A complete system has been simulated using experimentally obtained input parameters for the detection of special nuclear materials SNM). A variation of the associated particle imaging API) technique, referred to as reverse associated particle imaging detection RAPID), has been developed in the context of detecting 5-kg spherical samples of U-235 in cargo containers uniformly filled with wood low-Z) or iron high-Z) at densities ranging from 0.1 g/cm3 to 0.4 g/cm3, the maximal density for a uniformly fully loaded 40-ft standard cargo container. In addition, samples were located at the center of a given container to study worst-case scenarios. The RAPID technique allows for the interrogation of containers at neutron production rates between 1×108 neutrons/s and 4×108 neutrons/s, depending on cargo material and density. These rates are low enough to prevent transmutation of materials in cargo and radiation safety hazards are limited. The merit of performance for the system is the time to detect the threat material with 95% probability of detection and 10-4 false positive rate per interrogated voxel of cargo. The detection of 5-kg of U-235 was chosen because this quantity of material is near the lower limit of the amount of special nuclear material that might be used in a nuclear weapon. This is in contrast to the 25-kg suggested sensitivity proposed by the International Atomic Energy Agency IAEA).

Thermonuclear fusion holds the potential to be a source of clean abundant energy. Inertial confinement fusion ICF) is one means of achieving significant, controlled fusion burn. In ICF, a small amount of frozen deuterium/tritium fuel is compressed to many times solid density and temperatures greater than 10,000 eV. In these targets, fusion burn initiates in a low density hot spot and then propagates into the cold fuel. The burn wave propagates by way of fusion products being born in the hot spot then slowing down in the fuel and heating it in the process. In this thesis, we study the stopping power models that describe charged particle slowing. In particular, we analyze the assumptions made in theses models and how those assumptions limit the use of these models in ICF ignition conditions. We implement twelve of these models in a stopping power library called “Deeks” that includes both the stopping power calculations and the consistency constraints of the models. We then integrate Deeks into a 1D multi-physics radiation-hydrodynamics code called “Bucky” to perform integrated target implosions with the stopping power calculations of the fusion product transport performed by Deeks. We use a shock ignition target as a test bed to compare the effect of different stopping power models on target performance. As some fraction of target conditions are expected to be outside many models consistency constraints, we use a three tiered model for calculating stopping powers that gradually degrades to simpler models as target conditions get further away from conditions consistent with the stopping power models derivation. We find the conditions of the cold fuel to be substantially inconsistent with the ubiquitous assumption of weak plasma coupling and the application of weakly coupled stopping power models to ICF ignition to be very limited. Finally, facilitate the use of shock ignition targets as a fusion burn test-bed, we have developed a program for automatically tuning a shock ignition laser pulse for a given target.

This dissertation describes a novel Boron Neutron Capture Therapy BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive HER2＋) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2＋ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients images, cellular models, and Monte Carlo MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT for HER2＋ breast cancers for deep seated tumors using MITRII-FCB facility with an 8 cm diameter beam port closest-to-tumor position), with boron concentrations in the tumor higher than 32 mug/g, and for a tumor-to-healthy tissue boron concentration ratio of 8:1. The therapeutic ratios for the proposed treatment would be higher than five for skin and adipose tissue and higher than three for tumor surrounding fibroglandular tissue. The microdosimetry study shows potential improvements in the therapeutic ratios based on the expected sub-cellular boron biodistributions. The engineering simulation study of clinical cases shows the advantages of using BNCT for HER＋ breast cancers. Assuming an assured high efficiency of the boron agent delivery, the proposed concept can be considered for stage IV HER2＋ breast cancers in treating the metastasized tumors in brain, head and neck, and lungs.

Subradiant and superradiant plasmon modes in ring/disk nanocavities and dialers are investigated theoretically and experimentally. The subradiance is obtained through an overall reduction of the total dipole moment of the hybridized mode due to antisymmetric coupling of the dipole moments of the parent plasmons. We observe the appearance of Fano resonances in the optical response of plasmonic nanocavities due to the coherent coupling between their superradiant and subradiant plasmon modes due to structural symmetry breaking. Both subradiant modes and Fano resonances exhibit substantial reductions in linewidth compared to the parent plasmon resonances, opening up possibilities in optical and near IR sensing via plasmon lineshape design. Four reduced-symmetry nanostructures Studied via Plasmon Hybridization and FDTD (Finite Difference Time Domain), a dolmen-style slab arrangement , a ring/disk dimer, a ring/disk cavity and a colloid dimer, clearly exhibit the strong polarization and geometry dependence expected for this behavior at the individual nanostructure level, confirmed by experimental result in each case, multiple Fano resonances occur as structure size is increased.

Radiation therapy is a widely used cancer treatment that has the potential to influence anti-tumor immune responses. Both myeloablative and non-myeloablative radiation are often used as part of preparatory regimens for hematopoetic stem cell transplantation, in combination with other chemotherapy or immuno-modulatory e.g. Anti-thymocyte globulin ATG)) therapies for both cytotoxic and immune modulatory purposes. However, the mechanisms responsible for the effect of radiation on antigen presenting cell APC) responsiveness and radioresistance are poorly understood. The first studies described in this thesis were designed to identify and characterize early radiation-induced signaling changes in antigen presenting cells and to determine the effects of these signaling changes on APC receptor expression and function. The NFkappaB pathway in antigen presenting cells was chosen for study because it is activated by radiation in a wide range of other cell types and plays a vital role in the maintenance and regulation of the immune system. The effects of therapeutically relevant doses radiation 2 and 20 Gy) were compared at various timepoints in the human monocytic cell line U937) using phospho-flow cytometry staining methods and cytometric analysis. These studies demonstrated that radiation-induced changes in the phosphorylation state of NFkappaB family members that were p53 independent. However, these changes were dependent upon activation of ATM in response to single or double-stranded breaks in DNA, as shown in experiments using an inhibitor of ATM and ATM siRNA knockdown U937 cells. In addition, studies examining the effect of radiation on co-stimulatory receptors with and without inhibition of the NFkappaB pathway via phospho-flow cytometry revealed that radiation-induced phosphorylation of NEMO promoted the activation and functional maturation of U937 cells. Furthermore, functional studies using both phospho-flow cytometry and/or mixed lymphocyte reactions to examine co-stimulatory receptor activation, pro-inflammatory cytokine release, and T cell proliferation with and without radiation and inhibition of the NFkappaB pathway, demonstrated that NEMO is necessary for the activation, maturation, and enhanced responsiveness of human subsets of antigen presenting cells that occur after radiation. These findings provided insight into the mechanism of action of radiation-enhanced promotion of the antigen presenting cell responses. The methods of analysis employed can be used for monitoring immune changes that impact immune modulation in transplantation and tumor vaccines studies. Furthermore, NFkappaB pathway proteins have the potential to serve as biomarkers for optimal antitumor responses. The NBD peptide may also have usefulness as a therapeutic agent for inhibition of graft versus host disease GVHD) in patients who have undergone transplantation. While the first set of experiments focused on antigen presenting cell responsiveness, the second set of experiments were designed to enhance our understanding of why antigen presenting cells, specifically monocytes and dendritic cells, are more radioresistant than conventional T cells. Flow cytometric analysis of various surface markers and intracellular signaling markers were used to examine the mechanisms behind the radioresistance of antigen presenting cells. The experiments described here showed a hierarchy of radiosensitivity among T cells, with naive CD8 T cells being the most radiosensitive and CD4 memory T cells being the most radioresistant. Antigen presenting cells were found to be significantly more radioresistant than T cell subsets &lt；10 fold decrease after radiation), and among APC, monocytes were more radiosensitive than either total or conventional dendritic cells. Furthermore APC expressed lower levels of Bax after radiation than T cells, and APC subsets that expressed high levels were also more sensitive to radiation induced cell death. These results demonstrate that T cell and APC subsets are dying by apoptosis after radiation, and that the differential level of Bax expression is an important determinant of the relative radiosensitivity of these immune cell subsets. Again, these findings are clinically relevant to transplant patients and patients with tumors receiving radiation therapy since APC survival may have importance for the generation of anti-tumor immunity and post-transplantation immune sequelae such as GVHD. In addition, elucidation of the mechanism of death of APC and T cell subsets, as described in chapter 3, provides potential markers of cell death that can be correlated to good graft versus tumor GVT) effects versus bad tumor recurrence and persistence) GVT effects. Thus, understanding the mechanistic basis for radiation-induced changes in APC and the effect of these changes on survival and function is essential for optimizing the use of radiation in transplantation and tumor vaccine treatment protocols.

Although breast conserving therapy has some advantages over the traditional mastectomy procedure, the biggest disadvantage is the chance of local re-occurrence in which a second surgery is often required. Adequate surgical removal of breast tumors requires accurate tumor localization in order to ensure a balance between optimal cosmetic results and minimization of the risk for local re-occurrence. These challenges have motivated the search for alternative, more accurate methods for intraoperative localization of non-palpable breast lesions. The overall goal of this project was to develop an innovative technique for radioguided localization of non-palpable breast lesions that is more accurate, easier for the breast surgeon, and more comfortable for the patient than the current practice of wire localization. The technique uses a dual modality breast imaging system to place a marker composed of radiolabeled albumin 99mTc-MAA or 111ln-MAA) into the lesion. Preliminary studies were made to evaluate the localization accuracy of the system, which showed that the dual modality breast scanner is capable of accurate 3-dimensional localization using either X-ray or gamma ray imaging. A 3-axis needle positioning system was built and integrated into the dual modality breast scanner and its accuracy tested. A pilot clinical trial to evaluate the dual-modality surgical guidance technique was designed and preliminary clinical data collected. Detailed results were presented on the first three subjects； although a total of seven subjects have been recruited to the study to date. So far, it has been demonstrated that the radioguided surgery technique can be performed with approximately 10 times less radiomarker activity than is currently being used by other researchers employing 99mTc-MAA as a radiomarker, while maintaining comparable localization accuracy. Although the DMSG technique has not been tested in a large cohort of subjects, the preliminary data on the first few are encouraging. Feedback on the technique from the surgeons, for this limited population, has been positive. Recruitment to the study is ongoing.

Hyperpolarized 129Xe HXe) is a non-invasive contrast agent for lung magnetic resonance imaging MRI), which upon inhalation follows the functional pathway of oxygen in the lung by dissolving into lung tissue structures and entering the blood stream. HXe MRI therefore provides unique opportunities for functional lung imaging of gas exchange which occurs from alveolar air spaces across the air-blood boundary into parenchymal tissue. However challenges in acquisition speed and signal-to-noise ratio have limited the development of a HXe imaging biomarker to diagnose lung disease. This thesis addresses these challenges by introducing parallel imaging to HXe MRI. Parallel imaging requires dedicated hardware. This work describes design, implementation, and characterization of a 32-channel phased-array chest receive coil with an integrated asymmetric birdcage transmit coil tuned to the HXe resonance on a 3 Tesla MRI system. Using the newly developed human chest coil, a functional HXe imaging method, multiple exchange time xenon magnetization transfer contrast MXTC) is implemented. MXTC dynamically encodes HXe gas exchange into the image contrast. This permits two parameters to be derived regionally which are related to gas-exchange functionality by characterizing tissue-to-alveolar-volume ratio and alveolar wall thickness in the lung parenchyma. Initial results in healthy subjects demonstrate the sensitivity of MXTC by quantifying the subtle changes in lung microstructure in response to orientation and lung inflation. Our results in subjects with lung disease show that the MXTC-derived functional tissue density parameter exhibits excellent agreement with established imaging techniques. The newly developed dynamic parameter, which characterizes the alveolar wall, was elevated in subjects with lung disease, most likely indicating parenchymal inflammation. In light of these observations we believe that MXTC has potential as a biomarker for the regional quantification of 1) emphysematous tissue destruction in chronic obstructive pulmonary disease using the tissue density parameter) and 2) parenchymal inflammation or thickening using the wall thickness parameter). By simultaneously quantifying two lung function parameters, MXTC provides a more comprehensive picture of lung microstructure than existing lung imaging techniques and could become an important non-invasive and quantitative tool to characterize pulmonary disease.

The existence of Dark Matter was first proposed by Fritz Zwicky in 1933, based on the observed velocity distribution of galaxies in the Coma Cluster. Subsequent studies of visible mass and velocity distributions in other galaxies have confirmed Zwicky’s original observation； there is now little doubt that Dark Matter exists. However, due to the fact that Dark Matter interacts very weakly through non-gravitational forces, nothing is known about the nature of Dark Matter. It is believed that Dark Matter particles are streaming toward the Earth, in the Earth’s rest frame, from the direction of the constellation Cygnus. Observation of this so-called Dark Matter ‘wind’ with a direction-sensitive dark matter particle detector would be compelling evidence that Dark Matter does consist of a gas of discrete particles as a new form of matter. The DMTPC collaboration is developing such a detector, and this thesis describes R&D work in support of that project. The DMTPC technique for looking for Dark Matter relies on Dark Matter particles interacting with atomic nuclei, causing the nuclei to recoil and to leave optical signals that can be detected. Since neutrons are electrically neutral and collide with nuclei, they can mimic Dark Matter signals. Therefore, the reduction of neutron background is critical to the successful detection and identification of Dark Matter particles. One important aspect of this thesis is to fully understand and quantify neutron interactions with our detector. In addition to providing information for understanding Dark Matter experiments, this work also allows us to understand how our device can be used as a neutron detector. We have been able to measure a number of neutron events in a variety of experimental runs both with and without neutron sources such as a neutron generator and 252Cf. From these runs, we have obtained data for both elastic and inelastic interactions of neutrons of various energy ranges with detector gas nuclei. In this thesis, I will also discuss our current background data taking for the Dark Matter research and our plan for scaling up the detector to 100 m3 for a competitive Dark Matter search.