背景：目前已有研究报道了一种MATLAB的定制算法，用于Triton光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)图像的中心凹无血管区(fovea avascular zone，FAZ)的自动测量。由于这种算法非开源，且难以获取，因而大大限制了其在临床实践和科学研究中的应用。本研究提出一种用于Triton OCTA图像的FAZ自动分割的开源算法，即Smooth Level Sets macro(SLSM)算法，并将其测量结果与MATL AB和人工方法相比较，评估该算法分割的准确性和可靠性。方法：纳入35位健康受试者的35只健眼，选用Triton OCTA机器中的3 mm×3 mm扫描模式，对其黄斑区进行连续4次扫描。分别用人工和自动方法(包括MATL AB和SLSM)，测量浅层毛细血管图像中FAZ的面积、周长和圆度。分析各种自动算法的准确性、重复性，以及与人工方法结果的一致性。结果：SLSM算法的准确性仅低于人工方法，而高于MATLAB算法(Dice系数：人工方法，0.9568；SLSM，0.9506；MATL AB，0.9483)。SLSM和MATL AB测量FAZ面积的重复性均很高[组内相关系数(intraclass correlation coefficient，ICC)：SLSM，0.987；MATLAB，0.983]。SLSM、MATLAB测量FAZ面积的结果均与人工方法呈很高的一致性(ICC：SLSM，0.973；MATL AB，0.968)。结论：SLSM在Triton OCTA图像的FAZ自动分割中的准确性高于MATL AB，其测量结果与人工测量结果很相近。作为免费和开源的资源，SLSM有望成为Triton OCTA图像中有效可靠的FAZ自动分割和测量方法。
Background: Previous studies have proposed an automated customized program named MATLAB used in the foveal avascular zone (FAZ) measurements in Triton optical coherence tomography angiography (OCTA) images. But it is not open-source and not easy to obtain, which will largely restrict its application in clinical practice and medical research. In this study, we aimed to investigate the feasibility of the Smooth Level Sets macro (SLSM), a free and open-source program, and compared with the manual measurements and MATLAB in the FAZ quantification in Triton OCTA. Methods: Thirty-five eyes of 35 healthy subjects were scanned four times continuously using Triton OCTA. Manual and automated methods including the SLSM and MATLAB were used in the FAZ metrics (area, perimeter, and circularity) of the superficial capillary plexus. The accuracy, repeatability of all methods, and agreement between automated and manual methods were analyzed. Results: The SLSM presented higher accuracy with a higher average Dice coefficient (0.9506) than MATLAB (0.9483), which was just second to the manual method (0.9568). Both the SLSM [intraclass correlation coefficient (ICC) =0.987; coefficient of variation (CoV) =3.935%] and MATLAB (ICC =0.983; CoV =4.165%) showed excellent repeatability for the FAZ area. They also had excellent agreement with manual measurement (SLSM, ICC =0.973; MATLAB, ICC =0.968). Conclusion: The SLSM exhibits better accuracy than MATLAB in the automated FAZ measurement in Triton OCTA, the results of which were comparable to those obtained by manual measurement. This free and open-source program may be an accessible and feasible option for automated FAZ segmentation on Triton OCTA images.
