基于全视场光学相干断层扫描的高分辨率角膜成像研究

Corneal imaging plays an irreplaceable role in the diagnosis and treatment of corneal diseases. Developing high-resolution in vivo human corneal imaging technique for more accurate and effective diagnosis and pathogenesis analysis of corneal diseases is a hot topic in the cross-cutting areas of ophthalmology and imaging. Currently, corneal imaging with in vivo confocal microscopy (IVCM) or optical coherence tomography (OCT) either has a limited field of view or cannot achieve cellular resolution. Our previous studies have shown that Full-field OCT (FFOCT) combines the advantages of OCT's non-contact, large imaging field of view and high axial resolution with the high lateral resolution of IVCM. This project aims to design an in vivo FFOCT human corneal imaging system. By using a high-speed CCD camera, the system imaging speed would be increased to improve the in vivo imaging quality. An adaptive defocus correction algorithm would be developed to correct the deviation of the system coherence plane and the focal plane in real time, thus realizing in vivo cellular imaging of human cornea at various depths. In vivo FFOCT imaging of normal and diseased cornea would be performed and accurate biometric parameters would be measured to study the FFOCT imaging features of typical structural characteristics of healthy and diseased human corneas. Furthermore, a corneal biometric parametric model and corneal disease progression analysis model would be established, providing a new imaging technique for clinical and basic researches of corneal diseases.

角膜成像技术在角膜疾病诊断与治疗中具有无可替代的作用。发展高分辨率活体角膜成像技术，对角膜疾病进行更精准有效的诊断及病理分析，是眼科学及影像学交叉领域的重要研究问题。目前活体共聚焦显微镜（IVCM）和光学相干断层扫描仪（OCT）的角膜成像各自存在视野局限或无法高清成像的限制。我们前期研究证实全视场光学相干断层扫描仪（FFOCT）具有OCT的非接触、大成像视野和高轴向分辨率及IVCM的高平面分辨率的优势。本项目研究设计FFOCT活体人眼角膜成像系统，采用高速面阵相机提高系统成像速度，改善活体成像质量。开发自适应离焦矫正方法实时修正相干平面和焦平面的偏离，实现活体角膜各深度细胞结构成像。对正常及病变角膜进行FFOCT成像及精准生物学参数测量，研究角膜疾病结构FFOCT影像特征，建立基于FFOCT图像的角膜生物学参数模型及疾病转归规律分析模型，为角膜疾病的临床与基础研究提供全新的成像分析技术。

发展高分辨率角膜成像技术，对角膜疾病进行更精准有效的早期诊断、鉴别诊断、发病机理及转归规律分析，是角膜疾病临床诊疗重要需求和技术发展方向。全视场光学相干断层扫描技术（FFOCT）具有传统光学相干断层扫描仪（OCT）的非接触、大成像视野和高轴向分辨率及活体共聚焦显微镜（IVCM）的高平面分辨率的优势，在角膜高分辨率成像领域具有重要应用前景。. 本项目设计并搭建FFOCT高分辨率角膜成像系统，采用高速面阵相机提高系统成像速度，结合传统OCT解决FFOCT活体人眼角膜成像深度信息不精准问题，实现角膜高分辨、非接触成像，系统横向分辨率1.7μm，纵向分辨率7.7μm；开发FFOCT信号处理系统及自适应离焦矫正方法实时修正相干平面和焦平面的偏离，实现活体角膜各深度细胞结构成像；通过对正常及病变角膜（圆锥角膜、Peter异常、病毒性角膜溃疡、角膜基质营养不良等）进行FFOCT成像及精准生物学参数测量，建立了基于FFOCT图像的角膜生物学参数模型及角膜疾病FFOCT影像特征规律，为角膜疾病的临床与基础研究提供全新的成像分析技术。此外基于角膜成像FFOCT系统研发技术基础，创新拓展了基于细胞内部新陈代谢活动引起相干信号变化为成像信号源的高分辨率、无创、无标记细胞功能影像技术动态FFOCT（D-FFOCT）；创新集成了结合超高分辨率OCT和眼微血管成像的多模态眼前段成像系统；开发了系列眼科影像智能量化分析系统。项目研究成果为角膜及其他眼科疾病研究提供了全新的影像装备及智能分析技术，具有广泛的临床应用及转化前景。. 本项目研究成果在Eclinicalmedicine（IF17）、Bioengineering（IF5）、Biomedical Optics Express等高水平期刊发表论文9篇，获授权发明专利5项、实用新型专利2项、软件著作权3项，获中国医疗器械创新创业大赛一等奖。眼科FFOCT成像技术完成转化评估，进入落地转化流程。