Purpose To examine soft contact lens fitting characteristics using anterior segment imaging techniques and comfort. The specific aims of each chapter are as follows: Chapter 2: To calibrate the new ZEISS VisanteTM anterior segment optical coherence tomographer (OCT) using references with known physical thickness and refractive index equal to the human cornea and to compare the Visante measures to those from a previous generation OCT (Zeiss-Humphrey OCT II). Chapter 3: The first purpose of this study was to measure the repeatability of the Visante TM OCT in a normal sample. The second was to compare corneal thickness measured with the Visante TM OCT to the Zeiss-Humphrey OCT II (model II, Carl Zeiss Meditec, Jena Germany) adapted for anterior segment imaging and to the Orbscan II TM (Bausch and Lomb, Rochester New York). Chapter 4: Conjunctival displacement observed with the edges of the contact lens, when imaged may be real or may be an artefact of all OCT imagers. A continuous surface appears displaced when the refractive index of the leading medium changes at the edge of a contact lens. To examine this effect, edges of the contact lenses were imaged on a continuous surface using the UHR-OCT. Contact lens edges on the human conjunctival tissue were also imaged to see if the lens indentation on the conjunctival tissue is real or an artefact at the edge of the lens. Chapter 5: The main purpose of this study was to determine if we can predict end of the day discomfort and dryness using clinical predictive variables. The second purpose of the study was to determine if there was any relationship between lens fitting characteristics and clinical complications and especially to the superior cornea and conjunctiva with a dispensing clinical trial. Methods Chapter 2: Twenty two semi-rigid lenses of specified thicknesses were manufactured using a material with refractive index of 1.376. Central thickness of these lenses was measured using VisanteTM OCT and Zeiss-Humphrey OCT II (Zeiss, Germany). Two data sets consisting of nominal measures (with a standard pachymeter of the lenses and one obtained using a digital micrometer) were used as references. Regression equations between the physical and optical (OCT) measures were derived to calibrate the devices. Chapter 3: Fifteen healthy participants were recruited. At the Day 1 visit the epithelial and total corneal thickness, across the central 10mm of the horizontal meridian were measured using the OCT II and the Visante TM OCT. Only total corneal thickness across the central 10mm of the horizontal meridian was measured using the Orbscan II. The order of these measurements was randomized. These measurements were repeated on Day 2. Each individual measurement was repeated three times and averaged to give a single result. Chapter 4: (2-D) Images of the edges of marketed silicone hydrogel and hydrogel lenses with refractive indices (n) ranging from 1.41-1.51 were taken placing them concave side down on a continuous surface. Five images for each lens were taken using a UHR-OCT system, operating at 1060 nm with ~3.2um (axial) and 10μm (lateral) resolution at the rate of 75,000 A-scans/s. The displacement of the glass slide beneath the lens edge was measured using Image J. Chapter 5: Thirty participants (neophytes) were included in the study and the four lenses (Acuvue Advance 8.3, Acuvue Advance 8.7, Pure Vision 8.3, and Pure Vision 8.6) were randomly assigned for each eye. The lenses were worn for a period of two weeks on a daily wear basis for 8 to 10hrs per day. Lens performance was monitored over the 2week period. Assessment of subjective comfort was made using visual analogue scales. Total corneal and epithelium thickness was measured using the Visante OCT, the lens edge profiles of the contact lenses were observed using the ultra-high resolution OCT and the conjunctival epithelial thinning was measured using the RTVue OCT. Conjunctival blood velocity was measured at the baseline and 2 week visit using a high magnification camera. Results Chapter 2: Before calibration, repeated measures ANOVA showed that there were significant differences between the mean lens thicknesses from each of the measurement methods (p<0.05), where Visante measurements were significantly different from the other three (OCT II, MG and OP) methods (p<0.05). Visante thickness was significantly higher than the microgauge measures (453±37.6 µm compared to 445.1±38.2 µm) and the OCT II was significantly lower (424.5±36.1 µm both, p<0.05). After calibration using the regression equations between the physical and optical measurements, there were no differences between OCT II and Visante OCT (p<0.05). Chapter 3: Mean central corneal and epithelial thickness using the Visante™ OCT after calibration at the apex of the cornea was 536± 27 µm (range, 563-509 µm) and 55± 2.3 µm (range, 57.3-52.7 µm), respectively. The mean corneal and epithelial thickness using OCT II at the apex was 520±25µm and 56±4.9 µm, respectively. The mean of total corneal thickness measured with the Orbscan II was 609±29µm. Visante OCT was the most repeatable for test-retest at the apex, nasal and temporal quadrants of the cornea compared to OCT II and Orbscan II. COR’s of Visante OCT ranged from ±7.71µm to ±8.98µm for total corneal thickness and ± 8.72 µm to ± 9.92 µm for epithelial thickness. CCC’s with Visante OCT were high for total corneal thickness for test-retest differences ranging from 0.97 to 0.99, CCC’s for epithelial thickness showed moderate concordance for both the instruments. Chapter 4: Results showed that artefactual displacement of the contact lens edge was observed when the lenses were imaged on the glass reference sphere, custom made rigid contact lenses (1.376) and on the conjunctival tissue. The displacement measured on the conjunctival tissue ranged from 7.0±0.86 µm for the Air Optix Night and Day to 17.4±0.22 µm for the Acuvue Advance contact lenses. The range of displacement with the soft lens edges imaged on the rigid contact lens was from 5.51±0.03 µm to 9.72±0.12 µm. Chapter 5: The lenses with the steepest sag (Acuvue Advance 8.3, Pure Vision 8.3) resulted not only with the tightest fit, but with compromise to the superior conjunctiva. This was especially seen with the Acuvue Advance lenses. The steeper lenses caused more total corneal swelling, superior epithelial thinning, mechanical compression of conjunctiva, conjunctival staining, bulbar hyperemia, conjunctival indentation and reduced blood flow at the lens edge. Not many associations were observed between baseline clinical and 2 weeks sensory variables. However, significant associations were observed when comparing the baseline clinical variables to end of the day sensory variables. Baseline clinical variables compared to 2 week clinical variables also showed significant correlations. Conclusions Chapter 2: Using reference lenses with refractive index of the cornea (1.376) allows rapid and simple calibration and cross calibration of instruments for measuring the corneal thickness. The Visante and OCT II do not produce measurements that are equal to physical references with refractive index equal to the human cornea. Chapter 3: There is good repeatability of corneal and epithelial thickness using each OCT for test-retest differences compared to the between instruments repeatability. Measurements of epithelial thickness are less repeatable compared to the total corneal thickness for the instruments used in the study. Chapter 4: When contact lenses are imaged in-situ using UHR-OCT the conjunctival tissue appeared displaced. This experiment indicates that this displacement is an artefact of all OCT imagers since a continuous surface (glass slide) was optically displaced indicating that the displacement that is observed is a function of the refractive index change and also the thickness of the contact lens edges. Chapter 5: Discomfort is a complex issue to resolve since it appears to be related to ocular factors such as the corneal and conjunctival topography and sagittal depth; to lens factors that is 1) how the sag depth of the lenses relate to the corneal/conjunctival shape and depth and therefore how well it moves on the eye. 2) Also with the lens material; whether they are high or low modulus, low or high water content, dehydration properties, wetting agents used and its resistance to deposits, lens edge profile and thickness and its interaction with the upper eyelid.

