Computational and experimental time domain, one dimensional models of air wave propagation in human airways

This thesis was submitted for the degree of Doctor of Philosophy and was awarded by Brunel University.The scientific literature on airflow in the respiratory system is usually associated with rigid ducts. Many studies have been conducted in the frequency domain to assess respiratory system mechanics. Time-domain analyses appear more independent from the hypotheses of periodicity, required by frequency analysis, providing data that are simpler to interpret since features can be easily associated to time. However, the complexity of the bronchial tree makes 3-D simulations too expensive computationally, limiting the analysis to few generations. 1-D modelling in space-time variables has been extensively applied to simulate blood pressure and flow waveforms in arteries, providing a good compromise between accuracy and computational cost. This work represents the first attempt to apply this formulation to study pulse waveforms in the human bronchial tree. Experiments have been carried out, in this work, to validate the model capabilities in modelling pressure and velocity waveforms when air pulses propagate in flexible tubes with different mechanical and geometrical properties. The experiments have shown that the arrival of reflected air waves occurs in correspondence of the theoretical timing once the wave speed is known. Reflected backward compression waves have generated an increase of pressure (P) and decrease of velocity (U) while expansion backward waves have produced a decrease of P and increase of U according to the linear analysis of wave reflections. The experiments have demonstrated also the capabilities of Wave intensity analysis (WIA), an analytical technique used to study wave propagation in cardiovascular system, in separating forward and backward components of pressure and velocity also for the air case. After validating the 1-D modelling in space and time variables, several models for human airways have been considered starting from simplified versions (bifurcation trachea- main bronchi, series of tubes) to more complex systems up to seven generations of bifurcations according to both symmetrical and asymmetrical models. Calculated pressures waveforms in trachea are shown to change accordingly to both peripheral resistance and compliance variations, suggesting a possible non-invasive assessment of peripheral conditions. A favourable comparison with typical pressure and flow waveforms from impulse oscillometry system, which has recently been introduced as a clinical diagnostic technique, is also shown. The results suggested that a deeper investigation of the mechanisms underlying air wave propagation in lungs could be a useful tool to better understand the differences between normal and pathologic conditions and how pathologies may affect the pattern of pressure and velocity waveforms

Investigating the flow dynamics in the obstructed and stented ureter by means of a biomimetic artificial model.

Double-J stenting is the most common clinical method employed to restore the upper urinary tract drainage, in the presence of a ureteric obstruction. After implant, stents provide an immediate pain relief by decreasing the pressure in the renal pelvis (P). However, their long-term usage can cause infections and encrustations, due to bacterial colonization and crystal deposition on the stent surface, respectively. The performance of double-J stents - and in general of all ureteric stents - is thought to depend significantly on urine flow field within the stented ureter. However very little fundamental research about the role played by fluid dynamic parameters on stent functionality has been conducted so far. These parameters are often difficult to assess in-vivo, requiring the implementation of laborious and expensive experimental protocols. The aim of the present work was therefore to develop an artificial model of the ureter (i.e. ureter model, UM) to mimic the fluid dynamic environment in a stented ureter. The UM was designed to reflect the geometry of pig ureters, and to investigate the values of fluid dynamic viscosity (?), volumetric flow rate (Q) and severity of ureteric obstruction (OB%) which may cause critical pressures in the renal pelvis. The distributed obstruction derived by the sole stent insertion was also quantified. In addition, flow visualisation experiments and computational simulations were performed in order to further characterise the flow field in the UM. Unique characteristics of the flow dynamics in the obstructed and stented ureter have been revealed with using the developed UM

Fluid mechanical performance of ureteral stents: The role of side hole and lumen size

