Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Patients with Normal- and High-Tension Glaucoma.

PURPOSE: To study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in patients with glaucoma. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: Two hundred twenty-nine patients with primary open-angle glaucoma (subdivided into 115 patients with high-tension glaucoma [HTG] and 114 patients with normal-tension glaucoma [NTG]). METHODS: For 1 eye of each patient, we imaged the ONH using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 35 mmHg) achieved through ophthalmodynamometry. A 3-dimensional strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e., deformation) in each ONH. Strains in the prelaminar tissue (PLT), the retina, the choroid, the sclera, and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec). This was performed globally, then locally according to a previously published regionalization scheme. MAIN OUTCOME MEASURES: Associations between ONH strains and values of retinal sensitivity from visual field testing. RESULTS: For patients with HTG, we found (1) significant negative linear associations between ONH strains and retinal sensitivity (P < 0.001; on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 decibels [dB]), (2) that high-strain regions colocalized with anatomically mapped regions of high visual field loss, and (3) that the strongest negative associations were observed in the superior region and in the PLT. In contrast, for patients with NTG, no significant associations between strains and retinal sensitivity were observed except in the superotemporal region of the LC. CONCLUSIONS: We found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, patients with HTG who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend in general was less pronounced in patients with NTG, which could suggest a distinct pathophysiologic relationship between the two glaucoma subtypes.

A mechanistic model of a PDGFRα(+) cell.

A novel platelet-derived growth factor receptor alpha-positive cell (PDGFRα(+)) has recently been identified as part of the purinergic inhibitory neural control mechanism in the gastrointestinal (GI) tract. The mechanism through which PDGFRα(+) cells mediate GI muscle relaxation has been found to be associated with the purine receptors P2Y1 and apamin-sensitive SK3 channels that are highly expressed in these cells. This study aims to develop a mechanistic model elucidating a proposed mechanism through which PDGFRα(+) cells contribute to purinergic inhibitory neuromuscular transmission. In accordance with recent experimental findings, the model describes how the binding of neurotransmitters, released from enteric neurons, triggers the release of Ca(2+) from the endoplasmic reticulum in the PDGFRα(+) cells, and how this subsequently leads to large amplitude transient outward currents, which in turn hyperpolarize the cell. The model has been validated against experimental recordings and good agreement was found under normal and pharmacologically-altered conditions. This model demonstrates the feasibility of the proposed mechanism and provides a basis for understanding the mechanism underlying purinergic control of colonic motility.

Comparing finite viscoelastic constitutive relations and variational principles in modeling gastrointestinal soft tissue deformation.

The mechanical attributes of soft tissues within the gastrointestinal (GI) tract are crucial for the effective operation of the GI system, and alterations in these properties may play a role in motility-related disorders. Various constitutive modeling approaches have been suggested to comprehend the response of soft tissues to diverse loading conditions. Among these, hyperelastic constitutive models based on finite elasticity have gained popularity. However, these models fall short in capturing rate- and time-dependent tissue properties. In contrast, finite viscoelastic models offer a solution to overcome these limitations. Nevertheless, the development of a suitable finite viscoelastic model, coupled with a variational formulation for efficient finite element (FE) implementation, remains an ongoing challenge. This study aims to address this gap by developing diverse finite viscoelastic constitutive relations and applying them to characterize soft tissue. Furthermore, the research explores the creation of compressible, nearly incompressible, and incompressible versions of viscoelastic constitutive relations, along with their variational formulation, to facilitate efficient FE implementation. The proposed model demonstrates remarkable accuracy in replicating experimental results, achieving an R2 value exceeding 0.99.

The origin of intraluminal pressure waves in gastrointestinal tract.

The gastrointestinal (GI) peristalsis is an involuntary wave-like contraction of the GI wall that helps to propagate food along the tract. Many GI diseases, e.g., gastroparesis, are known to cause motility disorders in which the physiological contractile patterns of the wall get disrupted. Therefore, to understand the pathophysiology of these diseases, it is necessary to understand the mechanism of GI motility. We present a coupled electromechanical model to describe the mechanism of GI motility and the transduction pathway of cellular electrical activities into mechanical deformation and the generation of intraluminal pressure (IP) waves in the GI tract. The proposed model consolidates a smooth muscle cell (SMC) model, an actin-myosin interaction model, a hyperelastic constitutive model, and a Windkessel model to construct a coupled model that can describe the origin of peristaltic contractions in the intestine. The key input to the model is external electrical stimuli, which are converted into mechanical contractile waves in the wall. The model recreated experimental observations efficiently and was able to establish a relationship between change in luminal volume and pressure with the compliance of the GI wall and the peripheral resistance to bolus flow. The proposed model will help us understand the GI tract's function in physiological and pathophysiological conditions.