Fluorescence enhanced optical tomography is a promising molecular imaging modality which employs a near infrared fluorescent molecule as an imaging agent and time-dependent measurements of fluorescent light propagation and generation. In this dissertation a novel fluorescence tomography algorithm is proposed to reconstruct images of targets contrasted by fluorescence within the tissues from boundary fluorescence emission measurements. An adaptive finite element based reconstruction algorithm for high resolution, fluorescence tomography was developed and validated with non-contact, planewave frequency-domain fluorescence measurements on a tissue phantom. The image reconstruction problem was posed as an optimization problem in which the fluorescence optical property map which minimized the difference between the experimentally observed boundary fluorescence and that predicted from the diffusion model was sought. A regularized Gauss-Newton algorithm was derived and dual adaptive meshes were employed for solution of coupled photon diffusion equations and for updating the fluorescence optical property map in the tissue phantom. The algorithm was developed in a continuous function space setting in a mesh independent manner. This allowed the meshes to adapt during the tomography process to yield high resolution images of fluorescent targets and to accurately simulate the light propagation in tissue phantoms from area-illumination. Frequency-domain fluorescence data collected at the illumination surface was used for reconstructing the fluorescence yield distribution in a 512 cm3, tissue phantom filled with 1% Liposyn solution. Fluorescent targets containing 1 micro-molar Indocyanine Green solution in 1% Liposyn and were suspended at the depths of up to 2cm from the illumination surface. Fluorescence measurements at the illumination surface were acquired by a gain-modulated image intensified CCD camera system outfitted with holographic band rejection and optical band pass filters. Excitation light at the phantom surface source was quantified by utilizing cross polarizers. Rayleigh resolution studies to determine the minimum detectable sepatation of two embedded fluorescent targets was attempted and in the absence of measurement noise, resolution down to the transport limit of 1mm was attained. The results of this work demonstrate the feasibility of high-resolution, molecular tomography in clinic with rapid non-contact area measurements.

