Evaluation of a diffraction-enhanced imaging (DEI) prototype and exploration of novel applications for clinical implementation of DEI

Conventional mammographic image contrast is derived from x-ray absorption, resulting in breast structure visualization due to density gradients that attenuate radiation without distinction between transmitted, scattered, or refracted x-rays. Diffraction-enhanced imaging (DEI) allows for increased contrast with decreased radiation dose compared to conventional mammographic imaging due to monochromatic x-rays, its unique refraction-based contrast mechanism, and excellent scatter rejection. Although laboratory breast imaging studies have demonstrated excellent breast imaging, important clinical translation and application studies are needed before the DEI system can be established as a useful breast imaging modality. This dissertation focuses on several important studies toward the development of a clinical DEI system. First, contrast-enhanced DEI was explored using commercially available contrast agents. Phantoms were imaged at a range of x-ray energies and relevant contrast agent concentrations. Second, we performed a reader study to determine if superior DEI contrast mechanisms preserve image quality as tissue thickness increases. Breast specimens were imaged at several thicknesses, and radiologist perception of lesion visibility was recorded. Lastly, a prototype DEI system utilizing an x-ray tube source was evaluated through a reader study. Breast tissue specimens were imaged on the traditional and prototype DEI systems, and expert radiologists evaluated image quality and pathology correlation. This dissertation will demonstrate proof-of-principle for contrast-enhanced DEI, establishing the feasibility of contrast-enhanced DEI using commercially available contrast agents. Further, it will show that DEI might be able to reduce breast compression, and thus the perception of pain during mammography, without significantly decreasing breast lesion visibility. Finally, this research shows the successful implementation of a DEI prototype, displaying breast features with approximately statistically equivalent visibility to the traditional DEI system. Together, this research is an important step toward the clinical translation of DEI, a technology with the potential to facilitate early breast cancer detection and diagnosis

Discrete mathematical models for electrical impedance tomography

Electrical Impedance Tomography (EIT) is a non-invasive, portable and low-cost medical imaging technique. Different current patterns are injected to the surface of a conductive body and the corresponding voltages are measured also on the boundary. These mea-surements are the data used to infer the interior conductivity distribution of the object. However, it is well known that the reconstruction process is extremely ill-posed due to the low sensitivity of the boundary voltages to changes in the interior conductivity distribution. The reconstructed images also suffer from poor spatial resolution. In tomographic systems, the spatial resolution is related to the number of applied current patterns and to the number and positions of electrodes which are placed at the surface of the object under examination. Two mammographic sensors were recently developed at the University of Mainz in collaboration with Oxford Brookes University. These prototypes consist of a planar sensing head of circular geometry with twelve large outer (active) electrodes arranged on a ring of radius 4.4cm where the external currents are injected and a set of, respectively thirty six and fifty four point-like high-impedance inner (passive) electrodes arranged in a hexagonal pattern where the induced voltages are measured. Two 2D reconstruction methods were proposed for these devices, one based on resistor network models and another one which uses an integral equation formulation. The novelty of the device and hence of these imaging techniques consists exactly in the distinct use of active and passive electrodes. The 2D images of the conductivity distribution of the interior tissue of the breast provide only information about the existence and location of the tumour. In this thesis different circular designs for the sensing head of this EIT device were analysed. The 2D resistor network approach was adapted to the different data collection geometries and the sensitivity of the reconstructions with respect to errors in the simulate data were investigated before any modifications to the original design were made. A novel 3D reconstruction algorithm was also developed for a simpler geometry of the sensing head which consisted of a rectangular array of thirty six electrodes (twenty active+ sixteen passive). This electrode configuration as well as the proposed imaging technique are intended to be used for breast cancer detection. The algorithm is based on linearizing the conductivity about a constant value and allows real-time reconstructions. The perfor-mance of the algorithm was tested on numerically simulated data and small inclusions with conductivities three or four times the background lying beneath the data collection surface were successfully detected. The results were fairly stable with respect to the noise level in the data and displayed very good spatial resolution in the plane of electrodes

Mammography Techniques and Review

Mammography remains at the backbone of medical tools to examine the human breast. The early detection of breast cancer typically uses adjunct tests to mammogram such as ultrasound, positron emission mammography, electrical impedance, Computer-aided detection systems and others. In the present digital era it is even more important to use the best new techniques and systems available to improve the correct diagnosis and to prevent mortality from breast cancer. The first part of this book deals with the electrical impedance mammographic scheme, ultrasound axillary imaging, position emission mammography and digital mammogram enhancement. A detailed consideration of CBR CAD System and the availability of mammographs in Brazil forms the second part of this book. With the up-to-date papers from world experts, this book will be invaluable to anyone who studies the field of mammography

