Mounting evidence suggests that the superposition of anatomical clutter in x-ray chest radiography poses a major impediment to the detectability of subtle lung nodules. Through decomposition of projections acquired using different x-ray energy spectra, dual-energy (DE) imaging offers to dramatically improve lung nodule conspicuity. The development of a high-performance DE chest imaging system is reported, with design and implementation guided by fundamental imaging performance metrics. Analytical and experimental studies of imaging performance guided the optimization of key acquisition technique parameters, including x-ray filtration, allocation of dose between low- and high-energy projections, and peak-kilovoltage selection. To minimize anatomical misregistration between images, a cardiac gating system was designed and implemented to direct x-ray exposures to within the quiescent period of the heart cycle. The instrumentation and optimal imaging techniques have been incorporated in a DE imaging prototype system now deployed in a clinical study to evaluate the diagnostic performance of DE imaging.

Molecular imaging using fluorescence spectroscopy-based techniques is generally inefficient due to the low quantum yield of most naturally occurring biomolecules. Current fluorescence imaging techniques tag these biomolecules chemically or through genetic manipulation, increasing the complexity of the system. A technique capable of imaging these biomolecules without modifying the chromophore and/or its environment could provide vital biometric parameters and unique insights into various biological processes at a molecular level. Pump probe spectroscopy has been used extensively to study the molecular properties of poorly fluorescing biomolecules, because it utilizes the known absorption spectrum of these chromophores. Optical Coherence Tomography (OCT) is an optical imaging modality that harnesses the power of low coherence interferometry to measure the 3-D spatially resolved reflectivity of a tissue sample. We plan to develop a new molecular imaging modality that combines these techniques to provide 3-D, highresolution molecular images of various important biomolecules. The system uses a Fourier domain OCT setup with a modified sample arm that combines the "pump" and "probe" beams. The pump beam drives the molecules from the ground state to excited state and the probe interrogates the population change due to the pump and is detected interferometrically. The pump and the probe beam wavelengths are optimized to maximize absorption at the pump wavelength and maximize the penetration depth at the probe wavelength. The pump-probe delay can be varied to measure the rate at which the excited state repopulates the ground state, i.e., the ground state recovery time. The ground state recovery time varies for different chromophores and can potentially be used to identify different biomolecules. The system was designed and optimized to increase the SNR of the PPOCT signals. It was tested by imaging hemoglobin and melanin samples and yielded encouraging results. Potential applications of imaging hemoglobin using this technique include the mapping of tissue microvasculature and measuring blood-oxygen saturation levels. These applications could be used to identify hypoxic areas in tissue. Melanin imaging can provide means of demarcation of melanoma in various organs such as skin, eye and intestines.

New elastographic techniques such as poroelastography and viscoelasticity imaging aim at imaging the temporal mechanical behavior of tissues. These techniques usually involve the use of curve fitting methods as applied to noisy data to estimate new elastographic parameters. As of today, however, image quality performance of these new elastographic imaging techniques is still largely unknown due to a paucity of data and the lack of systematic studies that analyze performance limitations of estimators suitable for these novel applications. Furthermore, current elastographic implementations of poroelasticity and viscoelasticity imaging methods are in general too slow and not optimized for clinical applications. In this paper, we propose a new elastographic time constant (TC) estimator, which is based on the use of the Least Square Error (LSE) curve-fitting method and the Levenberg-Marquardt (LM) optimization rule as applied to noisy elastographic data obtained from a tissue under creep compression. The estimator's performance is analyzed using simulations and quantified in terms of accuracy, precision, sensitivity, signal-to-noise ratio (SNR) and speed. Experiments are performed as a proof of principle of the technical applicability of the new estimator on real experimental data. The results of this study demonstrate that the new elastographic estimator described in this thesis can produce highly accurate, sensitive and precise time constant estimates in real-time and at high SNR. In the future, the use of this estimator could allow real-time imaging of the temporal behavior of complex tissues and provide advances in lymphedema and cancer imaging.

We investigate the possibility of extracting accurate functional information such as local blood oxygenation level using multi-wavelength photoacoustic measurements. Photoacoustic microscope is utilized to acquire images of microvasculature in smallanimal skin. Owing to endogenous optical contrast, optical spectral information obtained from spectral photoacoustic measurements are successfully inverted to yield oxygenation level in blood. Analysis of error propagation from photoacoustic measurements to inverted quantities showed minimum inversion error in the optical wavelength region of 570-600 nm. To obtain accurate and vessel size independent blood oxygenation measurements, transducers with central frequency of more than 25 MHz are needed for the optical region of 570-600 nm used in this study. The effect of transducer focal position on accuracy of blood oxygenation level quantification was found to be negligible. To obtain accurate measurements in vivo, one needs to compensate for factors such as spectral dependent optical attenuation.

Thesis (M.S.)--California Polytechnic State University, 2009. / Title from PDF title page; viewed on January 5, 2010. Major professor: Lily Laiho, Ph.D. "Presented to the faculty of California Polytechnic State University, San Luis Obispo." "In partial fulfillment of the requirements for the degree [of] Master of Science in Engineering." "December 2009." Includes bibliographical references (p. 79-83). Also available on microfiche.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 158-162).

Cancer is a major public health problem worldwide due to its poor prognosis. Detection of cancer in the earliest stages is crucial for the success of therapeutic strategies to truly cure the disease. Molecular imaging provides the potential to diagnose and image cancers at an asymptomatic stage. In molecular imaging, the nanoparticles are designed to target the cancer cells. Molecular imaging is capable of assessing the molecular processes within the tumors by detecting the accumulated or targeted nanoparticles. However, for most molecular imaging systems, the background signal is a common problem, obscuring signals from specific probes and limiting sensitive detection. A hybrid imaging technique, entitled magneto-photo-acoustic (MPA) imaging, was developed as a non-invasive imaging tool to detect nanoparticles, which are used to target pathologies, with high sensitivity and specificity. Based on dual-contrast of both optical absorption and magnetic susceptibility, MPA imaging can significantly improve the molecular contrast specificity as well as investigate the interaction of nanoparticles with cells. Studies were performed using tissue-mimicking phantoms, ex vivo tissue sample and in vivo animal models of cancer. The results indicate that, coupled with dual-contrast agent, the molecular MPA imaging will allow not only mapping the pathologies located in the body, but also sensing the molecular and physiological processes. / text

Molecular photoacoustic imaging is an exciting new field that promises to visualize molecular indicators of disease. The objective of this dissertation is to progress molecular imaging by providing a photoacoustic microscopy platform to better validate in vivo molecular photoacoustic imaging, diagnose disease, and study fundamental photoacoustic processes. Initially, a custom photoacoustic microscope was developed to provide high-sensitivity and high-resolution of both endogenous and exogenous contrast agents in thin cell or tissue samples. After characterization, the photoacoustc microscope was first used to image the hemoglobin distribution in the spleen and liver. The photoacoustic microscope was then used to image nanoparticles in injured and diseased cell and tissues samples. These images can be used for in vivo photoacoustic image validation or, independently, as a diagnostic tool for disease. To enhance the utility of photoacoustic microscopy, a quantitation technique was developed for nanoparticles in cells and tissues. Quantitative photoacoustic imaging has the potential to replace mass spectrometry and histology for a wide array of molecular imaging and targeting studies. Finally, photoacoustic microscopy was used to study the nonlinear dependence of the photoacoustic pressure with laser fluence of nanoparticle-loaded cells. New discoveries about the nonlinear dependence with nanoparticle concentration and cell type are presented. These new discoveries may provide the framework for a new type of photoacoustic imaging with contrast that is cell-type specific. Overall, the work described in this dissertation can be used to improve diagnosis and accelerate clinical translation of new and emerging molecular imaging techniques. / text

The Best PhD Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,2009-2010 / published_or_final_version / Electrical and Electronic Engineering / Doctoral / Doctor of Philosophy