Retinal hypoxia is associated with many retinal diseases, such as diabetic retinopathy. Current retinal research suggests that retinal hypoxia appears prior to the onset of diabetic retinopathy. The preliminary association of retinal hypoxia to the early stages of diabetic retinopathy is stimulating the development of new technologies to measure the oxygen content of retinal tissue. Frequency domain phosphoresence lifetime imaging (PLI) is a promising technology that enables the mapping of the oxygen content across the entire retina in the form of two-dimensional images. The two-dimensional images generated from the PLI process are a spatial mapping of the retinal tissue's oxygen tension. Currently, the phosphorescent based oxygen tension PLI measurements contain contaminating auto-fluorescent signals in addition to the desired phosphorescent signals. These auto-fluorescent signals artificially inflate the oxygen tension readings due to the nature of fluorescent signals in phosphorescent imaging. Additionally, the maps generated through PLI appear to contain oxygen tension information from both the retinal vasculature and the choroidal vasculature. The choroidal vasculature is situated directly behind the retina and can have a different oxygen tension value than the retinal vasculature. This research enhanced the PLI system by mathematically eliminating the contaminating auto-fluorescent signals and investigated the methods aimed at separating the PO2s of the retinal and choroidal vasculature beds. In addition, the application of the enhanced PLI technology to the investigation of retinal oxygen changes in a rat model of type I diabetes yielded results that suggest a hyperoxic to hypoxic trend prior to the onset of diabetic retinopathy.

Fluorescence microscopy is a powerful imaging technique used in the biological sciences to identify labeled components of a sample with specificity. This is usually accomplished through labeling with fluorescent dyes, isolating these dyes by their spectral signatures with optical filters, and recording the intensity of the fluorescent response. Although these techniques are widely used, fluorescence intensity images can be negatively affected by a variety of factors that impact the fluorescence intensity. Fluorescence lifetime imaging microscopy (FLIM) is an imaging technique that is relatively immune to intensity fluctuations and also provides the unique ability to directly monitor the microenvironment surrounding a fluorophore. Despite the benefits associated with FLIM, the applications to which it is applied are fairly limited due to long image acquisition times and high cost of traditional hardware. Recent advances in complementary metal-oxide-semiconductor (CMOS) single-photon avalanche diodes (SPADs) have enabled the design of low-cost imaging arrays that are capable of recording lifetime images with acquisition times greater than one order of magnitude faster than existing systems. However, these SPAD arrays have yet to realize the full potential of the technology due to limitations in their ability to handle the vast amount of data generated during the commonly used time-correlated single-photon counting (TCSPC) lifetime imaging technique. This thesis presents the design, implementation, characterization, and demonstration of a high speed FLIM imaging system. The components of this design include a CMOS imager chip in a standard 0.13 μm technology containing a custom CMOS SPAD, a 64-by-64 array of these SPADs, pixel control circuitry, independent time-to-digital converters (TDCs), a FLIM specific datapath, and high bandwidth output buffers. In addition to the CMOS imaging array, a complete system was designed and implemented using a printed circuit board (PCB) for capturing data from the imager, creating histograms for the photon arrival data using field-programmable gate arrays, and transferring the data to a computer using a cabled PCIe interface. Finally, software is used to communicate between the imaging system and a computer.The dark count rate of the SPAD was measured to be only 231 Hz at room temperature while maintaining a photon detection probability of up to 30\%. TDCs included on the array have a 62.5 ps resolution and a 64 ns range, which is suitable for measuring the lifetime of most biological fluorophores. Additionally, the on-chip datapath was designed to handle continuous data transfers at rates capable of supporting TCSPC-based lifetime imaging at 100 frames per second. The system level implementation also provides sufficient data throughput for transferring up to 750 frames per second from the imaging system to a computer. The lifetime imaging system was characterized using standard techniques for evaluating SPAD performance and an electrical delay signal for measuring the TDC performance. This thesis concludes with a demonstration of TCSPC-FLIM imaging at 100 frames per second -- the fastest 64-by-64 TCSPC FLIM that has been demonstrated. This system overcomes some of the limitations of existing FLIM systems and has the potential to enable new application domains in dynamic FLIM imaging.