Optical imaging of soft biological tissues is highly desirable since it is nonionizing and provides sensitive contrast information which enables detection of physiological functions and abnormalities, including potentially early cancer detection. However, due to the diffusion of light, it is dificult to achieve simultaneously both good spatial resolution and good imaging depth with the pure optical imaging modalities. This work focuses on the ultrasound-modulated optical tomography - a hybrid technique which combines advantages of ultrasonic resolution and optical contrast. In this technique, focused ultrasound and optical radiation of high temporal co-herence are simultaneously applied to soft biological tissue, and the intensity of the ultrasound-modulated light is measured. This provides information about the optical properties of the tissue, spatially localized at the interaction region of the ultrasonic and electromagnetic waves. In experimental part of this work we present a novel implementation of high-resolution ultrasound-modulated optical tomography that, based on optical contrast, can image several millimeters deep into soft biological tissues. A long-cavity confocal Fabry-Perot interferometer was used to detect the ultrasound-modulated coherent light that traversed the scattering biological tissue. Using 15-MHz ultrasound, we imaged with high contrast light absorbing structures placed 3 mm below the surface of chicken breast tissue. The resolution along the axial and the lateral directions with respect to the ultrasound propagation direction was better than 70 and 120¹m, respectively. This technology is complementary to other imaging technologies, such as confocal microscopy and optical-coherence tomography, and has potential for broad biomedical applications. In the theoretical part we present various methods to model interaction be-tween the ultrasonic and electromagnetic waves in optically scattering media. We first extend the existing theoretical model based on the diffusing-wave spectroscopy approach to account for anisotropic optical scattering, Brownian motion, pulsed ul-trasound, and strong correlations between the ultrasound-induced optical phase in-crements. Based on the Bethe-Salpeter equation, we further develop a more general correlation transfer equation, and subsequently a correlation diffusion equation, for ultrasound-modulated multiply scattered light. We expect these equations to be applicable to a wide spectrum of conditions in the ultrasound-modulated optical tomography of soft biological tissues.

Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 115-117). Also available on the World Wide Web.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 113-124).

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: oxygen consumption; PET; blood flow. Includes bibliographical references (p. 58-61).

