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Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix and exhibit high tolerance towards environmental stress. Despite the plethora of research on biofilms, most biofilm models are produced using mono-interface culture in static flow conditions, and knowledge of the effects of interfaces and mechanical forces on biofilm development remains fragmentary. This study elucidated the effects of air-liquid (ALI) or liquid-liquid (LLI) interfaces and mechanical shear forces induced by airflow and hydrodynamic flow on biofilm growing using a custom-designed dual-channel microfluidic platform. Results from this study showed that comparing biofilms developed under continuous nutrient supply and shear stresses free condition to those developed with limited nutrient supply, ALI biofilms were four times thicker, 60% less permeable, and 100 times more resistant to antibiotics, while LLI biofilms were two times thicker, 20% less permeable, and 100 times more resistant to antibiotics. Subjecting the biofilms to mechanical shear stresses affected the biofilm structure across the biofilm thickness significantly, resulting in generally thinner and denser biofilm compared to their controlled biofilm cultured in the absence of shear stresses, and the ALI and LLI biofilm's morphology was vastly different. Biofilms developed under hydrodynamic shear stress also showed increased antibiotic resistance. These findings highlight the importance of investigating biofilm growth and its mechanisms in realistic environmental conditions and demonstrate a feasible approach to undertake this study using a novel platform.

Abstract Biofilms are ubiquitous and notoriously difficult to eradicate and control, complicating human infections and industrial and agricultural biofouling. However, most of the study had used the biofilm model that attached to solid surface and developed in liquid submerged environments which generally have neglected the impact of interfaces. In our study, a reusable dual-chamber microreactor with interchangeable porous membranes was developed to establish multiple growth interfaces for biofilm culture and test. Protocol for culturing Pseudomonas aeruginosa (PAO1) on the air–liquid interface (ALI) and liquid–liquid interface (LLI) under static environmental conditions for 48 h was optimized using this novel device. This study shows that LLI model biofilms are more susceptible to physical disruption compared to ALI model biofilm. SEM images revealed a unique “dome-shaped” microcolonies morphological feature, which is more distinct on ALI biofilms than LLI. Furthermore, the study showed that ALI and LLI biofilms produced a similar amount of extracellular polymeric substances (EPS). As differences in biofilm structure and properties may lead to different outcomes when using the same eradication approaches, the antimicrobial effect of an antibiotic, ciprofloxacin (CIP), was chosen to test the susceptibility of a 48-h-old P. aeruginosa biofilms grown on ALI and LLI. Our results show that the minimum biofilm eradication concentration (MBEC) of 6-h CIP exposure for ALI and LLI biofilms is significantly different, which are 400 μg/mL and 200 μg/mL, respectively. These results highlight the importance of growth interface when developing more targeted biofilm management strategies, and our novel device provides a promising tool that enables manipulation of realistic biofilm growth. Key points • A novel dual-chamber microreactor device that enables the establishment of different interfaces for biofilm culture has been developed. • ALI model biofilms and LLI model biofilms show differences in resistance to physical disruption and antibiotic susceptibility.

Biofilms are communities of bacterial cells encased in a self-produced polymeric matrix that exhibit high tolerance toward environmental stress. Despite the plethora of research on biofilms, most P. aeruginosa biofilm models are cultured on a solid-liquid interface, and the longitudinal growth characteristics of P. aeruginosa biofilm are unclear. This study demonstrates the real-time and noninvasive monitoring of biofilm growth using a novel dual-chamber microfluidic device integrated with electrochemical detection capabilities to monitor pyocyanin (PYO). The growth of P. aeruginosa biofilms on the air-liquid interface (ALI) was monitored over 48 h, and its antibiotic susceptibility to 6 h exposure of 50, 400, and 1600 µg/ml of ciprofloxacin solutions was analyzed. The biofilm was treated directly on its surface and indirectly from the substratum by delivering the CIP solution to the top or bottom chamber of the microfluidic device. Results showed that P. aeruginosa biofilm developed on ALI produces PYO continuously, with the PYO production rate varying longitudinally and peak production observed between 24 and 30 h. In addition, this current study shows that the amount of PYO produced by the ALI biofilm is proportional to its viable cell numbers, which has not been previously demonstrated. Biofilm treated with ciprofloxacin solution above 400 µg/ml showed significant PYO reduction, with biofilms being killed more effectively when treatment was applied to their surfaces. The electrochemical measurement results have been verified with colony-forming unit count results, and the strong correlation between the PYO electrical signal and the viable cell number highlights the usefulness of this approach for fast and low-cost ALI biofilm study and antimicrobial tests.

