Jinxiang Xi

• Ph.D.
• Professor (Associate) at University of Massachusetts Lowell

This study investigated the role of synthetic mucus coatings in enhancing the physiological relevance of in vitro nasal spray deposition assessments using 3D-printed nasal cavity models. Synthetic mucus solutions, representing normal (0.25% w/v xanthan gum) and diseased (1% w/v xanthan gum) nasal conditions, were developed to mimic the viscoelastic...

Background/Objectives: Mask-wearing-induced discomfort often leads to unconscious loosening of the mask to relieve the discomfort, thereby compromising protective efficacy. This study investigated how leakage flows affect mask-associated thermoregulation and vapor trapping to inform better mask designs. An integrated ambience–mask–face–airway model...

Background: Acute and chronic sinusitis significantly impact patients’ quality of life. Effective drug delivery to paranasal sinuses is crucial for treating these conditions. However, medications from conventional devices like nasal drops, sprays, and nebulized mists often fail to penetrate the small ostia and reach the sinuses. This study aims to...

This dataset comprises a comprehensive collection of videos and images illustrating the fluid dynamics of swallowing and aspiration in a patient-specific pharyngolaryngeal model with varying epiglottis angles. The data also includes the physical properties of the fluids used, comprising dynamic viscosity, surface tension, and contact angle. Videos...

Metered Dose Inhalers (MDIs) play a crucial role in managing respiratory diseases, but their effectiveness depends on whether the intended dose is delivered to the target, which can be influenced by various factors. Accurate assessment of MDI performance is crucial for optimizing MDI delivery and ensuring drug efficacy. This study numerically exami...

Impaired swallowing, or dysphagia, significantly affects patients' well-being and health. Nearly half of the patients with head and neck cancers experience dysphagia or aspiration following radiation therapy or surgery. However, current dysphagia management approaches are primarily symptom-based rather than etiology-specific, owing to a lack of cle...

Although mask-wearing is now widespread, the knowledge of how to quantify or improve their performance remains surprisingly limited and is largely based on empirical evidence. The objective of this study was to visualize the expiratory airflows from facemasks and evaluate aerosol transmission between two persons. Different visualization methods wer...

Although mask-wearing is now widespread, knowledge of how to quantify or improve its performance remains surprisingly limited and largely based on empirical evidence. The objective of this study was to visualize the expiratory airflows from facemasks and evaluate aerosol transmission between two persons. Different visualization methods were explore...

Understanding the mechanisms underlying dysphagia is crucial in devising effective, etiology-centered interventions. However, current clinical assessment and treatment of dysphagia are still more symptom-focused due to our limited understanding of the sophisticated symptom-etiology associations causing swallowing disorders. This study aimed to eluc...

Speech is a highly coordinated process that requires precise control over vocal tract morphology/motion to produce intelligible sounds while simultaneously generating unique exhaled flow patterns. The schlieren imaging technique visualizes airflows with subtle density variations. It is hypothesized that speech flows captured by schlieren, when anal...

The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle’s insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentiall...

Swallowing disorders, or dysphagia, can lead to bolus aspiration in the airway, causing serious adverse health effects. Current clinical interventions for dysphagia are mainly empirical and often based on symptoms rather than etiology, of which a thorough understanding is still lacking. However, it is challenging to study the swallowing process tha...

Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, a...

Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, a...

The human tongue has highly variable morphology. Its role in regulating respiratory flows and deposition of inhaled aerosols remains unclear. The objective of this study was to quantify the uncertainty of nanoparticle deposition from the variability in tongue shapes and positions and to rank the importance of these morphological factors. Oropharyng...

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P...

Elevated face temperature due to mask wearing can cause discomfort and skin irritation, making mask mandates challenging. When thermal discomfort becomes intolerable, individuals instinctively or unknowingly loosen or remove their facemasks, compromising the mask’s protective efficacy. The objective of this study was to numerically quantify the mic...

In this study, we present a novel approach to differentiate normal and diseased lungs based on exhaled flows from 3D-printed lung models simulating normal and asthmatic conditions. By leveraging the sequential learning capacity of the Long Short-Term Memory (LSTM) network and the automatic feature extraction of convolutional neural networks (CNN),...

Chronic and allergic rhinosinusitis impacts approximately 12% of the global population. Challenges in rhinosinusitis treatment include paranasal sinus inaccessibility and variability in delivery efficiency among individuals. This study addresses these challenges of drug delivery by developing a high-efficiency, low-variability protocol for nasal dr...

