGJ opening to borderline EGJ opening in 31% of achalasia patients and in 2% of patients with normal motility or IEM. EGJ opening classification was unchanged in 69% achalasia and 96% of normal motility/IEM. CONCLUSIONS AND INFERENCES: This study suggests that isotonic or auxotonic relaxation of the lower esophageal sphincter occurs with reduced volume distension in patients with achalasia and normal motility. The study also supports the importance of utilizing a standardized FLIP motility study protocol (i.e., controlled, stepwise filling to 50 mL, 60 mL, then 70 mL) to provide reliable and generalizable FLIP metrics to facilitate diagnosis of esophageal motility disorders.

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.

An artificial intelligence platform provides an accurate interpretation of esophageal motility from Functional Lumen Imaging Probe Panometry studies.

BACKGROUND: Functional lumen imaging probe (FLIP) Panometry is performed at the time of sedated endoscopy and evaluates esophageal motility in response to distension. This study aimed to develop and test an automated artificial intelligence (AI) platform that could interpret FLIP Panometry studies. METHODS: The study cohort included 678 consecutive patients and 35 asymptomatic controls that completed FLIP Panometry during endoscopy and high-resolution manometry (HRM). "True" study labels for model training and testing were assigned by experienced esophagologists per a hierarchical classification scheme. The supervised, deep learning, AI model generated FLIP Panometry heatmaps from raw FLIP data and based on convolutional neural networks assigned esophageal motility labels using a two-stage prediction model. Model performance was tested on a 15% held-out test set (n = 103); the remainder of the studies were utilized for model training (n = 610). KEY RESULTS: "True" FLIP labels across the entire cohort included 190 (27%) "normal," 265 (37%) "not normal/not achalasia," and 258 (36%) "achalasia." On the test set, both the Normal/Not normal and the achalasia/not achalasia models achieved an accuracy of 89% (with 89%/88% recall, 90%/89% precision, respectively). Of 28 patients with achalasia (per HRM) in the test set, 0 were predicted as "normal" and 93% as "achalasia" by the AI model. CONCLUSIONS: An AI platform provided accurate interpretation of FLIP Panometry esophageal motility studies from a single center compared with the impression of experienced FLIP Panometry interpreters. This platform may provide useful clinical decision support for esophageal motility diagnosis from FLIP Panometry studies performed at the time of endoscopy.

Identifying spastic variant of type II achalasia after treatment with high-resolution manometry and FLIP Panometry.

BACKGROUND: Panesophageal pressurization (PEP) defines type II achalasia on high-resolution-manometry (HRM) but some patients exhibit spasm after treatment. The Chicago Classification (CC) v4.0 proposed high PEP values as predictor of embedded spasm, yet supportive evidence is lacking. METHODS: Fifty seven type II achalasia patients (47 ± 18 years, 54% males) with HRM and LIP Panometry before and after treatment were retrospectively identified. Baseline HRM and FLIP studies were analyzed to identify factors associated with post-treatment spasm, defined on HRM per CC v4.0. RESULTS: Seven patients (12%) had spasm following treatment (peroral endoscopic myotomy 47%; pneumatic dilation [PD] 37%; laparoscopic Heller myotomy 16%). At baseline, greater median maximum PEP pressure (MaxPEP) values on HRM (77 vs 55 mmHg, p = 0.045) and spastic-reactive contractile response pattern on FLIP (43% vs 8%, p = 0.033) were more common in patients with post-treatment spasm while absent contractile response on FLIP was more common in patients without spasm (14% vs 66%, p = 0.014). The strongest predictor of post-treatment spasm was the percentage of swallows with MaxPEP ≥70 mmHg (best cut-off: ≥30%), with AUROC of 0.78. A combination of MaxPEP <70 mmHg and FLIP 60 mL pressure < 40 mmHg identified patients with lower rates of post-treatment spasm (3% overall, 0% post-PD) compared to those with values above these thresholds (33% overall, 83% post-PD). CONCLUSIONS: High maximum PEP values, high FLIP 60 mL pressures and contractile response pattern on FLIP Panometry prior to treatment identified type II achalasia patients more likely to exhibit post-treatment spasm. Evaluating these features may guide personalized patient management.

