34 research outputs found
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
Dose and image quality in X-ray phase contrast breast imaging
Nowadays, mammographic examination is the gold standard technique for detecting breast cancer in asymptomatic women. However, it presents some limitations, mainly due to the superimposition of the tissues in the 2D mammograms, which may hide tumor lesions. Partially (digital breast tomosynthesis) and fully (CT dedicated to the breast) 3D breast imaging techniques have been developed in order to have a better tissues separation and to overcome such a limitation. Along with 3D breast imaging, the use of the X-ray beam phase shift, via so-called phase-contrast imaging techniques, has been shown to be a promising method in order to increase the image contrast between glandular tissue and tumor lesions. Indeed, in phase-contrast the image contrast is due to the X-ray wave phase-shift between different imaged materials, while in conventional imaging the image contrast arises from the different attenuation they introduce.
Among all phase-contrast techniques, propagation based phase-contrast imaging does not need any special optical elements in the beam path, but only an X-ray beam with a certain degree of coherence and enough distance between imaged object and detector. It can be implemented either with synchrotron radiation source or with a compact X-ray tube. The 3D propagation based phase-contrast breast imaging devices are not yet employed in the routine clinical exams but they are available only at experimental level, and appropriate evaluations of image quality and dose are necessary. This is needed in order to optimize the various techniques and to understand the corresponding dose limitations.
In this thesis, the dose paradigms in X-ray breast imaging are revisited and specific Monte Carlo simulation codes have been developed. A part of this work focuses on the breast dose aiming at studying the adopted breast models and the effects of the breast partial irradiation on the dose estimates, as occurs in 2D spot mammography clinical examinations as well as by adopting a narrow beam produced via synchrotron radiation.
The second part of this work focuses on the image quality obtainable in 3D images of the breast by adopting propagation based phase-contrast imaging. We present the CT scanner dedicated to the breast developed within the SYRMA-CT project at Elettra synchrotron radiation facility. We evaluate its imaging performance in terms of spatial resolution, image noise properties and capability of showing breast lesions and microcalcification clusters.
Finally, the CT scanner dedicated to the breast, developed at the University of Naples, which relies on compact X-ray source with a 7-ÎĽm focal spot is presented and its image performance at dose comparable to that adopted in two-view digital mammography is explored together with its capability of producing phase-contrast effects. This scanner was developed and studied in order to compare a scanner which is clinical feasible in terms of cost, setup dimension and scan time to the results obtainable via the high flux and monochromatic X-ray beam synchrotron based experimental scanner
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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
High Resolution Active Pixel Sensor X-Ray Detectors for Digital Breast Tomosynthesis
Current large area x-ray detectors for digital breast tomosynthesis (DBT) are based on the amorphous silicon (a-Si:H) passive pixel sensor (PPS) technology. However, PPS detectors suffer from a limited resolution and high electronic noise. In this dissertation, we propose high resolution large area active pixel sensor (APS) x-ray detectors based on the complementary metal-oxide-semiconductor (CMOS) and amorphous In-Sn-Zn-O (a-ITZO) thin-film transistor (TFT) technologies to improve the imager resolution and noise properties.
We evaluated the two-dimensional (2D) x-ray imaging performance as measured by the modulation transfer function (MTF), noise power spectrum (NPS) and detective quantum efficiency (DQE) for both 75 µm (Dexela 2923 MAM) and 50 µm pixel pitch (DynAMITe) CMOS APS x-ray detectors. Excellent imaging performance (DQE in the range of 0.7 – 0.3) has been achieved over the entire spatial frequency range (0 – 6.7 mm-1) at low air kerma below 10 µGy using the 75 µm pixel pitch Dexela 2923 MAM detector. The 50 μm pixel pitch DyAMITe detector has further extended the spatial resolution of the detector to 10 mm-1 with a low electronic noise of 150 e-. Also, a 2D cascaded system analysis model has been developed to describe the signal and noise transfer for the CMOS APS x-ray imaging systems. We also implemented three-dimensional (3D) cascaded system analysis to simulated the 3D MTF, NPS and DQE characteristics using DBT radiation conditions and acquisition geometries. The 3D cascaded system analysis for the DynAMITe detector was integrated with an object task function, a medical imaging display model, and the human eye contrast sensitivity function to calculate the detectability index and area under the ROC curve (AUC). It has been demonstrated that the display pixel pitch and zoom factor should be optimized to improve the AUC for detecting high contrast objects such as microcalcifications. Also, detector electronic noise of smaller than 300 e- and a high display maximum luminance (>1000 cd/cm2) are desirable to distinguish microcalcifications of 150 µm or smaller in size. For low contrast object detection, a medical imaging display with a minimum of 12 bits gray levels is needed to realize accurate luminance levels. A wide projection angle range (≥ ±30°) combined with the image gray level magnification could improve the detectability for low contrast objects especially when the anatomical background noise is high.
CMOS APS x-ray detectors demonstrate both a high pixel resolution and low electronic noise, but are challenging to be fabricated in a large detector size greater than the wafer scale. Alternatively, current-mode APS (C-APS) based on a-ITZO TFTs was proposed for DBT due to the high gain, low noise, and capability to realize a large detector area. Specifically, we fabricated a-ITZO TFTs and achieved a high field-effect mobility of >30 cm2/Vs. We have also evaluated the electrical performance of a 50 µm pixel pitch a-ITZO TFT C-APS combined with an a-Si:H p+-i-n+ photodiode using SPICE simulation. The proposed C-APS circuit demonstrates a high charge gain of 885 with data line loadings considered. A pixel circuit layout and fabrication process have also been suggested. Finally, noise analysis has been applied to the a-ITZO TFT C-APS. A low electronic noise of around 239 e- has been established.
The research presented in this thesis indicates that APS x-ray detectors based on both CMOS and a-ITZO TFT technologies are promising for next generation DBT systems.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/136983/1/zhaocm_1.pd
Optical Contrast Agents to Visualize Molecular Expression in Breast Cancer
Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care.
The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence.
This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxy-glucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation.
To image these contrast agents in cancerous tissue, a portable, inexpensive device was developed as a tool to help physicians visualize expression of surface markers. The system visualizes absorbance from nanoshell aggregates and fluorescence in the visible and near-infrared light spectrum. This study represents the first step in the development of an intraoperative optical imaging device to enhance the visualization of molecular markers overexpressed in cancerous cells