Dissertation/Thesis Abstract

Exploration of nanoscale structural sensitivity and chemical specificity by interferometric spectral analysis in optical coherence tomography
by Yi, Ji, Ph.D., Northwestern University, 2012, 163; 3527651
Abstract (Summary)

This dissertation is intended to non-invasively quantify the structural properties and functionality of biological tissue using interferometric spectral analysis in optical coherence tomography (OCT). More specifically, the investigation is focused on quantifying the tissue mass density correlation functions and measuring the oxygen saturation in blood vessels.

Across the whole spectrum of electromagnetic radiation from Gamma ray to microwave and radio, the optical wave from visible to near-IR range takes only a small fraction of wavelength (∼400nm to ∼1500nm) yet play an essential part of nowadays biomedical applications. Optical wave is considered to be safe (non-ionizing), easy to miniaturize, capable of high resolution (micron-level) and less expensive, which grants an excellent means to perform non-invasive in vivo detection. Amongst all the optical imaging and diagnosis modalities, optical coherence tomography (OCT), first demonstrated in early 90s for retinal imaging, exhibits its unique advantage of 3D imaging capability with the penetration depth of ∼1mm and the micron-level resolution similar to histology.

Analogous to ultrasound, OCT sends optical waves into the tissue and collects the echo along the penetration depth to form a depth-resolved image (B-scan). Because the light travels much faster than sounds, the detection of time delay is by an interferometry, which requires a broadband incident wave. Thus the spectral information is encrypted inside the OCT signal and can be investigated from a local microscopic region.

The spectrum contains valuable information based on various contrast mechanisms. One of the contrast investigated in this dissertation is optical absorption. Chromophores usually have distinct absorption spectra depending on their chemical compositions, which can be identified by spectral analysis. The feasibility of using OCT interferometric spectrum to identify the particular chromophores is demonstrated on microscopic length scale. The same working principle applies on hemoglobin, which is the oxygen transporting protein primarily in erythrocytes. The absorption spectrum varies with oxygen partial pressure so that it can be used to characterize oxygen saturation rate in blood vessel. An experimental demonstration in rat retina in vivo is presented here.

Besides the absorption contrast, the elastic scattering from the heterogeneity of biological tissue is also explored. Since the microscopic refractive index fluctuation causes the light scattering, it allows to quantify tissue physical structure by the scattering measurement. Quantifying the tissue mass density correlation function and the complete set of optical properties is demonstrated using a technique called inverse spectroscopic optical coherence tomograph (ISOCT). Further, ISOCT is found to be sensitive to the nano-scale structural features even though the resolution limit of OCT is of several microns. This sensitivity gives unique advantage to detect field effect of carcinogenesis, which states that subtle structural change can be detected throughout a particular pre-cancerous organ even apart from the eventual tumor site, as we presented here with rectal ex vivo measurements for screening early colonrectal cancer.

Moreover, a novel technique called structured interference OCT is presented in this dissertation to break the diffraction limited transverse resolution. The enhanced resolution benefits every aspect of the OCT applications.

Indexing (document details)
Advisor: Backman, Vadim
Commitee: Li, Xingde, Messersmith, Phillip B., Sahakian, Alan V.
School: Northwestern University
Department: Biomedical Engineering
School Location: United States -- Illinois
Source: DAI-B 74/02(E), Dissertation Abstracts International
Subjects: Biochemistry, Biomedical engineering
Keywords: Biophotonics, Molecular specificity, Nanometer, Optical coherence tomography, Oximetry, Oxygen saturation
Publication Number: 3527651
ISBN: 978-1-267-62068-2
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