A dual modality, DCE-MRI and x-ray, physical phantom for quantitative evaluation of breast imaging protocols

The current clinical standard for breast cancer screening is mammography. However, this technique has a low sensitivity which results in missed cancers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising technique for breast cancer diagnosis and has been reported as being superior to mammography for screening of high-risk women and evaluation of extent of disease. At the same time, low and variable specificity has been documented in the literature as well as a rising number of mastectomies possibly due to the increasing use of DCE-MRI. In this study, we developed and characterized a dual-modality, x-ray and DCE-MRI, anthropomorphic breast phantom for the quantitative assessment of breast imaging protocols. X-ray properties of the phantom were quantitatively compared with patient data, including attenuation coefficients, which matched human values to within the measurement error, and tissue structure using spatial covariance matrices of image data, which were found to be similar in size to patient data. Simulations of the phantom scatter-to-primary ratio (SPR) were produced and experimentally validated then compared with published SPR predictions for homogeneous phantoms. SPR values were as high as 85% in some areas and were heavily influenced by the heterogeneous tissue structure. MRI properties of the phantom, T1 and T2 relaxation values and tissue structure, were also quantitatively compared with patient data and found to match within two error bars. Finally, a dynamic lesion that mimics lesion border shape and washout curve shape was included in the phantom. High spatial and temporal resolution x-ray measurements of the washout curve shape were performed to determine the true contrast agent concentration as a function of time. DCE-MRI phantom measurements using a clinical imaging protocol were compared against the x-ray truth measurements. MRI signal intensity curves were shown to be less specific to lesion type than the x-ray derived contrast agent concentration curves. This phantom allows, for the first time, for quantitative evaluation of and direct comparisons between x-ray and MRI breast imaging modalities in the context of lesion detection and characterization

Quality control in digital breast tomosynthesis: compliance of two phantoms with the EUREF protocol

Ever since the integration of Digital Breast Tomosynthesis (DBT) into breast cancer screening programmes, it has been a European endeavour to draw up standard guidelines for the assessment of the imaging performance of DBT systems. The quantitative evaluation of the quality of reconstructed tomosynthesis images is still an active area of research. In fact, the current version of the EUREF DBT QC protocol represents a preliminary set of guidelines to be used at acceptance, and to establish baseline values for constancy testing. New phantoms for QC in DBT have also been developed. Together, Sun Nuclear's Mammo 3D Performance Kits and CIRS DBT QC Phantom, model 021, have been shown to provide adequate test objects and background material for the assessment of the Automatic Exposure Control system performance, image receptor response function and noise analysis, system sharpness measured in projection images, and in-plane and out-of-plane spatial resolution in the reconstructed tomosynthesis image. From the comparison with the available literature, the use of the two phantoms with the Hologic Selenia Dimensions and Fujifilm AMULET Innovality systems has been validated

Advancing the Clinical Potential of Carbon Nanotube-enabled stationary 3D Mammography

Scope and purpose. 3D imaging has revolutionized medicine. Digital breast tomosynthesis (DBT), also recognized as 3D mammography, is a relatively recent example. stationary DBT (sDBT) is an experimental technology in which the single moving x-ray source of conventional DBT has been replaced by a fixed array of carbon nanotube (CNT)-enabled sources. Given the potential for a higher spatial and temporal resolution compared to commercially-available, moving-source DBT devices, it was hypothesized that sDBT would provide a valuable tool for breast imaging. As such, the purpose of this work was to explore the clinical potential of sDBT. To accomplish this purpose, three broad Aims were set forth: (1) study the challenges of scatter and artifact with sDBT, (2) assess the performance of sDBT relative to standard mammographic screening approaches, and (3) develop a synthetic mammography capability for sDBT. Throughout the work, developing image processing approaches to maximize the diagnostic value of the information presented to readers remained a specific goal. Data sources and methodology. Sitting at the intersection of development and clinical application, this work involved both basic experimentation and human study. Quantitative measures of image quality as well as reader preference and accuracy were used to assess the performance of sDBT. These studies imaged breast-mimicking phantoms, lumpectomy specimens, and human subjects on IRB-approved study protocols, often using standard 2D and conventional 3D mammography for reference. Key findings. Characterizing scatter and artifact allowed the development of new processing approaches to improve image quality. Additionally, comparing the performance of sDBT to standard breast imaging technologies helped identify opportunities for improvement through processing. This line of research culminated in the incorporation of a synthetic mammography capability into sDBT, yielding images that have the potential to improve the diagnostic value of sDBT. Implications. This work advanced the evolution of CNT-enabled sDBT toward a viable clinical tool by incorporating key image processing functionality and characterizing the performance of sDBT relative to standard breast imaging techniques. The findings confirmed the clinical utility of sDBT while also suggesting promising paths for future research and development with this unique approach to breast imaging.Doctor of Philosoph

