Development of nonlinear endomicroscopy: toward assessing articular cartilage repair In vivo

非线性内窥镜的发展：评估体内关节软骨修复

基本信息

批准号：
10244921
负责人：
Tong Ye
金额：
$ 25.41万
依托单位：
CLEMSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10244921
关键词：
3-Dimensional Affect Age Animals Architecture Arthroscopy Assessment tool Biopsy Cartilage Cavia Cell Survival Cells Centers of Research Excellence Chondrocytes Clinic Clinical Clinical Research Collagen Complex Data Defect Degenerative polyarthritis Dermatologic Development Diagnostic radiologic examination Dyes Elastin Fiber Endoscopy Evaluation Evaluation Studies Fluorescence Future Generations Goals Gold Health Histologic Histology Human Image Imaging Device Imaging Techniques Imaging technology Knee joint Label Lasers Lesion Magnetic Resonance Imaging Medical Imaging Microscopy Modeling Monitor Morphology Musculoskeletal Natural regeneration Needles Operative Surgical Procedures Optical Coherence Tomography Optics Outcome Pathology Performance Preparation Problem Solving Procedures Process Property Research Resolution Rod Roentgen Rays Scanning Signal Transduction Source Speed Stains Structure System Techniques Technology Testing Thick Thinness Time Tissue Engineering Tissue imaging Tissues Translating Translational Research Ultrasonography Visualization X-Ray Computed Tomography articular cartilage base cartilage repair cell dimension clinical application clinical examination clinical imaging design disability follow-up healing imaging modality imaging probe imaging study imaging system improved in vivo in vivo imaging intravital imaging method development microendoscopy microscopic imaging minimally invasive models and simulation novel optical imaging quantitative imaging repair model repaired research clinical testing second harmonic success two-photon

项目摘要

SUMMARY Repair and regeneration of articular cartilage remains a clinical and scientific challenge. Reliable assessment tools for evaluating outcomes of cartilage repair are critical for both refinement of existing methods and development of new techniques. Histological analysis of biopsies is the gold standard for repair assessment; however, biopsies are invasive procedures and therefore limited in clinical evaluation and studies of the cartilage repair. The common medical imaging methods, such as x-ray radiography, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound, can perform imaging non-destructively; however, their spatial resolutions are not sufficient to reveal the complex cell and matrix architecture of articular cartilage. Though some imaging techniques are non-destructive and can image tissue, such as arthroscopy, laser scanning confocal arthroscopy (LSCA) and optical coherence tomography (OCT), they are all performed as surgical procedures because of using thick endoscopy probes. The inability to perform clinical in vivo imaging on cartilage tissue with high spatial resolution remains a problem. To solve the problem, we propose to develop a nonlinear optical microscopy (NLOM) based endomicroscopy system for assessment of cartilage repair in vivo. In NLOM imaging of cartilage tissue, second harmonic generation (SHG) signal provides high- resolution information of fibril organization of collagen while two-photon excited fluorescence (TPEF) enables visualization of chondrocytes and elastin fibers. However, the current cartilage NLOM imaging devices all use tabletop systems that are too bulky to be used directly in clinical applications. Thus, our long-term goal is to translate this technology into a clinical imaging tool for assessment of articular cartilage repair and treatment at the cellular level. In this application, we will focus on three specific aims as follows. (1) We will determine the efficacy of using NLOM to evaluate morphological changes of articular cartilage. Using spontaneous OA guinea pigs as an articular cartilage pathology model, we will test if NLOM imaging can detect the quantitative differences among the early stages of OA cartilage tissues. (2) We will design and build a compact and high- speed NLOM imaging system with a thin rod objective as the imaging probe. A numerical simulation model will be developed to help optimize the system design. (3) With the developed endomicroscope, we will first evaluate its performance by performing a similar quantitative imaging study as described in Aim1 on excised cartilage tissues from guinea pigs with OA. We will then use the endomicroscope and tabletop system to perform a quantitative imaging study on a cartilage repair model to test if the endomicroscope can detect morphological differences between tissues in non-treated and microfracture treated defects. With the success of this study, we will be able to determine the usefulness and limitation for using NLOM to assess cartilage repair and to perform further in vivo animal study in preparation for future clinical studies on cartilage repair with the developed endomicroscope system.

概括关节软骨的修复和再生仍然是临床和科学挑战。可靠的评估评估软骨修复结果的工具对于改进现有方法和新技术的开发。活检组织学分析是修复评估的金标准；然而，活检是侵入性操作，因此在临床评估和研究中受到限制软骨修复。常见的医学影像方法，如X射线摄影、计算机断层扫描（CT）、磁共振成像（MRI）、超声波，可以进行非破坏性成像；然而，它们的空间分辨率不足以揭示关节软骨的复杂细胞和基质结构。尽管一些成像技术是非破坏性的并且可以对组织进行成像，例如关节镜检查、激光扫描共焦关节镜检查 (LSCA) 和光学相干断层扫描 (OCT)，它们的执行方式均为由于使用粗内窥镜探头而导致的外科手术。无法进行临床体内成像具有高空间分辨率的软骨组织仍然是一个问题。为了解决这个问题，我们建议开发基于非线性光学显微镜 (NLOM) 的内窥镜系统，用于评估软骨体内修复。在软骨组织的 NLOM 成像中，二次谐波发生 (SHG) 信号提供高胶原纤维组织的分辨率信息，而双光子激发荧光 (TPEF) 可以实现软骨细胞和弹性蛋白纤维的可视化。然而，目前的软骨NLOM成像设备均采用桌面系统体积太大而无法直接用于临床应用。因此，我们的长期目标是将这项技术转化为临床成像工具，用于评估关节软骨修复和治疗细胞水平。在此应用程序中，我们将重点关注以下三个具体目标。 (1) 我们将确定使用 NLOM 评估关节软骨形态变化的功效。使用自发 OA 豚鼠作为关节软骨病理模型，我们将测试NLOM成像是否可以检测定量 OA软骨组织早期阶段的差异。 (2)我们将设计和建造一个紧凑、高速度 NLOM 成像系统，以细棒物镜作为成像探头。数值模拟模型将被开发以帮助优化系统设计。 (3)随着内窥镜的研制，我们首先通过执行 Aim1 中描述的类似定量成像研究来评估其性能来自患有 OA 的豚鼠的软骨组织。然后我们将使用内窥镜和桌面系统对软骨修复模型进行定量成像研究，以测试内窥镜是否可以检测到未治疗和微骨折治疗缺陷组织之间的形态差异。随着成功通过这项研究，我们将能够确定使用 NLOM 评估软骨的有用性和局限性修复并进行进一步的体内动物研究，为未来软骨修复的临床研究做准备与开发的内窥镜系统。