【作者】 江旻珊；

【导师】 任秋实； Shuliang Jiao；

【作者基本信息】 上海交通大学 ， 生物医学工程， 2011， 博士

【摘要】 无论是在发达国家还是发展中国家,视网膜疾病都是导致失明的最主要原因之一。目前各种先进眼科成像技术已经在视网膜疾病的早期诊断中发挥了至关重要的作用。在这些成像技术中,近年来新兴的光学相干层析成像技术和光致超声成像技术以其非侵入性及高分辨率等特点,在视网膜疾病的研究及临床诊断中日趋体现出巨大的潜力。光学相干层析技术(OCT)是一种基于光学相干特性的在体、实时、高分辨率的三维断层成像技术,可以协助医生作出早期的诊断,了解病理的变化过程并作出相应的疗程安排,目前这种成像技术已经成为眼科临床检验标准之一。而光致超声成像技术(PA)则是近年新兴起来的热点,基于生物组织的光学吸收特性,实现无创、高分辨率、高对比成像机制以及厘米量级的平均探测深度。本文的工作以这两种成像方式为主,结合自适应光学技术(AO),研究新型的眼科多模态成像系统。将OCT和PA分别与AO相结合的AO-OCT和AO-PAOM系统分别提高了OCT和PA的横向分辨率;将OCT与PA相结合的OCT-PAOM系统可以同时反映生物组织的散射特性及光吸收特性,并同步获取生物组织的结构与功能成像。多模态成像系统可以对由眼底视网膜病变所带来的眼底组织结构及功能上的变化进行观测和估计,进而对视网膜疾病实现准确的早期诊断。本工作可根据应用技术的不同划分为以下几个部分:首先,搭建高分辨率频域OCT系统,成功实现了人眼和活体大鼠眼的在体视网膜成像。并通过频域OCT实现了小鼠全眼的快速成像,准确地计算出小鼠眼的各项结构参数指标,证实了利用频域OCT实现全眼结构参数测量可行性和优越性。其二,为了提高OCT系统的横向分辨率,将AO和OCT相结合,搭建AO-OCT系统。首先通过薄膜变形镜(MMDM)和压电变形镜(PDM)这两种常用的变形镜的对比实验,分析不同种类的变形镜在实际处理像差时的有效性和可靠性。基于对比实验的结果,选择合适的变形镜和波前像差传感器,对大鼠眼的像差进行了测量和校正。对比校正前后采集到的OCT图像的差异,评估引入自适应系统后对OCT成像质量的影响。其三,研究多模态光致超声成像系统。为提高PA系统的横向分辨率,将AO和PA相结合,搭建AO-PAM系统,闭环校正照明激光的波前像差,并由自制的超声传感器检测激发出的光声信号。经过像差校正之后,PAM系统的横向分辨率可以达到2.5μm以内。通过猪眼样品的体外成像,发现像差校正之后PA图像质量有明显的提高,并首次观察到视网膜色素上皮细胞的PA图像。为了弥补PA在结构成像方面的不足,将OCT与PA相结合,搭建了OCT-PAOM系统。该系统可以充分发挥OCT技术和PA技术的互补性的优势,为对视网膜更好的实现结构和功能成像提供了解决方案。本文的研究成果为临床医生和患者提供了比现有眼科成像技术更为先进的多模态成像方法。在提高现有成像技术分辨率的基础上,在结构成像和功能成像方面充分发挥了两种成像技术的互补作用,进而为临床眼科疾病的早期诊断开辟出一条新路。更多还原

【Abstract】 Retinal diseases are one of the major causes of blindness in both developed and developing countries. Ophthalmic imaging technology has played a crucial role in the diagnosis and management of retinal diseases. Optical coherence tomography (OCT) and photoacoustic imaging (PA) are two recently developed non-invasive high resolution imaging technologies. With the capability of strauctural and functional imaging these imaging technologies have potentially significant impact on the research and diagnosis of retinal diseases.OCT is based on low coherence optical interferometry which uses the coherence properties of broadband light to achieve depth resolving capability. The state-of-the-art OCT can provide in vivo real-time high-resolution three-dimensional imaging of the retina, which can help doctors in the early diagnosis, understanding the pathological development and making treatment planning. PA imaging has been becoming a hot research topic in recent years due to its advantages of scalability and novel contrast mechanisms. PA imaging is based on the optical absorption properties of biological tissues. My doctoral research was focused on the development of multimodal ophthalmic imaging technology to provide comprehensive diagnostic information for retinal diseases. By combining OCT with PA imaging we were able to image the scattering and absorption contrasts simultaneously. By further combining OCT and PA imaging with adaptive optics we were able to significantly improve the spatial resolution. Although we only tested the technology on imaing ex-vivo ocular samples, it laid the foundation for future in vivo applications.The research work can be summarized as following:First, a high-resolution spectral-domain OCT system was built to image the retina of human eye and the eye of small animals. We were able to use SD-OCT to calculate the dimensional parameters of the whole mouse eye with single-shot imaging. This experimentdemonstrated the capability of SD-OCT for single-shot biometric measurement of the eye, which is important for myopia research.Second, the technology of adaptive optics was applied in SD-OCT to improve its lateral resolution. We first systematically analyzed and compared the aberration generation capabilities of the membrane deformable mirror (MMDM) and piezoelectric deformable mirror (PDM). We then combined adaptive optics system into OCT and conducted experiments on rat eye for aberration measurement and correction. We evaluated the influence of AO system by comparing the OCT images acquired before and after the aberration correction.Third, we did research on the technology of multimodal photoacoustic microscopy . For the first time AO technology was applied in PAM to improve the lateral resolution. The aberrations of the optical system delivering the illuminating light to the sample in PAM were corrected with a close-loop AO system. The photoacoustic signal induced by the illuminating laser beam was detected by a custom-built needle ultrasonic transducer. When the wavefront errors were corrected by the AO system, the lateral resolution of PAM was measured to be better than 2.5μm using a low NA objective lens. We tested the system on imaging ex vivo ocular samples, e.g., the ciliary body and retinal pigment epithelium (RPE) of a pig eye. The AO-PAM images showed significant quality improvement. For the first time we were able to resolve single RPE cells with PAM. As a model of multimodal ophthalmic imaging, we developt an OCT-guided photoacoustic ophthalmoscopy (PAOM). This system demonstrated the advantages of OCT and PA technologies, realizing the structural and functional imaging of the retina.The research demonstrated the potential of providing clinicians a more advanced multimodal ophthalmic imaging technology, not only maintaining the advantages of the original two imaging techniques, but also improving their imaging resolution. The multimodal imaging technology extended the capability of each individual imaging technique in tructural imaging and functional imaging and opened a new window for the early diagnosis of eye diseases.更多还原