This study uses computational fluid dynamics to model powder fluidisation in a turbulent channel flow. A two-fluid model is adopted for simulations. Closures are provided through the kinetic theory of granular flow where particle energy fluctuations are captured through granular temperature. Simulation results are compared to the experimental evacuation time data for a lactose carrier powder across different inlet Reynolds numbers. Different turbulence closures were tested, with the k-e RNG model most aligned to experimental data. The effects of packing limit, coefficient of restitution and turbulence dispersion were also studied. Results show that the inlet turbulence intensity and dispersion models have marginal effects on evacuation, whereas maximum packing limit significantly influences powder fluidisation. The two-fluid model generates excellent agreement with the experimental data for all tested Reynolds numbers. Additionally, powder size distribution is studied, with results showing no significant difference in evacuation time between monodisperse and polydisperse particle size distributions.

A human nasal epithelial mucosa (NEM) on-a-chip is developed integrated with a novel carbon nanofibers-modified carbon electrode for real-time quantitative monitoring of in vitro nasal drug deliver...

The probability of agglomerate-to-wall collision was quantified using a unique image processing technique applied to high-speed microscopic images. The study aimed to investigate the effects of flow rate and particle size on the percentage of colliding agglomerates detected within an in-house powder dispersion device.The device consists of a swirl chamber and two tangential inlets in various configurations, designed to emulate the geometric features of commercial devices such as the Aerolizer® and Osmohaler®. The test cases were conducted with constant flow rates of 30 SLPM and 60 SLPM. Four powder samples were tested, including carrier Respitose® SV010 (median volume diameter 104 µm, span 1.7) and mannitol of three constituent primary particle sizes (3 µm, 5 µm and 7 µm; span 1.6 - 1.9).At the lower flow rate of 30 SLPM, collision frequencies were significantly different between powders of different constituent particle sizes, but the effects of powder properties diminished on increasing the flow rate to 60 SLPM. At the higher flow rate, all powders experienced a significant increase in the proportion of colliding particles.Analysis of collision events showed that the probability of collision for each agglomerate increased with agglomerate diameter and velocity. Experimental data of agglomerate-to-wall collision were utilised to develop a logistic regression model that can accurately predict collisions with various powders and flow rates.

Developing effective oral inhaled drug delivery treatment strategies for respiratory diseases necessitates a thorough knowledge of the respiratory system physiology, such as the differences in the airway channel's structure and geometry in health and diseases, their surface properties, and mechanisms that maintain their patency. While respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma and their implications on the lower airways have been the core focus of most of the current research, the role of the upper airway in these diseases is less known, especially in the context of inhaled drug delivery. This is despite the fact that the upper airway is the passageway for inhaled drugs to be delivered to the lower airways, and their replicas are indispensable in current standards, such as the cascade impactor experiments for testing inhaled drug delivery technology. This review provides an overview of upper airway collapsibility and their mechanical properties, the effects of age and gender on upper airway geometry, and surface properties. The review also discusses how COPD and asthma affect the upper airway and the typical inhalation flow characteristics exhibited by the patients with these diseases.

The local dynamics of fluidized pharmaceutical carrier powders in a turbulent channel flow was studied using particle image velocimetry (PIV) and High-speed, long-distance microscopy (HS-LDM). Four different lactose powders which have been used as a drug carrier in dry powder inhalers were used in this study. These powders have median powder particle diameters ranging between 61 and 121 µm. Air flow velocities ranging between 13.3 m/s and 66.7 m/s were examined. In addition, the effect of grid blockage ratio (ranging from ~25% to ~40% of the area of channel cross-section) was also investigated. Results show that the high-speed, long-distance microscopy (HS-LDM) technique was able to capture the mean velocity of the particles, and the results corresponded well with the PIV measurements. Results from the high-speed, long-distance microscopy (HS-LDM) method also demonstrate that the span of particle velocity closely follows that of the particle size distribution both for cohesive and non-cohesive powders. This study contributes towards an improved understanding of pharmaceutical carrier dynamics in turbulent channel flows and demonstrates how advanced image processing can be used to capture local particle dynamics.

