OPTIMIZATION OF LASER MEDIATED CARTILAGE RESHAPING

该指导临床科学家发展奖（MCSDA）提案的目的是为申请人提供足够的指导和培训，以发展成为生物医学光学领域成功的独立研究者。提出的研究和伴随的职业发展计划侧重于激光介导的软骨重塑过程中的生物物理变化，以及非侵入性光学和热技术的发展，以优化临床疗效和安全性。在激光照射期间，机械变形的软骨经历了温度依赖的相变，导致加速应力松弛。临床上，重塑的软骨组织可用于重建头颈部结构（如耳、鼻、喉和气管）的底层软骨框架。使用激光辐射的主要优点是精确控制时空温度分布和随时间变化的热变性动力学。为了优化重塑过程（热介导的应力松弛），软骨组织对激光照射的热光学响应和伴随重塑过程的相变将被检查和数学建模，并与软骨细胞活力相关。热光学和相变模型将用于设计安全软骨重塑的反馈控制系统，并使用兔鼻中隔软骨进行体内测试。该提案和随附的职业发展计划涉及激光与组织相互作用的三个基本过程：1)光传播；2)传热；3)相变（结构改性）。在为期五年的培训期间，申请人将获得必要的先进工程和数学技术以及研究这些生物物理过程所需的物理方法。申请者还将通过拟定的职业发展计划来发展激光组织相互作用领域的专业知识，该计划围绕以下方面进行：1)正式的课程指导；2)与物理学、电气工程和生物物理学的教师进行教学；3)参加加州大学欧文分校贝克曼激光研究所和医学诊所的每周小组会议/部门研讨会。申请人是一名经过认证的头颈外科医生和工程师，在生物医学光学方面拥有广泛的研究背景，涵盖了他的学术和临床培训的各个阶段。MCSDA将为申请人提供成为生物医学光学独立研究者所需的基本技能，并允许进一步发展为基础科学家。

The purpose of this Mentored Clinical Scientist Development Award (MCSDA) proposal is to provide the applicant with the adequate instruction and training needed to develop into a successful independent investigator in the field of biomedical optics. The proposed research and accompanying career development plan focuses on the biophysical changes in cartilage during laser mediated reshaping, and the development of non-invasive optical and thermal techniques to optimize clinical efficacy and safety. During laser irradiation, mechanically deformed cartilage undergoes a temperature dependent phase transformation which results in accelerated stress relaxation. Clinically, reshaped cartilage tissue can be used to recreate the underlying cartilaginous framework of structures in the head and neck such as the ear, nose, larynx, and trachea. The principal advantages of using laser radiation are precise control of both the space- time temperature distribution and time-dependent thermal denaturation kinetics. In order to optimize the reshaping process (thermally mediated stress relaxation), the thermo-optical response of cartilage tissue to laser irradiation and the phase transformation accompanying the reshaping process will be examined and mathematically modeled and correlated with chondrocytes viability. The thermo-optical and phase transformation models will be used to design a feedback-control system for safe cartilage reshaping, and tested in-vivo using a rabbit nasal septal cartilage. The proposal and accompanying career development plan address the three fundamental processes of laser-tissue interactions: 1) light propagation; 2) heat transfer; and 3) phase transformations (structural modification). Over the proposed five year training period, the applicant will acquire the requisite advanced engineering and mathematical techniques and physical methods necessary to study these biophysical processes. The applicant will also develop expertise in the field of laser-tissue interactions via the proposed career development plan structured around: 1) formal course instruction; 2) didactic sessions with faculty in physics, electrical engineering, and biophysics; and 3) attendance at weekly group meetings/departmental seminars at the Beckman Laser Institute and Medical Clinic at the University of California, Irvine. The applicant is a board-certified head and neck surgeon and engineer with an extensive research background in biomedical optics spanning all phases of his academic and clinical training. The MCSDA will provide the applicant with the fundamental skills needed to become an independent investigator in biomedical optics, and allow further development as a basic scientist.