This study presents a data-driven approach to identifying anomaly-sensitive parameters through a multiscale, multifaceted analysis of simulated respiratory flows. The anomalies under consideration include a pharyngeal model with three levels of constriction (M1, M2, M3) and a flapping uvula with two types of kinematics (K1, K2). Direct numerical si...

Featured Application Despite their reported high accuracy, a significant limitation of current AI-assisted COVID-19 diagnostic models is that they are often trained on datasets sourced from specific clinics or possessing a limited number of training images. This raises an important question: Will these models maintain high accuracy when deployed in...

Aim The study aimed to deliver sprays to the posterior nose for mucosa immunization or short-term protection. Background Respiratory infectious diseases often enter the human body through the nose. Sars-Cov-2 virus preferentially binds to the ACE2-rich tissue cells in the nasopharynx (NP). Delivering medications to the nose, especially to the NP r...

Although exhaled aerosols and their patterns may seem chaotic in appearance, they inherently contain information related to the underlying respiratory physiology and anatomy. This study presented a multi-level database of simulated exhaled aerosol images from both normal and diseased lungs. An anatomically accurate mouth-lung geometry extending to...

Animals have been widely utilized as surrogate models for humans in exposure testing, infectious disease experiments, and immunology studies. However, respiratory diseases affect both humans and animals. These disorders can spontaneously affect wild and domestic animals, impacting their quality and quantity of life. The origin of such responses can...

Aerosols exhaled from the lungs have distinctive patterns that can be linked to the abnormalities of the lungs. Yet, due to their intricate nature, it is highly challenging to analyze and distinguish these aerosol patterns. Small airway diseases pose an even greater challenge, as the disturbance signals tend to be weak. The objective of this study...

Background: Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while minimizing dose variability and drug losse...

Snoring and obstructive sleep apnea (OSA) are often associated with uvula vibrations and pharynx constrictions. However, successful treatment of snoring or accurate diagnosis of OSA has been proven challenging. This study aimed to identify acoustic indexes that were sensitive to underlying airway structural or kinematic variations. Six physiologica...

Delivering vaccines to the posterior nose has been proposed to induce mucosal immunization. However, conventional nasal devices often fail to deliver sufficient doses to the posterior nose. This study aimed to develop a new delivery protocol that can effectively deliver sprays to the caudal turbinate and nasopharynx. High-speed imaging was used to...

Accurate modeling and simulation of metered-dose inhaler (MDI) drug delivery require detailed information about the spray aerosols and carrier airflows, which are sensitive to the geometry and formulation of the inhaler. This study aimed to systemically examine the effects of the MDI canister—holder guiding vanes and the orifice airflow on inhalati...

As a means of harvesting solar energy for water treatment, solar-driven vapor generation is becoming more appealing. Due to their entangled fibrous networks and high surface area, fibers can be used as building blocks to generate water vapor. In this paper, using a two-dimensional fiber bundle model, we studied the generation of solar vapor based o...

Pulmonary gas exchanges are vital to human health, and disruptions to this process have been associated with many respiratory diseases. Previous gas exchange studies have predominately relied on whole-body testing and theoretical analysis with 1D or static models. However, pulmonary gas exchanges are inherently a dynamic process in 3D spaces with i...

Glottal vibration is fundamental to breathing-related disorders and respiratory sound generation. However, responses of the flow and acoustics to glottal vibrations of different frequencies are unclear. The objective of this study is to numerically evaluate the influences of glottal vibration frequencies on inspiratory airflow dynamics and flow-ind...

The development of nose-to-brain drug delivery and therapies for olfactory dysfunctions has been hurdled by the challenges to delivering clinically significant doses to the olfactory mucosa, as well as to accurately quantifying the olfactory dosages. This chapter presents a numerical study that tested the feasibility of gravitationally driven dropl...

One of the principal issues in the phase change heat transfer at the vertical channel that changes the vapour fraction in the two-phase system is the presence of a grid spacer which prompts the temperature and velocity jump. In this study, the subcooled fluid stream rising inside the annular tube with grid spacer has been concentrated to investigat...

Previous numerical studies of pulmonary drug delivery using metered-dose inhalers (MDIs) often neglected the momentum transfer from droplets to fluid. However, Kolmogorov length scales in MDI flows can be comparable to the droplet sizes in the orifice vicinity, and their interactions can modify the spray behaviors. This study aimed to evaluate the...

Snoring and obstructive sleep apnea (OSA) are often associated with uvula vibrations and pharynx constrictions. However, successful treatment of snoring or accurate diagnosis of OSA has been proven challenging. This study aimed to identify acoustic indexes that were sensitive to underlying airway structural or kinematic variations. Six physiologica...

Nose-to-brain (N2B) drug delivery is a new approach to neurological disorder therapy as medications can bypass the blood-brain barrier and directly enter the brain. However, the delivery efficiency to the olfactory region using the conventional delivery method is impractically low because of the region's secluded position in a convoluted nasal cavi...

Effective pulmonary drug delivery using a metered-dose inhaler (MDI) requires a match between the MDI sprays, the patient’s breathing, and respiratory physiology. Different inhalers generate aerosols with distinct aerosol sizes and speeds, which require specific breathing coordination to achieve optimized delivery efficiency. Inability to perform t...

Most previous numerical studies of inhalation drug delivery used monodisperse aerosols or quantified deposition as the ratio of deposited particle number over the total number of released particles (i.e., count-based). These practices are reasonable when the aerosols have a sufficiently narrow size range. However, spray droplets from metered-dose i...

Knowing the deposition rate and distribution of administered pharmaceuticals in the human respiratory tract is crucial to establish dose-response relationships and optimize therapeutic outcomes. Recent advances in imaging technology have made it practical to generate respiratory tract models with great details and anatomical accuracy. Pharmaceutics...

Leakage flows due to a poor fit can greatly reduce the mask protection efficiency. However, accurate quantification of leakages is lacking due to the absence of standardized tests and difficulties in quantifying mask gaps. The objective of this study is to quantify the leakage flows around surgical masks with gaps of varying areas and locations. An...

The use of impulse oscillometry (IOS) for lung function testing does not need patient cooperation and has gained increasing popularity among both young and senior populations, as well as in patients with breathing difficulties. However, studies of the IOS sensitivity to regional lung obstructions are limited and have shown mixed results. The object...

Accurate knowledge of the delivery of locally acting drug products, such as metered-dose inhaler (MDI) formulations, to large and small airways is essential to develop reliable in vitro/in vivo correlations (IVIVCs). However, challenges exist in modeling MDI delivery, due to the highly transient multiscale spray formation, the large variability in...

This study aimed to evaluate optimal aerosol and oxygen delivery with a hood on an infant model and a paediatric model. A facemask and a hood with three inlets, with or without a front cover, were used. A small-volume nebuliser with a unit-dose of salbutamol was used for drug delivery and an air entrainment nebuliser was used to deliver oxygen at 3...

Ultrafine particle (i.e., smaller than 100 nm) in the ambient air is a significant public health issue. The inhalation and deposition of ultrafine particles in the human airways can lead to various adverse health effects. Loose-fitting types of masks are commonly used by the general public in some developing countries for protecting against ultrafi...

The nose is the initial site of viral infection, replication, and transmission in the human body. Nasally inhaled vaccines may act as a promising alternative for COVID-19 management in addition to intramuscular vaccination. In this review, the latest developments of nasal sprays either as repurposed or antiviral formulations were presented. Nasal v...

In response to the unmet need for effective treatments for symptomatic patients, research efforts of inhaled therapy for COVID-19 patients have been pursued since the pandemic began. However, inhalation drug delivery to the lungs is sensitive to the lung anatomy and physiology, which can be significantly altered due to the viral infection. The ensu...

In this work, a local adaptive mesh refinement (AMR) embedded incompressible flow solver is developed for biomedical flows. This AMR technique is based on the block-structured mesh and adapted from an in-house numerical solver for the Navier-Stokes equations with immersed-boundary method embedded, which is suitable for flows with complex and moving...

Respiratory diseases often show no apparent symptoms at their early stages and are usually diagnosed when permanent damages have been made to the lungs. A major site of lung pathogenesis is the small airways, which make it highly challenging to detect using current techniques due to the diseases’ location (inaccessibility to biopsy) and size (below...

Previous in vivo and ex vivo studies have tested nasal sprays with varying head positions to enhance the olfactory delivery; however, such studies often suffered from a lack of quantitative dosimetry in the target region, which relied on the observer’s subjective perception of color changes in the endoscopy images. The objective of this study is to...

Objective: Respiratory diseases are often accompanied by alterations to airway morphology. However, inhalation dosimetry data in remodeled airways are scarce due to the challenges in reconstructing diseased respiratory morphologies. This study aims to study the airway remodeling effects on the inhalation dosimetry of nasally inhaled nanoparticles i...

Radioactive aerosols that arise from natural sources and nuclear accidents can be a long-term hazard to human health. Despite the heterogeneous particle deposition in the respiratory tract, uniform aerosol doses have long been assumed in respiratory radiation dosimetry predictions such as in the compartment and uniform distribution models. It is un...

Background and Objective : Accurate knowledge of the delivered doses to the diseased site in the respiratory tract is crucial to elicit desired therapeutic outcomes. However, such information is still difficult to obtain due to inaccessibility for measurement or visualization, complex network structure, and challenges in reconstructing lung geometr...

One hallmark of emphysema is the breakdown of inter-alveolar septal walls in pulmonary acini. How the acinar dosimetry of environmental aerosols varies at different stages of emphysema remains unclear; this is specifically pertinent to users of tobacco products, which is the leading cause of emphysema. The objective of this study is to systematical...

When an infected person coughs, many virus-laden droplets will be exhaled out of the mouth. Droplets from deep lungs are especially infectious because the alveoli are the major sites of coronavirus replication. However, their exhalation fraction, size distribution, and exiting speeds are unclear. This study investigated the behavior and fate of res...

Emphysema is a chronic respiratory disease characterized by interalveolar septa destruction and enlarged air sacs. How the inhalation dosimetry in the pulmonary acini varies in the time course of emphysema is still unclear. The aim of this study is to numerically evaluate the impact of septal destructions on particle deposition in a pyramid-shape s...

Even though face masks are well accepted as tools useful in reducing COVID-19 transmissions, their effectiveness in reducing viral loads in the respiratory tract is unclear. Wearing a mask will significantly alter the airflow and particle dynamics near the face, which can change the inhalability of ambient particles. The objective of this study is...

Uvula‐induced snoring and associated obstructive sleep apnea is a complex phenomenon characterized by vibrating structures and highly transient vortex dynamics. This study aimed to extract signature features of uvula wake flows of different pathological origins and develop a linear reduced‐order surrogate model for flow control. Six airway models w...

This chapter provides the latest research trends in applications of CFD for investigating nasal drug delivery. Contributions include research and outcomes from the regulatory body, US Food Drug Administration on recent projects. Additionally, the chapter showcases the application of multiphase flow for capturing nasal spray drug delivery for improv...

Snoring is a common breathing disorder during sleep. It is hypothesized that head posture during sleep could change the bending angle and the cross-sectional area of the airway, which could cause changes in airflow and aerodynamic pressure during sleep. In this work, an experiment-driven computational study was conducted to examine the aerodynamics...

Even with the advance in medical imaging techniques such as CT/MRI, it is still challenging and time-consuming to reconstruct anatomically accurate lung geometries. It is even more challenging to study variability in inhalation dosimetry or pulmonary drug delivery, which requires a large cohort of lung models to ensure statistically significant res...

3D printers have been widely used as a tool for prototype manufacturing in industries, schools, and homes. During operation, 3D printers emit ultrafine particles that could be inhaled by the user and induce adverse health effects. Thus, exposure to ultrafine 3D-printing generated particles has drawn the attention of occupational and environmental h...

Significant differences in alveolar size exist in humans of different ages, gender, health, and among different species. The effects of alveolar sizes, as well as the accompanying breathing frequencies, on regional and local dosimetry of inhaled nanoparticles have not been sufficiently studied. Despite a well-accepted qualitative understanding of t...

Simple Summary The rabbit nose has a very complex structure. How this structure accomplishes functions such as olfaction and the filtration of nanoparticles is not well understood. Moreover, rabbits often sniff; how this sniffing helps them smell better is still a myth. In this study, we examined the anatomy of a New Zealand white (NZW) rabbit nose...

Despite extensive efforts in studying radioactive aerosols, including the transmission of radionuclides in different chemical matrices throughout the body, the internal organ-specific radiation dose due to inhaled radioactive aerosols has largely relied on experimental deposition data and simplified human phantoms. Computational fluid-particle dyna...

Unsteady uvula motions and the resultant pressure oscillations within the pharyngeal airway are critical for the pathology of snoring and sleeping apnea. In this paper, an immersed-boundary-method based direct numerical simulation flow solver was adopted to simulate the unsteady flows in an anatomically accurate pharynx model reconstructed from hum...

Background: The integration of inhalation drug delivery and nanotechnology offers exciting potentials to enhance the targeting, release, diagnostic, and therapeutic outcomes of drugs. Human lungs provide many advantages over other routers such as noninvasive delivery, a large surface area for absorption, avoiding the first-pass metabolism, and quic...

Pulmonary delivery of nanomedicines has been extensively studied in recent years because of their enhanced biocompatibility, sustained-release properties, and surface modification capability. The lung as a target also offers many advantages over other routers, such as large surface area, noninvasive, quick therapeutic onset, and avoiding first-pass...

Ultrafine particles (UFPs) in workplaces have been and continue to be an important occupational health concern. The inhalation and the consequent deposition of UFPs in workers’ lower airways can lead to many adverse health effects. Therefore, it is vital to study the deposition of UFPs in the human respiratory tract from the viewpoint of occupation...

Human tongue is a highly compliant entity and its position has significant effects on the delivery efficiency of orally inhaled pharmaceuticals. However, studies of tongue postures on aerosol transport and deposition are rare due to technical challenges in developing such models. This study presents a computational oropharyngeal model with varying...

Background Exhaled aerosols from lungs have unique patterns, and their variation can be correlated to the underlying lung structure and associated abnormities. However, it is challenging to characterize such aerosol patterns and differentiate their difference because of their complexity. This challenge is even greater for small airway diseases, whe...

A list of the images of exhaled aerosol distributions under different airway constriction levels. (GIF)

Images of exhaled aerosol distributions under different airway constriction levels. (ZIP)

Unique features exist in acinar units such as multiple alveoli, interalveolar septal walls, and pores of Kohn. However, the effects of such features on airflow and particle deposition remain not well quantified due to their structural complexity. This study aims to numerically investigate particle dynamics in acinar models with interalveolar septal...

The particle dynamics in an oscillating alveolus under tidal breathing can be dramatically different from those in a static alveolus. Despite its close relevance to pulmonary drug delivery and health risk from airborne exposure, quantifications of alveolar deposition are scarce due to its inaccessibility to in vivo measurement instruments, tiny siz...

The fluid dynamics of air flow in the pharynx is critical to the vibration of the uvula and to the generation of the snoring sound. In this work, a combined experimental and computational approach was conducted to study the aerodynamics of the flow field in the human airway. An anatomically accurate pharynx model associated with different uvula kin...

Background: Human snores are caused by vibrating anatomical structures in the upper airway. The glottis is a highly variable structure and a critical organ regulating inhaled flows. However, the effects of the glottis motion on airflow and breathing sound are not well understood, while static glottises have been implemented in most previous in sil...

The periodic movement of the glottal aperture during tidal breathing has been long recognized as a physiological factor in regulating the respiratory airflow dynamics. However, studies of the dynamic glottis and its functions are scarce due to the complex respiratory anatomy, lack of glottis kinematics, and challenges in simulating moving structure...

Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decr...

The human nose can expand either actively or passively to increase airflow. Nasal dilation may alter drug delivery efficiencies in the nasal airway or olfactory region. However, the dosage enhancement from nasal dilations has not been quantified. The mechanisms underlying the dilation-induced deposition variation are also not clear. This study aims...

Knowing aerosol deposition distribution (ADD) in the respiratory tract is crucial in assessing dose–response relationship and optimizing inhalation therapy. However, characterization of ADD inside the airway is challenging, due to its inaccessibility to standard measurement instruments. Radioactive imaging techniques such as gamma scintigraphy, SPE...

In order to advance the understanding of biological fluid dynamics and its effects on the acoustics of human snoring, the study pursued a physics-based computational approach. From human magnetic resonance image (MRI) scans, the researchers were able to develop both anatomically and dynamically accurate airway-uvula models. With airways defined as...

Inhalation dosimetry in the alveolar region is critical in assessing health risks of inhaled toxicants and therapeutic outcomes of systemic pulmonary drug delivery. Most previous studies of acinar deposition focused on respiratory bronchioles or alveolated ducts with either steady unidirectional or tidal flow through the duct. The precise nature of...