Exploring Novel Contrast Agents with Anthropomorphic Mesh Models in MCNP

Breast cancer is the leading cancer in women with an estimated 13% of women in the United States developing a form of invasive breast cancer in her lifetime. The survival rate is estimated to be 85%, but the American Cancer Society estimates that early detection of breast cancer in the localized stage increases the breast cancer survival rate to 99%. However, early detection is dependent on the sensitivity of breast imaging techniques and currently, the sensitivity is suboptimal for women with dense breasts and obscure cancers. Recently, studies have indicated that exploring new contrast agents can provide access to improved sensitivity because of their potential to increase the effective Z of the target tissue. Furthermore, contrast-enhanced tomosynthesis is a viable imaging method that can provide a 3D view of the breast while providing tumor enhancement for improved visibility. This project aims to facilitate the search for practical contrast agents that can improve sensitivity during breast imaging. More specifically, the objective of this project is to find novel ways to improve the differentiation between tumor and glandular tissue by creating a realistic anthropomorphic model that not only considers the geometry of the breast but its physiological components as well. This project aims to combine tomosynthesis breast imaging methods with novel contrast agents to explore their efficacy and limitations. To achieve the goals of this project, several techniques are employed. A realistic tomosynthesis environment is created by constructing a detailed Hologic tomosynthesis breast imaging machine, including the source, flat-panel detector, and support equipment, using MCNP. Realistic breast phantoms that consider geometric and biophysical accuracy are created by incorporating a time dependency into the model. Once the contrast agents are incorporated, their efficacy is calculated by quantifying tumor visibility as a function of breast size, density, tumor location, tumor stage, and tumor type. After running simulations, this project will generate clear and accurate radiographs demonstrating the structural components of the breast and the effects of contrast enhancement on any embedded tumors. The results will provide an indication of the contrast agents that provide promise. The data acquired in this project will provide insight on the process of creating an anthropomorphic breast phantom for tomosynthesis studies, as well as insight on setbacks that are identified with the methods used. Contrast-enhanced tomosynthesis is clinically possible and is a promising technique for improving sensitivity. This project explores this technique and provides insight on possible ways to improve breast imaging sensitivity

STATIONARY DIGITAL TOMOSYNTHESIS: IMPLEMENTATION, CHARACTERIZATION, AND IMAGE PROCESSING TECHNIQUES

The use of carbon nanotube cathodes for x-ray generation was pioneered and perfected by our team in the Applied Nanotechnology Laboratory at the University of North Carolina at Chapel Hill. Over the past decade, carbon nanotube (CNT) field emission x-ray source technology has matured and translated into multiple pre-clinical and clinical devices. One of the most prominent implementations of CNT x-ray technology is a limited angle tomography method called tomosynthesis, which is rapidly emerging in clinical radiography. The purpose of this project is two-fold, to develop and characterize to the latest iteration, stationary intraoral tomosynthesis, and develop a low-dose, effective scatter reduction technique for breast and chest tomosynthesis. The first portion of this project was to develop and evaluate a new quasi-3D imaging modality for dental imaging. My work consists of experiments which dictated the design parameters and subsequent system evaluation of the dedicated s-IOT clinical prototype system currently installed in the UNC Department of Oral and Maxillofacial Radiology clinic in the School of Dentistry. Experiments were performed in our lab to determine optimal source array geometry and system configuration. The system was fabricated by our commercial partner then housed in our research lab where I performed initial characterization and assisted with software development. After installation in the SOD, I performed additional system characterization, including source output validation, dosimetry, and quantification of resolution. The system components and software were refined through a rapid feedback loop with the engineers involved. Four pre-clinical imaging studies have been performed in collaboration with several dentists using phantoms, extracted teeth, and cadaveric dentition. I have generated an operating manual and trained four dental radiologists in the use of the s-IOT device. The system has now been vetted and is ready for patient use. The second portion of this project consists of hardware development and implementation of an image processing technique for scatter correction. The primary sampling scatter correction (PSSC) is a beam pass technique to measure the primary transmission through the patient and calculate the scatter profile for subtraction. Though developed for breast and chest tomosynthesis, utilization in mammography and chest radiography are also demonstrated in this project. This dissertation is composed of five chapters. Chapters one and two provide the basics of x-ray generation and a brief history of the evolution of carbon nanotube x-ray source technology in our lab at UNC. Chapter three focuses on stationary intraoral tomosynthesis. The first section provides background information on dental radiology and project motivation. Sections 3.2 and 3.3 detail my work in benchtop feasibility and optimization studies, as well as characterization and evaluation of the clinical prototype. Chapter four introduces scatter in imaging, providing motivation for my work on primary sampling scatter correction (PSSC) image processing method, detailed in chapter five.Doctor of Philosoph

Selection and Evaluation of a Silver Nanoparticle Imaging Agent for Dual-Energy Mammography

Over the past decade, contrast-enhanced (CE) dual-energy (DE) x-ray breast imaging has emerged as an exciting, new modality to provide high quality anatomic and functional information of the breast. The combination of these data in a single imaging procedure represents a powerful tool for the detection and diagnosis of breast cancer. The most widely used implementation of CEDE imaging is k-edge imaging, whereby two x-ray spectra are placed on either side of the k-edge of the contrast material. Currently, CEDE imaging is performed with iodinated contrast agents. The lower energies used in clinical DE breast imaging systems compared to imaging systems for other organs suggest that an alternative material may be better suited. We developed an analytical model to compare the contrast of various elements in the periodic table. The model predicts that materials with atomic numbers from 42 to 52 should provide the best contrast in DE breast imaging while still providing high-quality anatomical images. Upon consideration, silver was chosen for more detailed study. Through simulation and experimental validation, we determined that not only does silver perform better than iodine when imaged at their respective optimal conditions, but silver is able to provide higher levels of contrast than iodine when imaged with current protocols that are optimal for iodine. Therefore, a silver agent could be translated to the clinic without modification of existing imaging systems or techniques. A prototype silver agent was designed. The agent consists of (i) a silver core for DE contrast, (ii) a silica shell to prevent the release of toxic silver cations, and (iii) a polyethylene glycol layer to improve the biocompatibility of the entire nanostructure. DE imaging with the particles showed a 9-fold increase in contrast when injected into mice, while displaying no acutely toxic effects. The prototype silica-silver nanoparticles represent a first step in developing a biologically stable contrast agent that is specifically suited for DE breast imaging

DEVELOPMENT AND CHARACTERIZATION OF A HIGH-ENERGY IN-LINE PHASE CONTRAST TOMOSYNTHESIS PROTOTYPE

Phase sensitive 3D imaging techniques have been an emerging field in x-ray imaging for two decades. Among them, in-line phase contrast tomosynthesis has been investigated with great potential for translation into clinical applications in the near future, due to combining the advantages of configuration simplicity, structural noise elimination and potentially low radiation dose delivery. The high-energy in-line phase contrast tomosynthesis technique developed and presented in this dissertation initiates this translational procedure by optimizing the imaging conditions, performing phase retrieval, offering opportunities to further reduce radiation dose delivery, improving detectability and specificity with the employment of auxiliary phase contrast agents, and potentially performing quantitative imaging. First, the high-energy in-line phase contrast tomosynthesis prototype was developed and characterized in this dissertation as the first of its kind following a number of engineering trade-off considerations. The quantitative results as well as the imaging results of tissue-simulating phantoms and biology-related phantoms demonstrate the extensive capability of this imaging prototype in improving tumor detectability. In addition, the optimization of the x-ray prime beam toward the PAD phase retrieval method proved the potential of high-energy imaging and predicated the solution toward imaging time reduction by employing photon counting based imaging techniques. In the past several years, applications of microbubbles as a phase contrast agent have shown the capability for image quality improvement in quantitative imaging. In this dissertation, a preliminary study of quantitative imaging of microbubbles using the in-line phase contrast projection mode imaging prototype, which is a system without tomosynthesis capability, provided a discussion on how the materials of the bubble shells and gas infills could impact the imaging capabilities and resulting image detectability. In addition, the results of the study provided a guideline for microbubble selections for in-line phase contrast mode imaging modalities. Based on this criterion discussed in the study, the albumin-shell microbubbles were selected as the phase contrast agent for the imaging prototype presented in this dissertation. The imaging results showed the feasibility of performing quantitative imaging by employing microbubbles as the auxiliary phase contrast agent. Clinical conditions were simulated by distributing microbubbles on the interface between two tissue-like phantom structures. The quantitative imaging results provided clinical motivation for translating phantom studies into more biology-related investigations providing radiation dose reductions in the future