基于液晶自适应光学技术的视网膜微血管成像研究
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摘要
人眼视网膜中的微血管是人体唯一可在体外进行无创观察的细小血管。任何血液性的病理破坏，确切地说任何脏器性、内分泌疾病都会引起血液成分改变，造成微细血管的病变，因此高分辨率的视网膜微细血管状态检查对重大疾病的病理学、早期诊断研究具有重要的意义。但由于人眼像差的影响，普通眼底检查设备的眼底成像分辨率只有15~20μm，无法满足早期疾病微小症状检查的要求。自适应光学技术的应用突破了人眼像差限制，将眼底成像设备的分辨率提高至接近衍射极限的水平。但是最常用的波前校正器，即变形镜，由于其空间分辨率低、校正量小、体积大、价格高，很难在眼底自适应光学成像领域实用推广。因此本文采用高分辨率的液晶波前校正器，研制了高分辨率视网膜微血管自适应光学成像系统。
针对系统普适性不高的问题，分析了深度像差对波前探测精度的影响，使用补偿镜并微调照明光焦面的方法对人眼近视与散光的低阶像差进行了补偿，使照明光焦面可以准确聚焦在眼底，提高了波前探测光斑的信噪比；在调节焦面时，引入一个与波前探测器中光点形态相关的参数，辅助照明光焦面位置的判断；在此基础上通过减小照明光焦深的方法消除了神经纤维层反射杂光的干扰；另外，还使用探测器去噪算法抑制校正器中非调制杂光的影响，进一步提高了系统的普适性。
对视网膜微血管的成像机制进行了模拟实验，并以人眼最稳定时的0D屈光为基准完成了光学系统设计；在补偿1D人眼色差的基础上，利用对人眼刺激很小的近红外光，对活体视网膜微血管进行连续对焦摄像，解决了视网膜微血管像面难以捕捉和定位的问题，获得了直径7μm的清晰微血管图像。
在此基础上，研究了眼底出射光的能量利用率问题。通过对人眼偏振特性的探讨，将眼底照明光改造为线偏振光，使眼底出射光的能量利用率提高了20%；分析和测试了系统的成像分辨率约3.5μm，表明系统具备对最细小视网膜血管分辨的能力；对环形光阑的中心遮拦比进行了优化，将微血管的成像对比度从0.13提高到0.23；采用短曝光避免眼底抖动，并将多次曝光图像进行配准叠加，有效抑制了图像中的散粒噪声，提高了信噪比，使微血管图像对比度进一步上升到0.3。
The retinal capillaries are the only microvasculature which could be imaged invivo and non-invasively. Any blood pathological destruction, or rather any organs andendocrine diseases will change the blood components and lead to vasculopathy. So thehigh resolution retinal microvacular imaging is significant for pathology research anddiagnose of the critical disease. However, due to aberration of human eyes, theresolution of the common inspection equipment was only about15-20μm, which canminot meet the demand for early diagnosis. The application of adaptive optics couldresolve the limit of human eye aberration. With AO, the imaging resolution could beclose to the optical diffraction limit. Although deformable mirror was widely used inadaptive optics systems, but it is less practicality in the field of fundus imagingbecause of its low spatial resolution, small stroke,large size and costly. In this paper,the liquid crystal spatial light modulator has been used as a wavefront corrector andthe high resolution retinal microvasculature imaging system based on liquid crystaladaptive optics has been studied.
In order to improve the universality of the system, the factors,which affect theaccuracy of wavefront sensor has been discussed comprehensively.The deep low orderaberrations of the human eye has been corrected by trial lens. And then, the focalplane of the illumination light source has been adjusted to the fundus to increase the signal to noise ratio of the wavefront sensor. The position of the focal plane of theillumination light source can be monitored by introducing a parameter, which isrelated to the morphological characteristics of the light spot in the wavefront sensor.On this basis, the modified centroid algorithm has been used and the depth of focus ofthe illumaination light has been shortened to further eliminate the influence of theunmodulated beam and the reflection of the multilayers in retina.
The mechanism of the retinal microvasculature and the stability of the humaneyes has been analysed through experiments. The system has been designed based on0diopter. After compansation the chromatic aberrations of the eye, which scale isabout1Diopter, the image plane of the capillaries has been searched by theharmlessness near infrared light source at the same time of imaging. Living humaneye fundus image experiments were carried out and the clear images of the retinalcapillaries, which diameters are about7μm have been obtained.
