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“理想”的声音锻炼（或休息）方案，以优化急性和慢性声音损伤的组织愈合。在本系列中，我们着重于急性病例。短期目标是(a)建立一种定量表征患者当前炎症特征的方法，以及(b)开发复杂系统的混合空气力学/生物硅模型，该模型可以最终确定语音使用和休息方案，该方案应该随着时间的推移优化分子/细胞特征，给定不同的初始炎症状态。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进展。具体来说，我们已经开发了一种体内技术，似乎可以定量表征喉部当前的炎症状态。我们还完成了第二个目标的前期工作。我们已经开发了初步的空气动力学，基于agent和常微分方程模型的声带炎症校准到人类和动物的数据。在本系列中，我们建议(1)：建立一种非侵入性的方法来估计发声过程中的总机械剂量，以及基于高速成像数据和空气力学模型的发声机械剂量的组成指标（如距离剂量、能量耗散剂量和时间剂量），用于一系列声带结构；(2)：确定机械剂量参数、组织炎症状态和组织中时变生物学后果之间的数学关系，最长可达急性声音损伤后3周；(3)：建立一个声带炎症和治疗的混合物理-生物模型，以确定应在3周内优化创伤后伤口愈合的发声模式，用于一系列急性声部创伤条件；(4)：对混合治疗模型在人类受试者中预测理想治疗结果的能力进行初步测试，并根据需要迭代校准模型，以实现预测和实际结果之间的匹配。我们的假设是，通过这种方法，可以开发一个平台，最终允许针对急性声音创伤的患者特异性治疗处方，从而优化长期愈合，并且最终结果将表明，与声音休息相比，某些形式的声音锻炼可能促进组织中的生物恢复，对于某些声音创伤条件。

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.