目的：开发细胞级高分辨率、结构与功能一体化的双模态全视场光学相干层析系统(full-field optical coherence tomography,FFOCT)，实现角膜缘组织的双模态FFOCT成像。方法：基于Linnik干涉成像原理，利用高数值孔径显微物镜(NA=0.8)及高速平面互补金属氧化物半导体(complementary metal oxide semiconductor,CMOS)相机，设计搭建高分辨率的组织静态结构和内源动态功能成像一体化双模态FFOCT系统；构建基于四相位调制结构影像提取及时域干涉信号动态频谱分析的功能影像重建算法；对人供体角膜缘组织开展各深度层的双模式FFOCT成像有效性验证。结果：搭建的双模态FFOCT成像系统可实现横向分辨率0.5 μ m，轴向分辨率1.7 μ m，成像视野320 μ m×320 μ m，相机采集速度100 Hz。系统实现角膜缘组织无外源标记情况下的细胞级分辨率三维结构和内源功能成像，FFOCT静态结构影像清晰显示角膜缘上皮、Vogt栅栏、隐窝、基质、血管及淋巴管等结构，FFOCT动态功能影像突出显示了代谢活跃细胞(角膜缘上皮细胞、免疫细胞等)。结论：双模态FFOCT高分辨率成像系统可提供角膜缘微观结构和活细胞无标记内源功能可视化信息，将为角膜缘疾病的研究及临床诊疗提供全新的成像分析技术。
Objective: To develop a cellular-level, high-resolution, integrated dual-modal full-field optical coherence tomography (FFOCT) system capable of simultaneously imaging the structure and function of limbus tissue. Methods: Utilizing the Linnik interference imaging principle, a high-resolution dual-modal FFOCT system was designed and constructed using a high numerical aperture (NA=0.8) microscope objective and a high-speed flat CMOS camera. A functional imaging reconstruction algorithm based on four-phase modulation structure image extraction and dynamic frequency spectrum analysis of temporal interference signals was developed. The effectiveness of dual-mode FFOCT imaging at various depth layers of human corneal limbal tissue was validated. Results: The constructed dual-modal FFOCT imaging system achieved lateral resolution of 0.5 μ m, axial resolution of 1.7 μ m, imaging field of view of 320 μ m × 320 μ m, and camera acquisition speed of 100 Hz. The system enabled cellular-level resolution three-dimensional structural and intrinsic functional imaging of corneal limbal tissue without exogenous labeling. Static structural FFOCT images clearly displayed limbal epithelium, palisades of Vogt, crypts, stroma, blood vessels, and lymphatic vessels, while dynamic functional FFOCT images highlighted metabolically active cells (limbal epithelial cells, immune cells, etc.). Conclusion: The dual-modal FFOCT high-resolution imaging system provides visualization of corneal limbal microstructural and live cell intrinsic functional information without labeling, offering a novel imaging analysis technique for research and clinical diagnosis and treatment of limbal diseases.
光学相干断层成像(optical coherence tomography，OCT)自1991年发明以来，在生物成像尤其在眼科和心血流成像中起越来越重要的作用。OCT的发展经历了早期的时域系统及最新的频域系统。其中频域系统又分为谱域OCT(spectral domain OCT，SD-OCT)系统和扫频OCT(swept source OCT，SS-OCT)系统。随着眼科临床应用对系统速度、灵敏度及功能化要求的不断提升，眼科扫频OCT已经走向成熟并逐步商用化。本文将简介扫频OCT的原理，并归纳扫频OCT相对于时域和谱域OCT系统的优势，并展示其在眼科临床的应用。
Optical coherence tomography (OCT) has played an important role in biomedical imaging, especially in ocular and cardiovascular imaging. OCT technology has evolved to frequency domain technology from early time-domain technology due to the advantages of high sensitivity and high speed of frequency domain techniques. The swept source OCT is a type of frequency domain OCT. With the increasing requirements for system speed, sensitivity, and functionality in clinical application, swept source OCT is gradually becoming commercially available and widespread in clinical application. In this paper, the principle of swept source OCT was introduced, the advantages of swept source OCT over time domain and spectral domain OCT systems were summarized, and its clinical application in ophthalmology was demonstrated.
帕金森病(Parkinson’s disease，PD)是老年人常见的神经系统退行性疾病，眼部及视觉功能障碍是PD常见的非运动症状之一，进一步影响其生活质量。已有研究表明PD患者视网膜内存在多巴胺浓度的减少以及α突触核蛋白的沉积。目前，PD仍缺乏有效的早期诊断及病情评估工具，光学相干断层扫描及光学相干断层扫描血管成像技术可以显示视网膜各层微细结构及微血管的异常，应用该技术研究者发现PD患者视乳头旁视网膜神经纤维层及黄斑区视网膜的厚度均存在不同程度的变薄，视网膜浅层及深层毛细血管丛的毛细血管密度和复杂性下降。进一步研究者应用该技术在PD临床应用中进行了探索，并发现其可用于检测早期PD中发生的病理变化，反映疾病的病程及严重程度，并且在鉴别诊断中起到一定的作用。总而言之，视网膜相关检测可能成为评估PD患者脑病理严重程度的指标，并且帮助疾病诊断和监测疾病的进展，不过这仍需要大样本、多中心的重复研究以提供更多理论依据。
Parkinson’s disease is a common neurodegenerative disease in the elderly, and ocular and visual dysfunction is one of the common non-motor symptoms of PD, further affecting PD patients’quality of life. Reduced dopamine concentrations and deposition of α-synuclein in the retina of PD patients have been shown in studies. At present, there is still a lack of effective tools for early diagnosis and assessment of PD. Optical coherence tomography and optical coherence tomography angiography can reveal abnormalities in the microstructure and microvasculature of the retinal layers, and researchers applying these techniques have found that the thickness of the parapapillary retinal nerve fiber layer and the retina in the macula in PD patients have had varying degrees of thinning, and the density and complexity of capillaries in the superficial and deep capillary plexus of the retina have been reduced. Further, investigators have explored the clinical application of these techniques in PD and have found that they can be used to detect pathological changes occurring in early PD, reflect the course and severity of the disease, and play a role in differential diagnosis. In conclusion, retinal-correlated testing may be an indicator to assess the severity of brain pathology in PD patients and to aid in disease diagnosis and monitoring the progression of PD, although large sample, multicenter replication studies are still needed to provide more reliable results.
角膜缘的细胞，特别是角膜缘干细胞，对于维持角膜的透明和健康至关重要。基于影像技术对角膜缘进行高精度可视化评价是相关疾病诊疗的重要手段。眼科临床使用的裂隙灯显微镜、共聚焦显微镜、眼前节光学相干断层扫描仪(optical coherence tomography,OCT)等成像技术，因低分辨、低对比度、侵入性等原因，限制了其在角膜缘细胞结构及功能影像评估中的应用。本团队创新研发新型双模态全视场光学相干断层扫描仪(full-field OCT，FFOCT)，成功实现了无标记的角膜缘细胞级分辨率结构及功能成像。FFOCT基于空间非相干光平面干涉原理提取组织内部散射光，获得微米级分辨率三维结构成像；通过FFOCT原始相干信号的高时空分辨率采集及动态特征解析，实现源于活细胞新陈代谢运动的无标记细胞功能影像可视化。双模态FFOCT创新性地整合了高分辨率、无标记的结构及功能成像模态，不仅清晰获取角膜缘组织的高精结构特征如Vogt栅栏、角膜缘隐窝、血管壁等，同时还能捕捉不同角膜缘细胞内的代谢活性动态变化，无需使用外源荧光染料或标记剂，为角膜缘生物学及疾病机制研究提供全新细胞水平结构及功能成像方法，具有广泛应用前景。
角膜缘的细胞，特别是角膜缘干细胞，对于维持角膜的透明和健康至关重要。基于影像技术对角膜缘进行高精度可视化评价是相关疾病诊疗的重要手段。眼科临床使用的裂隙灯显微镜、共聚焦显微镜、眼前节光学相干断层扫描仪(optical coherence tomography,OCT)等成像技术，因低分辨、低对比度、侵入性等原因，限制了其在角膜缘细胞结构及功能影像评估中的应用。本团队创新研发新型双模态全视场光学相干断层扫描仪(full-field OCT，FFOCT)，成功实现了无标记的角膜缘细胞级分辨率结构及功能成像。FFOCT基于空间非相干光平面干涉原理提取组织内部散射光，获得微米级分辨率三维结构成像；通过FFOCT原始相干信号的高时空分辨率采集及动态特征解析，实现源于活细胞新陈代谢运动的无标记细胞功能影像可视化。双模态FFOCT创新性地整合了高分辨率、无标记的结构及功能成像模态，不仅清晰获取角膜缘组织的高精结构特征如Vogt栅栏、角膜缘隐窝、血管壁等，同时还能捕捉不同角膜缘细胞内的代谢活性动态变化，无需使用外源荧光染料或标记剂，为角膜缘生物学及疾病机制研究提供全新细胞水平结构及功能成像方法，具有广泛应用前景。
剥脱综合征(exfoliation syndrome,XFS)以眼内异常纤维样物质沉积为特征，临床典型表现为裂隙灯下瞳孔缘和(或)晶状体前囊膜存在灰白色粉末状的剥脱物(exfoliation material,XFM)。XFM可阻塞小梁网引起剥脱性青光眼(exfoliaiton glaucoma,XFG)，并可通过房水循环进入血液，引起血管性损害。眼底病变视力损伤通常不可逆，XFM可进入眼底微血管及毛细血管，引起眼底结构和血管异常。基于光学相干断层成像技术的光学相干断层扫描(optical coherence tomography,OCT)及光学相干断层扫描血管成像(optical coherence tomography angiography,OCTA)以实时、非侵入性、高分辨率等优势，已广泛应用于眼底组织结构及血管病变检查。文章对XFS眼底病变在OCT和OCTA上的表现进行综述。
