A New Stationary Digital Breast Tomosynthesis System: Implementation and Characterization

Digital breast tomosynthesis systems (DBT) use a single thermionic x-ray source that moves around the breast in a fixed angular span. As a result, all current DBT system requires the mechanical motion of the x-ray source during the scan, limiting image quality either due to the focal spot blurring or a long scan time. This causes an unfavorable reduction in the in-plane resolution compared to 2D mammography. Our research group developed and demonstrated a first generation stationary digital breast tomosynthesis (s-DBT) system that uses a linear carbon nanotube (CNT) x-ray source array. Since the stationary sources are not subject to focal spot blurring, and images can be acquired rapidly, the in-plane system resolution is improved. Additionally, image acquisition time is independent of angular span since there is no motion, allowing for large angular spans, and increased depth resolution. The improved resolution of the first generation s-DBT system over continuous motion (CM) DBT has been demonstrated with image evaluation phantoms and a human specimen study. The first generation s-DBT is currently undergoing clinical trials at the University of North Carolina Cancer Hospital. Limitations associated with the first generation system, such as limited tube flux, and limited x-ray energy, placed limitations on our clinical trials and future clinical implementation. Also, the limited angular span could be improved for increased depth resolution, as there is no cost on patient imaging time. The goal of this thesis work was to design construct and characterize a second generation s-DBT system, capable of faster image acquisition times, and higher depth resolution than our first generation system. The second generation s-DBT system was built using a newly designed distributed CNT x-ray source array. The system was then characterized and compared to the first generation system and two commercially available DBT systems. Using physical measurements that are used in medical imaging, the system showed significant improvement in resolution over the first generation system and both commercially available systems, coupled with equal or faster image acquisition times. A separate study investigating the feasibility of contrast enhanced (CE) imaging was conducted, where the system showed capability in both temporal subtraction (TS) and dual energy (DE) imaging.Doctor of Philosoph

Optimization of a High-Energy X-Ray Inline Phase Sensitive Imaging System for Diagnosis of Breast Cancer

Breast cancer screening modalities have received constant research attention that are mainly focused on their abilities to detect cancer at an early stage while reducing the risks of harmful radiation dose delivered to the patient. As a result, numerous advancements have been made over the last two decades which include the introduction of digital mammography (DM) and digital breast tomosynthesis (DBT). Numerous clinical trials have demonstrated the decrease in mortality rates by employing these modalities. Significant research attention remains focused on investigating methods for further improving the detection capabilities and reducing the radiation dose. The conventional x-ray imaging technique relies on the attenuation characteristics of a tissue to produce imaging contrast. However, the similar attenuation characteristics of normal and malignant breast tissue present a challenge in differentiating between them using conventional x-ray imaging. The current technique for providing higher image quality involves the introduction of anti-scatter grids and operating the x-ray tubes at much lower x-ray energies as compared to the other radiography fields, both of which results in an increased radiation dose. The current method for providing higher image quality involves utilizing anti-scatter grids and operating at much lower x-ray energies than other radiography fields, both of which result in an increased radiation dose. Phase sensitive imaging is an emerging technique, which relies not only on attenuation coefficients but also the effects produced by x-ray phase shift coefficients. Within the diagnostic energy range, it has been estimated that the phase shift coefficients of a breast tissue are at least 2-3 orders of magnitude larger than their attenuation coefficients. Thus, this technique holds the potential to increase the x-ray energy and remove the grid without compromising the image quality, which could potentially reduce the patient dose. The inline phase sensitive approach involves the simplest implementation—provided that the imaging system is spatially coherent — as it does not involve the introduction of any optical element between the object and detector. Preclinical studies with the inline phase sensitive imaging technique at the same energy as conventional imaging have indicated the ability to reduce the radiation dose without negatively impacting the diagnostic capabilities. However, there are some existing challenges that have prevented this technique in its clinical implementation. Responding to the challenges, an inline phase sensitive imaging prototype has been developed in the advanced biomedical imaging laboratory. The goal of the research presented in this dissertation comprises a thorough investigation in optimizing a high energy phase sensitive imaging prototype efficiently in terms of its geometric and operating parameters. Once optimized, the imaging performance of this phase sensitive x-ray imaging prototype is going to be compared with the commercial digital mammography and digital breast tomosynthesis (DBT) imaging systems using modular breast phantoms at similar and reduced mean glandular dose (Dg) dose levels. This dissertation includes numerous original contributions, perhaps the most significant of which were the demonstration of the ability of inline phase sensitive imaging prototype to deliver higher image quality required for tumor detection and diagnosis at higher x-ray energies in comparison with low energy commercial imaging systems at similar or less radiation dose levels. These results clearly demonstrate the ability of the high energy inline phase sensitive imaging system to maintain the image quality improvement that is necessary for diagnosis at high x-ray energies without an increase in the radiation dose

