In vivo measurement of vocal fold surface resistance

Abstract

Objective A custom-designed probe was developed to measure vocal fold surface resistance in vivo. The purpose of this study was to demonstrate proof of concept of using vocal fold surface resistance as a proxy of functional tissue integrity after acute phonotrauma using an animal model. Study Design Prospective animal study. Methods New Zealand White breeder rabbits received 120 minutes of airflow without vocal fold approximation (control), or 120 minutes of raised intensity phonation (experimental). The probe was inserted via laryngoscope and placed on the left vocal fold under endoscopic visualization. Vocal fold surface resistance of the middle 1/3 of the vocal fold was measured after 0 (baseline), 60, and 120 minutes of phonation. After the phonation procedure, the larynx was harvested and prepared for transmission electron microscopy. Results In the control group, vocal fold surface resistance values remained stable across time points. In the experimental group, surface resistance (X±Y% relative to baseline) was significantly decreased after 120 minutes of raised intensity phonation. This was associated with structural changes using transmission electron microscopy, which revealed damage to the vocal fold epithelium after phonotrauma, including disruption of the epithelium and basement membrane, dilated paracellular spaces, and alterations to epithelial microprojections. In contrast, control vocal fold specimens showed well-preserved stratified squamous epithelia. Conclusion These data demonstrate the feasibility of measuring vocal fold surface resistance in vivo as a means of evaluating functional vocal fold epithelial barrier integrity. Device prototypes are in development for additional testing, validation and for clinical applications in laryngology.

Epithelial response to vocal fold microflap injury in a preclinical model

“…Quantification of paracellular spaces has been employed extensively to characterize vocal fold barrier function, specifically in models of reflux and phonotrauma. 34,35 Dilation of paracellular pathways is known to increase permeability and drug development efforts commonly target increased paracellular permeability to deliver drugs across epithelial barriers. 36 Compounds that increase permeability also increase paracellular spaces.…”

“…Epithelial barrier integrity was also investigated by imaging cell–cell junctions following microflap injury. Quantification of paracellular spaces has been employed extensively to characterize vocal fold barrier function, specifically in models of reflux and phonotrauma 34,35 . Dilation of paracellular pathways is known to increase permeability and drug development efforts commonly target increased paracellular permeability to deliver drugs across epithelial barriers 36 .…”

“…Although recovery of the vocal fold epithelium is thought to be rapid and normal vibratory function is typically observed within 7 days after microflap, immediate and long-term functional alterations to the epithelia are largely unknown. Broadly, reduced transepithelial resistance, [19][20][21] increased paracellular flux, 22 and downregulation of junction proteins such as Occludin, E-cadherin, and ZO-1, which maintain paracellular spaces 7,[23][24][25][26] have been reported following more substantive vocal fold injury. Persistent functional alterations to vocal fold epithelia after microflap may be clinically important.…”