Biventricular finite element modeling of the fetal heart in health and during critical aortic stenosis.

Finite Element simulations are a robust way of investigating cardiac biomechanics. To date, it has only been performed with the left ventricle (LV) alone for fetal hearts, even though results are likely different with biventricular (BiV) simulations. In this research, we conduct BiV simulations of the fetal heart based on 4D echocardiography images to show that it can capture the biomechanics of the normal healthy fetal heart, as well as those of fetal aortic stenosis better than the LV alone simulations. We found that performing LV alone simulations resulted in overestimation of LV stresses and pressures, compared to BiV simulations. Interestingly, inserting a compliance between the LV and right ventricle (RV) in the lumped parameter model of the LV only simulation effectively resolved these overestimations, demonstrating that the septum could be considered to play a LV-RV pressure communication role. However, stresses and strains spatial patterns remained altered from BiV simulations after the addition of the compliance. The BiV simulations corroborated previous studies in showing disease effects on the LV, where fetal aortic stenosis (AS) drastically elevated LV pressures and reduced strains and stroke volumes, which were moderated down with the addition of mitral regurgitation (MR). However, BiV simulations enabled an evaluation of the RV as well, where we observed that effects of the AS and MR on pressures and stroke volumes were generally much smaller and less consistent. The BiV simulations also enabled investigations of septal dynamics, which showed a rightward shift with AS, and partial restoration with MR. Interestingly, AS tended to enhance RV stroke volume, but MR moderated that down.

Adduction induces large optic nerve head deformations in subjects with normal-tension glaucoma.

PURPOSE: To assess intraocular pressure (IOP)-induced and gaze-induced optic nerve head (ONH) strains in subjects with high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). DESIGN: Clinic-based cross-sectional study. METHODS: The ONH from one eye of 228 subjects (114 subjects with HTG (pre-treatment IOP≥21 mm Hg) and 114 with NTG (pre-treatment IOP<21 mm Hg)) was imaged with optical coherence tomography (OCT) under the following conditions: (1) OCT primary gaze, (2) 20° adduction from OCT primary gaze, (3) 20° abduction from OCT primary gaze and (4) OCT primary gaze with acute IOP elevation (to approximately 33 mm Hg). We then performed digital volume correlation analysis to quantify IOP-induced and gaze-induced ONH tissue deformations and strains. RESULTS: Across all subjects, adduction generated high effective strain (4.4%±2.3%) in the LC tissue with no significant difference (p>0.05) with those induced by IOP elevation (4.5%±2.4%); while abduction generated significantly lower (p=0.01) effective strain (3.1%±1.9%). The lamina cribrosa (LC) of HTG subjects exhibited significantly higher effective strain than those of NTG subjects under IOP elevation (HTG: 4.6%±1.7% vs NTG: 4.1%±1.5%, p<0.05). Conversely, the LC of NTG subjects exhibited significantly higher effective strain than those of HTG subjects under adduction (NTG: 4.9%±1.9% vs HTG: 4.0%±1.4%, p<0.05). CONCLUSION: We found that NTG subjects experienced higher strains due to adduction than HTG subjects, while HTG subjects experienced higher strain due to IOP elevation than NTG subjects-and that these differences were most pronounced in the LC tissue.

Are Macula or Optic Nerve Head Structures Better at Diagnosing Glaucoma? An Answer Using Artificial Intelligence and Wide-Field Optical Coherence Tomography.

