Breast Tomosynthesis: Aspects on detection and perception of simulated lesions

The aim of this thesis was to investigate aspects on detectability of simulated lesions (microcalcifications and masses) in digital mammography (DM) and breast tomosynthesis (BT). Perception in BT image volumes were also investigated by evaluating certain reading conditions. The first study concerned the effect of system noise on the detection of masses and microcalcification clusters in DM images using a free-response task. System noise has an impact on image quality and is related to the dose level. It was found to have a substantial impact on the detection of microcalcification clusters, whereas masses were relatively unaffected. The effect of superimposed tissue in DM is the major limitation hampering the detection of masses. BT is a three-dimensional technique that reduces the effect of superimposed tissue. In the following two studies visibility was quantified for both imaging modalities in terms of the required contrast at a fixed detection performance (92% correct decisions). Contrast detail plots for lesions with sizes 0.2, 1, 3, 8 and 25 mm were generated. The first study involved only an in-plane BT slice, where the lesion centre appeared. The second study repeated the same procedure in BT image volumes for 3D distributed microcalcification clusters and 8 mm masses at two dose levels. Both studies showed that BT needs substantially less contrast than DM for lesions above 1 mm. Furthermore, the contrast threshold increased as the lesion size increased for both modalities. This is in accordance with the reduced effect of superimposed tissue in BT. For 0.2 mm lesions, substantially more contrast was needed. At equal dose, DM was better than BT for 0.2 mm lesions and microcalcification clusters. Doubling the dose substantially improved the detection in BT. Thus, system noise has a substantial impact on detection. The final study evaluated reading conditions for BT image volumes. Four viewing procedures were assessed: free scroll browsing only or combined with initial cine loops at frame rates of 9, 14 and 25 fps. They were viewed on a wide screen monitor placed in vertical or horizontal positions. A free-response task and eye tracking were utilized to record the detection performance, analysis time, visual attention and search strategies. Improved reading conditions were found for horizontally aligned BT image volumes when using free scroll browsing only or combined with a cine loop at the fastest frame rate

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

Advancing the Clinical Potential of Carbon Nanotube-enabled stationary 3D Mammography

Scope and purpose. 3D imaging has revolutionized medicine. Digital breast tomosynthesis (DBT), also recognized as 3D mammography, is a relatively recent example. stationary DBT (sDBT) is an experimental technology in which the single moving x-ray source of conventional DBT has been replaced by a fixed array of carbon nanotube (CNT)-enabled sources. Given the potential for a higher spatial and temporal resolution compared to commercially-available, moving-source DBT devices, it was hypothesized that sDBT would provide a valuable tool for breast imaging. As such, the purpose of this work was to explore the clinical potential of sDBT. To accomplish this purpose, three broad Aims were set forth: (1) study the challenges of scatter and artifact with sDBT, (2) assess the performance of sDBT relative to standard mammographic screening approaches, and (3) develop a synthetic mammography capability for sDBT. Throughout the work, developing image processing approaches to maximize the diagnostic value of the information presented to readers remained a specific goal. Data sources and methodology. Sitting at the intersection of development and clinical application, this work involved both basic experimentation and human study. Quantitative measures of image quality as well as reader preference and accuracy were used to assess the performance of sDBT. These studies imaged breast-mimicking phantoms, lumpectomy specimens, and human subjects on IRB-approved study protocols, often using standard 2D and conventional 3D mammography for reference. Key findings. Characterizing scatter and artifact allowed the development of new processing approaches to improve image quality. Additionally, comparing the performance of sDBT to standard breast imaging technologies helped identify opportunities for improvement through processing. This line of research culminated in the incorporation of a synthetic mammography capability into sDBT, yielding images that have the potential to improve the diagnostic value of sDBT. Implications. This work advanced the evolution of CNT-enabled sDBT toward a viable clinical tool by incorporating key image processing functionality and characterizing the performance of sDBT relative to standard breast imaging techniques. The findings confirmed the clinical utility of sDBT while also suggesting promising paths for future research and development with this unique approach to breast imaging.Doctor of Philosoph