Measuring esophageal compliance using functional lumen imaging probe to assess remodeling in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is associated with fibrostenotic remodeling that can be objectively assessed using the functional lumen imaging probe (FLIP). This is typically done using a metric called distensibility plateau (DP). We aimed to describe a novel measure of compliance of the esophageal body and evaluate the associated clinical characteristics in EoE. METHODS: One hundred seventy-one adult patients with EoE (mean (SD) age 38 (12) years), 31% female and 35 healthy, asymptomatic controls who completed 16-cm functional luminal imaging probe (FLIP) during endoscopy, were evaluated in a cross-sectional study. The esophageal body DP and compliance were measured using a customized analysis program, with compliance calculated as (Δ esophageal body volume)/(Δ pressure) between two FLIP-filled volumes. RESULTS: In controls, the median (5-95th percentile) DP was 19.8 mm (17.9-21) and esophageal body compliance was 0.37 ml/mmHg (0.18-1.1), which was greater than in EoE (DP 19 (11-21)), compliance 0.19 (0.02-0.71), p-values <0.001. Among EoE patients, 70 (41%) had normal compliance (>0.2 ml/mmHg) and normal DP (>17 mm); 11 (6%) had normal compliance and reduced DP; 34 (20%) had reduced compliance and normal DP; and 56 (33%) had reduced compliance and reduce DP. Patients with both reduced compliance and DP had the greatest proportion of severe rings (61% with EREFS score 2-3) and stricture (100%). CONCLUSION: FLIP provides an objective evaluation of biomechanical properties of the esophageal wall that appears enhanced by complementary application of metrics of DP and esophageal body compliance.

Functional Lumen Imaging Probe Panometry Helps Identify Clinically Relevant Esophagogastric Junction Outflow Obstruction per Chicago Classification v4.0.

INTRODUCTION: Esophagogastric junction (EGJ) outflow obstruction (EGJOO) per Chicago Classification v4.0 (CCv4.0) represents a high-resolution manometry (HRM) diagnosis with uncertain clinical significance. This study aimed to evaluate functional lumen imaging probe (FLIP) panometry among patients with EGJOO on HRM/CCv4.0 to assess clinical/manometric associations and treatment outcomes. METHODS: An observational cohort study was performed on patients who completed FLIP during endoscopy and had an HRM/CCv4.0 diagnosis of EGJOO, i.e., HRM-EGJOO (inconclusive). Abnormal FLIP panometry motility classifications were applied to identify FLIP-confirmed conclusive EGJOO. Rapid drink challenge on HRM and timed barium esophagram were also assessed. Clinical management plan was determined by treating physicians and assessed through chart review. Clinical outcome was defined using the Eckardt score (ES) during follow-up evaluation: ES < 3 was considered a good outcome. RESULTS: Of 139 adult patients with manometric EGJOO (inconclusive per CCv4.0), a treatment outcome ES was obtained in 55 after achalasia-type treatment (i.e., pneumatic dilation, peroral endoscopic myotomy, laparoscopic Heller myotomy, or botulinum toxin injection) and 36 patients after other nonachalasia-type treatment. Among patients with conclusive EGJOO by HRM-FLIP complementary impression, 77% (33/43) had a good outcome after achalasia-type treatment, whereas 0% (0/12) of patients had a good outcome after nonachalasia-type treatment. Of patients with normal EGJ opening on FLIP, one-third of patients treated with achalasia-type treatment had a good outcome, while 9 of the 10 treated conservatively had a good outcome. DISCUSSION: FLIP panometry provides a useful complement to clarify the clinical significance of an HRM/CCv4.0 EGJOO diagnosis and help direct management decisions.

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.

Identifying hiatal hernia with impedance planimetry during esophageal distension testing.

INTRODUCTION: Functional luminal imaging probe (FLIP) Panometry evaluates the esophageal response to distension involving biomechanics and motility. We have observed that hiatus hernia (HH) is evident during FLIP studies as a separation between the crural diaphragm (CD) and lower esophageal sphincter (LES) like what is seen with high-resolution manometry (HRM). The aim of this study was to compare FLIP findings to endoscopy and HRM in the detection of HH. METHODS: A total of 100 consecutive patients that completed FLIP during sedated endoscopy and HRM were included. LES-CD separation was assessed on FLIP and HRM with the presence of HH defined as LES-CD ≥1 cm. The agreement was evaluated using the kappa (κ) statistic. RESULTS: Hiatal hernia was detected in 32% of patients on HRM and 44% of patients on FLIP with a substantial agreement between studies (84% agreement; κ = 0.667). On FLIP, a 'new' HH (i.e. HH not observed on HRM) occurred in 14 patients and an "enlarged" HH (i.e., LES-CD ≥2 cm larger than on HRM) occurred in 11 patients. Among patients that also completed, timed barium esophagogram (TBE), delayed esophageal emptying on TBE was more common in patients with new or enlarged HH on FLIP than those without: 7/11 (64%) versus 2/12 (17%); p = 0.017. CONCLUSION: FLIP can detect HH with a substantial agreement with HRM, though esophageal distension with FLIP testing appeared to elicit and/or enlarge a HH in an additional 25% of patients. Although this unique response to esophageal distension may represent a mechanism of dysphagia or susceptibility to reflux, additional study is needed to clarify its significance.

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.

Estimating Probability for Esophageal Obstruction: A Diagnostic Decision Support Tool Applying Machine Learning to Functional Lumen Imaging Probe Panometry.

