Virtual clinical trials in medical imaging: a review

The accelerating complexity and variety of medical imaging devices and methods have outpaced the ability to evaluate and optimize their design and clinical use. This is a significant and increasing challenge for both scientific investigations and clinical applications. Evaluations would ideally be done using clinical imaging trials. These experiments, however, are often not practical due to ethical limitations, expense, time requirements, or lack of ground truth. Virtual clinical trials (VCTs) (also known as in silico imaging trials or virtual imaging trials) offer an alternative means to efficiently evaluate medical imaging technologies virtually. They do so by simulating the patients, imaging systems, and interpreters. The field of VCTs has been constantly advanced over the past decades in multiple areas. We summarize the major developments and current status of the field of VCTs in medical imaging. We review the core components of a VCT: computational phantoms, simulators of different imaging modalities, and interpretation models. We also highlight some of the applications of VCTs across various imaging modalities

Objective Characterization of In-line Phase Contrast X-ray Imaging Prototype Using a Mid-energy Beam

The purpose of the research presented in this thesis is the characterization of an in-line phase contrast x-ray imaging prototype operating at mid-energy, and to compare the data to that of high energy imaging with the same prototype. The prototype of interest has already been well characterized for high energy in-line phase contrast imaging. High energy imaging was the primary research focus for this prototype because a technique called phase retrieval required high energy phase contrast images to be implemented properly. Phase retrieval recovers a map of the phase shifts detected within a phase contrast image. The phase retrieval algorithm used by partners of this lab group has historically relied on high energy imaging due to its dependence on the phenomenon known as phase-attenuation duality. That algorithm is now under development for mid-energy x-ray imaging as well. Though this research does not involve phase retrieval directly, it is still necessary to characterize the prototype for mid-energy phase contrast imaging, before phase retrieval at mid-energy can be evaluated. The research presented in this thesis involved investigations into three image quality metrics. First, images taken of an edge device were taken to calculate the modulation transfer function. An angle resolution pattern device was then imaged to corroborate the cutoff frequency indicated by the first study. Images were then obtained with no object but with a virtual detector to calculate the noise power spectrum. Finally, the first and second studies’ results were used to calculate the detective quantum efficiency of the prototype system. The study focused on images obtained with a source potential of 60kV, the results from which were compared to those from images obtained with source potentials of 90kV and 120kV. A micro focus x-ray source was used with a CMOS based flat panel detector. The source-to-object and source-to-image distances were set such that a magnification of 2.2 was introduced. Results indicate that the prototype system’s detective quantum efficiency at 60kVp was higher than it was for 90kVp and 120kVp. The mid-energy phase contrast imaging technique has potential for offering high detectability with lower dose to a patient for applications such as breast cancer diagnosis, as compared to current, conventional mammographic procedures.

Investigation of physical processes in digital x-ray tomosynthesis imaging of the breast

Early detection is one of the most important factors in the survival of patients diagnosed with breast cancer. For this reason the development of improved screening mammography methods is one of primary importance. One problem that is present in standard planar mammography, which is not solved with the introduction of digital mammography, is the possible masking of lesions by normal breast tissue because of the inherent collapse of three-dimensional anatomy into a two-dimensional image. Digital tomosynthesis imaging has the potential to avoid this effect by incorporating into the acquired image information on the vertical position of the features present in the breast. Previous studies have shown that at an approximately equivalent dose, the contrast-detail trends of several tomosynthesis methods are better than those of planar mammography. By optimizing the image acquisition parameters and the tomosynthesis reconstruction algorithm, it is believed that a tomosynthesis imaging system can be developed that provides more information on the presence of lesions while maintaining or reducing the dose to the patient. Before this imaging methodology can be translated to routine clinical use, a series of issues and concerns related to tomosynthesis imaging must be addressed. This work investigates the relevant physical processes to improve our understanding and enable the introduction of this tomographic imaging method to the realm of clinical breast imaging. The processes investigated in this work included the dosimetry involved in tomosynthesis imaging, x-ray scatter in the projection images, imaging system performance, and acquisition geometry. A comprehensive understanding of the glandular dose to the breast during tomosynthesis imaging, as well as the dose distribution to most of the radiosensitive tissues in the body from planar mammography, tomosynthesis and dedicated breast computed tomography was gained. The analysis of the behavior of x-ray scatter in tomosynthesis yielded an in-depth characterization of the variation of this effect in the projection images. Finally, the theoretical modeling of a tomosynthesis imaging system, combined with the other results of this work was used to find the geometrical parameters that maximize the quality of the tomosynthesis reconstruction.Ph.D.Andrew Karellas, John N. Oshinski, Xiaoping P. Hu, Carl J. D’Orsi and Ernest V. Garci

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

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