Hybrid Model of Vocal Inflammation and Tissue Mobilization

声带炎症和组织动员的混合模型

• 批准号: 7683332
• 负责人: Katherine Verdolini
• 金额: $ 8.8万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683332
• 关键词: Acute; Address; Adhesions; Anti-Inflammatory Agents; Anti-inflammatory; Behavior Therapy; Behavioral; Berry; Biological; Biological Models; Biomechanics; Calibration; Chronic; Collagen; Complex; Computer Simulation; Condition; Data; Deposition; Development; Docking; Dose; Dysphonia; Elastin; Elements; Equation; Exercise; Extracellular Matrix; Gene Expression; Generations; Goals; Gray unit of radiation dose; Healed; Human; Hybrids; IL8 gene; Image; In Vitro; Inflammation; Inflammatory; Inflammatory Response; Injury; Interleukin-10; Interleukin-6; Interstitial Collagenase; Intervention; Invasive; Laboratories; Larynx; Lead; Lesion; Link; Matrix Metalloproteinases; Mechanical Stress; Mechanics; Mediator of activation protein; Methodology; Metric; Modality; Modeling; Molecular; Morphology; Motion; Neutrophil Collagenase; Numbers; Outcome; Output; Paper; Patients; Pattern; Phonation; Preparation; Property; Qi; Quality of life; Range; Recovery; Research; Research Personnel; Rest; Series; Source; Speed; Stress; System; Technology; Testing; Time; Tissue Inhibitor of Metalloproteinase-1; Tissues; Treatment Protocols; Treatment outcome; Validation; Voice; Week; Work; Wound Healing; animal data; base; clinically relevant; follow-up; healing; human data; human subject; in vivo; kinematics; mathematical model; physical insult; physical model; physical property; prescription document; prescription procedure; programs; response; sound; two-dimensional; vocal cord

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.

描述（由申请人提供）：长期目标是开发一种技术，使临床医生能够制定“理想”的声音锻炼（或休息）计划，以优化急性和慢性声损伤的组织愈合。在本系列中，我们重点关注紧急案例。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况，以及（b）开发复杂系统的混合空气力学/生物计算机模型，该模型最终可以确定应采用的发声和休息方案。考虑到不同的初始炎症状态，随着时间的推移优化分子/细胞特征。我们实验室的工作在实现第一个短期目标方面取得了良好进展。具体来说，我们开发了一种体内技术，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。我们已经开发了根据人类和动物数据校准的声带炎症的初步空气动力学、基于代理和常微分方程模型。在本系列中，我们建议（1）：建立一种非侵入性方法，用于估计发声期间的总体机械剂量，以及高速成像中发声机械剂量的组成指标（例如距离剂量、能量耗散剂量和时间剂量）针对一系列声带配置的数据和空气力学建模； (2)：确定机械剂量参数、组织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，持续时间长达急性声损伤后 3 周； (3)：开发声带炎症和治疗的混合物理生物学模型，以确定针对一系列急性声音创伤条件，应在 3 周优化创伤后伤口愈合的发声模式，以及 (4)：提供初步测试混合治疗模型预测人类受试者理想治疗结果的能力，并根据需要迭代校准模型以实现预测结果和获得结果之间的匹配。假设通过这种方法，可以开发一个平台，最终允许为急性语音创伤患者制定具体的治疗方案，从而优化长期愈合，并且最终结果将表明某些形式的发声练习可能对于某些声音创伤情况，与发声休息相比，有利于组织的生物恢复。