Publications by authors named "Nicole Y K Li-Jessen"

12 Publications

  • Page 1 of 1

Pediatric Vocal Fold Paresis and Paralysis: A Narrative Review.

JAMA Otolaryngol Head Neck Surg 2021 Jun 10. Epub 2021 Jun 10.

School of Communication Sciences and Disorders, McGill University, Montreal, Canada.

Importance: Vocal fold paralysis (VFP) results from the disruption of neural motor outputs to laryngeal muscles. Children with VFP manifest various degrees of difficulties in phonation, breathing, and swallowing. Although the etiologic characteristics and symptoms of VFP are well established in adults, corresponding clinical profiles are notably different in children. Clinical management of VFP is particularly challenging in children because their larynges are still actively developing and the recovery of disrupted laryngeal nerves is often unpredictable. This review discusses the neurologic conditions and diagnostic and treatment considerations in pediatric VFP.

Observations: Injury to the peripheral laryngeal nerves and certain central nervous system diseases, such as Arnold-Chiari malformation type II, can result in VFP in infants and children. The incidence of unilateral vs bilateral VFP is variable across pediatric studies. Most reported VFP cases are associated with injury of the recurrent laryngeal nerve. Laryngeal electromyography requires needle insertion that must be performed under anesthesia with special care in the pediatric setting. Neither normative values nor standardized procedures of laryngeal electromyography are currently established for the pediatric population. Laryngeal reinnervation, endoscopic arytenoid abduction lateropexy, and laryngeal pacing are plausible treatment options for pediatric VFP. Despite these new advances in the field, no corresponding efficacy data are available for clinicians to discern which type of patients would be the best candidates for these procedures.

Conclusions And Relevance: The neuroanatomy and neurophysiology of VFP remain more elusive for the pediatric population than for adults. Basic and clinical research is warranted to fully comprehend the complexity of this laryngeal movement disorder and to better inform and standardize clinical practice.
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http://dx.doi.org/10.1001/jamaoto.2021.1050DOI Listing
June 2021

An in vitro assessment of the response of THP-1 macrophages to varying stiffness of a glycol-chitosan hydrogel for vocal fold tissue engineering applications.

J Biomed Mater Res A 2021 Aug 6;109(8):1337-1352. Epub 2020 Nov 6.

School of Communication Sciences and Disorders, McGill University, Montreal, Canada.

The physical properties of a biomaterial play an essential role in regulating immune and reparative activities within the host tissue. This study aimed to evaluate the immunological impact of material stiffness of a glycol-chitosan hydrogel designed for vocal fold tissue engineering. Hydrogel stiffness was varied via the concentration of glyoxal cross-linker applied. Hydrogel mechanical properties were characterized through atomic force microscopy and shear plate rheometry. Using a transwell setup, macrophages were co-cultured with human vocal fold fibroblasts that were embedded within the hydrogel. Macrophage viability and cytokine secretion were evaluated at 3, 24, and 72 hr of culture. Flow cytometry was applied to evaluate macrophage cell surface markers after 72 hr of cell culture. Results indicated that increasing hydrogel stiffness was associated with increased anti-inflammatory activity compared to relevant controls. In addition, increased anti-inflammatory activity was observed in hydrogel co-cultures. This study highlighted the importance of hydrogel stiffness from an immunological viewpoint when designing novel vocal fold hydrogels.
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http://dx.doi.org/10.1002/jbm.a.37125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079542PMC
August 2021

Characterizing Vocal Fold Injury Recovery in a Rabbit Model With Three-Dimensional Virtual Histology.

Laryngoscope 2021 07 18;131(7):1578-1587. Epub 2020 Aug 18.

Department of Physics, McGill University, Montreal, Quebec, Canada.

Objectives/hypothesis: In animal studies of vocal fold scarring and treatment, imaging-based evaluation is most often conducted by tissue slicing and histological staining. Given variation in anatomy, injury type, severity, and sacrifice timepoints, planar histological sections provide limited spatiotemporal details of tissue repair. Three-dimensional (3D) virtual histology may provide additional contextual spatial information, enhancing objective interpretation. The study's aim was to evaluate the suitability of magnetic resonance imaging (MRI), microscale computed tomography (CT), and nonlinear laser-scanning microscopy (NM) as virtual histology approaches for rabbit studies of vocal fold scarring.

Methods: A unilateral injury was created using microcup forceps in the left vocal fold of three New Zealand White rabbits. Animals were sacrificed at 3, 10, and 39 days postinjury. ex vivo imaging of excised larynges was performed with MRI, CT, and NM modalities.

Results: The MRI modality allowed visualization of injury location and morphological internal features with 100-μm spatial resolution. The CT modality provided a view of the injury defect surface with 12-μm spatial resolution. The NM modality with optical clearing resolved second-harmonic generation signal of collagen fibers and two-photon autofluorescence in vocal fold lamina propria, muscle, and surrounding cartilage structures at submicrometer spatial scales.

Conclusions: Features of vocal fold injury and wound healing were observed with MRI, CT, and NM. The MRI and CT modalities provided contextual spatial information and dissection guidance, whereas NM resolved extracellular matrix structure. The results serve as a proof of concept to motivate incorporation of 3D virtual histology techniques in future vocal fold injury animal studies.

Level Of Evidence: NA Laryngoscope, 131:1578-1587, 2021.
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http://dx.doi.org/10.1002/lary.29028DOI Listing
July 2021

A paper-based microfluidic platform with shape-memory-polymer-actuated fluid valves for automated multi-step immunoassays.

Microsyst Nanoeng 2019 23;5:50. Epub 2019 Sep 23.

1Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON M5S 3G8 Canada.

Smart fluid manipulation with automatically controlled paper valves will enable automated and multi-step immunoassays on paper-based microfluidic devices. In this work, we present an integrated paper-based microfluidic platform with shape-memory polymer (SMP)-actuated fluid valves capable of automated colorimetric enzyme-linked immunosorbent assays (ELISAs). A single-layer microfluidic paper-based analytical device (μPAD) was designed to store all the reagents on the chip, and sequentially transfer reagents to a paper test zone following a specific ELISA protocol through automatic fluidic flow control by the multiple SMP-actuated valves. The actuation of a paper valve was based on the thermally responsive, duel-state shape transformation of a SMP sheet attached to the root of a paper cantilever beam for driving a hydrophilic paper bridge to connect and disconnect two paper channels. A portable colorimetric reader was developed to control the on-chip valve operations, quantify the colorimetric signal output, display the assay result, and wirelessly transmit the data to a smart phone for the application of telemedicine. Reliable operations of the paper valve and the entire μPAD were demonstrated with success rates of 97% and 93%, respectively. A detection mechanism for valve malfunction was designed and confirmed effective to identify any mal-operation of individual valves, thus rendering our platform reliable in real assays. For device calibration, we conducted direct ELISAs of rabbit IgG in phosphate-buffered saline (PBS), and achieved a low limit of detection (LOD) of 27 pM (comparable to that of standard and paper-based ELISAs). In order to demonstrate the clinical application of our multi-step immunoassay platform, we also conducted sandwich ELISAs to quantify the protein level of an inflammatory cytokine, namely tumor necrosis factor (TNF)-α, in surgically injured laryngeal tissues of rats. The protein levels of TNF-α were shown similar between the conventional and μPAD ELISAs.
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http://dx.doi.org/10.1038/s41378-019-0091-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799814PMC
September 2019

Towards a Physiological Scale of Vocal Fold Agent-Based Models of Surgical Injury and Repair: Sensitivity Analysis, Calibration and Verification.

Appl Sci (Basel) 2019 Aug 25;9(15). Epub 2019 Jul 25.

Department of Biological and Biomedical Engineering, McGill University, Montreal, QC H3A 0G4, Canada.

Agent based models (ABM) were developed to numerically simulate the biological response to surgical vocal fold injury and repair at the physiological level. This study aimed to improve the representation of existing ABM through a combination of empirical and computational experiments. Empirical data of vocal fold cell populations including neutrophils, macrophages and fibroblasts were obtained using flow cytometry up to four weeks following surgical injury. Random Forests were used as a sensitivity analysis method to identify model parameters that were most influential to ABM outputs. Statistical Parameter Optimization Tool for Python was used to calibrate those parameter values to match the ABM-simulation data with the corresponding empirical data from Day 1 to Day 5 following surgery. Model performance was evaluated by verifying if the empirical data fell within the 95% confidence intervals of ABM outputs of cell quantities at Day 7, Week 2 and Week 4. For Day 7, all empirical data were within the ABM output ranges. The trends of ABM-simulated cell populations were also qualitatively comparable to those of the empirical data beyond Day 7. Exact values, however, fell outside of the 95% statistical confidence intervals. Parameters related to fibroblast proliferation were indicative to the ABM-simulation of fibroblast dynamics in final stages of wound healing.
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http://dx.doi.org/10.3390/app9152974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675024PMC
August 2019

Multimodal virtual histology of rabbit vocal folds by nonlinear microscopy and nano computed tomography.

Biomed Opt Express 2019 Mar 11;10(3):1151-1164. Epub 2019 Feb 11.

Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, QC H3A 0B8, Canada.

Human vocal folds (VFs) possess a unique anatomical structure and mechanical properties for human communication. However, VFs are prone to scarring as a consequence of overuse, injury, disease or surgery. Accumulation of scar tissue on VFs inhibits proper phonation and leads to partial or complete loss of voice, with significant consequences for the patient's quality of life. VF regeneration after scarring provides a significant challenge for tissue engineering therapies given the complexity of tissue microarchitecture. To establish an effective animal model for VF injury and scarring, new histological methods are required to visualize the wound repair process of the tissue in its three-dimensional native environment. In this work, we propose the use of a combination of nonlinear microscopy and nanotomography as contrast methods for virtual histology of rabbit VFs. We apply these methods to rabbit VF tissue to demonstrate their use as alternatives to conventional VF histology that may enable future clinical studies of this injury model.
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http://dx.doi.org/10.1364/BOE.10.001151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420294PMC
March 2019

High-Performance Agent-Based Modeling Applied to Vocal Fold Inflammation and Repair.

Front Physiol 2018 12;9:304. Epub 2018 Apr 12.

School of Communication Sciences and Disorders, McGill University, Montreal, QC, Canada.

Fast and accurate computational biology models offer the prospect of accelerating the development of personalized medicine. A tool capable of estimating treatment success can help prevent unnecessary and costly treatments and potential harmful side effects. A novel high-performance Agent-Based Model (ABM) was adopted to simulate and visualize multi-scale complex biological processes arising in vocal fold inflammation and repair. The computational scheme was designed to organize the 3D ABM sub-tasks to fully utilize the resources available on current heterogeneous platforms consisting of multi-core CPUs and many-core GPUs. Subtasks are further parallelized and convolution-based diffusion is used to enhance the performance of the ABM simulation. The scheme was implemented using a client-server protocol allowing the results of each iteration to be analyzed and visualized on the server (i.e., ) while the simulation is running on the same server. The resulting simulation and visualization software enables users to interact with and steer the course of the simulation in real-time as needed. This high-resolution 3D ABM framework was used for a case study of surgical vocal fold injury and repair. The new framework is capable of completing the simulation, visualization and remote result delivery in under 7 s per iteration, where each iteration of the simulation represents 30 min in the real world. The case study model was simulated at the physiological scale of a human vocal fold. This simulation tracks 17 million biological cells as well as a total of 1.7 billion signaling chemical and structural protein data points. The visualization component processes and renders all simulated biological cells and 154 million signaling chemical data points. The proposed high-performance 3D ABM was verified through comparisons with empirical vocal fold data. Representative trends of biomarker predictions in surgically injured vocal folds were observed.
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http://dx.doi.org/10.3389/fphys.2018.00304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906585PMC
April 2018

In Situ Visualization for 3D Agent-Based Vocal Fold Inflammation and Repair Simulation.

Supercomput Front Innov 2017 Jul-Sep;4(3):68-79

McGill University, Montreal, Québec, Canada.

A fast and insightful visualization is essential in modeling biological system behaviors and understanding underlying inter-cellular mechanisms. High fidelity models produce billions of data points per time step, making visualization techniques extremely desirable as they mitigate I/O bottlenecks and provide computational steering capability. In this work, we present a novel high-performance scheme to couple visualization with the simulation of the vocal fold inflammation and repair using little to no extra cost in execution time or computing resources. The visualization component is first optimized with an adaptive sampling scheme to accelerate the rendering process while maintaining the precision of the displayed visual results. Our software employs VirtualGL to perform visualization . The scheme overlaps visualization and simulation, resulting in the optimal utilization of computing resources. This results in an system biology simulation suite capable of remote simulation of 17 million biological cells and 1.2 billion chemical data points, remote visualization of the results, and delivery of visualized frames with aggregated statistics to remote clients in real-time.
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http://dx.doi.org/10.14529/jsfi170304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5701753PMC
November 2017

Retention of Human-Induced Pluripotent Stem Cells (hiPS) With Injectable HA Hydrogels for Vocal Fold Engineering.

Ann Otol Rhinol Laryngol 2017 Apr 12;126(4):304-314. Epub 2017 Feb 12.

4 Division of Otolaryngology-Head and Neck Surgery, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Objective: One prospective treatment option for vocal fold scarring is regeneration with an engineered scaffold containing induced pluripotent stem cells (iPS). In the present study, we investigated the feasibility of utilizing an injectable hyaluronic acid (HA) scaffold encapsulated with human-iPS cell (hiPS) for regeneration of vocal folds.

Methods: Thirty athymic nude rats underwent unilateral vocal fold injury. Contralateral vocal folds served as uninjured controls. Hyaluronic acid hydrogel scaffold, HA hydrogel scaffold containing hiPS, and HA hydrogel scaffold containing hiPS with epidermal growth factor (EGF) were injected in both vocal folds immediately after surgery. One and 2 weeks after injection, larynges were excised for histology, immunohistochemistry, and fluorescence in situ hybridization (FISH).

Results: Presence of HA hydrogel was confirmed in vocal folds 1 and 2 weeks post injection. The FISH analysis confirmed the presence and viability of hiPS in the injected vocal folds. Histological results demonstrated that vocal folds injected with HA hydrogel scaffold containing EGF demonstrated less fibrosis than those with HA hydrogel only.

Conclusions: Human-iPS survived in injured rat vocal folds. The HA hydrogel with hiPS and EGF ameliorated the fibrotic response. Additional work is necessary to optimize hiPS differentiation and further confirm the safety of hiPS for clinical applications.
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http://dx.doi.org/10.1177/0003489417691296DOI Listing
April 2017

Cellular source and proinflammatory roles of high-mobility group box 1 in surgically injured rat vocal folds.

Laryngoscope 2017 06 24;127(6):E193-E200. Epub 2016 Oct 24.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, Wisconsin, U.S.A.

Objectives/hypothesis: High-mobility group box 1 (HMGB1) is a chromatin-binding protein located in the cell nucleus. Following injury, immunocompetent cells secrete HMGB1 to the extracellular milieu under the stimulation of proinflammatory cytokines. Extracellular HMGB1 acts a danger signal that instigates the innate immunity and tissue repair. We previously reported HMGB1 in the vocal fold extracellular compartment between day 3 and day 7 following surgical injury. In this study, we further investigated the cell source of HMGB1 and the relationship of proinflammatory cytokine expression and HMGB1 translocation in wounded vocal folds.

Study Design: Prospective animal study.