Background/Aims: This study aimed to develop a diagnostic tool using machine learning to apply functional luminal imaging probe (FLIP) panometry data to determine the probability of esophagogastric junction (EGJ) obstruction as determined using the Chicago Classification version 4.0 (CCv4.0) and high-resolution manometry (HRM). Methods: Five hundred and fifty-seven adult patients that completed FLIP and HRM (with a conclusive CCv4.0 assessment of EGJ outflow) and 35 asymptomatic volunteers ("controls") were included. EGJ opening was evaluated with 16-cm FLIP performed during sedated endoscopy via EGJ-distensibility index and maximum EGJ diameter. HRM was classified according to the CCv4.0 as conclusive disorders of EGJ outflow or normal EGJ outflow (timed barium esophagram applied when required and available). The probability tool utilized Bayesian additive regression treesBART, which were evaluated using a leave-one-out approach and a holdout test set. Results: Per HRM and CCv4.0, 243 patients had a conclusive disorder of EGJ outflow while 314 patients (and all 35 controls) had normal EGJ outflow. The model accuracy to predict EGJ obstruction (based on leave-one-out/holdout test set, respectively) was 89%/90%, with 87%/85% sensitivity, 92%/97% specificity, and an area under the receiver operating characteristic curve of 0.95/0.97. A free, open-source tool to calculate probability for EGJ obstruction using FLIP metrics is available at https://www.wklytics.com/nmgi/prob_flip.html. Conclusions: Application of FLIP metrics utilizing a probabilistic approach incorporates the diagnostic confidence (or uncertainty) into the clinical interpretation of EGJ obstruction. This tool can provide clinical decision support during application of FLIP Panometry for evaluation of esophageal motility disorders.

Normative values of intra-bolus pressure and esophageal compliance based on 4D high-resolution impedance manometry.

BACKGROUND: This study aimed to quantify normative values of phase-specific intra-bolus pressure (IBP) and esophageal distensibility using 4D analysis of high-resolution-impedance manometry (HRIM). METHODS: HRIM studies of supine swallows from 34 normal controls were analyzed with respect to the four phases of bolus transit: (1) accommodation, (2) compartmentalization, (3) peristalsis/esophageal emptying, and (4) ampullary emptying. Phase-specific IBP, bolus volume, and distensibility index (DI) in the esophageal body and esophagogastric junction (EGJ) during phases 1-3 were extracted. RESULTS: The median (5-95th/IQR) IBP values were as follows: phase 1: 4.0 (-2.0-10.4/1.9-5.8) mmHg, phase 2: 5.7 (0.2-14.1/3.6-8.9) mmHg, and phase 3: 11.2 (2.9-19.4/7.7-15.1) mmHg. The median bolus volume calculated by integrating impedance planimetry cross-sectional areas was 4.1 ml during the compartmentalization phase. The EGJ-DI at max EGJ diameter during phase 2 and 3 was 2.8 (1.1-9.5/1.8-3.7) mm2 /mmHg and 6.0 (3.2-20.3/5.1-7.8) mm2 /mmHg, respectively. The phase 3 EGJ-DI values (6.0 (3.2-20.3/5.1-7.8) mm2 /mmHg) were similar to those calculated using functional lumen imaging probe (FLIP) at the 60 ml volume on the same subjects (5.8 [3.5-7.2/5.0-6.4] mm2 /mmHg). CONCLUSIONS AND INFERENCES: 4D-HRIM provides a standardized methodology to track the nadir impedance and provide measurements of IBP during maximal distention across phases 1-3 of bolus transit. Median IBP and delta IBP were different across the phases, supporting the need to define IBP by phase. Additionally, the EGJ-DI calculated during phase 3 was similar to the 60-ml EGJ-DI from FLIP in the same subjects suggesting that 4D-HRIM can quantify EGJ opening during primary peristalsis.

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.

A multi-stage machine learning model for diagnosis of esophageal manometry.

High-resolution manometry (HRM) is the primary procedure used to diagnose esophageal motility disorders. Its manual interpretation and classification, including evaluation of swallow-level outcomes and then derivation of a study-level diagnosis based on Chicago Classification (CC), may be limited by inter-rater variability and inaccuracy of an individual interpreter. We hypothesized that an automatic diagnosis platform using machine learning and artificial intelligence approaches could be developed to accurately identify esophageal motility diagnoses. Further, a multi-stage modeling framework, akin to the step-wise approach of the CC, was utilized to leverage advantages of a combination of machine learning approaches including deep-learning models and feature-based models. Models were trained and tested using a dataset comprised of 1741 patients' HRM studies with CC diagnoses assigned by expert physician raters. In the swallow-level stage, three models based on convolutional neural networks (CNNs) were developed to predict swallow type and swallow pressurization (test accuracies of 0.88 and 0.93, respectively), and integrated relaxation pressure (IRP)(regression model with test error of 4.49 mmHg). 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. 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 esophageal motility (CC) diagnoses from HRM studies using raw multi-swallow data and it achieved high accuracy. Thus, this proposed modeling framework could be broadly applied to assist with HRM interpretation in a clinical setting.

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.