Measurement of Tumor Extent and Effects of Breast Compression in Digital Mammography and Breast Tomosynthesis

Breast cancer is the most common form of cancer affecting women in the western countries. Today x-ray digital mammography (DM) of the breast is commonly used for early detection of breast cancer. However, the sensitivity of mammography is limited, mainly due to the fact that a 3D volume is projected down to a 2D image. This problem can be partially solved by a tomographic technique. Breast tomosynthesis (BT) reduces the detrimental effect of the projected anatomy. Tumor size is an important predictor of prognosis and treatment effect. We hypothesized that the tumor outline would be better defined in BT and therefore tumor measurement in BT would be more accurate compared with DM. The results showed that breast tumor size measured on BT correlated better with the size measured by the pathologists on the surgical specimens compared with measurement on DM. Breast compression is important in mammography both to improve image quality and to reduce the radiation dose to the breast, but it also has a negative consequence as some women refrain from mammography due to the pain associated with the examination. Since BT is a 3D technique, it was hypothesized that less breast compression force can be applied. The results indicated that less compression force is possible without significantly compromising the diagnostic quality of the image and that the patient comfort was improved. An applied breast compression force as used in mammography results in a pressure distribution over the breast. The pressure distribution was assessed using thin pressure sensors attached to the compression plate. The results showed that the pressure distribution was heterogeneous in appearance and varied widely between different breasts. In almost half of the subjects most of the pressure was over the juxtathoracic part of the breast and the pectoral muscle with little or no pressure over the rest of the breast. Another concern regarding breast compression is the question whether the resulting pressure might damage tumors, causing a shedding of malignant cells into the blood system. Peripheral venous blood samples were drawn before and after breast compression and analyzed for circulating tumor cells. The study found no elevated number of circulating cancer cells in peripheral blood after breast compression. Future analysis of samples from veins draining the breast are needed to study if circulating tumor cells are being trapped in the lung capillaries

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

BACKGROUND: Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions. OBJECTIVES: The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions. STUDY POPULATION: Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent. INTERVENTION: All participants underwent a two-view 2D mammography of both breasts and two-view DBT imaging. Image-processing software generated a synthetic 2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY: In an independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT or (3) synthetic 2D + DBT images for each case without access to original screening mammograms or prior examinations. Sensitivities and specificities were calculated for each reading arm and by subgroup analyses. RESULTS: Data were available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and 1040 (two cancers) family history screening cases. Overall sensitivity was 87% [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%) for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07) and for synthetic 2D + DBT there was no significant difference (p = 0.6). Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D + DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was significantly higher in both DBT reading arms for all subgroups of age, density and dominant radiological feature (p < 0.001 all cases). In all reading arms, specificity tended to be lower for microcalcifications and higher for distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11-20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus 86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87% (p = 0.01); where the dominant radiological feature was a mass, sensitivities were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p = 0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm, with a sensitivity of 91%. CONCLUSIONS: The specificity of DBT and 2D was better than 2D alone but there was only marginal improvement in sensitivity. The performance of synthetic 2D appeared to be comparable to standard 2D. If these results were observed with screening cases, DBT and 2D mammography could benefit to the screening programme by reducing the number of women recalled unnecessarily, especially if a synthetic 2D mammogram were used to minimise radiation exposure. Further research is required into the feasibility of implementing DBT in a screening setting, prognostic modelling on outcomes and mortality, and comparison of 2D and synthetic 2D for different lesion types. STUDY REGISTRATION: Current Controlled Trials ISRCTN73467396. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.Gilbert FJ, Tucker L, Gillan MGC, Willsher P, Cooke J, Duncan KA, et al. The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme – a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone. Health Technol Assess 2015;19(4). © Queen’s Printer and Controller of HMSO 2015. This work was produced by Gilbert et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK