Li, Nicole Yee-Key
(2009)
Biosimulation of Vocal Fold Inflammation and Healing.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Personalized, pre-emptive and predictive medicine is the capstone of contemporary medical care. The central aim of this dissertation is to address clinical challenges in prescribing personalized therapy to patients with acute phonotrauma. Inflammation and healing, which are innate tissue responses to mechanical stress/ trauma, are regulated by a complex dynamic system. A systems biology approach, which combines empirical, mathematical and computational tools, was taken to study the biological complexity of this dynamic system in vocal fold injury.Computational agent-based models (ABMs) were developed to quantitatively characterize multiple cellular and molecular interactions around inflammation and healing. The models allowed for tests of various hypothetical effects of motion-based treatments in individuals with acute phonotrauma. A phonotrauma ABM was calibrated and verified with empirical data of a panel of inflammatory mediators, obtained from laryngeal secretions in individuals following experimentally induced phonotrauma and a randomly assigned motion-based treatment. A supplementary ABM of surgically induced vocal fold trauma was developed and subsequently calibrated and verified with empirical data of inflammatory mediators and extracellular matrix substances from rat studies, for the purpose of gaining insight into the &ldquo net effect &rdquo of cellular and molecular responses at the tissue level.ABM simulations reproduced and predicted trajectories of inflammatory mediators and extracellular matrix as seen in empirical data of phonotrauma and surgical vocal fold trauma. The simulation results illustrated a spectrum of inflammatory responses to phonotrauma, surgical trauma and motion-based treatments. The results suggested that resonant voice exercise may optimize the combination of para- and anti-inflammatory responses to accelerate healing. Moreover, the ABMs suggested that hyaluronan fragments might be an early molecular index of tissue damage that is sensitive to varying stress levels - from relatively low phonatory stress to high surgical stress.We propose that this translational application of biosimulation can be used to quantitatively chart individual healing trajectories, test the effects of different treatment options and most importantly provide new understanding of laryngeal health and healing. By placing biology on a firm mathematical foundation, this line of research has potential to influence the contour of scientific thinking and clinical care of vocal fold injury.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
5 June 2009 |
| Date Type: |
Completion |
| Defense Date: |
30 March 2009 |
| Approval Date: |
5 June 2009 |
| Submission Date: |
13 April 2009 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Health and Rehabilitation Sciences > Communication Science and Disorders |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
vocal folds; wound healing; inflammation; phonotrauma; patient-specific; agent-based model |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04132009-144235/, etd-04132009-144235 |
| Date Deposited: |
10 Nov 2011 19:37 |
| Last Modified: |
19 Dec 2016 14:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7122 |
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