Radiation Therapy Impact on Structure/Mechanics of Teeth

描述（由申请人提供）：本申请为指导患者导向研究职业发展奖（K23）申请的提案分为教学，应用临床和转化研究部分。教学部分将提供教育经验，使首席研究员能够设计、实施和分析以患者为导向的研究。详细的教学计划在申请表中有描述。临床和转化研究培训部分将为候选人提供与经验丰富的临床和基础科学研究人员密切合作的机会。该项目将结合1)在体内，回顾性评估任何放射后牙齿病变的严重程度与辐射场参数，牙齿暴露的辐射剂量以及唾液腺辐射防护药物的使用等因素有关；2)与未辐照牙齿相比，辐照牙齿的体外化学、力学和形态学结构和特性分析；3)结构/性能关系将用于模拟功能载荷条件下辐照牙内应力分布的有限元建模；4)发展基础设施和获取初步数据，以继续进行前瞻性、纵向临床试验，为未来的拨款申请提供依据，以便将辐射后牙齿病变的发生和发展与其他临床因素（如口干和咬合模式）、辐射剂量、场参数和辐射防护药物的使用联系起来。该项目将使候选人获得以下领域的研究技能：1)回顾性和前瞻性方法在临床评估与治疗性辐射引起的牙齿病变相关的患者因素；2)对治疗性辐射照射下牙齿结构和特性的相关变化进行实验室评价；3)模拟功能载荷作用下牙齿内部应力分布模式的有限元计算与建模。通过完成项目中概述的目标，Walker博士将培养作为独立临床研究人员所需的技能，并有机会与基础科学家合作，深入了解如何将实验室分析纳入基于患者的调查。该项目的一个关键优势是相关的反馈机制，将临床问题与临床和实验室数据联系起来，将科学原理整合到临床实践中。

DESCRIPTION (provided by applicant): This proposal for a Mentored Patient-Oriented Research Career Development Award (K23) application is divided into didactic, applied clinical and translational research components. The didactic component will provide educational experiences to allow the principal investigator to design, conduct, and analyze patient-oriented research. A detailed instructional plan is described in the application. The clinical and translational research training component will provide the candidate an opportunity to work closely with experienced clinical and basic science investigators. The project will combine 1) in vivo, retrospective assessment of the severity of any postradiation dental lesions as related to factors such as radiation field parameters, the radiation dose to which teeth were exposed, and the use of salivary gland radiation protector drugs; 2) in vitro chemical, mechanical, and morphologic analyses of structure and properties of in vivo irradiated teeth as compared to non-irradiated teeth; 3) the structure/property relationships will be used in finite element modeling of the stress distribution within irradiated teeth under simulated functional loading conditions; 4) developing the infrastructure and acquiring the preliminary data to continue the investigation as a prospective, longitudinal clinical trial for future grant applications in order to correlate the initiation and progression of post-radiation dental lesions to additional clinical factors such as xerostomia and occlusal patterns, as well as radiation dose, field parameters, and the use radiation protector drugs. This project will enable the candidate to obtain research skills in the following areas: 1) retrospective and prospective methodology in the clinical evaluation of patient factors related to therapeutic radiation-induced dental lesions; 2) laboratory evaluation of the associated changes in the structure and properties of teeth exposed to therapeutic radiation; 3) finite element calculation and modeling of stress distribution patterns that develop in these teeth under simulated functional loading. By completing the objectives outlined in the project, Dr. Walker will develop skills necessary to function as an independent clinical researcher and have the opportunity to collaborate with basic scientists to gain insight into how laboratory analyses can be incorporated into patient-based investigations. A key strength of this project is the associated feedback mechanism that relates the clinical problem to both clinical and laboratory data, the integration of scientific principles into clinical practice.