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

Complexity Reduction in Image-Based Breast Cancer Care

The diversity of malignancies of the breast requires personalized diagnostic and therapeutic decision making in a complex situation. This thesis contributes in three clinical areas: (1) For clinical diagnostic image evaluation, computer-aided detection and diagnosis of mass and non-mass lesions in breast MRI is developed. 4D texture features characterize mass lesions. For non-mass lesions, a combined detection/characterisation method utilizes the bilateral symmetry of the breast s contrast agent uptake. (2) To improve clinical workflows, a breast MRI reading paradigm is proposed, exemplified by a breast MRI reading workstation prototype. Instead of mouse and keyboard, it is operated using multi-touch gestures. The concept is extended to mammography screening, introducing efficient navigation aids. (3) Contributions to finite element modeling of breast tissue deformations tackle two clinical problems: surgery planning and the prediction of the breast deformation in a MRI biopsy device

Parametric Study of Infrared Imaging Based Breast Cancer Detection Program

Breast cancer is one of the most common cancers among women and is responsible for over 41,000 lives every year in the US according to The American Cancer Society. Current screening and imaging methods such as mammography, breast magnetic resonance imaging, and breast ultrasound imaging have helped in improving survival rate when the cancer is detected at an early stage. The problems with these techniques include: low sensitivity, patient discomfort, invasiveness, and cost. Due to current advancements in infrared and computational technologies, infrared thermography has been utilized as a noninvasive adjunctive screening modality. A computerized approach using infrared imaging (IRI) has been recently developed at RIT in collaboration with Rochester General Hospital for breast cancer detection and image localization. The parameters used in this simulation have been selected based on limited information available in the literature. This study focuses on analyzing the effects of different tissue thermal parameters used in the simulation on the accuracy of prediction. Thermal conductivity and perfusion rate are systematically varied, and their effects are presented by comparing simulated images with the actual infrared images captured from a biopsy-proven breast cancer patient. The results indicate a strong influence of perfusion rate within the breast tissue surrounding the tumor on heat transfer within the breast. This study is expected to help in proper selection of thermal properties while conducting the simulations. Future directions for research are also presented

Development of a novel probe integrated with a micro-structured impedance sensor for the detection of breast cancer

The work described in this thesis focuses on the development of an innovative bioimpedance device for the detection of breast cancer using electrical impedance as the detection method. The ability for clinicians to detect and treat cancerous lesions as early as possible results in improved patient outcomes and can reduce the severity of the treatment the patient has to undergo. Therefore, new technology and devices are continually required to improve the specificity and sensitivity of the accepted detection methods. The gold standard for breast cancer detection is digital x-ray mammography but it has some significant downsides associated with it. The development of an adjunct technology to aid in the detection of breast cancers could represent a significant patient and economic benefit. In this project silicon substrates were pattern with two gold microelectrodes that allowed electrical impedance measurements to be recorded from intact tissue structures. These probes were tested and characterised using a range of in vitro and ex vivo experiments. The end application of this novel sensor device was in a first-in-human clinical trial. The initial results of this study showed that the silicon impedance device was capable of differentiating between normal and abnormal (benign and cancerous) breast tissue. The mean separation between the two tissue types 4,340 Ω with p < 0.001. The cancer type and grade at the site of the probe recordings was confirmed histologically and correlated with the electrical impedance measurements to determine if the different subtypes of cancer could each be differentiated. The results presented in this thesis showed that the novel impedance device demonstrated excellent electrochemical recording potential; was biocompatible with the growth of cultured cell lines and was capable of differentiating between intact biological tissues. The results outlined in this thesis demonstrate the potential feasibility of using electrical impedance for the differentiation of biological tissue samples. The novelty of this thesis is in the development of a new method of tissue determination with an application in breast cancer detection

Proceedings of the International Workshop on Medical Ultrasound Tomography: 1.- 3. Nov. 2017, Speyer, Germany

Ultrasound Tomography is an emerging technology for medical imaging that is quickly approaching its clinical utility. Research groups around the globe are engaged in research spanning from theory to practical applications. The International Workshop on Medical Ultrasound Tomography (1.-3. November 2017, Speyer, Germany) brought together scientists to exchange their knowledge and discuss new ideas and results in order to boost the research in Ultrasound Tomography

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise