Quantitative imaging of gold nanoparticle distribution for preclinical studies of gold nanoparticle-aided radiation therapy

Gold nanoparticles (GNPs) have recently attracted considerable interest for use in radiation therapy due to their unique physical and biological properties. Of interest, GNPs (and other high-atomic-number materials) have been used to enhance radiation dose in tumors by taking advantage of increased photoelectric absorption. This physical phenomenon is well-understood on a macroscopic scale. However, biological outcomes often depend on the intratumoral and even intracellular distribution of GNPs, among other factors. Therefore, there exists a need to precisely visualize and accurately quantify GNP distributions. By virtue of the photoelectric effect, x-ray fluorescence (XRF) photons (characteristic x-rays) from gold can be induced and detected, not only allowing the distribution of GNPs within biological samples to be determined but also providing a unique molecular imaging option in conjunction with bioconjugated GNPs. This work proposes the use of this imaging modality, known as XRF imaging, to develop experimental imaging techniques for detecting and quantifying sparse distributions of GNPs in preclinical settings, such as within small-animal-sized objects, tissue samples, and superficial tumors. By imaging realistic GNP distributions, computational methods can then be used to understand radiation dose enhancement on an intratumoral scale and perhaps even down to the nanoscopic, subcellular realm, elucidating observed biological outcomes (e.g., radiosensitization of tumors) from the bottom-up. Ultimately, this work will result in experimental and computational tools for developing a better understanding of GNP-mediated dose enhancement and associated radiosensitization within the scope of GNP-aided radiation therapy.Ph.D

X-RAY SPECTRAL ANALYSIS IN X-RAY FLUORESCENCE IMAGING FOR BREAST CANCER DETECTION

The knowledge of X-ray spectrum plays a major role in exploiting and optimizing the X-ray utilizations, especially in biomedical application fields. Over the past decades, extensive research efforts have been made in better characterizing the X-ray spectral features in experimental and simulation studies. The objectives of this dissertation are to investigate the applications of X-ray spectral measurement and analysis in X-ray fluorescence (XRF) and micro-computed tomography (micro-CT) imaging modalities, to facilitate the development of new imaging modalities or to optimize the imaging performance of currently available imaging systems. The structure and primary discoveries of this dissertation are as follows: after a brief introduction of the objectives of this dissertation in Chapter 1, Chapter 2 gives a comprehensive background including electromagnetic properties, various applications, and different generation mechanisms of X-rays and their interactions with matter, X-ray spectral measurement and analysis methods, XRF principles and applications for cancer detection, and micro-CT system. Considering relatively high fluorescence production probability and sufficient penetrability of gold Kα fluorescence signals, Chapter 3 establishes a theoretical model of a gold nanoparticle (GNP) K-shell XRF imaging prototype consisting of a pencil-beam X-ray for excitation and a single collimated spectrometer for XRF detection. Then, the optimal energy windows of 66.99±0.56keV and 68.80±0.56keV for two gold Kα fluorescence peaks are determined in Chapter 4. Also, the linear interpolation method for background estimation under the Kα fluorescence peaks is suggested in this chapter. Chapters 5 and 6 propose a novel XRF based imaging modality, X-ray fluorescence mapping (XFM) for the purpose of breast cancer detection, especially emphasizing on the detection of breast tumor located posteriorly, close to the chest wall musculature. The mapping results in these two chapters match well with the known spatial distributions and different GNP concentrations in 2D/3D reconstructions. Chapter 7 presents a method for determining the modulation transfer function (MTF) in XRF imaging modality, evaluating and improving the imaging performance of XFM. Moreover, this dissertation also investigates the importance of X-ray spectral measurement and analysis in a rotating gantry based micro-CT system. A practical alignment method for X-ray spectral measurement is first proposed using 3D printing technology in Chapter 8. With the measured results and corresponding spectral analysis, Chapter 9 further evaluates the impact of spectral filtrations on image quality indicators such as CT number uniformity, noise, and contrast to noise ratio (CNR) in the micro-CT system using a mouse phantom comprising 11 rods for modeling lung, muscle, adipose, and bones (various densities). With a baseline of identical entrance exposure to the imaged mouse phantom, the CNRs are degraded with improved beam quality for bone with high density and soft tissue, while are enhanced for bone with low density, lung, and muscle. Finally, Chapter 10 summarizes the whole dissertation and prospects the future research directions

Molecular Imaging

The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world