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

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

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

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

Simulations and experimental assessment of dosimetric evaluations for breast imaging studies with Synchrotron Radiation

openNel migliorare la diagnosi precoce del tumore al seno, a partire dal 2006, è attivo a Trieste uno studio clinico che utilizza la luce di sincrotrone come sorgente di raggi x per eseguire l’esame mammografico (Castelli and et al., 2011). Il sincrotrone Elettra (situato sull’altopiano carsico di Basovizza, Trieste) ospita infatti una facility per l’esecuzione dell’esame mammografico lungo la linea di luce SYRMEP (SYnchrotron Radiation for MEdical Physics). A partire dal 2013 è attivo il progetto SYRMA-CT (finanziato dall’Istituto Nazionale di Fisica Nucleare) che ha come principale obbiettivo quello di attuare il primo studio clinico di Breast Computed Tomography con luce di sincrotone. Il progetto SYRMA-CT (SYnchrotron Radiation for MAmmograpy - Computed Tomography) si inserisce nel trend globale di passaggio dalle immagini 2D a quelle 3D e ingloba al suo interno l’esperienza maturata durante la sperimentazione clinica del programma di Mammografia con la Radiazione di Sincrotrone (MSR). Scopo del presente lavoro di dottorato è quello di estendere la grandezza utilizzata per il calcolo della dose in breast-CT (i.e. Mean Glandular Dose, MGD) alla particolare situazione dell’esame con luce di Sincrotrone. L’esame prevede infatti una situazione di irraggiamento parziale dell’organo (da 3 cm fino ad un massimo di 5 cm) e l’utilizzo di una sorgente monocromatica. Nel corso del lavoro di tesi è stato sviluppato un codice di simulazione Monte Carlo basato sul toolkit GEANT4 che permettesse di calcolare i coefficienti necessari per la stima della dose (DgNct ). Il codice è stato validato confrontandolo sia con la letteratura che con specifiche misure sperimentali alla linea di luce SYRMEP. Due grandezze (che estendono il concetto di MGD) per la stima della dose sono state proposte (Mettivier et al., 2016): MGDt (che tiene conto della dose dovuta alla radiaizone diffusa all’esterno della zona irragiata) e MGDv (che considera solo la dose nella regione irraggiata dell’organo). Il codice sviluppato è inoltre utilizzato per l’ottimizzazione dei parametri energetici che saranno alla base del protocollo d’esame da sottoporre al comitato etico. Sono in fase di studio le distribuzioni di dose che tengono conto delle diverse modalità di ir- raggiamento (quali spiral-CT, irraggiamento di tipi step and go, etc.) nonchè la possibilità di stimare le dosi post-exam attraverso l’ implementazione all’interno del codice delle immagini delle pazienti stesse ottenute durante l’esame.SCUOLA DI DOTTORATO DI RICERCA IN FISICATROMBA GIULIANAembargoed_20170317Fedon, ChristianFedon, Christia

REDUCING THE BURDEN OF CANCER WITH ARTIFICIAL INTELLIGENCE: IMAGE-BASED MODELS FOR BREAST CANCER DETECTION, ADVANCED STAGE RISK, AND CROSS-MODALITY VISUALIZATION

Ph.D