Purpose: We wanted to develop a deep-learning algorithm to automatically segment optic nerve head (ONH) and macula structures in three-dimensional (3D) wide-field optical coherence tomography (OCT) scans and to assess whether 3D ONH or macula structures (or a combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed using 319 OCT scans of glaucoma eyes and 298 scans of nonglaucoma eyes. Scans were compensated to improve deep-tissue visibility. We developed a deep-learning algorithm to automatically label major tissue structures, trained with 270 manually annotated B-scans. The performance was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D-CNN) was then designed using 500 OCT volumes and corresponding automatically segmented labels. This algorithm was trained and tested on three datasets: cropped scans of macular tissues, those of ONH tissues, and wide-field scans. The classification performance for each dataset was reported using the area under the curve (AUC). Results: Our segmentation algorithm achieved a DC of 0.94 ± 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field scans, followed by ONH scans, and finally macula scans, with AUCs of 0.99 ± 0.01, 0.93 ± 0.06 and 0.91 ± 0.11, respectively. Conclusions: This study showed that wide-field OCT may allow for significantly improved glaucoma diagnosis over typical OCTs of the ONH or macula. Translational Relevance: This could lead to mainstream clinical adoption of 3D wide-field OCT scan technology.

Antral recirculation in the stomach during gastric mixing.

We investigate flow in the stomach during gastric mixing using a numerical simulation with an anatomically realistic geometry and free-surface flow modeling. Because of momentum differences between greater and lesser curvatures during peristaltic contractions, time-averaged recirculation is generated in the antrum, with retropulsive flow away from the pylorus and compensation flow along the greater curvature toward the pylorus. Gastric content in the distal stomach is continuously transported to the distal antrum by the forward flow of antral recirculation, and it is then mixed by the backward retropulsive flow. Hence, the content inside the antral recirculation is well mixed independently of initial location, whereas the content outside the recirculation is poorly mixed. Free-surface modeling enables us to analyze the effects of posture on gastric mixing. In the upright, prone, and right lateral positions, most of the antrum is filled with content, and the content is well mixed by antral recirculation. In contrast, in the supine and left lateral positions, most of the content is located outside antral recirculation, which results in poor mixing. The curved, twisted shape of the stomach substantially supports gastric mixing in fluid mechanical terms.

Contribution of Ventricular Motion and Sampling Location to Discrepancies in Two-Dimensional Versus Three-Dimensional Fetal Ventricular Strain Measures.

BACKGROUND: Echocardiographic quantification of fetal cardiac strain is important to evaluate function and the need for intervention, with both two-dimensional (2D) and three-dimensional (3D) strain measurements currently feasible. However, discrepancies between 2D and 3D measurements have been reported, the etiologies of which are unclear. This study sought to determine the etiologies of the differences between 2D and 3D strain measurements. METHODS: A validated cardiac motion-tracking algorithm was used on 3D cine ultrasound images acquired in 26 healthy fetuses. Both 2D and 3D myocardial strain quantifications were performed on each image set for controlled comparisons. Finite element modeling of 2 left ventricle (LV) models with minor geometrical differences were performed with various helix angle configurations for validating image processing results. RESULTS: Three-dimensional longitudinal strain (LS) was significantly lower than 2D LS for the LV free wall and septum but not for the right ventricular (RV) free wall, while 3D circumferential strain (CS) was significantly higher than 2D CS for the LV, RV, and septum. The LS discrepancy was due to 2D long-axis imaging not capturing the out-of-plane motions associated with LV twist, while the CS discrepancy was due to the systolic motion of the heart toward the apex that caused out-of-plane motions in 2D short-axis imaging. A timing mismatch between the occurrences of peak longitudinal and circumferential dimensions caused a deviation in zero-strain referencing between 2D and 3D strain measurements, contributing to further discrepancies between the 2. CONCLUSIONS: Mechanisms for discrepancies between 2D and 3D strain measurements in fetal echocardiography were identified, and inaccuracies associated with 2D strains were highlighted. Understanding of this mechanism is useful and important for future standardization of fetal cardiac strain measurements, which we propose to be important in view of large discrepancies in measured values in the literature.

Quantification of gastrointestinal sodium channelopathy.

Na(v)1.5 sodium channels, encoded by SCN5A, have been identified in human gastrointestinal interstitial cells of Cajal (ICC) and smooth muscle cells (SMC). A recent study found a novel, rare missense R76C mutation of the sodium channel interacting protein telethonin in a patient with primary intestinal pseudo-obstruction. The presence of a mutation in a patient with a motility disorder, however, does not automatically imply a cause-effect relationship between the two. Patch clamp experiments on HEK-293 cells previously established that the R76C mutation altered Na(v)1.5 channel function. Here the process through which these data were quantified to create stationary Markov state models of wild-type and R76C channel function is described. The resulting channel descriptions were included in whole cell ICC and SMC computational models and simulations were performed to assess the cellular effects of the R76C mutation. The simulated ICC slow wave was decreased in duration and the resting membrane potential in the SMC was depolarized. Thus, the R76C mutation was sufficient to alter ICC and SMC cell electrophysiology. However, the cause-effect relationship between R76C and intestinal pseudo-obstruction remains an open question.