A polarization sensitive optical coherence tomography (PS-OCT) instrument is presented for the study of glaucoma. Glaucoma is the second leading cause of blindness worldwide and causes irreversible damage to the retina. This PS-OCT system was built to perform retinal imaging with a swept source laser providing a 28 kHz A-scan repetition rate. Thickness, phase retardation, birefringence and reflectance index measurements were taken from the primate eyes on a weekly or semi-weekly basis through the course of a 30 week study. Statistical analysis of these measurements indicates that the reflectance index is the earliest measured indicator of glaucomatous changes and a potential marker for early glaucoma diagnosis. / text

This thesis discusses certain aspects of the noninvasive imaging technique known as optical coherence tomography (OCT). Topics include three-dimensional image rendering as well as application of the Fast Fourier Transform to reconstruct the axial scan as a function of depth. Implementations use LabVIEW system design software and a Xilinx Spartan-6 field-programmable gate array (FPGA). The inherent parallel-processing capability of an FPGA opens the possibility of designing a "super-sensor" which entails simultaneous capturing of image and sensor data, giving medical practitioners more data for potentially improved diagnosis. FPGA-based processing would benefit many methods of characterizing biological samples; OCT and photonic crystal microarray biosensors are discussed. / text

The crust and upper mantle seismic structure beneath southwestern Mexico was investigated using several techniques including teleseismic tomography using 3D raytracing, a joint tomographic inversion of teleseismic and regional data that included relocation of regional seismicity, and a P to S converted wave study. The data used in these studies came from a broadband seismic deployment called MARS. The seismic deployment lasted 1.5 years from January 2006 to June 2007 and the stations covered much of Jalisco and Colima states as well as the western part of Michoacan states. At depth less than 50 km, P-wave receiver function images show a clear dipping slow velocity anomaly above a fast velocity layer. The slow anomaly convertor seen in receiver functions is directly above a fast dipping seismic anomaly seen in regional tomography results. The slow velocity with high Vp/Vs ratio is interpreted as a high pore fluid pressure zone within the upper layer of subducting oceanic crust. Regional seismicity was located using the double difference technique and then relocated in a tomography inversion. The seismicity is located very close to the slow dipping boundary to depths of 30-35 km and thus along the plate interface between the subducted and overlying plate. Deeper events are below the slow layer and thus are intraplate. Receiver function results also show a weaker continental Moho signal above the dipping slab that I interpret as a region of mantle serpentinization in the mantle wedge. Inland of the subduction zone, a clear Moho is observed with a maximum thickness of near 42 km although it thins to near 36 km depth towards the north approaching the Tepic-Zacoalco Rift. Using H-K analysis to examine Vp/Vs ratios in the crust, I find a band of very high Vp/Vs along the Jalisco Volcanic lineament as well as beneath the Michoacan-Guanajuato volcanic field. These observations suggest the continental crust is warm and possibly partially molten over broad areas associated with these two magmatic regions and not just locally beneath the volcanoes. I also found seismicity associated with the Jalisco Volcanic Lineament but it was trenchward of the volcanoes. This may indicate extension in this region is part of the explanation for this magmatic activity. At depths below 100 km, the tomography results show clear fast anomalies, about 0.3 km/s faster than the reference model, dipping to the northeast that I interpret as the subducting Rivera and Cocos plates. Tomography models show that the Rivera slab is dipping much steeper than the Cocos plate at depth. Below 150 km depth, the Rivera plate shows an almost vertical dip supporting the interpretation that the slab has steepened through time beneath Jalisco leading to a coastward migration of young volcanism with mixed geochemical signatures. The location of the young volcanism of the Jalisco Volcanic Lineament is just at the edge of the steeply dipping slab seen in the tomography. The magmatism is thus likely a nascent arc. The models also display evidence of a gap between the Rivera and Cocos plates that increases in width with depth marking the boundary between the two plates. The gap lies just to the west of Colima graben and allows asthenosphere to rise above the plates feeding Colima volcano. Another interesting finding from this study is a possibility of a slab tear along the western edge of the Cocos plate at a depth of about 50 km extending 60 km horizontally. The tear is coincident with a lack of seismicity in this region although there are events below and above the tear. / text

published_or_final_version / Electrical and Electronic Engineering / Master / Master of Philosophy