Computational Tools for the Investigation of the Male Lower Urinary Tract Functionality in Health and Disease

Purpose This paper aims to show the potentialities of computational bioengineering in the field of lower urinary tract pathophysiology. Engineering methods allow the investigation of urine flow in healthy and pathologic conditions and the analysis of urethral occlusion by means of artificial urinary sphincters. Methods Computational models of bladder and urethra were developed and exploited to investigate the lower urinary tract physiology in health and in disease. Average male morphometric configurations were assumed, together with typical properties of both biological tissues and fluids. The reliability of the models was assessed by the mutual comparison of results and the investigation of data from experimental and clinical activities. Results The developed models allowed to analyze typical situations, such as the micturition in health and in disease, and the lumen occlusion by external devices. The models provided information that clinical and experimental tests barely provide, as the occurrence of turbulent phenomena within urine flow, the shear stresses at the lumen wall, the external pressure that is strictly required to occlude the lumen. Conclusions The methods of bioengineering allow broadening and deepening the knowledge of the lower urinary tract functionality. More in detail, modeling techniques provide information that contributes to explain the occurrence of pathological situations, and allows to design and to optimize clinical-surgical procedures and devices

An Integration Solution of a Simulator Implemented in Software and a Component Synthesized in Reconfigurable Hardware for a Neuroregulator System

Los trabajos para el desarrollo de un sistema artificial que aporte al mejoramiento de disfunciones del Tracto Urinario Inferior (LUT-Lower Urinary Tract) fundamentados en un marco formal y que emplea sistemas multiagentes para el modelado del sistema neurorregulador y diseños particulares se inscriben en los esfuerzos de aplicar soluciones de hardware como tendencia a desarrollar dispositivos implantables en humanos. Para ello, ha sido necesario diseñar y construir herramientas de software representativas de un modelo teórico-matemático con funcionalidades para simular el comportamiento del tracto urinario inferior y, al mismo tiempo, diseñar prototipos de centros neurorreguladores que se alojen en hardware reconfigurable (FPGA, Field Programmable Gate Array) en una especie de plataforma híbrida para la experimentación sobre diferentes soluciones y arquitecturas candidatas. Esta investigación parte de un modelo teórico-matemático, que conlleva a un simulador en software, al diseño de componentes particulares que implementan funciones de determinados centros neurorreguladores en hardware reconfigurable y que conduce a la necesidad de desarrollar por la vía de la integración una plataforma híbrida software-hardware. En este trabajo se expone una aproximación que diseña e implementa el proceso de integración y que se constituye en una solución imprescindible en este contexto.The work for the development of an artificial system that contributes to the improvement of lower urinary tract dysfunctions (LUT-Lower Urinary Tract) based on a formal framework and that uses multiagent systems for the modeling of the neuroregulatory system and particular designs are part of the efforts to apply hardware solutions as a tendency to develop implantable devices in humans. For this, it has been necessary to design and build software tools representative of a theoretical-mathematical model with functionalities to simulate the behavior of the lower urinary tract and, at the same time, design prototypes of neuroregulatory centers that are housed in reconfigurable hardware (FPGA-Field Programmable Gate Array) in a kind of hybrid platform for experimentation on different solutions and candidate architectures. This research is based on a theoretical-mathematical model, which involves a software simulator, the design of particular components that implement functions of certain neuroregulatory centers in reconfigurable hardware and that leads to the need to develop a hybrid platform through integration. software-hardware. This paper presents an approach that designs and implements the integration process and constitutes an essential solution in this context

System-on-chip design of the cortical-diencephalic centre of the lower urinary tract

This article presents the design of a field programmable gate array (FPGA)-based prototype of a system on chip (SoC) capable of behaving as one of the nerve centres comprising the neuroregulatory system in humans: the cortical-diencephalic nerve centre. The neuroregulatory system is a complex nerve system consisting of a heterogeneous group of nerve centres. These centres are distributed throughout the length of the spinal cord, are autonomous, communicate via interneurons, and govern and regulate the behaviour of multiple organs and systems in the human body. As a result of years of study of the functioning and composition of the neuroregulatory system of the lower urinary tract (LUT), the centres that regulate this system have been isolated. The objective of this study is to understand the individual functioning of each centre in order to create a general model of the neuroregulatory system that is capable of operating at the level of the actual nerve centre. This model represents an advancement of the current black box models that do not allow for isolated or independent treatment of system dysfunction. In this study, we re-visit our research into the viability of the hardware design of one of these centres—the cortical-diencephalic centre. We describe this hardware because functioning of the centre is completely configurable and programmable, which validates the design for other centres that comprise the neuroregulatory system. In this document, we succinctly present the formal model of the centre, propose a hardware design and an FPGA-based prototype, construct a testing and simulation environment to evaluate it and, lastly, analyse and contrast the results using data obtained from real patients, verifying that the functional behaviour fits that observed in humans.This work has been supported by grant University of Alicante projects GRE14-02 and Smart University