Methods: Bilateral vocal fold injury was performed on 122 Sprague-Dawley rats. An additional 18 rats served as uninjured controls. Animals were sacrificed at multiple time points up to 4 weeks after surgery. Immunohistochemical costaining was performed to identify the cell source of HMGB1. Cell markers ED1, fibroblast-specific protein 1 (FSP1), and alpha smooth muscle actin (α-SMA) were used to identify macrophages, fibroblasts, and myofibroblasts, respectively. Enzyme-linked immunosorbent assays were performed to measure cytokine levels of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in vocal fold tissue.

Results: Costaining of HMGB1 was strong with ED1 and FSP1 but was minimal with α-SMA in injured vocal folds. Compared to uninjured controls, IL-1β and TNF-α expression increased significantly the first 2 days after injury.

Conclusions: Macrophages and fibroblasts were a major cell source of vocal fold HMGB1. Translocation of HMGB1 may be an active response to the early accumulation of IL-1β and TNF-α in the wounded vocal folds.

Level Of Evidence: NA Laryngoscope, 127:E193-E200, 2017.
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http://dx.doi.org/10.1002/lary.26333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403630PMC
June 2017

Real-Time Agent-Based Modeling Simulation with in-situ Visualization of Complex Biological Systems: A Case Study on Vocal Fold Inflammation and Healing.

IEEE Int Symp Parallel Distrib Process Workshops Phd Forum 2016 May;2016:463-472

School of Communication Sciences and Disorders - McGill University, Montreal, Canada.

We present an efficient and scalable scheme for implementing agent-based modeling (ABM) simulation with In Situ visualization of large complex systems on heterogeneous computing platforms. The scheme is designed to make optimal use of the resources available on a heterogeneous platform consisting of a multicore CPU and a GPU, resulting in minimal to no resource idle time. Furthermore, the scheme was implemented under a client-server paradigm that enables remote users to visualize and analyze simulation data as it is being generated at each time step of the model. Performance of a simulation case study of vocal fold inflammation and wound healing with 3.8 million agents shows 35× and 7× speedup in execution time over single-core and multi-core CPU respectively. Each iteration of the model took less than 200 ms to simulate, visualize and send the results to the client. This enables users to monitor the simulation in real-time and modify its course as needed.
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http://dx.doi.org/10.1109/IPDPSW.2016.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988409PMC
May 2016

A Flow Perfusion Bioreactor System for Vocal Fold Tissue Engineering Applications.

Tissue Eng Part C Methods 2016 09 15;22(9):823-38. Epub 2016 Aug 15.

1 Department of Mechanical Engineering, McGill University , Montreal, Canada .

The human vocal folds (VFs) undergo complex biomechanical stimulation during phonation. The aim of the present study was to develop and validate a phono-mimetic VF flow perfusion bioreactor, which mimics the mechanical microenvironment of the human VFs in vitro. The bioreactor uses airflow-induced self-oscillations, which have been shown to produce mechanical loading and contact forces that are representative of human phonation. The bioreactor consisted of two synthetic VF replicas within a silicone body. A cell-scaffold mixture (CSM) consisting of human VF fibroblasts, hyaluronic acid, gelatin, and a polyethylene glycol cross-linker was injected into cavities within the replicas. Cell culture medium (CCM) was perfused through the scaffold by using a customized secondary flow loop. After the injection, the bioreactor was operated with no stimulation over a 3-day period to allow for cell adaptation. Phonation was subsequently induced by using a variable speed centrifugal blower for 2 h each day over a period of 4 days. A similar bioreactor without biomechanical stimulation was used as the nonphonatory control. The CSM was harvested from both VF replicas 7 days after the injection. The results confirmed that the phono-mimetic bioreactor supports cell viability and extracellular matrix proteins synthesis, as expected. Many scaffold materials were found to degrade because of challenges from phonation-induced biomechanical stimulation as well as due to biochemical reactions with the CCM. The bioreactor concept enables future investigations of the effects of different phonatory characteristics, that is, voice regimes, on the behavior of the human VF cells. It will also help study the long-term functional outcomes of the VF-specific biomaterials before animal and clinical studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035918PMC
http://dx.doi.org/10.1089/ten.tec.2016.0053DOI Listing
September 2016
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