An attempt to estimate out-of-plane lung nodule elongation in tomosynthesis images

In chest tomosynthesis (TS) the most commonly used reconstruction methods are based on Filtered Back Projection (FBP) algorithms. Due to the limited angular range of x-ray projections, FBP reconstructed data is typically associated with a low spatial resolution in the out-of-plane dimension. Lung nodule measures that depend on depth information such as 3D shape and volume are therefore difficult to estimate. In this paper the relation between features from FBP reconstructed lung nodules and the true out-of-plane nodule elongation is investigated and a method for estimating the out-of-plane nodule elongation is proposed. In order to study these relations a number of steps that include simulation of spheroidal-shaped nodules, insertion into synthetic data volumes, construction of TS-projections and FBP-reconstruction were performed. In addition, the same procedure was used to simulate nodules and insert them into clinical chest TS projection data. The reconstructed nodule data was then investigated with respect to in-plane diameter, out-of-plane elongation, and attenuation coefficient. It was found that the voxel value in each nodule increased linearly with nodule elongation, for nodules with a constant attenuation coefficient. Similarly, the voxel value increased linearly with in-plane diameter. These observations indicate the possibility to predict the nodule elongation from the reconstructed voxel intensity values. Such a method would represent a quantitative approach to chest tomosynthesis that may be useful in future work on volume and growth rate estimation of lung nodules

Advancing combined radiological and optical scanning for breast-conserving surgery margin guidance

Breast cancer is one of the most common types of cancer worldwide, and standard-of-care for early-stage disease typically involves a lumpectomy or breast-conserving surgery (BCS). BCS involves the local resection of cancerous tissue, while sparring as much healthy tissue as possible. State-of-the-art methods for intraoperatively evaluating BCS margins are limited. Approximately 20% of BCS cases result in a tissue resection with cancer at or near the resection surface (i.e., a positive margin). A two-fold increase in ipsilateral breast cancer recurrence is associated with the presence of one or more positive margins. Consequently, positive margins often necessitate costly re-excision procedures to achieve a curative outcome. X-ray micro-computed tomography (CT) is emerging as a powerful ex vivo specimen imaging technology, as it provides robust three-dimensional sensing of tumor morphology rapidly. However, X-ray attenuation lacks contrast between soft tissues that are important for surgical decision making during BCS. Optical structured light imaging, including spatial frequency domain imaging and active line scan imaging, can act as adjuvant tools to complement micro-CT, providing wide field-of-view, non-contact sensing of relevant breast tissue subtypes on resection margins that cannot be differentiated by micro-CT alone. This thesis is dedicated to multimodal imaging of BCS tissues to ultimately improve intraoperative BCS margin assessment, reducing the number of positive margins after initial surgeries and thereby reducing the need for costly follow-up procedures. Volumetric sensing of micro-CT is combined with surface-weighted, sub-diffuse optical reflectance derived from high spatial frequency structured light imaging. Sub-diffuse reflectance plays the key role of providing enhanced contrast to a suite of normal, abnormal benign, and malignant breast tissue subtypes. This finding is corroborated through clinical studies imaging BCS specimen slices post-operatively and is further investigated through an observational clinical trial focused on combined, intraoperative micro-CT and optical imaging of whole, freshly resected BCS tumors. The central thesis of this work is that combining volumetric X-ray imaging and sub-diffuse optical scanning provides a synergistic multimodal imaging solution to margin assessment, one that can be readily implemented or retrofitted in X-ray specimen imaging systems and that could meaningfully improve surgical guidance during initial BCS procedures

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

Modeling the Anisotropic Resolution and Noise Properties of Digital Breast Tomosynthesis

Digital breast tomosynthesis (DBT) is a 3D imaging modality in which a reconstruction of the breast is generated from various x-ray projections. Due to the newness of this technology, the development of an analytical model of image quality has been on-going. In this thesis, a more complete model is developed by addressing the limitations found in the previous linear systems (LS) model [Zhao, Med. Phys. 2008, 35(12): 5219-32]. A central assumption of the LS model is that the angle of x-ray incidence is approximately normal to the detector in each projection. To model the effect of oblique x-ray incidence, this thesis generalizes Swank\u27s calculations of the transfer functions of x-ray fluorescent screens to arbitrary incident angles. In the LS model, it is also assumed that the pixelation in the reconstruction grid is the same as the detector; hence, the highest frequency that can be resolved is the detector alias frequency. This thesis considers reconstruction grids with smaller pixelation to investigate super-resolution, or visibility of higher frequencies. A sine plate is introduced as a conceptual test object to analyze super-resolution. By orienting the long axis of the sine plate at various angles, the feasibility of oblique reconstruction planes is also investigated. This formulation differs from the LS model in which reconstruction planes are parallel to the breast support. It is shown that the transfer functions for arbitrary angles of x-ray incidence can be modeled in closed form. The high frequency modulation transfer function (MTF) and detective quantum efficiency (DQE) are degraded due to oblique x-ray incidence. In addition, using the sine plate, it is demonstrated that a reconstruction can resolve frequencies exceeding the detector alias frequency. Experimental images of bar patterns verified the existence of super-resolution. Anecdotal clinical examples showed that super-resolution improves the visibility of microcalcifications. The feasibility of oblique reconstructions was established theoretically with the sine plate and was validated experimentally with bar patterns. This thesis develops a more complete model of image quality in DBT by addressing the limitations of the LS model. In future studies, this model can be used as a tool for optimizing DBT

System Characterizations and Optimized Reconstruction Methods for Novel X-ray Imaging

In the past decade there have been many new emerging X-ray based imaging technologies developed for different diagnostic purposes or imaging tasks. However, there exist one or more specific problems that prevent them from being effectively or efficiently employed. In this dissertation, four different novel X-ray based imaging technologies are discussed, including propagation-based phase-contrast (PB-XPC) tomosynthesis, differential X-ray phase-contrast tomography (D-XPCT), projection-based dual-energy computed radiography (DECR), and tetrahedron beam computed tomography (TBCT). System characteristics are analyzed or optimized reconstruction methods are proposed for these imaging modalities. In the first part, we investigated the unique properties of propagation-based phase-contrast imaging technique when combined with the X-ray tomosynthesis. Fourier slice theorem implies that the high frequency components collected in the tomosynthesis data can be more reliably reconstructed. It is observed that the fringes or boundary enhancement introduced by the phase-contrast effects can serve as an accurate indicator of the true depth position in the tomosynthesis in-plane image. In the second part, we derived a sub-space framework to reconstruct images from few-view D-XPCT data set. By introducing a proper mask, the high frequency contents of the image can be theoretically preserved in a certain region of interest. A two-step reconstruction strategy is developed to mitigate the risk of subtle structures being oversmoothed when the commonly used total-variation regularization is employed in the conventional iterative framework. In the thirt part, we proposed a practical method to improve the quantitative accuracy of the projection-based dual-energy material decomposition. It is demonstrated that applying a total-projection-length constraint along with the dual-energy measurements can achieve a stabilized numerical solution of the decomposition problem, thus overcoming the disadvantages of the conventional approach that was extremely sensitive to noise corruption. In the final part, we described the modified filtered backprojection and iterative image reconstruction algorithms specifically developed for TBCT. Special parallelization strategies are designed to facilitate the use of GPU computing, showing demonstrated capability of producing high quality reconstructed volumetric images with a super fast computational speed. For all the investigations mentioned above, both simulation and experimental studies have been conducted to demonstrate the feasibility and effectiveness of the proposed methodologies

X-ray Phase-Contrast Tomography: Underlying Physics and Developments for Breast Imaging

X-ray phase-contrast tomography is a powerful tool to dramatically increase the visibility of features exhibiting a faint attenuation contrast within bulk samples, as is generally the case of light (low-Z) materials. For this reason, the application to clinical tasks aiming at imaging soft tissues, as e.g., breast imaging, has always been a driving force in the development of this field. In this context, the SYRMA-3D project, which constitutes the framework of the present work, aims to develop and implement the first breast computed tomography system relying on the propagation-based phase-contrast technique at the Elettra synchrotron facility (Trieste, Italy). This thesis finds itself in the \u2018last mile\u2019 towards the in-vivo implementation, and the obtained results add some of the missing pieces in the realization of the project. The first part of the work introduces a homogeneous mathematical framework describing propagation-based phase contrast from the sample-induced X-ray refraction, to detection, processing and tomographic reconstruction. The original results reported in the following chapters include the implementation of a pre-processing procedure dedicated for a novel photon-counting CdTe detector; a study, supported by a rigorous theoretical model, on signal and noise dependence on physical parameters such as propagation distance and detector pixel size; hardware and software developments for improving signal-to-noise ratio and reducing the scan time; and, finally, a clinically-oriented study based on comparisons with clinical mammographic and histological images. The last part of the thesis attempts to widen the experimental horizon: first, a quantitative image comparison of the synchrotron-based setup and a clinically available breast-CT scanner is presented and then a practical laboratory implementation is detailed, introducing a monochromatic propagation-based micro-tomography setup making use on a high-power rotating anode source