Exfoliation syndrome (XFS) was characterized by the abnormal deposition of the fber-like material intraocularly, and manifested as white or gray, powdery exfoliation material (XFM) on the pupillary border and (or) anterior lens capsule under slit lamp microscopy. XFM could obstruct the trabecular meshwork and cause exfoliation glaucoma (XFG). In addition, XFM that entered aqueous humor circulation could enter bloodstream and result in vascular damage. XFM could enter ocular fundus microvascular and capillary vessels, causing abnormalities of fundus structures and vessels. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA), which were based on optical coherence tomography technology, had the advantages of real-time, non-intrusive and high resolution, et al. OCT and OCTA were widely used in detection of fundus structural and vascular abnormalities. Tis study was to review the fundus lesion of XFS on OCT and OCTA.
视网膜微循环与脑小血管具有相似的特征。视网膜被认为是可检测到的“窗口”，以检测在神经退行性疾病中发生的微血管损伤。光学相干断层扫描血管造影(optical coherence tomography angiography，OCTA)是一种非侵入性成像方式，可提供视网膜、脉络膜和视神经中血流的深度分辨图像。现总结有关OCTA在与眼科相关的阿尔茨海默病、帕金森病、多发性硬化症及视神经退行性疾病等神经系统疾病中的应用，并讨论其可否作为早期诊断和监测神经退行性疾病的重要工具。
Retinal microcirculation shares similar features with cerebral small blood vessels. Thus, the retina may be considered as an accessible ‘window’ to detect the microvascular damage occurred during the development and progression of neurodegenerative disorders. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality providing in-depth and high-resolved images of blood flow in the retina, choroid,and optic nerve. In this review, we summarize the current advances in the application of OCT-A in neurological diseases associated with ophthalmology such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and optic nerve degenerative diseases. Future directions for evaluating whether OCTA can be used as an important tool to early diagnose and monitor the neurodegenerative disorders are also discussed.
光学相干断层扫描血管成像(optical coherence tomography angiography，OCTA)是一种非接触、无创的、快速的血管造影技术，它通过检测红细胞在血管内的光学相干断层扫描(optical coherence tomography，OCT)信号的变化来提供血管影像。由于这项技术不需要注射血管造影剂，使得它比传统的眼科血管造影技术更安全。在前节疾病的检查中，OCTA不仅能够量化前节血管的范围和密度，还显示出良好的成像质量，为临床监测疾病的病程和对治疗的反应提供客观的评价。
Optical coherence tomography angiography (OCTA) is a noncontact, noninvasive, and rapid angiography technique. It provides vascular images by detecting changes in the optical coherence tomography (OCT) signal of red blood cells in the blood vessel. Since this technique does not require injection of angiography, it is safer than traditional ophthalmic angiography. In the examination of anterior segment diseases, OCTA can not only quantify the range and density of anterior segment blood vessels, but also shows good imaging quality, providing an objective evaluation for clinical monitoring of the disease course and response to treatment.
光学相干断层扫描血管成像术(optical coherence tomography angiography，OCTA)作为一项新兴的检查手段，现已被广泛应用于眼科临床及科研工作中。鉴于OCTA在血管成像方面的独特优势，近年来关于其在眼前段的临床应用和研究也愈发得到关注。关于OCTA对结膜、巩膜、角膜以及虹膜的血管和相关眼表疾病的研究日益增多，其在眼前段应用潜力巨大。
As a new examination method, optical coherence tomography angiography (OCTA) has been increasingly used in ophthalmology clinical work and scientific research. In view of the unique advantages of OCTA in angiography,the clinical application and research of OCTA in the anterior segment have attracted more and more attention in recent years. Studies of OCTA in vessels of conjunctiva, sclera, cornea, iris, and related ocular surface diseases have shown great potential for its application in the anterior segment.
