Economics of Breast Cancer Screening, Genetic Testing, and Treatment

Breast cancer is the most common female cancer worldwide. This thesis aims to evaluate the cost-effectiveness of breast cancer control across different healthcare contexts and estimate the costs of breast cancer treatment. Four case studies are presented providing detailed estimates of the cost-effectiveness of risk-based breast screening in urban China, the cost-effectiveness of population-based breast screening in rural China, the cost-effectiveness of panel genetic testing among unselected breast cancer patients in the UK and US, and cost of breast cancer treatment by stage at diagnosis in England. The economic evaluation studies on breast cancer screening show that in urban China, high-risk population-based screening for breast cancer is very likely to be cost-effective. But in rural China, breast screening among the general population reports uncertain costeffectiveness and could potentially harm women’s health due to false positives with the current screening tools. In a rural setting with such low breast cancer incidence, priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms. The economic evaluation on genetic testing based on a microsimulation model showed that unselected panel genetic-testing for all breast cancer patients is extremely costeffective compared to the current practice of family-history/clinical-criteria based genetic (BRCA)-testing for both UK and US health systems. This supports changing the current policy to expand genetic-testing to all women with breast cancer. Costs of breast cancer care increased with increasing stage of the disease at diagnosis in England. Considerable cost savings could be made if breast cancer was detected and treated earlier. Variations in breast cancer costs by age and region raise questions about the efficiency and consistency of breast cancer treatment patterns. Future research could be conducted by undertaking multiple imputation for missing data and censored-adjusted analysis

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

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

Conflicting health-related scientific evidence in news reports: effects of presentation format and hedging on perceived issue uncertainty and source credibility

2016 Summer.Includes bibliographical references.This study examined the effects of two journalistic practices in reporting conflicting health-related scientific evidence on journalists’ and scientists’ credibility and whether the effects were mediated by perceived issue uncertainty. The two practices examined were presentation format and hedging. When conflicting findings are reported, journalists can use either a one-article format, using one story to report the conflict, or a two-article format, using two stories with each story representing one side of the conflict. When conflicting findings are reported, journalists can use hedging (e.g., reporting the limitations of scientific studies) to present the conflicting information. An online experiment was conducted to examine the two journalistic practices’ effects. Results include the following: 1) the one-article format was beneficial to journalists’ competence, but detrimental to scientists’ competence, as compared with the two-article format; 2) journalists’ and scientists’ credibility in the hedged news conditions did not differ from those in the non-hedged news conditions; and 3) perceived issue uncertainty did not mediate presentation format’s or hedging’s effects on journalists’ or scientists’ credibility. An exploratory follow-up mediation analysis found that perceived message believability mediated presentation format’s effects on journalists’ and scientists’ credibility. Theoretical, practical, and methodological implications are discussed

System Optimization and Iterative Image Reconstruction in Photoacoustic Computed Tomography for Breast Imaging

Photoacoustic computed tomography(PACT), also known as optoacoustic tomography (OAT), is an emerging imaging technique that has developed rapidly in recent years. The combination of the high optical contrast and the high acoustic resolution of this hybrid imaging technique makes it a promising candidate for human breast imaging, where conventional imaging techniques including X-ray mammography, B-mode ultrasound, and MRI suffer from low contrast, low specificity for certain breast types, and additional risks related to ionizing radiation. Though significant works have been done to push the frontier of PACT breast imaging, it is still challenging to successfully build a PACT breast imaging system and apply it to wide clinical use because of various practical reasons. First, computer simulation studies are often conducted to guide imaging system designs, but the numerical phantoms employed in most previous works consist of simple geometries and do not reflect the true anatomical structures within the breast. Therefore the effectiveness of such simulation-guided PACT system in clinical experiments will be compromised. Second, it is challenging to design a system to simultaneously illuminate the entire breast with limited laser power. Some heuristic designs have been proposed where the illumination is non-stationary during the imaging procedure, but the impact of employing such a design has not been carefully studied. Third, current PACT imaging systems are often optimized with respect to physical measures such as resolution or signal-to-noise ratio (SNR). It would be desirable to establish an assessing framework where the detectability of breast tumor can be directly quantified, therefore the images produced by such optimized imaging systems are not only visually appealing, but most informative in terms of the tumor detection task. Fourth, when imaging a large three-dimensional (3D) object such as the breast, iterative reconstruction algorithms are often utilized to alleviate the need to collect densely sampled measurement data hence a long scanning time. However, the heavy computation burden associated with iterative algorithms largely hinders its application in PACT breast imaging. This dissertation is dedicated to address these aforementioned problems in PACT breast imaging. A method that generates anatomically realistic numerical breast phantoms is first proposed to facilitate computer simulation studies in PACT. The non-stationary illumination designs for PACT breast imaging are then systematically investigated in terms of its impact on reconstructed images. We then apply signal detection theory to assess different system designs to demonstrate how an objective, task-based measure can be established for PACT breast imaging. To address the slow computation time of iterative algorithms for PACT imaging, we propose an acceleration method that employs an approximated but much faster adjoint operator during iterations, which can reduce the computation time by a factor of six without significantly compromising image quality. Finally, some clinical results are presented to demonstrate that the PACT breast imaging can resolve most major and fine vascular structures within the breast, along with some pathological biomarkers that may indicate tumor development