Thesis (S.M.)--Joint Program in Oceanography/Applied Ocean Science and Engineering (Massachusetts Institute of Technology, Dept. of Mechanical Engineering; and the Woods Hole Oceanographic Institution), September 2011. / "September 2011." "©2011"--P. 2. Cataloged from PDF version of thesis. / Includes bibliographical references (p. 97-101). / The ocean depths provide an ever changing and complex imaging environment. As scientists and researches strive to document and study more remote and optically challenging areas, specifically scatter-limited environments. There is a requirement for new illumination systems that improve both image quality and increase imaging distance. One of the most constraining optical properties to underwater image quality are scattering caused by ocean chemistry and entrained organic material. By reducing the size of the scatter interaction volume, one can immediately improve both the focus (forward scatter limited) and contrast (backscatter limited) of underwater images. This thesis describes a relatively simple, cost-effective and field-deployable low-power dynamic lighting system that minimizes the scatter interaction volume with both subjective and quantifiable improvements in imaging performance. / by Geoffrey Allen Gorman. / S.M.

The use of high technology in common daily tasks is boarding all areas of civil engineering; pavement evaluation is not the exception. Accordingly, current pavement imaging systems have been able to collect images at highway speeds and with the use of proper software, this digital information can be translated into pavement distress reports in which all distresses are classified and presented by their type, extent, severity, and location. However, a number of issues regarding the quality of pavement images and the appropriate conditions to acquire them, remain to be addressed. These issues surfaced during the development of a pavement evaluation vehicle for the Florida Department of Transportation (FDOT). The work involved in this thesis proposes basic criteria to evaluate the performance of pavement imaging systems. Mainly four parameters (1) spatial resolution, (2) brightness resolution, (3) optical distortion, and (4) signal to noise ratio, have been identified to assess the quality of a pavement imaging system. First, each of the four parameters is studied in detail in USF's Visual Imaging Laboratory to formulate relevant criteria that can be used to evaluate imaging systems. Then, the developed criteria are used to evaluate the FDOT Survey Vehicle's pavement imaging system. The evaluation speed does not seem to have any significant influence on the spatial resolution, brightness resolution and signal to noise ratio. Little or no optical distortion was observed on the images on wheel paths. Limitations of the imaging system were also determined in terms of the brightness resolution and noise. The conclusions drawn from this study can be used to (1) enhance pavement imaging systems and (2) setup appropriate guidelines to perform automated distress surveys, under varying lighting conditions and speeds to obtain good quality images.

Synthetic aperture radar (SAR) is one of the most versatile tools ever invented for imaging. Due to its better Rayleigh resolution, SAR imaging provides the highest quality radar imagery. These images are used for many applications including but not limited to terrestrial mapping, disaster reconnaissance, medical imaging and military applications. Imaging techniques or geometries which can improve the resolution of the reconstructed imagery is always desired in the SAR imaging. In this dissertation both the linear and nonlinear frequency modulated chirp signals are discussed. The most widely used frequency modulated chirp signal, linear frequency modulated chirp signal, and some of its properties such as spectrum, point spread function and matched filter are summarized. A new nonlinear frequency modulated chirp signal which can be used to improve the image resolution is introduced. In order to validate the offered chirp signal, spotlight SAR imaging geometry together with 2D polar and Stolt format reconstruction algorithms are considered. The synthetic examples are generated using both chirps both with polar and Stolt format processing. Additionally a new change detection method which depends on the idea of generating two different final change maps of the initial and final images in a sequence is offered. The specific algorithms utilized for testing this method are the widely used correlation coefficient change statistic and the intensity ratio change statistic algorithms. This method together with the algorithms mentioned is first applied to synthetic data generated by Stolt format processing. It is shown that the method works on synthetic data. The method together with the algorithms mentioned is also applied to two case studies dfreal disasters, one is 2010 Gulf of Mexico oil spill and the second is 2008 China Sichuan earthquake. It is shown that two final change map method can reduce the false identifications of the changes. Also it is shown that intensity ratio change statistics is a better tool for identifying the changes due to oil contamination. The data used in this study is acquired by Japanese Aerospace Agency's Advanced Land Observing Satellite (ALOS) through Alaska SAR Facility (ASF), at the University of Alaska, Fairbanks.

The material properties of the mitral valve chordae tendineae are important for the understanding of leaflet coaptation configuration and chordal pathology. This research combines basic histology with standard mechanical tests to determine the functioning role of the chordae tendineae during the cardiac cycle. Dual camera stereo photogrammetry was used to measure strains of the chordae in vitro under normal physiologic loading conditions. A uniaxial test simulating the same loading conditions was conducted. Histology and biochemical assays were performed on the chordae to determine chordal microstructure. Six porcine mitral valves were used for the in vitro flow loop study. The maximum strain experienced was 4.29% l 3.43% and was experienced at 249 msec after the start of valve closure. The loading rate was slightly higher than the unloading rate. The anterior lateral strut chordae had a higher maximum strain and loading rate than the posterior medial strut chordae. The posterior medial strut chordae had a higher unloading rate than the anterior lateral strut chordae. Histological examination revealed blood vessels in the chordae. The anterior strut chordae contain significantly more vessels than the other chordae. Different structural levels were observed for all chordae. The inner layer was characterized by a higher concentration of collagen; whereas, the middle layer was collagen with interwoven elastin fibers. The collagen microstructure was characterized by directional crimping. The anterior and posterior marginal chordae contained significantly more DNA than the other chordae (p<0.01). The anterior strut chord was found to contain significantly less DNA than all the other chordae (p<0.01). The collagen assay results showed that the posterior marginal chord contained significantly more collagen than the other chordae (p<0.01). The Fastin Elastin assay results showed no significant difference in the amount of elastin between the chordae. This study demonstrates the first in vitro examination of the strain experienced by the chordae tendineae of the mitral valve. This technique allows the investigation of the behavior of biological tissues under physiologic loading conditions. Contrary to earlier belief, vessels were found in the chordae. The microstructure and biochemical composition of the chordae tendineae is related to their function during coaptation.

This dissertation presents a fully automatic segmentation algorithm for cardiac MR data. Some of the currently published methods are automatic, but they only work well in 2D and sometimes in 3D and do not perform well near the extremities (apex and base) of the heart. Additionally, they require substantial user input to make them feasible for use in a clinical environment. This dissertation introduces novel approaches to improve the accuracy, robustness, and consistency of existing methods. Segmentation accuracy can be improved by knowing as much about the data as possible. Accordingly, we compute a single 4D active surface that performs segmentation in space and time simultaneously. The segmentation routine can now take advantage of information from neighboring pixels that can be adjacent either spatially or temporally. Robustness is improved further by using confidence labels on shape priors. Shape priors are deduced from manual segmentation of training data. This data may contain imperfections that may impede proper manual segmentation. Confidence labels indicate the level of fidelity of the manual segmentation to the actual data. The contribution of regions with low confidence levels can be attenuated or excluded from the final result. The specific advantages of using the 4D segmentation along with shape priors and regions of confidence are highlighted throughout the thesis dissertation. Performance of the new method is measured by comparing the results to traditional 3D segmentation and to manual segmentation performed by a trained clinician.

