Using Multi-Layer Perceptron Driven Diagnosis to Compare Biomarkers for Primary Open Angle Glaucoma.

Purpose: To use neural network machine learning (ML) models to identify the most relevant ocular biomarkers for the diagnosis of primary open-angle glaucoma (POAG).

Methods: Neural network models, also known as multi-layer perceptrons (MLPs), were trained on a prospectively collected observational dataset comprised of 93 glaucoma patients confirmed by a glaucoma specialist and 113 control subjects. The base model used only intraocular pressure, blood pressure, heart rate, and visual field (VF) parameters to diagnose glaucoma.

Onset of Spontaneous Filling and Voiding Cycles in the Lower Urinary Tract: A Modeling Study.

Spontaneous filling and voiding cycles represent a key dynamical feature of the healthy lower urinary tract. Some urinary tract dysfunctions, such as over-flow incontinence, may alter the natural occurrence of these cycles. As the function of the lower urinary tract arises from the interplay of a multitude of factors, it is difficult to determine which of them can be modulated to regain spontaneous cycles.

The Eye as the Window to the Heart: Optical Coherence Tomography Angiography Biomarkers as Indicators of Cardiovascular Disease.

Alterations in microvasculature represent some of the earliest pathological processes across a wide variety of human diseases. In many organs, however, inaccessibility and difficulty in directly imaging tissues prevent the assessment of microvascular changes, thereby significantly limiting their translation into improved patient care. The eye provides a unique solution by allowing for the non-invasive and direct visualization and quantification of many aspects of the human microvasculature, including biomarkers for structure, function, hemodynamics, and metabolism.

The ocular mathematical virtual simulator: A validated multiscale model for hemodynamics and biomechanics in the human eye.

We present our continuous efforts from a modeling and numerical viewpoint to develop a powerful and flexible mathematical and computational framework called Ocular Mathematical Virtual Simulator (OMVS). The OMVS aims to solve problems arising in biomechanics and hemodynamics within the human eye. We discuss our contribution towards improving the reliability and reproducibility of computational studies by performing a thorough validation of the numerical predictions against experimental data.

Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.

In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation.

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source.

Heterogeneity of Ocular Hemodynamic Biomarkers among Open Angle Glaucoma Patients of African and European Descent.

This study investigated the heterogeneity of ocular hemodynamic biomarkers in early open angle glaucoma (OAG) patients and healthy controls of African (AD) and European descent (ED). Sixty OAG patients (38 ED, 22 AD) and 65 healthy controls (47 ED, 18 AD) participated in a prospective, cross-sectional study assessing: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), visual field (VF) and vascular densities (VD) via optical coherence tomography angiography (OCTA). Comparisons between outcomes were adjusted for age, diabetes status and BP.

Artificial Intelligence to Aid Glaucoma Diagnosis and Monitoring: State of the Art and New Directions.

Recent developments in the use of artificial intelligence in the diagnosis and monitoring of glaucoma are discussed. To set the context and fix terminology, a brief historic overview of artificial intelligence is provided, along with some fundamentals of statistical modeling. Next, recent applications of artificial intelligence techniques in glaucoma diagnosis and the monitoring of glaucoma progression are reviewed, including the classification of visual field images and the detection of glaucomatous change in retinal nerve fiber layer thickness.

Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced () analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level.

Mathematical modeling of the lower urinary tract: A review.

Aims: Understand what progress has been made toward a functionally predictive lower urinary tract (LUT) model, identify knowledge gaps, and develop from them a path forward.

Methods: We surveyed prominent mathematical models of the basic LUT components (bladder, urethra, and their neural control) and categorized the common modeling strategies and theoretical assumptions associated with each component. Given that LUT function emerges from the interaction of these components, we emphasized attempts to model their connections, and highlighted unmodeled aspects of LUT function.

Mechanism-Driven Modeling to Aid Non-invasive Monitoring of Cardiac Function Ballistocardiography.

Left ventricular (LV) catheterization provides LV pressure-volume (P-V) loops and it represents the gold standard for cardiac function monitoring. This technique, however, is invasive and this limits its applicability in clinical and in-home settings. Ballistocardiography (BCG) is a good candidate for non-invasive cardiac monitoring, as it is based on capturing non-invasively the body motion that results from the blood flowing through the cardiovascular system.

Ocular blood flow as it relates to race and disease on glaucoma.

Glaucoma is a multifactorial progressive and degenerative optic neuropathy representing one of the world's leading cause of irreversible blindness. Currently, reduction of intraocular pressure remains the only universally approved therapy, yet a wealth of studies has identified significant vascular contributions to the disease process in certain individuals. Population-based studies have identified important racial disparities and differential risk factors in glaucoma prevalence, incidence, and progression.

Combining Physiology-Based Modeling and Evolutionary Algorithms for Personalized, Noninvasive Cardiovascular Assessment Based on Electrocardiography and Ballistocardiography.

This study proposes a novel approach to obtain personalized estimates of cardiovascular parameters by combining (i) electrocardiography and ballistocardiography for noninvasive cardiovascular monitoring, (ii) a physiology-based mathematical model for predicting personalized cardiovascular variables, and (iii) an evolutionary algorithm (EA) for searching optimal model parameters. Electrocardiogram (ECG), ballistocardiogram (BCG), and a total of six blood pressure measurements are recorded on three healthy subjects. The R peaks in the ECG are used to segment the BCG signal into single BCG curves for each heart beat.

Noninvasive cardiovascular monitoring based on electrocardiography and ballistocardiography: a feasibility study on patients in the surgical intensive care unit.

The time interval between the peaks in the electroccardiogram (ECG) and ballistocardiogram (BCG) waveforms, TEB, has been associated with the pre-ejection period (PEP), which is an important marker of ventricular contractility. However, the applicability of BCG-related markers in clinical practice is limited by the difficulty to obtain a replicable and consistent signal on patients. In this study, we test the feasibility of BCG measurements within a complex clinical setting, by means of an accelerometer under the head pillow of patients admitted to the Surgical Intensive Care Unit (SICU).

Cubature Kalman Filter Based Training of Hybrid Differential Equation Recurrent Neural Network Physiological Dynamic Models.

Modeling biological dynamical systems is challenging due to the interdependence of different system components, some of which are not fully understood. To fill existing gaps in our ability to mechanistically model physiological systems, we propose to combine neural networks with physics-based models. Specifically, we demonstrate how we can approximate missing ordinary differential equations (ODEs) coupled with known ODEs using Bayesian filtering techniques to train the model parameters and simultaneously estimate dynamic state variables.

A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data.

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking.

Fluid and protein exchange in microvascular networks: Importance of modelling heterogeneity in geometrical and biophysical properties.

Key Points: Microvascular network architecture defines coupling of fluid and protein exchange. Network arrangements markedly reduce capillary hydrostatic pressures and resting fluid movement at the same time as increasing the capacity for change The presence of vascular remodelling or angiogenesis puts constraints of network behaviour The sites of fluid and protein exchange can be segregated to different portions of the network Although there is a net filtration of fluid from a network of exchange vessels, there are specific areas where fluid moves into the circulation (reabsorption) and, when protein is moving into tissue, the amount is insufficient under basal conditions to result in changes in oncotic pressure.

Abstract: Integration of functional results obtained across scales, from chemical signalling to the whole organism, is a daunting task requiring the marriage of experimental data with mathematical modelling.

Physics-based modeling of Age-related Macular Degeneration-A theoretical approach to quantify retinal and choroidal contributions to macular oxygenation.

We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption.

Neurodegenerative Disorders of the Eye and of the Brain: A Perspective on Their Fluid-Dynamical Connections and the Potential of Mechanism-Driven Modeling.

Neurodegenerative disorders (NDD) such as Alzheimer's and Parkinson's diseases are significant causes of morbidity and mortality worldwide. The pathophysiology of NDD is still debated, and there is an urgent need to understand the mechanisms behind the onset and progression of these heterogenous diseases. The eye represents a unique window to the brain that can be easily assessed via non-invasive ocular imaging.

Corrections to "Cardiovascular Function and Ballistocardiogram: A Relationship Interpreted via Mathematical Modeling" [Oct 19 2906-2917].

Presents a missing funding acknowledgment for Dr. Mihail Popescu in the above named paper.

Using Sensor Signals in the Early Detection of Heart Failure: A Case Study.

Early detection of heart failure in older adults will be a significant issue for the foreseeable future. The current article presents a case study to describe how monitoring ballistocardiogram (BCG) waveforms captured non-invasively using sensors placed under a bed mattress can detect early heart failure changes. Heart and respiratory rates obtained from the bed sensor of a female older adult who was hospitalized with acute mixed congestive heart failure, clinic notes, and data from computer simulations reflecting increasing diastolic dysfunction were analyzed.

Ocular blood flow as a clinical observation: Value, limitations and data analysis.

Alterations in ocular blood flow have been identified as important risk factors for the onset and progression of numerous diseases of the eye. In particular, several population-based and longitudinal-based studies have provided compelling evidence of hemodynamic biomarkers as independent risk factors for ocular disease throughout several different geographic regions. Despite this evidence, the relative contribution of blood flow to ocular physiology and pathology in synergy with other risk factors and comorbidities (e.

A Theoretical Approach for the Electrochemical Characterization of Ciliary Epithelium.

The ciliary epithelium (CE) is the primary site of aqueous humor (AH) production, which results from the combined action of ultrafiltration and ionic secretion. Modulation of ionic secretion is a fundamental target for drug therapy in glaucoma, and therefore it is important to identify the main factors contributing to it. As several ion transporters have been hypothesized as relevant players in CE physiology, we propose a theoretical approach to complement experimental methods in characterizing their role in the electrochemical and fluid-dynamical conditions of CE.

On the role of compressibility in poroviscoelastic models.

In this article we conduct an analytical study of a poroviscoelastic mixture model stemming from the classical Biot's consolidation model for poroelastic media, comprising a fluid component and a solid component, coupled with a viscoelastic stress-strain relationship for the total stress tensor. The poroviscoelastic mixture is studied in the one-dimensional case, corresponding to the experimental conditions of confined compression. Upon assuming (i) negligible inertial effects in the balance of linear momentum for the mixture, (ii) a Kelvin-Voigt model for the effective stress tensor and (iii) a constant hydraulic permeability, we obtain an initial value/boundary value problem of pseudo-parabolic type for the spatial displacement of the solid component of the mixture.

Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions.

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions.