Mechanical Characterization of Vocal Fold Tissue: A Review Study

doi:10.1016/j.jvoice.2014.03.001

Journal of Voice

Volume 28, Issue 6, November 2014, Pages 657-667

https://doi.org/10.1016/j.jvoice.2014.03.001 Get rights and content

Summary

Human vocal folds undergo self-sustaining oscillations during phonation. The phonatory functions of the vocal folds depend on their mechanical properties. This article presents a review of various mechanical testing methods and constitutive models that are currently in use for the characterization of mechanical properties of the vocal fold tissue. Special attention is given to tissue deformation under mechanical loading at different length scales. The wide range of elastic modulus values reported in the literature is discussed and justified using a multiscale perspective. This study aims to provide a better understanding of mechanical properties that can be used to build computational simulations of vocal fold vibrations and pave the way for the design of biomaterials to restore biomechanical properties in damaged vocal folds.

Introduction

Involving flow-induced vibrations in the head and neck, the human voice is one component in the production of speech. The primary source of voice production is self-sustained oscillations of the vocal folds,¹ traditionally known as “vocal cords,” located within the larynx (Figure 1). Many instances of voice abuse can lead to benign or malignant voice disorders. It is estimated that 3–9% of the general population, including children and adults, suffers from a voice-related problem at any given point in time.² Estimates are considerably higher for at-risk people, such as teachers and professional singers.

Phonotrauma is believed to be a result of high impact stresses between two colliding vocal fold membranes,³ although the inaccessibility of impact stress in vivo prevents verification of the hypothesis. Impact stress stands for the contact force per unit area of the colliding surface. The limited knowledge of voice biomechanics affects the success of clinical treatments, such as laryngoplastic surgeries.⁴ Moreover, the stiffness of the vocal fold tissue determines the wave motion within the mucosal layer.⁵ The efficiency of computational simulations of vocal fold vibrations is thus associated with the accuracy of the input mechanical properties.⁶ The study of tissue biomechanics in pathological states of the larynx may help in understanding their etiology. The tissue stiffness is believed to be the single measure of choice for many treatments.⁷

The dynamics of the glottal airflow, the geometry of vocal folds, and their biomechanical properties may define voice parameters, such as the fundamental frequency of phonation (FFP). Many studies have investigated the effects of geometry on vocal fold modal properties (eg, Cook and Mongeau⁸) and the effects of tissue biomechanics on vibratory motion (eg, Berry and Titze⁹). Computational models of the elastic deformation of the mucosa require proper constitutive equations that relate tissue strain to the associated mechanical stress.¹⁰ In this review, different approaches used to determine the mechanical properties of the vocal fold tissue are classified. The scale and type of tissue deformation in each testing method constitute the criteria of the classification. The present work intends to review the existing mechanical testing methods and constitutive models to help researchers to choose better characterization methods to evaluate tissue mechanical properties.

This article first covers an overview of vocal fold biomechanics then examines the mechanical testing methods used to characterize the vocal fold tissue. The methods are reviewed considering the type of loading and the scale of deformation. From a structure-function perspective, vocal folds act at the macroscale (ie, millimeter range). The vocal fold ligaments elongate 5–15 mm, and their mucosas oscillate with an amplitude of 0.1–0.5 mm.¹¹ The ultrastructure, including the extracellular matrix (ECM), mostly interacts at the micrometer scale, known as the mesoscale. The reader is referred to Goodyer et al¹² to review the functionality and applicability of the testing methods and the related instrumentation. The relevant constitutive models of the human and animal vocal folds, which fulfill data analysis needs, are presented and categorized from the perspective of their applications in computational simulations. A discussion regarding the range of values reported as vocal fold stiffness will conclude this review.

Section snippets

Anatomy and physiology of the vocal folds

Vocal folds are a pair of soft mucosal membranes stretched across the larynx located between the trachea and the pharynx, as depicted in Figure 1. Each fold has a length of 10–20 mm along the anterior-posterior direction, a length of 8–12 mm along the medial-lateral direction, and a thickness of 3–10 mm.¹ The anatomy of the human vocal fold can be divided into the epithelium, lamina propria, and vocalis muscle, as demonstrated by a coronal cross section in Figure 2. The lamina propria is mainly

Uniaxial traction testing

The goal of uniaxial traction testing is to determine the normal (ie, Young) modulus of the vocal fold tissue along the anterior-posterior direction. Traction testing involves pulling the tissue along a predefined straight direction, as depicted in Figure 4. Although biaxial testing is ideal for biological soft tissues,³³ performing multiaxial testing on dissected vocal folds is very challenging because of their large length-to-width ratio and structural heterogeneity. The vocal folds can

Traction testing

A miniaturized setup was built to perform unidirectional traction testing on rat vocal folds with an effective length of nearly 1 mm.⁶⁴ A custom-designed acrylic-plastic clamp attached to a load sensor of 100 μN resolution and a linear actuator of 1 μm resolution was molded. The average Young modulus was reported as 50 kPa. The methodology suffered from slippage of tissue samples under the clamp and edge effects on uniaxial tension conditions.

Indentation testing

The first indentation-like experiment on the vocal

Lumped-mass models

There are two approaches to simulate the biomechanical behavior of the vocal folds: continuum models and discrete or lumped-mass systems. The latter group provides low-cost computations to understand the physics of phonation. They seem unsuitable for practical applications because of the lack of direct correspondence to directly measurable properties of the vocal folds. Cveticanin²⁹ reviewed the lumped-mass models of vocal fold phonations; thus, they are excluded from the current article.

Continuum models

Concluding remarks

A wide range of values for the linear elastic modulus of the vocal fold tissue has been reported in the literature (Figure 4). The traction testing elucidated a Young modulus of 15–40 kPa for 15% strain (in vitro length reference), whereas the indentation modulus was obtained as 2–5 kPa. The rheometry data led to 0.5–2 kPa (assuming incompressibility of the tissue) for low frequencies. The unidirectional traction testing yields the modulus along the axis of anisotropy, in which the vocal folds

Acknowledgments

I dedicate this work to Prof Luc Mongeau (Department of Mechanical Engineering, McGill University) who was a great source of inspiration for my research on biomechanics of vocal folds.

References (81)

P. Gomez-Vilda et al.
Evaluation of voice pathology based on the estimation of vocal fold biomechanical parameters
J Voice
(2007)
H. Bakhshaee et al.
Determination of strain field on the superior surface of excised larynx vocal folds using DIC
J Voice
(2013)
M. Hirano et al.
Structure and mechanical properties of the vocal folds
T.H. Hammond et al.
The intermediate layer: a morphologic study of the elastin and hyaluronic acid constituents of normal human vocal folds
J Voice
(1997)
J. Moore et al.
Insights into the role of elastin in vocal fold health and disease
J Voice
(2012)
G.S. Berke et al.
Laryngeal biomechanics: an overview of mucosal wave mechanics
J Voice
(1993)
I.R. Titze
Mechanical stress in phonation
J Voice
(1994)
F. Alipour et al.
Vocal fold elasticity in the pig, sheep, and cow larynges
J Voice
(2011)
J.E. Kelleher et al.
Spatially varying properties of the vocal ligament contribute to its eigenfrequency response
J Mech Behav Biomed Mater
(2010)
A.K. Miri et al.
Effects of dehydration on the viscoelastic properties of vocal folds in large deformations
J Voice
(2012)

E. Goodyer et al.

The shear modulus of the human vocal fold in a transverse direction

J Voice

(2009)

D.K. Chhetri et al.

Measurement of Young's modulus of vocal folds by indentation

J Voice

(2011)

T.Y. Hsiao et al.

Elasticity of human vocal folds measured in vivo using color Doppler imaging

Ultrasound Med Biol

(2002)

T. Riede et al.

Elasticity and stress relaxation of a very small vocal fold

J Biomech

(2011)

H.K. Heris et al.

Indentation of poroviscoelastic vocal fold tissue using an atomic force microscope

J Mech Behav Biomed Mater

(2013)

H.J. Butt et al.

Force measurements with the atomic force microscope: technique, interpretation and applications

Surf Sci Rep

(2005)

C. Tao et al.

A fluid-saturated poroelastic model of the vocal folds with hydrated tissue

J Biomech

(2009)

C. Tao et al.

Liquid accumulation in vibrating vocal fold tissue: a simplified model based on a fluid-saturated porous solid theory

J Voice

(2010)

A.K. Miri et al.

Nanoscale viscoelasticity of extracellular matrix proteins in soft tissues: a multiscale approach

J Mech Behav Biomed Mater

(2014)

A.K. Miri et al.

Quantitative assessment of the anisotropy of vocal fold tissue using shear rheometry and traction testing

J Biomech

(2012)

K. Zhang et al.

Modeling of the transient responses of the vocal fold lamina propria

J Mech Behav Biomed Mater

(2009)

A.K. Miri et al.

Microstructural characterization of vocal folds toward a strain-energy model of collagen remodeling

Acta Biomater

(2013)

I.R. Titze

Principles of Voice Production

(2000)

L.O. Ramig et al.

Treatment efficacy: voice disorders

J Speech Lang Hear Res

(1998)

H.E. Gunter

A mechanical model of vocal-fold collision with high spatial and temporal resolution

J Acoust Soc Am

(2003)

N. Isshiki

Vocal mechanics as the basis for phonosurgery

Laryngoscope

(1998)

I.R. Titze

The physics of small-amplitude oscillation of the vocal folds

J Acoust Soc Am

(1988)

D.D. Cook et al.

Ranking vocal fold model parameters by their influence on modal frequencies

J Acoust Soc Am

(2009)

D.D. Cook et al.

Sensitivity of a continuum vocal fold model to geometric parameters, constraints, and boundary conditions

J Acoust Soc Am

(2007)

D.A. Berry et al.

Normal modes in a continuum model of vocal fold tissues

J Acoust Soc Am

(1996)

I.R. Titze et al.

A theoretical study of the effects of various laryngeal configurations on the acoustics of phonation

J Acoust Soc Am

(1979)

E. Goodyer et al.

Devices and methods on analysis of biomechanical properties of laryngeal tissue and substitute materials

Curr Bioinformatics

(2011)

M. Hirano

Structure of the vocal fold in normal and disease states. Anatomical and physical studies

M. Hirano

Morphological structure of the vocal cord as a vibrator and its variations

Folia Phoniatr (Basel)

(1974)

S.D. Gray et al.

Vocal fold proteoglycans and their influence on biomechanics

Laryngoscope

(1999)

C.A. Rosen et al.

Nomenclature of voice disorders and vocal pathology

S.D. Gray et al.

Biomechanical and histologic observations of vocal fold fibrous proteins

Ann Otol Rhinol Laryngol

(2000)

M.S. Hahn et al.

Quantitative and comparative studies of the vocal fold extracellular matrix. I: Elastic fibers and hyaluronic acid

Ann Otol Rhinol Laryngol

(2006)

M.S. Hahn et al.

Quantitative and comparative studies of the vocal fold extracellular matrix. II: Collagen

Ann Otol Rhinol Laryngol

(2006)

D. Munoz-Pinto et al.

Lamina propria cellularity and collagen composition: an integrated assessment of structure in humans

Ann Otol Rhinol Laryngol

(2009)

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