Department of Physiology and Neurobiology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
PLoS One. 2013 Apr 23;8(4):e61599. doi: 10.1371/journal.pone.0061599. Print 2013.
To present a novel method for quantitative assessment of retinal vessel permeability using a fluorescein angiography-based computer algorithm.
Twenty-one subjects (13 with diabetic retinopathy, 8 healthy volunteers) underwent fluorescein angiography (FA). Image pre-processing included removal of non-retinal and noisy images and registration to achieve spatial and temporal pixel-based analysis. Permeability was assessed for each pixel by computing intensity kinetics normalized to arterial values. A linear curve was fitted and the slope value was assigned, color-coded and displayed. The initial FA studies and the computed permeability maps were interpreted in a masked and randomized manner by three experienced ophthalmologists for statistical validation of diagnosis accuracy and efficacy.
Permeability maps were successfully generated for all subjects. For healthy volunteers permeability values showed a normal distribution with a comparable range between subjects. Based on the mean cumulative histogram for the healthy population a threshold (99.5%) for pathological permeability was determined. Clear differences were found between patients and healthy subjects in the number and spatial distribution of pixels with pathological vascular leakage. The computed maps improved the discrimination between patients and healthy subjects, achieved sensitivity and specificity of 0.974 and 0.833 respectively, and significantly improved the consensus among raters for the localization of pathological regions.
The new algorithm allows quantification of retinal vessel permeability and provides objective, more sensitive and accurate evaluation than the present subjective clinical diagnosis. Future studies with a larger patients' cohort and different retinal pathologies are awaited to further validate this new approach and its role in diagnosis and treatment follow-up. Successful evaluation of vasculature permeability may be used for the early diagnosis of brain microvascular pathology and potentially predict associated neurological sequelae. Finally, the algorithm could be implemented for intraoperative evaluation of micovascular integrity in other organs or during animal experiments.
提出一种基于荧光素血管造影的新型计算机算法,用于定量评估视网膜血管通透性。
21 名受试者(13 名糖尿病视网膜病变患者,8 名健康志愿者)接受了荧光素血管造影(FA)检查。图像预处理包括去除非视网膜和噪声图像,并进行配准以实现基于空间和时间像素的分析。通过计算强度动力学来评估每个像素的通透性,将其归一化为动脉值。拟合线性曲线并分配斜率值,并用颜色编码并显示。三位经验丰富的眼科医生以掩蔽和随机的方式对初始 FA 研究和计算得到的通透性图进行解读,以验证诊断准确性和疗效的统计验证。
成功为所有受试者生成了通透性图。对于健康志愿者,通透性值呈正态分布,受试者之间的范围相似。基于健康人群的平均累积直方图,确定了病理性通透性的阈值(99.5%)。患者和健康受试者之间在病理性血管渗漏的像素数量和空间分布方面存在明显差异。计算得到的地图提高了患者和健康受试者之间的区分能力,分别达到了 0.974 和 0.833 的灵敏度和特异性,并且显著提高了观察者对病理性区域定位的共识。
新算法允许定量评估视网膜血管通透性,并提供比当前主观临床诊断更客观、更敏感和准确的评估。未来需要进行更大的患者队列和不同视网膜病变的研究,以进一步验证这种新方法及其在诊断和治疗随访中的作用。成功评估血管通透性可能用于早期诊断脑微血管病理学,并可能预测相关的神经后遗症。最后,该算法可用于其他器官的术中评估微血管完整性或在动物实验期间。