Visible Optical Coherence Tomography based Multimodal Imaging for Quantification of Retinal Lipofuscin

Authors

ZAHRA NAFARFollow

Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biomedical Engineering

First Advisor's Name

Shuliang Jiao

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Rong Wen

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Jessica Ramella-Roman

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Wei-Chiang Lin

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Richard Bone

Fifth Advisor's Committee Title

Committee Member

Keywords

Optical Coherence Tomography, Fundus Autofluorescence, Quantitative imaging, Lipofuscin, Retina

Date of Defense

3-16-2020

Abstract

Retinal degeneration is the leading cause of irreversible low vision and blindness in the world, that describes conditions characterized by progressive loss of photoreceptors. Retinal Pigment Epithelium (RPE) is located under photoreceptors’ outer segments and plays an important role in the maintenance of photoreceptors by completing the visual cycle and phagocytosis of shed photoreceptor outer segments. Lipofuscin, a byproduct of the visual cycle, is a nondegradable compound that accumulates in the RPE cells and eventually damages the RPE cells and inevitably causes photoreceptor degeneration. Lipofuscin is the major cause of fundus fluorescence that can be detected by Fundus Autofluorescent (FAF) imaging systems. Reliable and quantified FAF values are necessary for lipofuscin quantification which can be a significant tool in the diagnosis of retinal degenerative disease in early stages and provide a better opportunity for treatment before the loss of vision stage. However, FAF is attenuated by the ocular media prior to the RPE, including cornea, lens, vitreous body, retinal layers in front of the RPE, and the melanin granules within the RPE cells that migrate to the apical region upon light exposure. This attenuation varies among people and for an individual over time and cannot be measured directly, thus hurdles measurement of the true FAF values. Further, differences in acquisition systems such as illumination power and detector sensitivity, directly affect the measured FAF. This issue has been addressed by implementing a reference target in the FAF imaging system. Normalizing the FAF signal to that of the target eliminates the dependency on the acquisition parameters. However, the issue of pre-RPE and RPE melanin attenuation remains unresolved. Further, the fluorescence characteristics of the commercially available fluorescent reference are quite different than retinal lipofuscin that challenges the quantification of the absolute amount of lipofuscin in the RPE. In this dissertation, we propose a new multimodal imaging system based on visible-light optical coherence tomography (VIS-OCT) that provides a three-dimensional image. The technology simultaneously acquires VIS-OCT and FAF with a single broadband visible light source. Since both images are originated from the same group of photons and travel through the same ocular media at the same time, the attenuation factor is similar in both modalities. Therefore, by normalizing FAF by VIS-OCT of the RPE layer, the attenuation of the pre_RPE media can be eliminated. Further, we implemented two reference targets to quantify VIS-OCT and FAF and eliminate the dependency on acquisition parameters. These references were later substituted by a single customized reference that consists of the major lipofuscin fluorophore, called A2E. The quantitative imaging independent of system fluctuation, and attenuation of pre-RPE and RPE melanin was successfully tested on retinal simulating phantoms, in vivo on the animal retina, and human subjects. The in vivo quantification in small animals linearly correlates with A2E content measured by mass spectrometry. Quantitative imaging of human retinas is consistent with the linear accumulation of lipofuscin with age. The VIS-OCT-FAF has the potential for clinical diagnosis.

Identifier

FIDC008936

ORCID

https://orcid.org/0000-0002-6680-4234

Previously Published In

This dissertation contains material from 4 published papers in the following peer-reviewed journals.
The content of chapter 3 is published in Biomedical Optics Express as Zahra Nafar, Minshan Jiang, Rong Wen, and Shuliang Jiao,” Visible-light optical coherence tomography-based multimodal retinal imaging for improvement of fluorescent intensity quantification”.
The content of chapter 4 is published in Biomedical Optics Express as Zahra Nafar, Rong Wen, and Shuliang Jiao,” Visible light OCT-based quantitative imaging of lipofuscin in the retinal pigment epithelium with standard reference targets”.
The content of chapter 7 is published in Scientific Reports – Nature journal as Zahra Nafar, Rong Wen, Ziqiang Guan, Yiwen Li, and Shuliang Jiao,” Quantifying lipofuscin in retinal pigment epithelium in vivo by visible-light optical coherence tomography-based multimodal imaging”.
In addition, the content of this dissertation is partially reviewed and published in Experimental Biology and Medicine journal as Zahra Nafar, Rong Wen, and Shuliang Jiao, “Visible-light optical coherence tomography-based multimodal system for quantitative fundus autofluorescence imaging”.

Recommended Citation

NAFAR, ZAHRA, "Visible Optical Coherence Tomography based Multimodal Imaging for Quantification of Retinal Lipofuscin" (2020). FIU Electronic Theses and Dissertations. 4413.
https://digitalcommons.fiu.edu/etd/4413