目的：应用Cirrus HD-OCT 5000对正常眼黄斑及视盘血流参数进行血管成像测量，评估其可重复性及再现性。方法：纳入40只正常眼进行前瞻性研究。操作者A于一周内3天的同一时段(T1，T2，T3)对正常受试者的同一眼黄斑及视盘进行3次血管成像扫描，扫描过程中均开启FastTracTM图像跟踪功能，操作者B在T 2时间点再次对受试者同一眼进行相同程序扫描，使用Angio PlexMetrixTM量化软件(版本10.0)自动测量黄斑和视盘的血管长度密度(vessel length density，VD)和血管灌注密度(vascular perfusion density，PD)。应用单因素方差分析或非参数检验比较3次扫描的VD、PD是否有差异。采用组内相关系数(intraclass correlation coefficient，ICC)、变异系数(coefficient of variation，CV)评价操作者A的可重复性，采用一致性相关系数(consistent correlation coefficient，CCC)、重复性系数(repeatability coefficient，CR)、C V评价操作者间的再现性。结果：操作者A对黄斑及视盘各区域3次扫描的V D、P D之间差异无统计学意义(P >0.05)。操作者A对黄斑和视盘V D、PD 3次扫描的ICC值分别为0.260~0.517、0.362~0.898，黄斑及视盘各区域V D、P D的C V值均<8.1%。黄斑和视盘V D、P D的操作者间CCC值分别为0.3130~0.5665、0.5149~0.7801；黄斑VD和PD的CR值分别为3.2212~4.6399、0.0574~0.0832；视盘VD和PD的CR值分别为2.0675~4.0630、0.0447~0.0730。黄斑CV值均<9.0%，视盘CV值均<6.9%。结论：非同日的同一时段视盘浅层血流参数具有较好的重复性及再现性，黄斑浅层血流参数的重复性及再现性相对较差。
Objective: To evaluate the repeatability and reproducibility of quantification of macular and peri-papillary superficial capillaries in normal eyes using Cirrus HD-OCT 5000 angiography. Methods: Forty normal eyes were included in this prospective study. Angiography 3 mm × 3 mm scan protocol centered on the disc or macula of the same eye was repeated 3 times by operator A in the same period on 3 days (T1, T2, T3) within 1 week,and the FastTracTM image tracking function was turned on during the scan. Operator B repeated the same scan independently at T2 after operator A. Angio Plex MetrixTM quantification software (version 10.0) was used to automatically measure the vessel length density (VD) and vascular perfusion density (PD) of macular and peri-papillary superficial capillaries. One-way analysis of variance or nonparametric test was used to compare the VD and PD measurements of the 3 scans. The intraclass correlation coefficient (ICC) and coefficient of variation (CV)were calculated to evaluate the intra-operator repeatability. Consistent correlation coefficient (CCC), repeatability coefficient (CR), and CV were calculated to evaluate the inter-operator reproducibility. Results: There was no statistically significant difference in the measurements of VD and PD between the 3 scans of the macular and peri-papillary superficial capillaries by operator A (P>0.05). The ICC values for the 3 scans of VD and PD of the macular and peri-papillary superficial capillaries by operator A were 0.260–0.517 and 0.362~0.898, respectively.The CV values of the VD and PD of the macular and peri-papillary superficial capillaries were all <8.1%. The inter-operator CCC values of the macular and peri-papillary superficial capillaries were 0.3130–0.5665 and 0.5149~0.7801,respectively; the CR values of the VD and PD of macula were 3.2212–4.6399 and 0.0574–0.0832, respectively; the CR values of the VD and PD of optic disc were 2.0675–4.0630 and 0.0447–0.0730, respectively. The CV values of macular were all <9.0%, and the CV values of optic disc were all <6.9%. Conclusion:The macular and peri-papillary superficial capillaries parameters in the same period on different days have a good repeatability and reproducibility,while the superficial macular blood flow parameters have relatively poor repeatability and reproducibility.