Biventricular biaxial mechanical testing and constitutive modelling of fetal porcine myocardium passive stiffness.

The evaluation of fetal heart mechanical function is becoming increasingly important for determining the prognosis and making subsequent decisions on the treatment and management of congenital heart diseases. Finite Element (FE) modelling can potentially provide detailed information on fetal hearts, and help perform virtual interventions to assist in predicting outcomes and supporting clinical decisions. Previous FE studies have enabled an improved understanding of healthy and diseased fetal heart biomechanics. However, to date, the mechanical properties of the fetal myocardium have not been well characterized which limits the reliability of such modelling. Here, we characterize the passive mechanical properties of late fetal and neonatal porcine hearts via biaxial mechanical testing as a surrogate for human fetal heart mechanical properties. We used samples from both the right and left ventricles over the late gestational period from 85 days of gestation to birth. Constitutive modelling was subsequently performed with a transversely isotropic Fung-type model and a Humphrey-type model, using fiber orientations identified with histology. We found no significant difference in mechanical stiffness across all age groups and between the right and left ventricular samples. This was likely due to the similarity in LV and RV pressures in the fetal heart, and similar gestational maturity across these late gestational ages. We thus recommend using the constitutive model for the average stress-stress behaviour of the tissues in future modelling work. Furthermore, we characterized the variability of the stiffness to inform such work.

How does the Nature of an Excipient and an Atheroma Influence Drug-Coated Balloon Therapy?

The advent of drug-eluting stents and drug-coated balloons have significantly improved the clinical outcome of patients with vascular occlusions. However, ischemic vascular disease remains the most common cause of death worldwide. Improving the current treatment modalities demands a better understanding of the processes which govern drug uptake and retention in blood vessels. In this study, we evaluated the influence of urea and butyryl-trihexyl citrate, as excipients, on the efficacy of drug-coated balloon therapy. An integrated approach, utilizing both in-vitro and in-silico methods, was used to quantify the tracking loss, vessel adhesion, drug release, uptake, and distribution associated with the treatment. Moreover, a parametric study was used to evaluate the potential influence of different types of lesions on drug-coated balloon therapy. Despite the significantly higher tracking loss (urea: 35.5% vs. butyryl-trihexyl citrate: 8.13%) observed in the urea-based balloons, the drug uptake was almost two times greater than with its hydrophobic counterpart. Non-calcified lesions were found to delay the transmural propagation of sirolimus while calcification was shown to limit the retentive potential of lesions. Ultimately this study helps to elucidate how different excipients and types of lesions may influence the efficacy of drug-coated balloon therapy.

Describing the Structural Phenotype of the Glaucomatous Optic Nerve Head Using Artificial Intelligence.

PURPOSE: To develop a novel deep-learning approach that can describe the structural phenotype of the glaucomatous optic nerve head (ONH) and can be used as a robust glaucoma diagnosis tool. DESIGN: Retrospective, deep-learning approach diagnosis study. METHOD: We trained a deep-learning network to segment 3 neural-tissue and 4 connective-tissue layers of the ONH. The segmented optical coherence tomography images were then processed by a customized autoencoder network with an additional parallel branch for binary classification. The encoder part of the autoencoder reduced the segmented optical coherence tomography images into a low-dimensional latent space (LS), whereas the decoder and the classification branches reconstructed the images and classified them as glaucoma or nonglaucoma, respectively. We performed principal component analysis on the latent parameters and identified the principal components (PCs). Subsequently, the magnitude of each PC was altered in steps and reported how it impacted the morphology of the ONH. RESULTS: The image reconstruction quality and diagnostic accuracy increased with the size of the LS. With 54 parameters in the LS, the diagnostic accuracy was 92.0 ± 2.3% with a sensitivity of 90.0 ± 2.4% (at 95% specificity), and the corresponding Dice coefficient for the reconstructed images was 0.86 ± 0.04. By changing the magnitudes of PC in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a "nonglaucoma" to a "glaucoma" condition. CONCLUSIONS: Our network was able to identify novel biomarkers of the ONH for glaucoma diagnosis. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma.

The three-dimensional structural configuration of the central retinal vessel trunk and branches as a glaucoma biomarker.

PURPOSE: To assess whether the 3-dimensional (3D) structural configuration of the central retinal vessel trunk and its branches (CRVT&B) could be used as a diagnostic marker for glaucoma. DESIGN: Retrospective, deep-learning approach diagnosis study. METHODS: We trained a deep learning network to automatically segment the CRVT&B from the B-scans of the optical coherence tomography (OCT) volume of the optic nerve head. Subsequently, 2 different approaches were used for glaucoma diagnosis using the structural configuration of the CRVT&B as extracted from the OCT volumes. In the first approach, we aimed to provide a diagnosis using only 3D convolutional neural networks and the 3D structure of the CRVT&B. For the second approach, we projected the 3D structure of the CRVT&B orthographically onto sagittal, frontal, and transverse planes to obtain 3 two-dimensional (2D) images, and then a 2D convolutional neural network was used for diagnosis. The segmentation accuracy was evaluated using the Dice coefficient, whereas the diagnostic accuracy was assessed using the area under the receiver operating characteristic curves (AUCs). The diagnostic performance of the CRVT&B was also compared with that of retinal nerve fiber layer (RNFL) thickness (calculated in the same cohorts). RESULTS: Our segmentation network was able to efficiently segment retinal blood vessels from OCT scans. On a test set, we achieved a Dice coefficient of 0.81 ± 0.07. The 3D and 2D diagnostic networks were able to differentiate glaucoma from nonglaucoma subjects with accuracies of 82.7% and 83.3%, respectively. The corresponding AUCs for the CRVT&B were 0.89 and 0.90, higher than those obtained with RNFL thickness alone (AUCs ranging from 0.74 to 0.80). CONCLUSIONS: Our work demonstrated that the diagnostic power of the CRVT&B is superior to that of a gold-standard glaucoma parameter, that is, RNFL thickness. Our work also suggested that the major retinal blood vessels form a "skeleton"-the configuration of which may be representative of major optic nerve head structural changes as typically observed with the development and progression of glaucoma.

Assessing the influence of atherosclerosis on drug coated balloon therapy using computational modelling.

Interventional therapies such as drug-eluting stents (DES) and drug-coated balloons (DCB) have significantly improved the clinical outcomes of patients with coronary occlusions in recent years. Despite this marked improvement, ischemic cardiovascular disease remains the most common cause of death worldwide. To address this, research efforts are focused on improving the safety and efficacy of the next generation of these devices. However, current experimental methods are unable to account for the influence of atherosclerotic lesions on drug uptake and retention. Therefore, in this study, we used an integrated approach utilizing both in vitro and in silico methods to assess the performance of DCB therapy. This approach was validated against existing in vivo results before being used to numerically estimate the effect of the atheroma. A bolus release of sirolimus was observed with our coating matrix. This, coupled with the rapid saturation of specific and non-specific binding sites observed in our study, indicated that increasing the therapeutic dose coated onto the balloons might not necessarily result in greater uptake and/or retention. Additionally, our findings alluded to an optimal exposure time, dependent on the coating matrix, for the DCBs to be expanded against the vessel. Moreover, our findings suggest that a biphasic drug release profile might be beneficial for establishing and maintaining the saturation of bindings sites within severely occluded vessels. Ultimately, we have demonstrated that computational methods may be capable of assessing the efficacy of DCB therapy as well as predict the influence of atherosclerotic lesions on said efficacy.

Changes in Iris Stiffness and Permeability in Primary Angle Closure Glaucoma.

