Yes

Digital breast tomosynthesis (DBT) is a new technology for breast cancer screening that promises to complement mammography or supersede it to become the standard for breast imaging. DBT involves taking multiple images in order to synthesize a new image that represents a slice through the breast volume -- hence the term tomosynthesis. The primary advantage of this paradigm is that it can reduce the amount of overlapping anatomy in the data, leading to improved visualization of potentially-cancerous findings. The difficulty in DBT is quantifying the advantages of the technology and determining the optimal conditions for its clinical use. This dissertation describes a virtual trial framework for assessing and optimizing DBT technology for the specific task of detecting small, low-contrast masses in the breast. It addresses each component of the imaging chain to some degree, from the patients/phantoms to the imaging hardware to the model observers used to measure signal detectability. The main focus, however, is on quantifying tradeoffs between three key parameters that affect image quality: (1) scan angle, (2) number of projections, and (3) exposure. We show that in low-density breast phantoms, detectability generally increases with both scan angle and number of projections in the anatomical-variability-limited (high-exposure) regime. We also investigate how breast density affects the optimal DBT scan parameters. We show task-specific results that support using an adaptive paradigm in DBT, where the imaging system reconfigures itself in response to information about the patient's breast density. The virtual framework described in this dissertation provides a platform for further investigations of image quality in 3D breast imaging.

<p>The development of digital detectors for X-ray imaging in medical diagnostics receives an increasing amount of attention. The detector under development at the Department of Radiation Sciences at Uppsala University is a hybrid pixel detector, which consists of a semiconductor sensor mounted onto a readout chip. The readout chip is capable of performing photon counting and has an externally adjustable threshold.</p><p>A simulation tool for the detector and a model applying the linear-systems transfer theory to X-ray hybrid pixel detectors have been developed. Also a characterization of the readout chip has been done. In order to estimate the potential of the detector for diagnostic radiology, we investigate the image quality using the spatial frequency dependent detective quantum efficiency (DQE). By means of the detector simulations, the influence of threshold setting, noise sources, level of exposure and charge sharing on the DQE have been studied. By means of the linear-systems theory, a single analytical expression is provided to obtain the DQE of a hybrid pixel detector.</p><p>The method developed in this thesis will make it possible to optimize a detector design according to a particular medical application. It will also permit modifications and new features to be included without having to construct a full detector system.</p>

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The development of digital detectors for X-ray imaging in medical diagnostics receives an increasing amount of attention. The detector under development at the Department of Radiation Sciences at Uppsala University is a hybrid pixel detector, which consists of a semiconductor sensor mounted onto a readout chip. The readout chip is capable of performing photon counting and has an externally adjustable threshold. A simulation tool for the detector and a model applying the linear-systems transfer theory to X-ray hybrid pixel detectors have been developed. Also a characterization of the readout chip has been done. In order to estimate the potential of the detector for diagnostic radiology, we investigate the image quality using the spatial frequency dependent detective quantum efficiency (DQE). By means of the detector simulations, the influence of threshold setting, noise sources, level of exposure and charge sharing on the DQE have been studied. By means of the linear-systems theory, a single analytical expression is provided to obtain the DQE of a hybrid pixel detector. The method developed in this thesis will make it possible to optimize a detector design according to a particular medical application. It will also permit modifications and new features to be included without having to construct a full detector system.

The development of a non-invasive method of visualizing gene expression in larger animals could revolutionize some aspects of gene research by opening up a wider variety of animal systems to explore; some of which may be better models of human systems. Presently, most gene expression studies employ Green Fluorescent Protein (GFP) transfected into the genome of the animal system. For larger animals, an x-ray equivalent of GFP would be desirable due to the high penetrating power of x-rays. A model gene modification system is to use the Sodium (Na) Iodide Symporter (NIS) which will cause the accumulation of iodine in cells which express the NIS. To non-invasively observe the dilute iodine accumulated by the cancer cells transfected with NIS in the head of small animals, such as a rat, two synchrotron-based imaging methods were studied: K-Edge Subtraction (KES) imaging and Fluorescence Subtraction Imaging (FSI).<p> KES needs wide monochromatic x-ray beams at two energies bracketing the K-edge of the contrast agent existing or injected in the tissues. The monochromatic beam in the synchrotron facility normally is prepared by a double crystal monochromator. The appearance of the azimuthal angle (tilt error) in the double crystal monochromator creates intensity variations across the imaging field. This misalignment was studied through another two synchrotron-based imaging methods, Diffraction Enhanced Imaging (DEI) and Multi-Image Radiography (MIR), which show this problem clearly in their processed images. The detailed analysis of the effect of the tilt error, how it affects the resulting images, and how to quantify such an error were presented in the thesis. A post processing method was implemented and the artifacts caused by the improper experimental settings were discussed.<p> With the wide monochromatic beam prepared by the double crystal monochromator, a sequence of KES experiments were done and the detection limit of KES was quantified at a projected amount of 17.5mM-cm iodine in a physical model of a rat head with a radiation dose of 2.65mGy. With the raster scan of the object relative to the monochromatic pencil beam, FSI was studied to obtain higher Signal to Noise Ratio (SNR) for local area and better detection limit compared to KES. The detection limit of FSI was measured as a projected amount of 2.5mM-cm iodine in the same physical rat head with a tolerable radiation dose of 24mGy. According to the comparison of these two imaging techniques with references to imaging time and area, radiation dose, spatial resolution, and SNR, it was concluded that these two imaging techniques can be used complementarily in imaging dilute contrast material. Due to the short imaging time and large imaging area, KES is used first to provide a global view of the object, locate the area of interest, do the preliminary diagnosis, and decide whether the further FSI is necessary. Due to its high SNR for the dilute sample, FSI can be used when the area of interest is known. The combination of these two imaging techniques will be very promising and powerful. To facilitate the comparison of KES and FSI, a quality factor was developed to evaluate the performance of the imaging system.<p> The measured detection limits in our experiments are far beyond the thyroidal iodine concentration of a rat (around 1mM). To further improve the performance of KES, a bent Laue crystal monochromator was designed to do the simultaneous iodine KES imaging which overcomes the artifacts in the iodine image caused by the temporal difference for a single set of images. The designed monochromator can provide two separated x-ray beams bracketing the K-edge of iodine at the same time with a very high spatial resolution which is only depends on the source size, a very high energy resolution which can almost compete with that of the double crystal monochromator, and an acceptable photon flux.

Diffraction Enhanced X-ray Imaging (DEI) uses synchrotron X-ray beams prepared and analyzed by perfect single crystals to achieve imaging contrast from a number of phenomena taking place in an object under investigation. The crystals used in DEI for imaging requires high precision positioning due to a narrow rocking curve. Typically, the angular precision required should be on the order of tens of nanoradians.<p>One of the problems associated with DEI is the inability to control, set, and fix the angle of the analyzer crystal in relation to the beam exiting the monochromator in the system. This angle is used to interpret the images acquired with an object present and the usual approach is to determine where the image was taken after the fact. If the angle is not correct, then the image is wasted and has to be retaken. If time or dose is not an issue, then retaking the image is not a serious problem. However, since the technique is to be developed for live animal or eventually human imaging, the lost images are no longer acceptable from either X-ray exposure or time perspectives.<p>Therefore, a mechanical positioning system for the DEI system should be developed that allows a precise setting and measurement of the analyzer crystal angles. In this thesis, the fundamental principles of the DEI method, the DEI system at the National Synchrotron Light Source (NSLS) and the sensitivity of the DEI system to vibration and temperature has been briefly studied to gain a better understanding of the problem. The DEI design at the NSLS was analyzed using finite element analysis software (ANSYS) to determine the defects in the current design which were making the system dimensionally unstable. Using the results of this analysis, the new analyzer support was designed aiming to eliminate the problems with the current design. The new design is much stiffer with the natural frequency spectrum raised about eight times. <p> This new design will improve the performance of the system at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory, New York, USA and should assist in the development of a new DEI system for the Bio-Medical Imaging and Therapy (BMIT) beamline at the Canadian Light Source (CLS), Saskatoon, CANADA.

This work investigates the design, system integration, optimization, and evaluation of amorphous silicon (a-Si:H) active matrix flat panel imagers (AMFPI) for bio-medical applications. Here, two hybrid active pixel sensor (H-APS) designs are introduced that improve the dynamic range while maintaining the desirable attributes of high speed and low noise readout. Also presented is a systematic approach for noise analysis of thin film transistors (TFT) and pixel circuits in which circuit analysis techniques and TFT noise models are combined to evaluate circuit noise performance. We also explore different options of system integration and present measurement results of a high fill-factor (HFF) array with segmented photodiode.

This work investigates the design, system integration, optimization, and evaluation of amorphous silicon (a-Si:H) active matrix flat panel imagers (AMFPI) for bio-medical applications. Here, two hybrid active pixel sensor (H-APS) designs are introduced that improve the dynamic range while maintaining the desirable attributes of high speed and low noise readout. Also presented is a systematic approach for noise analysis of thin film transistors (TFT) and pixel circuits in which circuit analysis techniques and TFT noise models are combined to evaluate circuit noise performance. We also explore different options of system integration and present measurement results of a high fill-factor (HFF) array with segmented photodiode.

Diffraction Enhanced X-ray Imaging (DEI) uses synchrotron X-ray beams prepared and analyzed by perfect single crystals to achieve imaging contrast from a number of phenomena taking place in an object under investigation. The crystals used in DEI for imaging requires high precision positioning due to a narrow rocking curve. Typically, the angular precision required should be on the order of tens of nanoradians.<p>One of the problems associated with DEI is the inability to control, set, and fix the angle of the analyzer crystal in relation to the beam exiting the monochromator in the system. This angle is used to interpret the images acquired with an object present and the usual approach is to determine where the image was taken after the fact. If the angle is not correct, then the image is wasted and has to be retaken. If time or dose is not an issue, then retaking the image is not a serious problem. However, since the technique is to be developed for live animal or eventually human imaging, the lost images are no longer acceptable from either X-ray exposure or time perspectives.<p>Therefore, a mechanical positioning system for the DEI system should be developed that allows a precise setting and measurement of the analyzer crystal angles. In this thesis, the fundamental principles of the DEI method, the DEI system at the National Synchrotron Light Source (NSLS) and the sensitivity of the DEI system to vibration and temperature has been briefly studied to gain a better understanding of the problem. The DEI design at the NSLS was analyzed using finite element analysis software (ANSYS) to determine the defects in the current design which were making the system dimensionally unstable. Using the results of this analysis, the new analyzer support was designed aiming to eliminate the problems with the current design. The new design is much stiffer with the natural frequency spectrum raised about eight times. <p> This new design will improve the performance of the system at the National Synchrotron Light Source (NSLS) of Brookhaven National Laboratory, New York, USA and should assist in the development of a new DEI system for the Bio-Medical Imaging and Therapy (BMIT) beamline at the Canadian Light Source (CLS), Saskatoon, CANADA.