Nanoparticles possess unique characteristics that make them well suited for molecular imaging. Particles can be synthesized in a systematic fashion with tight control over diameter and surface chemistry. Contrary to existing gadolinium-based MRI contrast agents, nanoparticle MRI contrast agents circulate in the blood for long periods of time, offer higher sensitivity, and exhibit little known toxicity. The qualities of nanoparticles are also well suited to the design of PET probes. Because of their large surface area nanoparticles can be radiolabeled at high specific activity, increasing the sensitivity of detection as well as the payload of therapeutic isotopes. The work presented here focuses on the development and biological application of novel radiolabeled magnetic nanoparticles for multimodal PET/MRI imaging. The nanoparticle probes contained crystalline iron oxide cores capable of producing strong MRI contrast. Cores were coated with either a micelle composed of functionalized PEGylated lipids, or a cross-linked dextran shell modified with heterobifuntional PEG polymers. For PET imaging, magnetic nanoparticles were labeled with the radionuclide 64Cu. Copper‐64 is a cyclotron produced positron emitter used for PET imaging. With a 12.7 hour half-life, 64Cu can be used to image particles in vivo for up to 48 hr and can be used to evaluate ex vivo biodistribution for 72 hours. 64Cu nuclides also undergo β‐ decay, making it a useful isotope for radiotherapy. Nanoparticles were labeled with 64Cu and PET and MRI contrast and evaluated using phantoms. Pharmacokinetic information was measured using in vivo small animal PET/CT and ex vivo biodistribution at multiple time points. Particles were targeted to the angiogenesis marker αvβ3 integrin using a cyclized arginine-glycine-aspartic acid (RGD) peptide with high affinity for αvβ3 and tested in two tumor models. A unilateral tumor model was constructed using the αvβ3-positive U87MG glioblastoma line, and a bilateral model was constructed using the M21 (αvβ3 positive) and M21L (αvβ3 negative) melanoma lines. In vivo PET/CT and MRI showed that targeted nanoparticles produced both PET and MRI contrast in tumors. In conclusion, we report the development of magnetic nanoparticles for dual‐PET/MR imaging. These findings provide insight into the design and development of future multimodality PET/MRI probes.

This dissertation focuses on quantitative subsurface and mechanical properties imaging potential of AFM probes. Extensive modeling of AFM probes are presented for thorough understanding of capabilities and limitations of current techniques, these models are verified by various experiments, and different methods are developed by utilizing force-sensing integrated read-out active tip (FIRAT), which is an active AFM probe with broad bandwidth. For quantitative subsurface imaging, a 3-D FEA model of AFM tip-sample contact is developed and this model can simulate AFM tip scan on nanoscale-sized buried structures. FIRAT probe, which is active and broadband, is utilized for interaction forces imaging during intermittent contact mode and mechanical characterization capability of this probe is investigated. It is shown that probe dynamics, stiffness, stiffness ambiguity, assumed contact mechanics, and noise are important parameters for the accuracy of mechanical properties imaging. An active tip control mechanism is introduced to limit contact forces during intermittent contact mode. In addition to these, a combined ultrasonic AFM and interaction forces imaging method is developed and modeled to solve the reduced elasticity measurement sensitivity on composite materials. This method is capable of imaging a broader range of elasticity on combination samples such as metal nanoparticles in polymers at nanoscale.

Over the years, exemplar-based methods have yielded significant improvements over their model-based counterparts in image synthesis applications. Notably, texture synthesis algorithms using an exemplar-based approach have shown success where traditional stochastic methods failed. As an illustrative example, I will present an exemplar-based approach that yields substantial benefits for user-guided terrain synthesis using Digital Elevation Models (DEMs). This success is realized through exploitation of structural properties of natural terrain. In addition to their proliferation in the image synthesis domain, as annotated image datasets become increasingly available, exemplar-based methods are also gaining in popularity for image analysis applications. This thesis addresses the intersection between exemplar-based analysis and the problem of content-based image retrieval (CBIR). A basic problem in CBIR is the process by which the search criteria are refined by the user through the manipulation of returned exemplars. Exemplar-based analysis is particularly well-suited to query refinement due to its interpretability and the ease with which it can be incorporated into an interactive system. I investigate this connection in the domain of Computer-Assisted Diagnosis (CAD) of dermatological images. I demonstrate that exemplar-based approaches in CBIR can be effective for diagnosing pigmented skin lesions (PSLs). I will present an exemplar-based algorithm for segmenting PSLs in dermatoscopic images. In addition, I will present a generalized representation of dermoscopic features for detection and matching. This representation not only leads to an exemplar-based PSL diagnosis scheme, but it also enables us to realize interactive region-of-interest retrieval, which includes a relevance feedback mechanism to facilitate more flexible query-by-example analysis. Finally, I will assess the benefit of this CBIR-CAD approach through both quantitative evaluations and user studies.