The current organ-on-chip platforms used for studying respiratory drug delivery are limited to the administration of drug solutions and suspensions, lacking the in vivo aerosol drug administration and aerosol interaction with the respiratory tract barrier. Moreover, they mostly rely on conventional assays that require sample collection and 'off the chip' analyses, which can be labor-intensive and costly. In this study, a human nasal epithelial mucosa (NEM)-on-a-chip is developed that enables the deposition of aerosolized nasal formulations while emulating realistic shear stresses (0.23 and 0.78 Pa), exerted to the inferior and middle turbinate of the human nasal cavity. Under these different dynamic conditions in the donor channel of the NEM-on-a-chip, the deposited dose of aerosols and particle size distributions varied. In addition, the increase in the shear stress to 0.78 Pa adversely affected the cells' viability, reflected by a 36.9 ± 5.4% reduction in the transepithelial electrical resistance. The epithelial transport profiles of aerosolized ibuprofen formulations under 0.23 Pa shear stress were successfully monitored in real-time by an electrochemical sensor embedded in the acceptor channel, where the NEM-on-a-chip was able to monitor the effect of permeation enhancer in the test formulation on the rate of drug transport. The novel NEM-on-a-chip can potentially be a promising physiologically relevant tool for reliable nasal aerosol testing in vitro.

In order to better understand powder dispersion in dry powder inhaler (DPI) devices, a new powder disperser was designed, which uses flow modifiers to alter powder fluidization behavior so as to physically replicate various flow conditions observed in a range of commercial DPIs. The influence of these modifiers on the performance of the DPI was analyzed for flowrates progressing from laminar (15 L/min) to transitional (30 L/min), and finally turbulent flow regimes (60 L/min) in the device. The aerosol performance of the disperser was measured using a Next Generation Impactor. For flowrate in the laminar regime, powder evacuation from the disperser was generally insufficient (85% when the device was operated in the turbulent flow regime. In contrast, the highest fine particle fraction (FPF) and lowest throat deposition were achieved when operating in the transitional flow regime. The FPF could be increased further by applying flow modifications such as narrowing the air passage before the powder pocket, inducing localized turbulence (by a grid) near the powder pocket, and by changing the loading position of the powder. Flow modifiers had the most noticeable effect under a laminar flow regime, however, the device operated most efficiently under a transitional flow regime.

This study aims to systematically isolate different anatomical features of the human pharynx with the goal to investigate their independent influence on airflow dynamics and particle deposition characteristics in a geometrically realistic human airway. Specifically, the effects of the uvula, epiglottis and soft palate on drug particle deposition are studied systematically, by carefully removing each of these anatomical features from reconstructed models based on MRI data and comparing them to a benchmark realistic airway model. Computational Fluid Dynamics using established turbulence models is employed to simulate the transport of mono-dispersed particles (3 µm) in the airway at two flow-rates. The simulations suggest three findings: 1) widening the space between the oral cavity and oropharynx and where the soft palate is situated leads to the most dramatic reduction in drug deposition in the upper airway; 2) exclusion of the uvula and epiglottis: a) affects flow dynamics in the airway; b) alters regional deposition behaviour; c) does not significantly affect the total number of particles deposited in the pharynx; and 3) the space adjacent to the soft palate is a key determinant for aerosol deposition in the extrathoracic region and is related to mechanisms of flow acceleration, diversion and recirculation.

© 2019 Elsevier Inc. A new experimental platform is presented which enables investigation of the effects of turbulence, mean forces and powder properties on the fluidisation of lactose powders as relevant to pharmaceutical applications. The flow consists of a fully developed channel flow which delivers a well-defined velocity profile over a bed of powder. An in-house two beam line of sight attenuation method has been developed to extract quantitative information on powder fluidisation time, time-resolved fluctuations in powder concentration and frequencies associated with the powder fluidisation process. Four lactose powders are examined which have a range of mass mean diameters and cohesiveness. Reynolds numbers from approximately 9000 to 20,000 are examined in this study, representing one of a few quantitative examinations of lactose powder behaviour in a simple canonical flow, where the boundary conditions are well-defined and the flow is intentionally simple. Evacuation times show dependence on the Reynolds number varied both through changing the local velocity and channel dimension, whereas the Reynolds number dependence weakens at higher Reynolds numbers. Frequencies measured show physical consistency with theoretical frequencies defined through the turbulent velocity and characteristic length-scale of the powder pocket.

This study aims to utilise particle image velocimetry (PIV) techniques to investigate the time-dependant effects of respiratory rate in the extrathoracic airway, to show how they affect the flow field developed. There has been limited validation of computational fluid dynamics (CFD) models using experimental setups. Furthermore, the large majority of existing CFD models focus on rigid airways, not accounting for active deformation through the breathing cycle. Experiments were carried out to expand upon Zhao et al.’s previous study, in which a single respiratory rate was investigated. This studied utilised a transient, sinusoidal flow profile with two respiratory rates of 10 breaths per minute (BPM) and 25 BPM, both achieving a maximum flow rate correlating to 5 L/min in air to simulate tidal breathing. Results from this study showed that respiratory rate had the greatest influence near the onset of the inspiratory and expiratory manoeuvres, with the higher respiratory rate homogenising later in the cycle. It was shown that airway deformation at the level of the soft palate homogenised flow downstream of the deformation which resulted in a lower peak magnitude velocity for approximately 40% of the cycle at the level of the epiglottis, when compared to the rigid airway model.

A human nasal epithelial mucosa (NEM) on-a-chip is developed integrated with a novel carbon nanofibers-modified carbon electrode for real-time quantitative monitoring ofThe air-liquid interface culture of nasal epithelial RPMI 2650 cells in the NEM-on-a-chip was optimized to mimic the key functional characteristics of the human nasal mucosa. The epithelial transport of ibuprofen in the NEM-on-a-chip was electrochemically monitored in real-time under static and physiologically realistic dynamic flow conditions.The NEM-on-a-chip mimics the mucus production and nasal epithelial barrier function of the human nasal mucosa. The real-time drug quantification by the NEM-on-a-chip was validated versus the high-performance liquid chromatography method. The drug transport rate monitored in the NEM-on-a-chip was influenced by the flow in the bottom compartment of the chip, highlighting the importance of emulating the dynamicThis novel NEM-on-a-chip can be a low-cost and time-efficient alternative to the costly laborious conventional techniques for

This study investigates the fluidization of lactose carriers from a powder bed subjected to a normal force in a channel flow using high-speed imaging, particle image velocimetry (PIV), and high-speed, long-distance microscopy (HS-LDM). Pharmaceutical lactose carriers (LH200 and SV010) with different cohesiveness and fines percentages were examined in this study. Airflow velocities in the range of 1.4 m/s and 7m/s were tested, corresponding to flow rates ranging from 20 to 100 L/min. The use of HS-LDM in tandem with PIV has enabled measurement of the slip factor between particles and conveying airflow as well as metrics that help to identify dose homogeneity as a function of location in the channel flow. The results indicate a lower slip ratio and a larger change in powder particle size bands percentages along with channel height in the region near the powder bed, because of flow recirculation and higher velocity fluctuation observed in that region.

This paper introduces a novel image processing methodology to enable an extension of the range of applicability of the back-lit imaging method to provide the simultaneous measurement of size and velocity in turbulent flows with a high concentration of objects having various shapes and sizes. The new image processing methodology applies an interrogation-window method similar to that used in particle image velocimetry, alongside interface identification as used in backlight imaging. The matching of droplets or particles of arbitrary shape is achieved by dividing the image into several small windows and cross-correlating objects in each window to obtain a coefficient of dissimilarity, extracted using a variety of metrics of droplet or particle morphology. To demonstrate its utility this technique is applied to measurement of velocities from (i) a highly turbulent spray flow and (ii) a swirling particle-laden flow as applicable to dry powder inhalation systems. Results are validated against phase Doppler anemometry data and a sensitivity analysis of the controlling parameters of the image processing methodology demonstrate that the technique is robust for a variety of input conditions. A key advantage of this approach lies in complementing the diagnostics capability of PDA methods to span a broader range of particle sizes irrelevant of shape and particle concentration.

