Diagnostic Reference Levels for digital mammography in Australia

Aims: In 3 phases, this thesis explores: radiation doses delivered to women during mammography, methods to estimate mean glandular dose (MGD), and the use of mammographic breast density (MBD) in MGD calculations. Firstly, it examines Diagnostic reference levels (DRLs) for digital mammography in Australia, with novel focus on the use of compressed breast thickness (CBT) and detector technologies as a guide when determining patient derived DRLs. Secondly, it analyses the agreement between Organ Dose estimated by different digital mammography units and calculated MGD for clinical data. Thirdly, it explores the novel use of MBD in MGD calculations, suggesting a new dose estimation called the actual glandular dose (AGD), and compares MGD to AGD. Methods: DICOM headers were extracted from 52405 anonymised mammograms using 3rd party software. Exposure and QA information were utilised to calculate MGD using 3 methods. LIBRA software was used to estimate MBD for 31097 mammograms. Median, 75th and 95th percentiles were calculated across MGDs obtained for all included data and according to 9 CBT ranges, average population CBT, and for 3 detector technologies. The significance of the differences, correlations, and agreement between MGDs for different CBT ranges, calculation methods, and different density estimation methods were analysed. Conclusions: This thesis have recommended DRLs for mammography in Australia, it shows that MGD is dependent upon CBT and detector technology, hence DRLs were presented as a table for different CBTs and detectors. The work also shows that Organ Doses reported by vendors vary from that calculated using established methodologies. Data produced also show that the use of MGD calculated using standardised glandularities underestimates dose at lower CBTs compared to AGD by up to 10%, hence, underestimating radiation risk. Finally, AGD was proposed; it considers differences in breast composition for individualised radiation-induced risk assessment

Effective lifetime radiation risk for a number of national mammography screening programmes

Background and purpose: The performance of mammography screening programmes is focussed mainly on breast cancer detection rates. However, when the benefits and risks of mammography are considered, the risk of radiation-induced cancer is calculated for only the examined breast using Mean Glandular Dose (MGD). The risk from radiation during mammography is often described as low or minimal. This study aims to evaluate the effective lifetime risk from full field digital mammography (FFDM) for a number of national screening programmes. Material and Methods: Using an ATOM phantom, radiation doses to multiple organs were measured during standard screening mammography. Sixteen FFDM machines were used and the effective lifetime risk was calculated across the female lifespan for each machine. Once the risks were calculated using the phantom, the total effective lifetime risk across 48 national screening programmes was then calculated; this assumed that all these programmes use FFDM for screening. Results: Large differences exist in effective lifetime risk, varying from 42.21 [39.12 - 45.30] cases/106 (mean [95% CI]) in the Maltese screening programme to 1099.67 [1019.25 - 1180.09] cases/106 for high breast cancer risk women in the United States of America. These differences are mainly attributed to the commencement age of screening mammography and the time interval between successive screens. Conclusions: Effective risk should be considered as an additional parameter for the assessment of screening mammography programme performance, especially for those programmes which recommend an early onset and more frequent screening mammography

Risk of radiation-induced cancer from screening mammography

Background and Objectives: When the benefits and risks of mammography are considered, the risk of radiation-induced cancer is calculated only for the breast using the mean glandular dose (MGD). Whilst MGD is a useful concept, it has many limitations. This thesis aims to establish a novel method to determine and convey radiation risk from full field digital mammography (FFDM) screening using lifetime effective risk. Method: For effective risk calculations, organ doses as well as examined breast MGD are required. Screening mammography was simulated by exposing a breast phantom for cranio-caudal and medio-lateral oblique for each breast using 16 FFDM machines. An anthropomorphic dosimetry phantom loaded with thermo-luminescent detectors (TLDs) was positioned in contact with the breast phantom to simulate the client’s body. Once the risk per individual was calculated, total effective lifetime risk across 48 worldwide screening programmes was calculated. The total effective risk data sets were analysed to establish a regression model to predict the effective risk of any screening programme. Graphs were generated to extrapolate the total effective risk of any screening programme of specific screening commencement age and frequency considering the MGD differences of different FFDM machines. Since the highest radiation dose after examined breast was received by contralateral breast, the effect of a contralateral breast lead shield on effective risk was also investigated. Results: Large differences in the effective lifetime risk exist between worldwide screening programmes. The effective lifetime risk varied from approximately 50 cases/106 to more than 1000 cases/106. These differences were mainly attributed to the commencement age and frequency of screening. Since tissue radio-sensitivity reduces with age, the cessation age of screening mammography does not result in a noteworthy effect on the total effective risk. The use of contralateral breast shield reduces the total effective risk by about 1.5% for most worldwide screening programmes.Conclusion: A novel method has been proposed to assess radiation-induced cancer risk from FFDM screening which considers the radiation dose received by all body tissues in addition to the examined breast. Using effective risk, the data is more likely to be understandable by screening clients and referring clinicians, unlike MGD which is not readily available or understandable by the general populace. This novel method and the data are compatible with the incoming European Commission legislation about giving the patient information on radiation risk

Imaging of the Breast

Early detection of breast cancer combined with targeted therapy offers the best outcome for breast cancer patients. This volume deal with a wide range of new technical innovations for improving breast cancer detection, diagnosis and therapy. There is a special focus on improvements in mammographic image quality, image analysis, magnetic resonance imaging of the breast and molecular imaging. A chapter on targeted therapy explores the option of less radical postoperative therapy for women with early, screen-detected breast cancers