Evaluating Preventative Care and Post-Hospitalization Primary Care Follow-Up in Adults with Intellectual and/or Developmental Disabilities

Post-Hospitalization Primary Care Follow-Up Abstract Title: Characteristics that are associated with primary care follow-up and discharge summary receipt post-hospitalization in adults with intellectual and/or developmental disabilities. Background: Transition from an inpatient to an outpatient setting is a high risk time for patients. Studies in the general population find that poor post-hospitalization primary care follow-up results in higher rates of readmissions – a widely used indicator of healthcare quality. There is no research that evaluates post-hospitalization primary care follow-up or discharge summary receipt in the IDD population. Objective: To explore the demographic, socioeconomic, and clinical characteristics that are associated with whether an adult with IDD will achieve timely post-hospitalization primary care follow-up. Methods: A cross-sectional study evaluating 788 hospitalizations of adults with IDD from January 1, 2012 to December 31, 2016 and their primary care follow-up at an IDD-specific multi-specialty outpatient facility. Applicable inpatient admissions were identified using Medicare Quality and Resource Use Reports and linked to the outpatient facilities’ electronic medical records in order to capture demographic, socioeconomic, clinical, and follow-up variables on each subject. Results: A total of 788 hospital admissions completed by 341 unique individuals were identified. This population had a high rate of primary care follow-up (94.8%), and hospitalization discharge summary receipt (83.5%) within 30 days. Multivariate regression analysis, which controlled for demographics, living situation, level of intellectual disability, hospital, and principal hospital diagnosis, identified that living in non-group home settings was associated with a lower likelihood of timely primary care follow-up and discharge summary receipt when compared to adults with IDD who live in group homes. This analysis also detected that age over 40 was associated with a lower likelihood or primary care follow-up within 7 days (aOR: 0.2, 95% CI: 0.1-0.8) and non-Caucasian race to be associated with a higher likelihood of primary care follow-up within 14 days (aOR: 2.3, 95% CI: 1.0-5.3). Conclusion: The major variable that predicted timely primary care follow-up and discharge summary receipt was living in a group home. This is most likely due to state-mandated audits of group home policies and procedures. Nevertheless, primary care follow-up for the population evaluated in this study was much better than the general Medicare population. Primary care providers and hospital discharge teams should be cognizant of the challenges and barriers that adults with IDD who live in non-group home settings face. Further research should continue to evaluate the success that group homes have had in post-hospitalization primary care follow-up and communicate their success to other state regulatory groups

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

Numerical Approaches for Solving the Combined Reconstruction and Registration of Digital Breast Tomosynthesis

Heavy demands on the development of medical imaging modalities for breast cancer detection have been witnessed in the last three decades in an attempt to reduce the mortality associated with the disease. Recently, Digital Breast Tomosynthesis (DBT) shows its promising in the early diagnosis when lesions are small. In particular, it offers potential benefits over X-ray mammography - the current modality of choice for breast screening - of increased sensitivity and specificity for comparable X-ray dose, speed, and cost. An important feature of DBT is that it provides a pseudo-3D image of the breast. This is of particular relevance for heterogeneous dense breasts of young women, which can inhibit detection of cancer using conventional mammography. In the same way that it is difficult to see a bird from the edge of the forest, detecting cancer in a conventional 2D mammogram is a challenging task. Three-dimensional DBT, however, enables us to step through the forest, i.e., the breast, reducing the confounding effect of superimposed tissue and so (potentially) increasing the sensitivity and specificity of cancer detection. The workflow in which DBT would be used clinically, involves two key tasks: reconstruction, to generate a 3D image of the breast, and registration, to enable images from different visits to be compared as is routinely performed by radiologists working with conventional mammograms. Conventional approaches proposed in the literature separate these steps, solving each task independently. This can be effective if reconstructing using a complete set of data. However, for ill-posed limited-angle problems such as DBT, estimating the deformation is difficult because of the significant artefacts associated with DBT reconstructions, leading to severe inaccuracies in the registration. The aim of my work is to find and evaluate methods capable of allying these two tasks, which will enhance the performance of each process as a result. Consequently, I prove that the processes of reconstruction and registration of DBT are not independent but reciprocal. This thesis proposes innovative numerical approaches combining reconstruction of a pair of temporal DBT acquisitions with their registration iteratively and simultaneously. To evaluate the performance of my methods I use synthetic images, breast MRI, and DBT simulations with in-vivo breast compressions. I show that, compared to the conventional sequential method, jointly estimating image intensities and transformation parameters gives superior results with respect to both reconstruction fidelity and registration accuracy