Optical Coherence Tomography (OCT) is a high-resolution and non-invasive cross-sectional imaging technique mainly used for medical imaging and industrial non-destructive testing. However, its feasibility in the quantification of pulmonary drug deposition has not been investigated. In this study, an optically accessible airway model of the upper airway and the tracheobronchial tree was used, and experiments were performed at flow rates of 40 L/min, 60 L/min and 80 L/min. Drug deposition in different regions of the airway cast has been determined and quantified from OCT images of the deposition layer. Regionally resolved measurement of deposition shows that flow rate has a significant effect (p = 0.04) on the average thickness of the deposition layer in the upper airway but not in the tracheobronchial tree under these test conditions. These localized and high-resolution measurements of deposition also demonstrate that the flow rate can influence the spatial uniformity of the deposition layer. The technique is able to provide significant regional drug deposition details, including the thickness, spatial deposition pattern and micro-cavities in the deposition layer, that would potentially serve to assess the efficacy of inhalation drug delivery systems.

The de-agglomeration characteristics of single agglomerate-wall impaction are examined using high-resolution shadowgraph imaging. Experiments are performed to investigate the effects of constituent particle size (D50 from 3 to 7 μm) and air velocity on the individual size and velocity of de-agglomerated fragments at conditions relevant to dry powder inhalation systems. De-agglomerated fragment area and trajectories were used to differentiate between pseudo-elastic and inelastic collisions during de-agglomeration. Advanced image processing techniques have enabled provision of joint population distributions of fragment area and aspect ratio, which identify a bimodal dispersion of fragments during de-agglomeration. The bimodality is destroyed with increasing air velocity and also generally diminishes with time after impact. The experiment presented forms a platform for the detailed quantitative characterisation of de-agglomeration behaviour and can be useful towards the development and validation of related computational models for pharmaceutical dry powder inhalers.

This study proposes a novel dual-PCM configuration with outstanding solidification response in a horizontal shell-and-tube energy storage system. To demonstrate that the proposed PCM configuration is superior in its thermal responses, results from a range of numerical simulations are presented and compared between different configurations of dual-PCM. As the melting/solidus point is a crucial factor for the solidification rate, dual PCMs are chosen such that the average of their melting point is equal to the melting point of the single-PCM in the reference case. Additionally, equal-area sectors are considered for all cases to ensure the same quantities of PCMs are compared. The temporal liquid fraction and temperature contours reveal that solidification is delayed in the upper half of the system due to strong natural convection motions. Therefore, a dual-PCM configuration is offered to improve the solidification rate in this region and accelerate the full solidification process. Results show that placing a PCM with a lower solidus point in the lower half or an annulus-shaped zone around the cold tube can save the full recovery time up to 8.51% and 9.36%, respectively. The integration of these two strategies results in a novel and optimum design that saves the solidification time up to 15.09%.

© 2001-2012 IEEE. A highly accurate location estimation of a capsule endoscope in the gastrointestinal tract in the range of several millimeters is a challenging task, as radio-frequency signals encounter high power loss and a highly dynamic channel propagation environment. Therefore, an accurate path-loss model is required for the development of accurate localization algorithms. This paper presents an in-body path-loss model for the human abdomen region at 2.4 GHz. To develop the path-loss model, electromagnetic simulations using the finite-difference time-domain method were carried out on three different anatomical human models from the Virtual Family. A mathematical expression for the path-loss model was proposed based on analysis of the measured loss at different capsule locations inside the small intestine. The proposed path-loss model is a good approximation to model in-body RF propagation, since real measurements are not completely practical for the capsule-endoscope subject. Based on the proposed path-loss model, the article also presents the 2-D location estimation of a capsule endoscope inside the small intestine using the trilateration method as well as the non-linear least squares algorithm. It is shown that with 90% probability, the location estimation error is less than 4 cm.

The human upper airway is not only geometrically complex, but it can also deform dynamically as a result of active muscle contraction and motility during respiration. How the active transformation of the airway geometry affects airflow dynamics during respiration is not well understood despite the importance of this knowledge towards improving current understanding of particle transport and deposition. In this study, particle image velocimetry (PIV) measurements of the fluid dynamics are presented in a physiologically realistic human upper airway replica for i) the undeformed case and ii) the case where realistic soft tissue motion during breathing is emulated. Results from this study show that extrathoracic wall motion alters the flow field significantly such that the fluid dynamics is distinctly different from the undeformed airway. Distinctive flow field patterns in the physiologically realistic airway include i) fluid recirculation at the back of the tongue and cranial to the tip of the epiglottis during mid-inspiration, ii) horizontal and posteriorly directed flow at the back of tongue at the peak of inspiration and iii) concentrated flow directed towards the root of tongue near to the end of inspiration. These findings suggest that the active deformation of the human upper airway can potentially influence particle transport by increasing deposition at the back of the tongue and therefore, highlights the importance of considering extrathoracic wall motion in future airway flow studies.

The integrity of the nasal epithelium plays a crucial role in the airway defence mechanism. The nasal epithelium may be injured as a result of a large number of factors leading to nose bleeds, also known as epistaxis. However, local measures commonly used to treat epistaxis and improve wound healing present several side effects and patient discomfort. Hence, this study aims to address some of these drawbacks by developing a new formulation for nasal epithelial wound healing. Chitosan, a biodegradable and biocompatible polymer, was used to develop a thermosensitive nasal formulation for the delivery of tranexamic acid (TXA), one of the most effective pharmacological options to control bleeding with cost and tolerability advantages. The in situ gelation properties of the formulation upon administration in the nasal cavity were investigated in terms of gelation time and temperature. It was found that the developed formulation can undergo rapid liquid-to-gel phase change within approximately 5 min at 32°C, which is well within the human nasal cavity temperature range. The spray pattern, deposition and droplet size generated by the nasal spray was also characterised and were found to be suitable for nasal drug delivery. It was also observed that the in situ gelation of the formulation prevent nasal runoff, while the majority of drug deposited mainly in the anterior part of the nose with no lung deposition. The developed formulation was shown to be safe on human nasal epithelium and demonstrated six times faster wound closure compared to the control TXA solution.

The in-situ gelation of thermosensitive nasal formulations with desirable spray characteristics at room temperature and ability to undergo a phase change to a semi-solid state with mucoadhesive behavior at physiological temperature has the potential to efficiently deliver therapeutics to brain. However, their application in nasal spray generation with favorable characteristics has not been investigated.Thermosensitive chitosan (CS)-based formulations with different viscosities were prepared for intranasal delivery of ibuprofen using CS of various molecular weights. The formulation developed was optimized with regards to its physicochemical, rheological, biological properties and the generated aerosol characteristics.The formulations showed rapid gelation (4-7 min) at 30-35°C, which lies in the human nasal cavity temperature spectrum. The decrease in CS molecular weight to 110-150 kDa led to generation of optimum spray with lower DvA thermosensitive CS-based formulation has been successfully developed with suitable rheological properties, aerosol performance and biological properties that is beneficial for nose-to-brain drug delivery.

Background Fluid homeostasis in the central nervous system (CNS) is essential for normal neurological function. Cerebrospinal fluid (CSF) in the subarachnoid space and interstitial fluid circulation in the CNS parenchyma clears metabolites and neurotransmitters and removes pathogens and excess proteins. A thorough understanding of the normal physiology is required in order to understand CNS fluid disorders, including post-traumatic syringomyelia. The aim of this project was to compare fluid transport, using quantitative imaging of tracers, in the spinal cord from animals with normal and obstructed spinal subarachnoid spaces. Methods A modified extradural constriction model was used to obstruct CSF flow in the subarachnoid space at the cervicothoracic junction (C7–T1) in Sprague–Dawley rats. Alexa-Fluor 647 Ovalbumin conjugate was injected into the cisterna magna at either 1 or 6 weeks post–surgery. Macroscopic and microscopic fluorescent imaging were performed in animals sacrificed at 10 or 20 min post–injection. Tracer fluorescence intensity was compared at cervical and thoracic spinal cord levels between control and constriction animals at each post-surgery and post-injection time point. The distribution of tracer around arterioles, venules and capillaries was also compared. Results Macroscopically, the fluorescence intensity of CSF tracer was significantly greater in spinal cords from animals with a constricted subarachnoid space compared to controls, except at 1 week post-surgery and 10 min post-injection. CSF tracer fluorescence intensity from microscopic images was significantly higher in the white matter of constriction animals 1 week post surgery and 10 min post-injection. At 6 weeks post–constriction surgery, fluorescence intensity in both gray and white matter was significantly increased in animals sacrificed 10 min post-injection. At 20 min post-injection this difference was significant only in the white matter and was less prominent. CSF tracer was found predominantly in the perivascular spaces of arterioles and venules, as well as the basement membrane of capillaries, highlighting the importance of perivascular pathways in the transport of fluid and solutes in the spinal cord. Conclusions The presence of a subarachnoid space obstruction may lead to an increase in fluid flow within the spinal cord tissue, presenting as increased flow in the perivascular spaces of arterioles and venules, and the basement membranes of capillaries. Increased fluid retention in the spinal cord in the presence of an obstructed subarachnoid space may be a critical step in the development of post-traumatic syringomyelia. Electronic supplementary material The online version of this article (10.1186/s12987-019-0127-8) contains supplementary material, which is available to authorized users.

Knowledge that enables the accurate simulation of drug deposition in the human upper airway is necessary to develop robust platforms for efficient drug delivery by inhalation devices. The human upper airway is deformable during inhalation but how it could affect the deposition of inhaled drugs is unknown. We aimed to determine whether pharyngeal deformation at the soft palate level would have any significant effects on throat deposition, in vitro lung dose and fine particle fraction. In this study, dry mannitol powders were delivered to the next-generation cascade impactor (NGI) through the United States Pharmacopeia (USP) throat, and a realistic upper airway cast (RUPAC) at flow rates of 40, 60 and 80 L min−1. Deformation of the upper airway at 25%, 50%, and 75% in the lateral and antero-posterior directions were experimentally simulated in the RUPAC. Throat deposition (p = 0.04) is significantly affected when the upper airway deforms laterally but not antero-posteriorly.

Fat content on upper airway soft tissue can alter the geometry of the human pharynx, most notably through narrowing of the upper airway at the level of the epiglottis. Despite the important role of the epiglottis during respiration, there is a paucity of data on how its geometry can affect airway flow dynamics in an individual. This study shows how the narrowing of the human pharynx from lingual fats can potentially change airway flow dynamics and particle deposition. The velocity flow field in four geometrically realistic upper airway models representing a pharynx with different amounts of lingual fat was simulated using computational fluid dynamics (CFD) with the baseline case validated using particle imaging velocimetry (PIV). The deposition of particles was also computed using a standard discrete phase model (DPM) with results showing how particle deposition is affected by the narrowing of the pharynx.

© 2016 IEEE. This paper presents a theoretical analysis for location estimation of a wireless capsule endoscope (WCE) in the small-intestine region. Under three different shadowing scenarios by assuming standard deviation of the shadowing with the constant variance, parameter-dependent variance, or correlated and parameter-dependent variance, analytical formulas are derived for the Cramér-Rao lower bound (CRLB) for capsule positioning when distance and azimuth angle measurements are employed to estimate the location of the capsule. The CRLB analysis can be employed to quantify the best achievable location estimation performance. We also present some numerical results to show the CRLB for three scenarios. The results show that in the most realistic scenario, when the shadowing is spatially correlated and distance dependent and the standard deviation of noise is 7 dB, the maximum square root of CRLB is 3.8 mm. Moreover, the square root of CRLB experiences its minimum value of 2 mm, when the capsule is away from its first location about half of the capsule length. Overall, the result of this paper suggests that it is possible to use received signal strength such as measured by a radar system for location estimation of a WCE.

Information on pediatric brain tissue mechanical properties and, more pertinently, how they change during postnatal development remains scarce despite its importance to investigate mechanisms of neural injury. The aim of this study is to determine whether brain mechanical properties change in-vivo during early postnatal development in a rat model. Rat brain viscoelastic properties were measured longitudinally in ten healthy Sprague Dawley rats at five different time points from postnatal week one to week six using magnetic resonance elastography at 800Hz. Myelination and cell density were assessed histologically at the same time points to understand how the underlying tissue microstructure may be associated with changes in mechanical properties at different brain regions. Longitudinal changes in each variable were assessed using a generalized linear model with pairwise comparisons of means between weeks. The brain shear modulus in the cortical gray matter at postnatal week one was 6.3±0.4kPa, and increased significantly from week one to week two (pairwise comparison, p