A dual modality, DCE-MRI and x-ray, physical phantom for quantitative evaluation of breast imaging protocols

The current clinical standard for breast cancer screening is mammography. However, this technique has a low sensitivity which results in missed cancers. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has recently emerged as a promising technique for breast cancer diagnosis and has been reported as being superior to mammography for screening of high-risk women and evaluation of extent of disease. At the same time, low and variable specificity has been documented in the literature as well as a rising number of mastectomies possibly due to the increasing use of DCE-MRI. In this study, we developed and characterized a dual-modality, x-ray and DCE-MRI, anthropomorphic breast phantom for the quantitative assessment of breast imaging protocols. X-ray properties of the phantom were quantitatively compared with patient data, including attenuation coefficients, which matched human values to within the measurement error, and tissue structure using spatial covariance matrices of image data, which were found to be similar in size to patient data. Simulations of the phantom scatter-to-primary ratio (SPR) were produced and experimentally validated then compared with published SPR predictions for homogeneous phantoms. SPR values were as high as 85% in some areas and were heavily influenced by the heterogeneous tissue structure. MRI properties of the phantom, T1 and T2 relaxation values and tissue structure, were also quantitatively compared with patient data and found to match within two error bars. Finally, a dynamic lesion that mimics lesion border shape and washout curve shape was included in the phantom. High spatial and temporal resolution x-ray measurements of the washout curve shape were performed to determine the true contrast agent concentration as a function of time. DCE-MRI phantom measurements using a clinical imaging protocol were compared against the x-ray truth measurements. MRI signal intensity curves were shown to be less specific to lesion type than the x-ray derived contrast agent concentration curves. This phantom allows, for the first time, for quantitative evaluation of and direct comparisons between x-ray and MRI breast imaging modalities in the context of lesion detection and characterization

The Role Of Tissue Sound Speed As A Surrogate Marker Of Breast Density

Breast density is one of the strongest predictors of breast cancer risk as women with the densest breasts have a three- to five-fold increase in risk compared to women with the least dense breasts. Breast density is currently measured by using mammography, the current gold standard for breast imaging. There are many shortcomings to using mammography to measure breast density, including the use of ionizing radiation. Ultrasound tomography (UST) does not use ionizing radiation and can create tomographic breast sound speed images. These sound speed images are useful because breast density is proportional to sound speed. The purpose of this work was to assess the ability of UST to measure breast density and its ability to measure changes in breast density over short periods of time. A cohort of 251 patients was examined using both UST and mammography. Many different associations were found between the UST density measurement, the volume averaged sound speed, and the mammographic percent density. Additional associations were found between many other UST and mammographic imaging characteristics. UST density was found to correlate with various patient characteristics in a similar manner to mammographic density. Additionally, UST was used to examine the effects of tamoxifen on breast density. Tamoxifen has been shown to reduce mammographic density and breast cancer risk for some women. Preliminary data for 52 patients has shown promising results so far. UST density has decreased for approximately a similar percentage of patients as has been measured for mammographic density. These changes have been measured over short time frames that could not be achieved using mammography. These results show that UST\u27s ability to measure breast density is consistent with mammography, the current standard of care. UST has the potential to become a safe and effective device that can be used to reliably assess breast density and serial changes in breast density

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

Development and Validation of Mechatronic Systems for Image-Guided Needle Interventions and Point-of-Care Breast Cancer Screening with Ultrasound (2D and 3D) and Positron Emission Mammography

The successful intervention of breast cancer relies on effective early detection and definitive diagnosis. While conventional screening mammography has substantially reduced breast cancer-related mortalities, substantial challenges persist in women with dense breasts. Additionally, complex interrelated risk factors and healthcare disparities contribute to breast cancer-related inequities, which restrict accessibility, impose cost constraints, and reduce inclusivity to high-quality healthcare. These limitations predominantly stem from the inadequate sensitivity and clinical utility of currently available approaches in increased-risk populations, including those with dense breasts, underserved and vulnerable populations. This PhD dissertation aims to describe the development and validation of alternative, cost-effective, robust, and high-resolution systems for point-of-care (POC) breast cancer screening and image-guided needle interventions. Specifically, 2D and 3D ultrasound (US) and positron emission mammography (PEM) were employed to improve detection, independent of breast density, in conjunction with mechatronic and automated approaches for accurate image acquisition and precise interventional workflow. First, a mechatronic guidance system for US-guided biopsy under high-resolution PEM localization was developed to improve spatial sampling of early-stage breast cancers. Validation and phantom studies showed accurate needle positioning and 3D spatial sampling under simulated PEM localization. Subsequently, a whole-breast spatially-tracked 3DUS system for point-of-care screening was developed, optimized, and validated within a clinically-relevant workspace and healthy volunteer studies. To improve robust image acquisition and adaptability to diverse patient populations, an alternative, cost-effective, portable, and patient-dedicated 3D automated breast (AB) US system for point-of-care screening was developed. Validation showed accurate geometric reconstruction, feasible clinical workflow, and proof-of-concept utility across healthy volunteers and acquisition conditions. Lastly, an orthogonal acquisition and 3D complementary breast (CB) US generation approach were described and experimentally validated to improve spatial resolution uniformity by recovering poor out-of-plane resolution. These systems developed and described throughout this dissertation show promise as alternative, cost-effective, robust, and high-resolution approaches for improving early detection and definitive diagnosis. Consequently, these contributions may advance breast cancer-related equities and improve outcomes in increased-risk populations and limited-resource settings