Abstract Ureteral stents are indispensable devices in urological practice to maintain and reinstate the drainage of urine in the upper urinary tract. Most ureteral stents feature openings in the stent wall, referred to as side holes (SHs), which are designed to facilitate urine flux in and out of the stent lumen. However, systematic discussions on the role of SH and stent lumen size in regulating flux and shear stress levels are still lacking. In this study, we leveraged both experimental and numerical methods, using microscopic‐Particle Image Velocimetry and Computational Fluid Dynamic models, respectively, to explore the influence of varying SH and lumen diameters. Our results showed that by reducing the SH diameter from 1.1 to 0.4mm the median wall shear stress levels of the SHs near the ureteropelvic junction and ureterovesical junction increased by over 150%, even though the flux magnitudes through these SH decreased by about 40%. All other SHs were associated with low flux and low shear stress levels. Reducing the stent lumen diameter significantly impeded the luminal flow and the flux through SHs. By means of zero‐dimensional models and scaling relations, we summarized previous findings on the subject and argued that the design of stent inlet/outlet is key in regulating the flow characteristics described above. Finally, we offered some clinically relevant input in terms of choosing the right stent for the right patient

An in vitro bladder model with physiological dynamics: Vesicoureteral reflux alters stent encrustation pattern.

In vitro models are indispensable to study the physio-mechanical characteristics of the urinary tract and to evaluate ureteral stent performances. Yet previous models mimicking the urinary bladder have been limited to static or complicated systems. In this study, we designed a simple in vitro bladder model to simulate the dynamics of filling and voiding. The physio-mechanical condition of the model was verified using a pressure-flow test with different bladder outlet obstruction levels, and a reflux test was performed to qualitatively demonstrate the stent associated vesicoureteral reflux (VUR). Finally, the setup was applied with and without the bladder model to perform encrustation tests with artificial urine on commercially available double-J stents, and the volumes of luminal encrustations were quantified using micro-Computed Tomography and image segmentation. Our results suggest that, VUR is an important factor contributing to the dynamics in the upper urinary tract with indwelling stents, especially in patients with higher bladder outlet obstruction levels. The influence of VUR should be properly addressed in future in vitro studies and clinical analyses

Flow Dynamics in Stented Ureter

Urinary flow is governed by the principles of fluid mechanics. Urodynamic studies have revealed the fundamental kinematics and dynamics of urinary flow in various physiological and pathological conditions, which are cornerstones for future development of diagnostic knowledge and innovative devices. There are three primary approaches to study the fluid mechanical characteristics of urinary flow: reduced order, computational, and experimental methods. Reduced-order methods exploit the disparate length scales inherent in the system to reveal the key dominant physics. Computational models can simulate fully three-dimensional, time-dependent flows in physiologically-inspired anatomical domains. Finally, experimental models provide an excellent counterpart to reduced and computational models by providing physical tests under various physiological and pathological conditions. While the interdisciplinary approaches to date have provided a wealth of insight into the fluid mechanical properties of the stented ureter, the next challenge is to develop new theoretical, computational and experimental models to capture the complex interplay between the fluid dynamics in stented ureters and biofilm/encrustation growth. Such studies will (1) enable identification of clinically relevant scenarios to improve patients’ treatment, and (2) provide physical guidelines for next-generation stent design

Hemodynamic effects of a dielectric elastomer augmented aorta on aortic wave intensity: An in-vivo study

Dielectric elastomer actuator augmented aorta (DEA) represents a novel approach with high potential for assisting a failing heart. The soft tubular device replaces a section of the aorta and increases its diameter when activated. The hemodynamic interaction between the DEA and the left ventricle (LV) has not been investigated with wave intensity (WI) analysis before. The objective of this study is to investigate the hemodynamic effects of the DEA on the aortic WI pattern. WI was calculated from aortic pressure and flow measured in-vivo in the descending aorta of two pigs implanted with DEAs. The DEAs were tested for different actuation phase shifts (PS). The DEA generated two decompression waves (traveling upstream and downstream of the device) at activation followed by two compression waves at deactivation. Depending on the PS, the end-diastolic pressure (EDP) decreased by 7% (or increased by 5–6%). The average early diastolic pressure augmentation (P_dia) increased by 2% (or decreased by 2–3%). The hydraulic work (W_H) measured in the aorta decreased by 2% (or increased by 5%). The DEA-generated waves interfered with the LV-generated waves, and the timing of the waves affected the hemodynamic effect of the device. For the best actuation timing the upstream decompression wave arrived just before aortic valve opening and the upstream compression wave arrived just before aortic valve closure leading to a decreased EDP, an increased P_dia and a reduced W_H

