Hybrid Model of Vocal Inflammation and Tissue Mobilization

描述(由申请人提供)：长期目标是产生一种技术，使临床医生能够开出一种“理想的”发声练习(或休息)计划，以优化急性和慢性声音创伤的组织愈合。在本系列中，我们将重点介绍这一急性病例。短期目标是(A)建立一种方法来定量描述患者当前的炎症状态，以及(B)开发一种复杂系统的混合气动机械/生物计算机模型，该模型可以最终确定声音使用和休息的方案，在给定不同的初始炎症状态的情况下，随着时间的推移，应该优化分子/细胞特性。我们实验室的工作在解决第一个短期目标方面取得了良好的进展。具体地说，我们开发了一种活体技术，似乎可以定量描述喉部目前的炎症状态。我们还完成了实现第二个目标的初步工作。我们根据人类和动物的数据建立了初步的声带炎症空气动力学模型、基于代理的模型和常微分方程式模型。在本系列中，我们建议：(1)建立一种非侵入性的方法，用于估计发声过程中的总机械剂量，以及从高速成像数据和声带构型的空气力学模型中估计发声机械剂量的分量指标(例如，距离剂量、能量耗散剂量和时间剂量)；(2)：识别机械剂量参数、组织的炎症状态和组织中随时间变化的生物学后果之间的数学关系，在急性声音创伤后长达3周；(3)：开发声带炎症和治疗的混合物理-生物模型，以确定在一系列急性声音创伤条件下，应在3wk时优化创伤后伤口愈合的发声方式，以及(4)：对混合治疗模型预测人类受试者理想化治疗结果的能力进行初步测试，并根据需要反复校准该模型，以实现预测和获得的结果之间的匹配。假设通过这种方法，可以开发一个平台，最终允许为急性声音创伤患者开出针对患者的治疗处方，从而优化长期愈合，最终结果将表明，与声音休息相比，对于某些声音创伤条件，某些形式的发声练习可能会促进组织中的生物恢复。

DESCRIPTION (provided by applicant): The long-range goal is to generate a technology that will allow clinicians to prescribe an "ideal" vocal exercise (or rest) program that should optimize tissue healing for both acute and chronic phonotrauma. In the present series, we focus on the acute case. Short-term goals are (a) to establish a methodology to quantitatively characterize the patient's current inflammatory profile, and (b) to develop a hybrid aeromechanical/biological in silico model of complex systems that can ultimately identify regimens of voice use and rest that should optimize molecular/cellular profiles over time, given varying initial inflammatory states. Work from our laboratory has made good progress in addressing the first short-term goal. Specifically, we have developed an in vivo technology that appears to quantitatively characterize the current inflammatory status in the larynx. We have also completed preliminary work to address the second goal. We have developed preliminary aerodynamic, Agent-Based and Ordinary Differential Equation Models of vocal fold inflammation calibrated to human and animal data. In the present series, we propose to (1): establish a non-invasive methodology for estimating overall mechanical dose during phonation, and component metrics of phonatory mechanical dose (e.g., distance dose, energy dissipation dose and time dose) from high speed imaging data and aeromechanical modeling, for a range of vocal fold configurations; (2): identify mathematical relations between mechanical dose parameters, inflammatory state of the tissue and time-varying biological consequences in the tissue, up to 3 wk following acute phonotrauma; (3): develop a hybrid physical-biological model of vocal fold inflammation and treatment to identify phonation modalities that should optimize post-traumatic wound healing at 3 wk, for a range of acute phonotraumatic conditions, and (4): provide a preliminary test of the hybrid treatment models' ability to predict idealized treatment outcome in human subjects, and calibrate the model as needed iteratively to achieve a match between predicted and obtained outcomes. The hypothesis is that with this approach, a platform can be developed that will ultimately allow for the prescription of patient-specific treatments for acute phonotrauma that will optimize long-term healing, and that the final results will indicate that some forms of vocal exercise may facilitate biological recovery in the tissue, compared to voice rest, for some phonotraumatic conditions.