Purpose: To evaluate the biomechanical properties of the iris by evaluating iris movement during pupil constriction and to compare such properties between healthy and primary angle-closure glaucoma (PACG) subjects. Methods: A total of 140 subjects were recruited for this study. In a dark room, the anterior segments of one eye per subject were scanned using anterior segment optical coherence tomography imaging during induced pupil constriction with an external white light source of 1700 lux. Using a custom segmentation code, we automatically isolated the iris segments from the AS-OCT images, which were then discretized and transformed into a three-dimensional point cloud. For each iris, a finite element (FE) mesh was constructed from the point cloud, and an inverse FE simulation was performed to match the clinically observed iris constriction in the AS-OCT images. Through this optimization process, we were able to identify the elastic modulus and permeability of each iris. Results: For all 140 subjects (95 healthy and 45 PACG of Indian/Chinese ethnicity; age 60.2 ± 8.7 for PACG subjects and 57.7 ± 10.1 for healthy subjects), the simulated deformation pattern of the iris during pupil constriction matched well with OCT images. We found that the iris stiffness was higher in PACG than in healthy controls (24.5 ± 8.4 kPa vs. 17.1 ± 6.6 kPa with 40 kPa of active stress specified in the sphincter region; P < 0.001), whereas iris permeability was lower (0.41 ± 0.2 mm2/kPa s vs. 0.55 ± 0.2 mm2/kPa s; p = 0.142). Conclusions: This study suggests that the biomechanical properties of the iris in PACG are different from those in healthy controls. An improved understanding of the biomechanical behavior of the iris may have implications for the understanding and management of angle-closure glaucoma.

OCT-GAN: single step shadow and noise removal from optical coherence tomography images of the human optic nerve head.

Speckle noise and retinal shadows within OCT B-scans occlude important edges, fine textures and deep tissues, preventing accurate and robust diagnosis by algorithms and clinicians. We developed a single process that successfully removed both noise and retinal shadows from unseen single-frame B-scans within 10.4ms. Mean average gradient magnitude (AGM) for the proposed algorithm was 57.2% higher than current state-of-the-art, while mean peak signal to noise ratio (PSNR), contrast to noise ratio (CNR), and structural similarity index metric (SSIM) increased by 11.1%, 154% and 187% respectively compared to single-frame B-scans. Mean intralayer contrast (ILC) improvement for the retinal nerve fiber layer (RNFL), photoreceptor layer (PR) and retinal pigment epithelium (RPE) layers decreased from 0.362 ± 0.133 to 0.142 ± 0.102, 0.449 ± 0.116 to 0.0904 ± 0.0769, 0.381 ± 0.100 to 0.0590 ± 0.0451 respectively. The proposed algorithm reduces the necessity for long image acquisition times, minimizes expensive hardware requirements and reduces motion artifacts in OCT images.

Biomechanics of Human Fetal Hearts with Critical Aortic Stenosis.

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.

An extended bidomain framework incorporating multiple cell types.

The muscular layers within the walls of the gastrointestinal tract contain two distinct cell types, the interstitial cells of Cajal and smooth muscle cells, which together produce rhythmic depolarizations known as slow waves. The bidomain model of tissue-level electrical activity consists of single intracellular and extracellular domains separated by an intervening membrane at all points in space and is therefore unable to adequately describe the presence of two distinct cell types in its conventional form. Here, an extension to the bidomain framework is presented whereby multiple interconnected cell types can be incorporated. Although the derivation is focused on the interactions of the interstitial cells of Cajal and smooth muscle cells, the conceptual framework can be more generally applied. Simulations demonstrating the feasibility of the proposed model are also presented.

A viscoelastic framework for inflation testing of gastrointestinal tissue.

Gastrointestinal (GI) diseases are often associated with hypertrophy of the layers of the GI wall, along with dilatation and a denervation of smooth muscle cells which alters the biomechanical properties of the tissue. 'Balloon distension' is a specialised experimental protocol performed on hollow organs to investigate their biomechanical properties. A balloon is inserted and pressurized during this procedure and the change in external diameter is monitored as a function of the applied pressure. A hyperelastic framework is often used in this context to evaluate the stresses in the wall after inflation. However, this only gives an idea about the final equilibrium state of the tissue, whereas the intermediate states of deformations are overlooked. GI soft tissues are viscoelastic, thus, the stress values during inflation are loading rate dependent and are higher than the equilibrium state values. Therefore, it is necessary to consider the time- and rate-dependent material properties during a balloon distension test. The aim of this work was to develop a viscoelastic framework for interpreting balloon distension experiments under finite deformation. To demonstrate the efficacy of the framework, it was used to recreate experimental results from intestinal and colonic tissue segments. In all cases, the simulation results were well matched (R2>0.9) with the experimental data.