Development of a novel noninvasive system for measurement and imaging of the arterial phase oxygen density ratio in the retinal microcirculation
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This study was conducted in order to develop a novel noninvasive system for measurement and imaging of the arterial oxygen density ratio (ODR) in the retinal microcirculation.
We developed a system composed of two digital cameras with two different filters, which were attached to a fundus camera capable of simultaneously obtaining two images. Actual measurements were performed on healthy volunteer eyes (n = 61). A new algorithm for ODR measurement and pixel-level imaging of erythrocytes was constructed from these data. The algorithm was based on the morphological closing operation and the line convergence index filter. For system calibration, we compared and verified the ODR values in arterioles and venules that were specified in advance for 56 eyes with reproducibility. In 10 additional volunteers, ODR measurements and imaging of the arterial phase in the retinal microcirculation corresponding to changes in oxygen saturation of the peripheral arteries at normal breathing and breath holding were performed.
Estimation of incident light to erythrocytes and pixel-level ODR calculation were achieved using the algorithm. The mean ODR values of arterioles and venules were 0.77 ± 0.060 and 1.02 ± 0.067, respectively. It was possible to separate these regions, calibrate at the pixel level, and estimate the arterial phase. In each of the 10 volunteers, changes in the arterial phase ODR corresponding to changes in oxygen saturation of the peripheral arteries were observed before and after breath holding on ODR images. The mean ODR in 10 volunteers was increased by breath holding (p < 0.05).
We developed a basic system for arterial phase ODR measurement and imaging of the retinal microcirculation. With further validation and development, this may provide a useful tool for evaluating retinal oxygen metabolism in the retinal microcirculation.
KeywordsRetinal microcirculation region Oxygen density ratio Arterial phase Morphological closing operation Line convergence index filter
We thank Mr. Tokio Ueno (Nidek Co., Ltd.) for technical support for hardware and Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
This work was supported in part by the Translational Research Network Program (# 08061012) funded by the Japan Agency for Medical Research and Development (AMED) and by grants-in-aid (#18K09451) for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and the Public Interest Incorporated Foundation Research Foundation of Elderly Eye Disease. We asked Nedek Co., Ltd. to create a prototype as a joint research project.
Compliance with ethical standards
Conflicts of interest
Hiroshi Enaida has received the instrument lease used in this research from Nidek Co., Ltd. Hiroshi Enaida, Yukiyasu Yoshinaga, and Tatsuro Ishibashi developed algorithms for measurement of this system and submitted patent applications (Japanese Patent Nos. 4544891, 4951757, and 4951758). The remaining authors declare no conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This clinical study is registered with UMIN Clinical Trials Registry (UMIN000017580).
Informed consent was obtained from all of the subjects before participating in the study.
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