On the basis of the above analysis and testing, the polarization properties of thehuman eye has been discussed. By using the polarized light to illuminate the fundus,the energy utilization of the light reflected from fundus has been improved by20%.Further more, the actual resolution of the system has been discussed and the resultshows that the actual resolution of the system is about3.5micrometers. It indicatedthat the system has the ability to distinguish the smallest retinal capillaries. Because ofthe center obscuration ratio of the annular stop has been optimized, the contrast of theimage has been increased from0.13to0.23. In experiments, the fundus had beenexposured by short pulse, in order to avoid the image blur caused by eye movements.The signal to noise ratio has been improved by the superposition of fundus imagesand the contrast of the image after superposition has beed improved to0.3.
针对系统普适性不高的问题，分析了深度像差对波前探测精度的影响，使用补偿镜并微调照明光焦面的方法对人眼近视与散光的低阶像差进行了补偿，使照明光焦面可以准确聚焦在眼底，提高了波前探测光斑的信噪比；在调节焦面时，引入一个与波前探测器中光点形态相关的参数，辅助照明光焦面位置的判断；在此基础上通过减小照明光焦深的方法消除了神经纤维层反射杂光的干扰；另外，还使用探测器去噪算法抑制校正器中非调制杂光的影响，进一步提高了系统的普适性。
对视网膜微血管的成像机制进行了模拟实验，并以人眼最稳定时的0D屈光为基准完成了光学系统设计；在补偿1D人眼色差的基础上，利用对人眼刺激很小的近红外光，对活体视网膜微血管进行连续对焦摄像，解决了视网膜微血管像面难以捕捉和定位的问题，获得了直径7μm的清晰微血管图像。
在此基础上，研究了眼底出射光的能量利用率问题。通过对人眼偏振特性的探讨，将眼底照明光改造为线偏振光，使眼底出射光的能量利用率提高了20%；分析和测试了系统的成像分辨率约3.5μm，表明系统具备对最细小视网膜血管分辨的能力；对环形光阑的中心遮拦比进行了优化，将微血管的成像对比度从0.13提高到0.23；采用短曝光避免眼底抖动，并将多次曝光图像进行配准叠加，有效抑制了图像中的散粒噪声，提高了信噪比，使微血管图像对比度进一步上升到0.3。
The retinal capillaries are the only microvasculature which could be imaged invivo and non-invasively. Any blood pathological destruction, or rather any organs andendocrine diseases will change the blood components and lead to vasculopathy. So thehigh resolution retinal microvacular imaging is significant for pathology research anddiagnose of the critical disease. However, due to aberration of human eyes, theresolution of the common inspection equipment was only about15-20μm, which canminot meet the demand for early diagnosis. The application of adaptive optics couldresolve the limit of human eye aberration. With AO, the imaging resolution could beclose to the optical diffraction limit. Although deformable mirror was widely used inadaptive optics systems, but it is less practicality in the field of fundus imagingbecause of its low spatial resolution, small stroke,large size and costly. In this paper,the liquid crystal spatial light modulator has been used as a wavefront corrector andthe high resolution retinal microvasculature imaging system based on liquid crystaladaptive optics has been studied.
In order to improve the universality of the system, the factors,which affect theaccuracy of wavefront sensor has been discussed comprehensively.The deep low orderaberrations of the human eye has been corrected by trial lens. And then, the focalplane of the illumination light source has been adjusted to the fundus to increase the signal to noise ratio of the wavefront sensor. The position of the focal plane of theillumination light source can be monitored by introducing a parameter, which isrelated to the morphological characteristics of the light spot in the wavefront sensor.On this basis, the modified centroid algorithm has been used and the depth of focus ofthe illumaination light has been shortened to further eliminate the influence of theunmodulated beam and the reflection of the multilayers in retina.
The mechanism of the retinal microvasculature and the stability of the humaneyes has been analysed through experiments. The system has been designed based on0diopter. After compansation the chromatic aberrations of the eye, which scale isabout1Diopter, the image plane of the capillaries has been searched by theharmlessness near infrared light source at the same time of imaging. Living humaneye fundus image experiments were carried out and the clear images of the retinalcapillaries, which diameters are about7μm have been obtained.
On the basis of the above analysis and testing, the polarization properties of thehuman eye has been discussed. By using the polarized light to illuminate the fundus,the energy utilization of the light reflected from fundus has been improved by20%.Further more, the actual resolution of the system has been discussed and the resultshows that the actual resolution of the system is about3.5micrometers. It indicatedthat the system has the ability to distinguish the smallest retinal capillaries. Because ofthe center obscuration ratio of the annular stop has been optimized, the contrast of theimage has been increased from0.13to0.23. In experiments, the fundus had beenexposured by short pulse, in order to avoid the image blur caused by eye movements.The signal to noise ratio has been improved by the superposition of fundus imagesand the contrast of the image after superposition has beed improved to0.3.
引文
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