Thesis (Ph. D.)--University of Texas at Austin, 2003. / Supervisors: Thomas E. Milner and H. Grady Rylander III. Vita. Includes bibliographical references. Available also from UMI Company.

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Thesis (Ph. D.)--Worcester Polytechnic Institute. / Keywords: vulnerable plaque; optical spectroscopy; atherosclerosis; tissue lactate; tissue pH. Includes bibliographical references (p. 109-115).

Thesis (Ph. D.)--University of Texas at Austin, 2006. / Vita. Includes bibliographical references.

The design, processing, and sequential testing of a novel cylindrical diffusing optical fiber tip for ultraviolet light delivery is described. This device has been shown to uniformly(+/- 15%) illuminate angioplasty balloons, 20 mm in length, that are used in an experimental photochemotherapeutic treatment of swine intimal hyperplasia. Our experiments show that uniform diffusing tips of < 400 micron diameter can be reliably constructed for this and other interstitial applications. Modeling results indicate that this design is scalable to smaller diameters. The diffusing tips are made by stripping the protective buffer and etching away the cladding over a length of 20 mm from the fiber tip and replacing it with a thin layer of optical epoxy mixed with A/203 powder. To improve the uniformity and ease of fabrication, we have evaluated a new device configuration where the tip is etched into a modified conical shape, and the distal end face is polished and then coated with an optically opaque epoxy. This is shown to uniformly scatter - 70% of the light launched into the fiber without forward transmission. To our knowledge, we are the first to use this device configuration, and we have achieved a uniform cylindrical pattern of laser energy with uniformity < ± 15% of the average value. A simple computational model suitable for the interpretation of laser energy irradiance along the bare core surface of multimode optical fiber tips is proposed and experimentally verified. The model used is based on geometrical optics and Gaussian approximation. Good agreement is obtained between the calculation and experiment. We have measured the optical properties of the tips through all the sequences of the fabrication. The performances of the diffusing tips for illuminating angioplasty balloons are then evaluated by Ultraviolet Light at 365 nm. A Ti:Sapphire Ring Laser System with a doubling crystal pumped by an argon ion laser is used to generate the wavelength in this study.

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Thesis (Ph.D.)--Tufts University, 2004. / Adviser: David R. Walt. Submitted to the Dept. of Chemistry. Includes bibliographical references. Access restricted to members of the Tufts University community. Also available via the World Wide Web;

INTRODUCTION: The“vulnerable plaque" is defined as the“precursor lesion" that ultimately ends in acute coronary thrombi (clots) that create a heart attack. Macrophages and inflammatory cells, found preferentially in vulnerable plaque, sustain their activity in the plaque through anaerobic metabolism and lactate production. The ultimate goal is to assess anaerobic metabolism in-vivo by measuring tissue pH and lactate concentration in atherosclerotic plaques using optical spectroscopy. The proposed in-vitro optical probe design, experimental method, and spectroscopic data analysis methodology are established in this research. METHODS: A fiber optic probe was designed and built based on both Monte Carlo simulations and bench testing with the goal to collect light from a small volume of tissue. A simulation of the depth penetration of the proposed probe was performed on normal and atherosclerotic aortic tissue, and the final probe was bench tested using normal aorta. A method was developed to preserve plaque metabolic status of tissue harvested from patients. Human atherosclerotic tissue obtained immediately after carotid endarterectomy was placed in Minimum Essential Medium (MEM) with non-essential amino acids supplement, bubbled with 75%O2/20%N2/5%CO2 at 37°C. Tissue pH, pCO2, pO2 and temperature with (n=7) and without (n=2) the media preparation over time were reviewed to assess plaque viability and maintenance of physiological conditions. Additional plaques placed in media were used for development of chemometric methods to measure pH and lactate. Areas of each plaque were randomly chosen for analysis. Reflectance spectra were collected with a dispersive spectrometer (400-1100 nm) and a Fourier-transform near-infrared spectrometer (1100-2400 nm) using the fiber optic probe. Reference measurements for tissue pH and lactate were made with glass microelectrodes and micro-enzymatic assay, respectively. Partial least-squares (PLS) data analysis was used to develop multivariate calibration models on an initial set of 5-6 plaques relating the optical spectra to the reference tissue pH (n=20) or the lactate concentration (n=21) to assess data quality. The coefficient of multiple determination (R2), the standard error of cross-validation (SECV), and the number of factors were used to assess the model performance. Additional points were collected from ~14 plaques and added to preliminary data. Pre-processing techniques were then used to see if preliminary data results could be improved by reducing different sources of variability with the introduction of more points. RESULTS: Monte Carlo simulations and depth penetration tests with the final probe design showed light is collected from ~1 mm3 volume of tissue using a 50 micron source-receiver separation. Tissue pH, pCO2, pO2 and temperature values demonstrated that the plaques were viable and stable in the media preparation for a maximum of 4 hours. Data from the first six plaques collected for lactate analysis showed that for seventeen points, a six-factor model produced adequate results (R2=0.83 SECV=1.4 micromoles lactate/gram tissue). Data from the first five plaques collected for tissue pH analysis, showed for seventeen different points, a three-factor model produced adequate results (R2=0.75 SECV=0.09 pH units). When additional points were added to either data set, model results were degraded. CONCLUSIONS: The in-vitro optical probe design and experimental procedures was established and the feasibility of the optical method demonstrated with preliminary data. However, with the addition of more data points, different sources of tissue and spectral variability were observed to affect calibration. The gross pathology type and mismatched optical volume to reference measurement volume limited the tissue pH determination. The reference measurement precision, the spatial resolution of the reference lactate measurement, and unmodeled tissue variability (water and proteins) limited the lactate determination. Large variability in all optical measurements was observed. Additional in-vitro data collection would be required such that the variability due to the tissue is reduced and any spectrometer variability adequately compensated to be able to use the optical calibration in-vivo.

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Thesis (Ph. D.)--University of Texas at Austin, 2003. / Vita. Includes bibliographical references. Available also from UMI Company.