Over the past two decades, optical coherence tomography (OCT) has been successfully applied to various fields of biomedical researching and clinical studies, including cardiology, urology, dermatology, dentistry, oncology, and most successfully, ophthalmology. This dissertation seeks to extend the current OCT practice, which is still largely morphology-based, into a new dimension, functional analysis of metabolic activities in vivo. More specifically, the investigation is focused on retrieving blood oxygen saturation (sO2) using intrinsic hemoglobin optical absorption contrast. Most mammalian cells rely on aerobic respiration to support cellular function, which means they consume oxygen to create adenosine triphosphate (ATP). Metabolic rate of oxygen (MRO2), a key hemodynamic parameter, characterizes how much oxygen is consumed during a given period of time, reflecting the metabolic activity of the target tissue. For example, retinal neurons are highly active and almost entirely rely on the moment-to-moment oxygen supply from retinal circulations. Thus, variation in MRO2 reveals the instantaneous activity of these neurons, shedding light on the physiological and pathophysiological change of cellular functions. Eventually, measuring MRO2 can potentially provide a biomarker for early-stage disease diagnosis, and serve as one benchmark for evaluating effectiveness of medical intervention during disease management. Essential in calculating MRO2, blood sO2 measurements using spectroscopic OCT analysis has been attempted as early as 2003. OCT is intrinsically sensitive to the blood optical absorption spectrum due to its wide-band illumination and detection scheme relying on back-scattered photon. However, accurate retrieval of blood sO2 using conventional near infrared (NIR) OCT systems in vivo has remained challenging. It was not until the development of OCT systems using visible light illumination (vis-OCT) when accurate measurement of blood sO2 was reported in live animals in situ. Thus, one question demanding immediate investigation is how the choice of illumination wavelength bands affect the performance of OCT oximetry. This is addressed using two approaches, (1) a numerical study using Monte Carlo methods, and (2) animal experiments involving the development of a vis- and NIR- dual band OCT imaging system. It is indicated that visible light is more suitable for OCT oximetry applications due to the higher absorption contrast between oxyhemoglobin and deoxyhemoglobin. The accuracy of OCT retinal oximetry is established to be around 5 percentage points (pp) regardless of physiological variation of blood sO2, vessel diameter, and is robust over a reasonable selection of sampling geometry. Despite the higher optical scattering experienced in the visible wavelength range, vis-OCT also demonstrated comparable or better imaging capability in terms of resolving anatomical features, imaging resolution, and retrieving other functional indicators such as blood flow. Besides retrieving blood sO2 from vessels directly visualized in structural OCT images, the possibility of using dynamic motion contrast to enhance otherwise non-resolvable micro vessels is investigated. Using this approach, it is subsequently proved that OCT angiography (OCTA) encodes blood absorption contrast and can be used to calculate sO2 within microvasculature. For the first time, measurements of relative sO2 change are reported in choroidal capillaries following inhalation oxygen challenge. This dissertation also represents a translational study that seeks to move technologies developed in the laboratory into real clinical applications. A vis-OCT imaging system with integrated scanning laser ophthalmoscope (SLO) is developed for human subjects. This prototype system can provide three-dimensional (3D) structural images and cross-sections of human fundus similar to that from commercial NIR-OCT systems. In addition, blood sO2 within retinal circulation is successfully retrieved from healthy subjects following spectroscopic analysis. To improve the accuracy of sO2 measurements, a statistical model is formulized. This model describes the noise intensity distribution in Fourier domain (FD) OCT amplitude image, which enables retrieving unbiased true OCT intensity from low signal-to-noise ratio (SNR) images. Finally, a vis-OCT microscope is developed to monitor dynamic changes within the cerebral circulation following ischemic stroke. This study demonstrates the application of vis-OCT beyond ophthalmic imaging, and serves as a proof of concept that vis-OCT has the potential to be employed in a wide-array of biomedical research.

Last modified

• 04/09/2018

Creator

• Siyu Chen

DOI

• https://doi.org/10.21985/N2B11B

Subject

• Biomedical Engineering

Keyword

• Ophthalmic Imaging
• Optical Coherence Tomography
• Spectroscopic Analysis
• Blood Oxygen Saturation

Date created

• 2017-01-01

Resource type

• Dissertation

Rights statement

• In Copyright