Investigating the flow dynamics in the obstructed and stented ureter by means of a biomimetic artificial model

Double-J stenting is the most common clinical method employed to restore the upper urinary tract drainage, in the presence of a ureteric obstruction. After implant, stents provide an immediate pain relief by decreasing the pressure in the renal pelvis (P). However, their long-term usage can cause infections and encrustations, due to bacterial colonization and crystal deposition on the stent surface, respectively. The performance of double-J stents - and in general of all ureteric stents - is thought to depend significantly on urine flow field within the stented ureter. However very little fundamental research about the role played by fluid dynamic parameters on stent functionality has been conducted so far. These parameters are often difficult to assess in-vivo, requiring the implementation of laborious and expensive experimental protocols. The aim of the present work was therefore to develop an artificial model of the ureter (i.e. ureter model, UM) to mimic the fluid dynamic environment in a stented ureter. The UM was designed to reflect the geometry of pig ureters, and to investigate the values of fluid dynamic viscosity (μ), volumetric flow rate (Q ) and severity of ureteric obstruction (OB%) which may cause critical pressures in the renal pelvis. The distributed obstruction derived by the sole stent insertion was also quantified. In addition, flow visualisation experiments and computational simulations were performed in order to further characterise the flow field in the UM. Unique characteristics of the flow dynamics in the obstructed and stented ureter have been revealed with using the developed UM

Preventing Biofilm Formation and Encrustation on Urinary Implants: (Bio)molecular and Physical Research Approaches

Stents and catheters are used to facilitate urine drainage within the urinary system. When such sterile implants are inserted into the urinary tract, ions, macromolecules and bacteria from urine, blood or underlying tissues accumulate on their surface. We presented a brief but comprehensive overview of future research strategies in the prevention of urinary device encrustation with an emphasis on biodegradability, molecular, microbiological and physical research approaches. The large and strongly associated field of stent coatings and tissue engineering is outlined elsewhere in this book. There is still plenty of room for future investigations in the fields of material science, surface science, and biomedical engineering to improve and create the most effective urinary implants. In an era where material science, robotics and artificial intelligence have undergone great progress, futuristic ideas may become a reality. These ideas include the creation of multifunctional programmable intelligent urinary implants (core and surface) capable to adapt to the complex biological and physiological environment through sensing or by algorithms from artificial intelligence included in the implant. Urinary implants are at the crossroads of several scientific disciplines, and progress will only be achieved if scientists and physicians collaborate using basic and applied scientific approaches

Effect of Collateral Flow on Catheter-Based Assessment of Cardiac Microvascular Obstruction.

Cardiac microvascular obstruction (MVO) associated with acute myocardial infarction (heart attack) is characterized by partial or complete elimination of perfusion in the myocardial microcirculation. A new catheter-based method (CoFI, Controlled Flow Infusion) has recently been developed to diagnose MVO in the catheterization laboratory during acute therapy of the heart attack. A porcine MVO model demonstrates that CoFI can accurately identify the increased hydraulic resistance of the affected microvascular bed. A benchtop microcirculation model was developed and tuned to reproduce in vivo MVO characteristics. The tuned benchtop model was then used to systematically study the effect of different levels of collateral flow. These experiments showed that measurements obtained in the catheter-based method were adversely affected such that collateral flow may be misinterpreted as MVO. Based on further analysis of the measured data, concepts to mitigate the adverse effects were formulated which allow discrimination between collateral flow and MVO