Vocal fold scarring is a major cause of voice disorders like dysphonia, affecting an estimated 2 to 6 million people in the US alone. Vocal fold scarring results from the replacement of the vibratory superficial lamina propria (SLP) with stiff collagenous scar tissue. The modified viscoelastic properties of the SLP impairs vocal fold?s vibration and results in poor phonation. Over the last decade, injectable biomaterials have been investigated as a means to restore the viscoelasticity of scarred vocal folds. Unfortunately, poor localization due to increased resistance of biomaterial flow in stiff scar tissue adversely affects repeatable and reliable outcomes. To address this critical issue, we hypothesize that voids created by ultrafast laser pulses focused below the surface at the scar site will aid biomaterial injection and localization in the desired location. We base our hypothesis on a) the unique ability of ultrafast lasers to non-invasively create sub-surface cuts in bulk tissue, b) the fact that biomaterials preferentially flow through the path of least resistance, c) ex vivo experiments that resulted in reduced injection pressures and successful biomaterial localization in voids created by focused ultrafast laser pulses in scarred tissue, and d) Preliminary in vivo surgery experiments that resulted in long lasting biomaterial localization inside the ablated voids in healthy tissue with no detectable fibrosis (no scarring) around the void. To demonstrate the said hypothesis, we will develop larynx-specific, image guided ultrafast laser probes and test our surgery method in vivo using small (hamster) and large (canine) animal models. We will advance our goals in this project through three Specific Aims: 1) quantify the healing response of tissue to ultrafast laser ablation and characterize the void formation and biomaterial injection techniques in vivo in scar tissues using a table-top microscope and a proven hamster cheek pouch scar model, 2) design and develop larynx-specific ultrafast laser surgery probes that will be capable of sub-surface ablation in large animals (and eventually in human patients) and provide visual feedback and guidance through non-linear microscopy, and 3) evaluate the efficacy and ergonomics of the laser probes in a canine vocal fold scar model in vivo to ultimately assess the impact of localization of injected biomaterials on the functional improvement of vocal folds. Successful completion of the project will result in a new pre-clinically tested surgery tool that will enable controlled and repeatable testing of injectable biomaterials for the treatment of scarred vocal folds in human patients. This highly interdisciplinary project will provide innovations in achromatic, miniaturized optics, micro- manufacturing, large air-core optical fiber technologies for ultrafast laser delivery and non-linear endoscopy, high speed videostroboscopy image analysis and quantitative analysis methods for differentiating tissue morphologies using non-linear microscopy.
Vocal fold scarring is the cause of voice impairment or loss of voice in millions of Americans and disproportionately effects people in occupations that rely heavily upon their voice, such as teaching and singing, yet it lacks an effective means of treatment. One of the greatest hopes for treatment, injection of biomaterials into the superficial layer of the vocal fold to restore proper viscoelastic properties, is impaired by the difficulty in accurately and consistently localizing the injected material in the desired plane. By removing this barrier, we will enable controlled testing of biomaterial treatments, leading to identification of the optimal treatment material and improved treatment of this common yet difficult voice disorder.
| Yildirim, Murat; Quinn, Kyle P; Kobler, James B et al. (2016) Quantitative differentiation of normal and scarred tissues using second-harmonic generation microscopy. Scanning 38:684-693 |
| Subramanian, Kaushik; Gabay, Ilan; Ferhano?lu, Onur et al. (2016) Kagome fiber based ultrafast laser microsurgery probe delivering micro-Joule pulse energies. Biomed Opt Express 7:4639-4653 |
| Martin, Chris; Ben-Yakar, Adela (2016) Determination of scattering properties and damage thresholds in tissue using ultrafast laser ablation. J Biomed Opt 21:115004 |