Modelling and evaluation of interventions to support overactive bladder issues in spinal cord injury subjects

This thesis uses mathematical modelling to improve understanding and address the challenges associated with a neurogenic bladder in patients with spinal cord injuries (SCIs), focusing on an overactive bladder (OAB) and detrusor sphincter dyssynergia (DSD). OAB refers to the occurrence of unwanted and uncontrolled contractions during the bladder’s filling stage, while DSD involves simultaneous contractions of the detrusor and urethral sphincters [1]. Traditionally, OAB symptoms have been treated with anticholinergic drugs, particularly oxybutynin (OXY). However, due to the typical occurrence of adverse effects, a novel drug called mirabegron (MBG) has been developed with the aim of minimising these unwanted effects [2]. Botulinum toxin type A (BoNT/A) injections are also administered as a second-line treatment, every 6 to 9 months, depending on the reappearance of involuntary contractions [3]. Furthermore, clean intermittent catheterisation is typically performed for DSD every 4 to 6 hours [4], [5]. This thesis represents the initial phase of a larger project that aims to develop a “smart” catheter to assist SCI patients with OAB and DSD symptoms. The primary objective of this device is to estimate unwanted bladder contractions associated with OAB, facilitating patient monitoring by the clinician. The thesis specifically focuses on characterising the associated fluid dynamics and the development of structurally identifiable pharmacometrics models for the three different treatments (BoNT/A, OXY and MBG) targeting OAB, using the limited literature data available in these areas. In this thesis population pharmacokinetic (PK) models have been developed for OXY and MBG using mean human data from the literature. Covariate assessment methods have been employed to explore their potential influence on the PK, aiming to identify factors contributing to observed variability in plasma versus time profiles of OXY and MBG. BoNT/A has been characterised through a preliminary target-mediated drug disposition (TMDD) kinetic/pharmacodynamic (K-PD) model, based on limited contractility versus time data. This model is the first study that attempts to mathematically characterise the long-term effects of BoNT/A on the detrusor of SCI patients. The duration of the effects of BoNT/A is medically significant, considering the limited knowledge available on its long-term application, and the timing of re-treatment is of significant importance to SCI sufferers. Thus, once fully validated, this model could potentially determine the appropriate timing for rescheduling of BoNT/A treatment for each individual patient, based on minimal and appropriate effect versus time data. Additionally, a comprehensive investigation into the differences between males and females regarding estimation of urodynamic variables at the outlet of intermittent catheters has been conducted employing mathematical modelling methodologies and in vitro experimental techniques to support model validation. The thesis examines current data limitations in these fields, outlines subsequent steps in the longer-term project and establishes methodological foundations for PK/PD model development across the current drug treatments, to account for contractility effects in the detrusor of SCI patients. The findings from this study contribute to potential improvements in strategies and provide a basis for future research in this field

Mathematical modelling of the lower urinary tract

The lower urinary tract is one of the most complex biological systems of the human body as it involved hydrodynamic properties of urine and muscle. Moreover, its complexity is increased to be managed by voluntary and involuntary neural systems. In this paper, a mathematical model of the lower urinary tract it is proposed as a preliminary study to better understand its functioning. Furthermore, another goal of that mathematical model proposal is to provide a basis for developing artificial control systems. Lower urinary tract is comprised of two interacting systems: the mechanical system and the neural regulator. The latter has the function of controlling the mechanical system to perform the voiding process. The results of the tests reproduce experimental data with high degree of accuracy. Also, these results indicate that simulations not only with healthy patients but also of patients with dysfunctions with neurological etiology present urodynamic curves very similar to those obtained in clinical studies.This study has been supported as part of the research projects: Cooperative diagnosis system applied to urological dysfunctions (GV05/158) funded by the Government of Valencia (Spain); Ambulatory wireless system for prevention of female urinary incontinence (CIT-300100-2005-7) funded by the Spanish Ministry of Science