Publications by authors named "Louise Wilkinson"

23 Publications

  • Page 1 of 1

UK National Screening Committee's approach to reviewing evidence on artificial intelligence in breast cancer screening.

Lancet Digit Health 2022 07;4(7):e558-e565

Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.

Artificial intelligence (AI) could have the potential to accurately classify mammograms according to the presence or absence of radiological signs of breast cancer, replacing or supplementing human readers (radiologists). The UK National Screening Committee's assessments of the use of AI systems to examine screening mammograms continues to focus on maximising benefits and minimising harms to women screened, when deciding whether to recommend the implementation of AI into the Breast Screening Programme in the UK. Maintaining or improving programme specificity is important to minimise anxiety from false positive results. When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants). Enriched, multiple-reader, multiple-case, test set laboratory studies are also biased due to the laboratory effect (ie, radiologists' performance in retrospective, laboratory, observer studies is substantially different to their performance in a clinical environment). Therefore, assessment of the effect of incorporating any AI system into the breast screening pathway in prospective studies is required as it will provide key evidence for the effect of the interaction of medical staff with AI, and the impact on women's outcomes.
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http://dx.doi.org/10.1016/S2589-7500(22)00088-7DOI Listing
July 2022

Understanding and supporting peer relationships in adolescents with acquired brain injury: A stakeholder engagement study.

Neuropsychol Rehabil 2022 Apr 21:1-30. Epub 2022 Apr 21.

College of Life and Environmental Sciences, University of Exeter, Exeter, UK.

Peer relationship difficulties in adolescents with acquired brain injury (ABI) are under-recognized and targets for intervention are unclear. From a social constructionist position, this study aimed to engage with stakeholders to develop a collaborative understanding of peer relationship difficulties in adolescents with ABI and seek consultation on what might be required to improve them. Focus groups and semi-structured interviews were conducted with four stakeholder groups: adolescents with ABI ( = 4); parents of adolescents with ABI ( = 7); adults who sustained an ABI in adolescence ( = 2); and specialist practitioners ( = 3). Qualitative data were analysed using thematic analysis. The analysis yielded 11 themes, grouped into two domains. The first, , included themes from "exclusion and a need to belong", to "loss of past self". The second, , comprised themes of "building understanding" and "meaningful social connection", amongst others. A logic model of stakeholder experiences of peer relationship difficulties was constructed. Difficulties with peers can increase vulnerability to feelings of loneliness, shame, and hopelessness for adolescents post-ABI. Stakeholders described that a meaningful intervention would be multi-layered, targeting change within the adolescent's environment and within the adolescent themselves. The presented logic model provides a framework for future intervention development.
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http://dx.doi.org/10.1080/09602011.2022.2062006DOI Listing
April 2022

The Global Reading Room: Recovery of Breast Cancer Screening Services After the COVID-19 Pandemic First Wave.

AJR Am J Roentgenol 2022 May 25:1-2. Epub 2022 May 25.

Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, PA.

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http://dx.doi.org/10.2214/AJR.22.27416DOI Listing
May 2022

Understanding breast cancer as a global health concern.

Br J Radiol 2022 Feb 14;95(1130):20211033. Epub 2021 Dec 14.

Nuffield Department of Population Health, University of Oxford, Oxford, UK.

Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident breast cancer cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization's new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care. In this article, we discuss the key challenges of breast cancer care and control in a global context.
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http://dx.doi.org/10.1259/bjr.20211033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822551PMC
February 2022

Virtual clinical trial to compare cancer detection using combinations of 2D mammography, digital breast tomosynthesis and synthetic 2D imaging.

Eur Radiol 2022 Feb 30;32(2):806-814. Epub 2021 Jul 30.

National Coordinating Centre for the Physics in Mammography, Royal Surrey NHS Foundation Trust, Guildford, UK.

Objectives: This study was designed to compare the detection of subtle lesions (calcification clusters or masses) when using the combination of digital breast tomosynthesis (DBT) and synthetic mammography (SM) with digital mammography (DM) alone or combined with DBT.

Methods: A set of 166 cases without cancer was acquired on a DBT mammography system. Realistic subtle calcification clusters and masses in the DM images and DBT planes were digitally inserted into 104 of the acquired cases. Three study arms were created: DM alone, DM with DBT and SM with DBT. Five mammographic readers located the centre of any lesion within the images that should be recalled for further investigation and graded their suspiciousness. A JAFROC figure of merit (FoM) and lesion detection fraction (LDF) were calculated for each study arm. The visibility of the lesions in the DBT images was compared with SM and DM images.

Results: For calcification clusters, there were no significant differences (p > 0.075) in FoM or LDF. For masses, the FoM and LDF were significantly improved in the arms using DBT compared to DM alone (p < 0.001). On average, both calcification clusters and masses were more visible on DBT than on DM and SM images.

Conclusions: This study demonstrated that masses were detected better with DBT than with DM alone and there was no significant difference (p = 0.075) in LDF between DM&DBT and SM&DBT for calcifications clusters. Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses.

Key Points: • The detection of masses was significantly better using DBT than with digital mammography alone. • The detection of calcification clusters was not significantly different between digital mammography and synthetic 2D images combined with tomosynthesis. • Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses for the imaging technology used.
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http://dx.doi.org/10.1007/s00330-021-08197-xDOI Listing
February 2022

Quantitative breast density analysis to predict interval and node-positive cancers in pursuit of improved screening protocols: a case-control study.

Br J Cancer 2021 09 24;125(6):884-892. Epub 2021 Jun 24.

Centre for Cancer Prevention, Queen Mary University of London, Wolfson Institute of Preventive Medicine, London, UK.

Background: This study investigates whether quantitative breast density (BD) serves as an imaging biomarker for more intensive breast cancer screening by predicting interval, and node-positive cancers.

Methods: This case-control study of 1204 women aged 47-73 includes 599 cancer cases (302 screen-detected, 297 interval; 239 node-positive, 360 node-negative) and 605 controls. Automated BD software calculated fibroglandular volume (FGV), volumetric breast density (VBD) and density grade (DG). A radiologist assessed BD using a visual analogue scale (VAS) from 0 to 100. Logistic regression and area under the receiver operating characteristic curves (AUC) determined whether BD could predict mode of detection (screen-detected or interval); node-negative cancers; node-positive cancers, and all cancers vs. controls.

Results: FGV, VBD, VAS, and DG all discriminated interval cancers (all p < 0.01) from controls. Only FGV-quartile discriminated screen-detected cancers (p < 0.01). Based on AUC, FGV discriminated all cancer types better than VBD or VAS. FGV showed a significantly greater discrimination of interval cancers, AUC = 0.65, than of screen-detected cancers, AUC = 0.61 (p < 0.01) as did VBD (0.63 and 0.53, respectively, p < 0.001).

Conclusion: FGV, VBD, VAS and DG discriminate interval cancers from controls, reflecting some masking risk. Only FGV discriminates screen-detected cancers perhaps adding a unique component of breast cancer risk.
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http://dx.doi.org/10.1038/s41416-021-01466-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438060PMC
September 2021

OPTIMAM Mammography Image Database: A Large-Scale Resource of Mammography Images and Clinical Data.

Radiol Artif Intell 2021 Jan 25;3(1):e200103. Epub 2020 Nov 25.

Department of Scientific Computing (M.D.H.B., D.W., E.L.) and National Co-ordinating Centre for the Physics of Mammography (L.M.W., A.M., K.C.Y.), Royal Surrey NHS Foundation Trust, Egerton Road, Guildford GU2 7XX, England; Centre for Vision, Speech and Signal Processing (M.D.H.B., E.L.) and Department of Physics (K.C.Y.), University of Surrey, Guildford, England; Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, England (M.G.W.); NIHR Cambridge Biomedical Research Centre, Cambridge, England (M.G.W.); Oxford Breast Imaging Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, England (L.S.W.); Department of Radiology, St George's Healthcare NHS Trust, London, England (R.M.G.W.); and Jarvis Breast Screening Centre, Guildford, England (R.M.).

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http://dx.doi.org/10.1148/ryai.2020200103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082293PMC
January 2021

Digital breast tomosynthesis: sensitivity for cancer in younger symptomatic women.

Br J Radiol 2021 Mar 7;94(1119):20201105. Epub 2021 Jan 7.

School of Medicine, University of Dundee, Mailbox 4, Ninewells Hospital & Medical School, Dundee, UK.

Objective: Full-field digital mammography (FFDM) has limited sensitivity for cancer in younger women with denser breasts. Digital breast tomosynthesis (DBT) can reduce the risk of cancer being obscured by overlying tissue. The primary study aim was to compare the sensitivity of FFDM, DBT and FFDM-plus-DBT in women under 60 years old with clinical suspicion of breast cancer.

Methods: This multicentre study recruited 446 patients from UK breast clinics. Participants underwent both standard FFDM and DBT. A blinded retrospective multireader study involving 12 readers and 300 mammograms (152 malignant and 148 benign cases) was conducted.

Results: Sensitivity for cancer was 86.6% with FFDM [95% CI (85.2-88.0%)], 89.1% with DBT [95% CI (88.2-90%)], and 91.7% with FFDM+DBT [95% CI (90.7-92.6%)]. In the densest breasts, the maximum sensitivity increment with FFDM +DBT over FFDM alone was 10.3%, varying by density measurement method. Overall specificity was 81.4% with FFDM [95% CI (80.5-82.3%)], 84.6% with DBT [95% CI (83.9-85.3%)], and 79.6% with FFDM +DBT [95% CI (79.0-80.2%)]. No differences were detected in accuracy of tumour measurement in unifocal cases.

Conclusions: Where available, DBT merits first-line use in the under 60 age group in symptomatic breast clinics, particularly in women known to have very dense breasts.

Advances In Knowledge: This study is one of very few to address the accuracy of DBT in symptomatic rather than screening patients. It quantifies the diagnostic gains of DBT in direct comparison with standard digital mammography, supporting informed decisions on appropriate use of DBT in this population.
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http://dx.doi.org/10.1259/bjr.20201105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011263PMC
March 2021

Left-right breast asymmetry and risk of screen-detected and interval cancers in a large population-based screening population.

Br J Radiol 2020 Aug 22;93(1112):20200154. Epub 2020 Jun 22.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

Objectives: To assess the associations between automated volumetric estimates of mammographic asymmetry and breast cancers detected at the same ("contemporaneous") screen, at subsequent screens, or in between (interval cancers).

Methods: Automated measurements from mammographic images ( = 79,731) were used to estimate absolute asymmetry in breast volume (BV) and dense volume (DV) in a large ethnically diverse population of attendees of a UK breast screening programme. Logistic regression models were fitted to assess asymmetry associations with the odds of a breast cancer detected at contemporaneous screen (767 cases), adjusted for relevant confounders.Nested case-control investigations were designed to examine associations between asymmetry and the odds of: (a) interval cancer (numbers of cases/age-matched controls: 153/646) and (b) subsequent screen-detected cancer (345/1438), via conditional logistic regression.

Results: DV, but not BV, asymmetry was positively associated with the odds of contemporaneous breast cancer (P-for-linear-trend (Pt) = 0.018). This association was stronger for first (prevalent) screens (Pt = 0.012). Both DV and BV asymmetry were positively associated with the odds of an interval cancer diagnosis (Pt = 0.060 and 0.030, respectively). Neither BV nor DV asymmetry were associated with the odds of having a subsequent screen-detected cancer.

Conclusions: Increased DV asymmetry was associated with the risk of a breast cancer diagnosis at a contemporaneous screen or as an interval cancer. BV asymmetry was positively associated with the risk of an interval cancer diagnosis.

Advances In Knowledge: The findings suggest that DV and BV asymmetry may provide additional signals for detecting contemporaneous cancers and assessing the likelihood of interval cancers in population-based screening programmes.
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http://dx.doi.org/10.1259/bjr.20200154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446006PMC
August 2020

Radiological audit of interval breast cancers: Estimation of tumour growth rates.

Breast 2020 Jun 1;51:114-119. Epub 2020 Apr 1.

Leeds Teaching Hospital NHS Trust, Beckett Street, Leeds, LS9 7TF, UK. Electronic address:

Introduction: This multicentre, retrospective study aimed to establish correlation between estimated tumour volume doubling times (TVDT) from a series of interval breast cancers with their clinicopathological features. The potential impact of delayed diagnosis on prognosis was also explored.

Materials And Methods: Interval cancers, where screening mammograms demonstrated changes that were retrospectively classified as either uncertain or suspicious, were reviewed from five screening units within the UK NHS Breast Screening Programme (NHSBSP). Data collected included the time interval between screening mammogram and cancer diagnosis, the size of the initial mammographic abnormality and of the subsequent cancer, demographics, mammographic density and tumour biology. We estimated volume doubling times and the estimated change in size and node status, which would have followed if these cancers had been detected at the previous screen.

Results: 306 interval cancers meeting the inclusion criteria were identified. Average time from screening to diagnosis was 644 days (SD 276 days). 19% were diagnosed in the first twelve months, 42% in the subsequent twelve months and 39% thereafter. Overall average estimated TVDT was 167 days (95% CI 151-186). Significant differences were noted with age (p = 0.01), grade (p < 0.001) and ER status (p < 0.001) with women under 60, grade 3 cancers and ER negative cancers having shorter TVDTs. HER2 positive tumours had shorter doubling times than HER2 negative, but this difference was not statistically significant. It was estimated that diagnosing these cancers at the previous screen would have increased ten-year survival from 82% to 86%.

Conclusion: High grade, ER negativity and younger age were associated with shorter durations of TVDT. The role of HER2 status on interval cancer growth rate requires further assessment. It is likely that the delayed diagnosis of interval cancers confers a 4% reduction in ten-year survival.
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http://dx.doi.org/10.1016/j.breast.2020.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375675PMC
June 2020

An automated approach for the optimised estimation of breast density with Dixon methods.

Br J Radiol 2020 Feb 6;93(1106):20190639. Epub 2019 Nov 6.

CRUK Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden Foundation Trust, London, United Kingdom.

Objective: To present and evaluate an automated method to correct scaling between Dixon water/fat images used in breast density (BD) assessments.

Methods: Dixon images were acquired in 14 subjects with different weightings (flip angles, FA, 4°/16°). Our method corrects intensity differences between water () and fat () images via the application of a uniform scaling factor (SF), determined subject-by-subject. Based on the postulation that optimal SFs yield relatively featureless summed fat/scaled-water () images, each SF was chosen as that which generated the lowest 95th-percentile in the absolute spatial-gradient image-volume of . Water-fraction maps were calculated for data acquired with low/high FAs, and BD (%) was the total percentage water within each breast volume.

Results: Corrected/uncorrected BD ranged from, respectively, 10.9-71.8%/8.9-66.7% for low-FA data to 8.1-74.3%/5.6-54.3% for high-FA data. Corrected metrics had an average absolute increase in BD of 6.4% for low-FA data and 18.4% for high-FA data. BD values estimated from low- and high-FA data were closer following SF-correction.

Conclusion: Our results demonstrate need for scaling in such BD assessments, where our method brought high-FA and low-FA data into closer agreement.

Advances In Knowledge: We demonstrated a feasible method to address a main source of inaccuracy in Dixon-based BD measurements.
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http://dx.doi.org/10.1259/bjr.20190639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055430PMC
February 2020

Ethnic and age differences in right-left breast asymmetry in a large population-based screening population.

Br J Radiol 2020 Jan 4;93(1105):20190328. Epub 2019 Nov 4.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.

Objective: Exposure to sex hormones is important in the pathogenesis of breast cancer and inability to tolerate such exposure may be reflected in increased asymmetrical growth of the breasts. This study aims to characterize, for the first time, asymmetry in breast volume (BV) and radiodense volume (DV) in a large ethnically diverse population.

Methods: Automated measurements from digital raw mammographic images of 54,591 cancer-free participants (aged 47-73) in a UK breast screening programme were used to calculate absolute (cm) and relative asymmetry in BV and DV. Logistic regression models were fitted to assess asymmetry associations with age and ethnicity.

Results: BV and DV absolute asymmetry were positively correlated with the corresponding volumetric dimension (BV or DV). BV absolute asymmetry increased, whilst DV absolute asymmetry decreased, with increasing age (P-for-linear-trend <0.001 for both). Relative to Whites, Blacks had statistically significantly higher, and Chinese lower, BV and DV absolute asymmetries. However, after adjustment for the corresponding underlying volumetric dimension the age and ethnic differences were greatly attenuated. Median relative (fluctuating) BV and DV asymmetry were 2.34 and 3.28% respectively.

Conclusion: After adjusting for the relevant volumetric dimension (BV or DV), age and ethnic differences in absolute breast asymmetry were largely resolved.

Advances In Knowledge: Previous small studies have reported breast asymmetry-breast cancer associations. Automated measurements of asymmetry allow the conduct of large-scale studies to further investigate these associations.
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http://dx.doi.org/10.1259/bjr.20190328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948085PMC
January 2020

Implementation of the SMART MOVE intervention in primary care: a qualitative study using normalisation process theory.

BMC Fam Pract 2018 05 2;19(1):48. Epub 2018 May 2.

Discipline of General Practice, National University of Ireland, Galway, Ireland.

Background: Problematic translational gaps continue to exist between demonstrating the positive impact of healthcare interventions in research settings and their implementation into routine daily practice. The aim of this qualitative evaluation of the SMART MOVE trial was to conduct a theoretically informed analysis, using normalisation process theory, of the potential barriers and levers to the implementation of a mhealth intervention to promote physical activity in primary care.

Methods: The study took place in the West of Ireland with recruitment in the community from the Clare Primary Care Network. SMART MOVE trial participants and the staff from four primary care centres were invited to take part and all agreed to do so. A qualitative methodology with a combination of focus groups (general practitioners, practice nurses and non-clinical staff from four separate primary care centres, n = 14) and individual semi-structured interviews (intervention and control SMART MOVE trial participants, n = 4) with purposeful sampling utilising the principles of Framework Analysis was utilised. The Normalisation Process Theory was used to develop the topic guide for the interviews and also informed the data analysis process.

Results: Four themes emerged from the analysis: personal and professional exercise strategies; roles and responsibilities to support active engagement; utilisation challenges; and evaluation, adoption and adherence. It was evident that introducing a new healthcare intervention demands a comprehensive evaluation of the intervention itself and also the environment in which it is to operate. Despite certain obstacles, the opportunity exists for the successful implementation of a novel healthcare intervention that addresses a hitherto unresolved healthcare need, provided that the intervention has strong usability attributes for both disseminators and target users and coheres strongly with the core objectives and culture of the health care environment in which it is to operate.

Conclusion: We carried out a theoretical analysis of stakeholder informed barriers and levers to the implementation of a novel exercise promotion tool in the Irish primary care setting. We believe that this process amplifies the implementation potential of such an intervention in primary care. The SMART MOVE trial is registered at Current Controlled Trials (ISRCTN99944116; Date of registration: 1st August 2012).
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http://dx.doi.org/10.1186/s12875-018-0737-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932852PMC
May 2018

Design and validation of realistic breast models for use in multiple alternative forced choice virtual clinical trials.

Phys Med Biol 2017 04;62(7):2778-2794

Medical Imaging Group, Centre for Vision, Speech, and Signal Processing, University of Surrey, Guildford, GU2 7XH, United Kingdom. National Coordination Centre for the Physics of Mammography (NCCPM), Royal Surrey County Hospital, Guildford, GU2 7XX, United Kingdom.

A novel method has been developed for generating quasi-realistic voxel phantoms which simulate the compressed breast in mammography and digital breast tomosynthesis (DBT). The models are suitable for use in virtual clinical trials requiring realistic anatomy which use the multiple alternative forced choice (AFC) paradigm and patches from the complete breast image. The breast models are produced by extracting features of breast tissue components from DBT clinical images including skin, adipose and fibro-glandular tissue, blood vessels and Cooper's ligaments. A range of different breast models can then be generated by combining these components. Visual realism was validated using a receiver operating characteristic (ROC) study of patches from simulated images calculated using the breast models and from real patient images. Quantitative analysis was undertaken using fractal dimension and power spectrum analysis. The average areas under the ROC curves for 2D and DBT images were 0.51  ±  0.06 and 0.54  ±  0.09 demonstrating that simulated and real images were statistically indistinguishable by expert breast readers (7 observers); errors represented as one standard error of the mean. The average fractal dimensions (2D, DBT) for real and simulated images were (2.72  ±  0.01, 2.75  ±  0.01) and (2.77  ±  0.03, 2.82  ±  0.04) respectively; errors represented as one standard error of the mean. Excellent agreement was found between power spectrum curves of real and simulated images, with average β values (2D, DBT) of (3.10  ±  0.17, 3.21  ±  0.11) and (3.01  ±  0.32, 3.19  ±  0.07) respectively; errors represented as one standard error of the mean. These results demonstrate that radiological images of these breast models realistically represent the complexity of real breast structures and can be used to simulate patches from mammograms and DBT images that are indistinguishable from patches from the corresponding real breast images. The method can generate about 500 radiological patches (~30 mm  ×  30 mm) per day for AFC experiments on a single workstation. This is the first study to quantitatively validate the realism of simulated radiological breast images using direct blinded comparison with real data via the ROC paradigm with expert breast readers.
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http://dx.doi.org/10.1088/1361-6560/aa622cDOI Listing
April 2017

The B3 conundrum-the radiologists' perspective.

Br J Radiol 2017 Mar 12;90(1071):20160595. Epub 2016 Dec 12.

3 Department of Breast Pathology, King's College London and Guy's Hospital, London, UK.

The management of B3 lesions is both controversial and complicated. There have been recent publications regarding how best to manage this heterogeneous group particularly in light of the Marmot Review and with the advent of vacuum-assisted biopsy technique. It is recognized that B3 lesions on core biopsy can be upgraded to malignancy in up to one-third of cases, but this is predominantly to ductal carcinoma in situ or low-grade invasive tumours. The upgrade rate is mainly associated with B3 lesions with epithelial atypia. This review summarizes the current management and focuses on the proposed future management of these B3 lesions.
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http://dx.doi.org/10.1259/bjr.20160595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601507PMC
March 2017

Microcalcification on mammography: approaches to interpretation and biopsy.

Br J Radiol 2017 Jan 17;90(1069):20160594. Epub 2016 Oct 17.

1 Department of Breast Imaging, St Georges Hospital, Tooting, London.

This article discusses the significance of microcalcifications on mammography and the changes in technology that have influenced management; it also describes a pragmatic approach to investigation of microcalcification in a UK screening programme.
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http://dx.doi.org/10.1259/bjr.20160594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605030PMC
January 2017

Breast density across a regional screening population: effects of age, ethnicity and deprivation.

Br J Radiol 2015 2;88(1055):20150242. Epub 2015 Sep 2.

Department of Radiology, St. George's Hospital, London, UK.

Objective: Breast density (BD) is a recognized risk factor for breast cancer. This study maps density variation across a screening population and identifies demographic distinctions, which may affect density and so impact on cancer development/detection. We focus on the relationship between age, ethnicity and socioeconomic status on density.

Methods: This retrospective study on a screening population adheres to local patient confidentiality requirements. BD data from screening mammograms (March 2013 to September 2014) were measured using Volpara((®))Density(™) software (Volpara((®))Solutions(™), Wellington, New Zealand). Demographics, including patient age, ethnicity and deprivation index, were obtained from our breast screening database and analysed with respect to breast volume (BV), fibroglandular tissue volume (FGV), Volpara %BD and Volpara Grade (1-4 scale, lowest to highest).

Results: Study population demonstrates little difference for BV with respect to age, but a slight negative trend was noted when FGV was evaluated vs age. Density was linked to ethnicity: females of Chinese ethnicity had higher BD largely reflecting their lower BV. Females in the most deprived quintiles tended to have larger and therefore less dense breasts.

Conclusion: Our mapping of BD in a regional screening programme demonstrates impact of age, ethnicity and socioeconomic status on BD with attendant implications for breast cancer risk.

Advances In Knowledge: BD is a known risk factor for development of breast cancer. Density trends in a large regional screening population with respect to age, ethnicity and socioeconomics may eventually help identify the risk of breast cancer in certain subsets of the population.
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http://dx.doi.org/10.1259/bjr.20150242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4743450PMC
January 2016

Correlation of age and HRT use with breast density as assessed by Quantra™.

Breast J 2013 Jan-Feb;19(1):79-86. Epub 2012 Dec 10.

Department of Radiology, Frimley Park Hospital NHS Foundation Trust, Surrey, United Kingdom. [email protected]

Breast density is a significant predictor in the risk of developing breast cancer. Several methods are available for assessing breast density, but most are subject to intra-observer variability and are unable to assess the breast as a three-dimensional structure. Using Quantra(™) to quantify breast density, we have correlated this with risk factors to determine what impact these variables have on breast density. Women attending for full field digital mammography at the South West London Breast Screening Unit between December 2008 and March 2009 were invited to participate in the study by questionnaire. Consenting women returned the questionnaire allowing further data collection including demographics, menopausal status and hormone replacement therapy (HRT) use. Data were correlated against breast density measurements to determine the degree of association. Mammograms were assessed on a Hologic(™) workstation and breast density calculated using Quantra(™). Quantra(™) is an automated algorithm for volumetric assessment of breast tissue composition from digital mammograms. Six-hundred and eighty-three women were invited to participate. Those with implants or mastectomy were excluded. Three-hundred and twenty questionnaires were fully completed and able to be assessed. The mean age of participants was 59 years (range 49-81). Mean density was 19.7% (range 8.5-48.5%). There was a decrease in density with age (Pearson product-moment correlation coefficient -0.17). Correlation between density and HRT use showed a significant positive result (correlation coefficient 0.07). Quantra(™) has shown to be an accurate, reproducible tool for quantifying breast density, demonstrated by its correlation with lifestyle and demographic data. Given its ease of acquisition this may be the future of breast density quantification in the digital age.
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http://dx.doi.org/10.1111/tbj.12046DOI Listing
June 2013

Conformational flexibility determines selectivity and antibacterial, antiplasmodial, and anticancer potency of cationic α-helical peptides.

J Biol Chem 2012 Oct 6;287(41):34120-33. Epub 2012 Aug 6.

Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH, United Kingdom.

We used a combination of fluorescence, circular dichroism (CD), and NMR spectroscopies in conjunction with size exclusion chromatography to help rationalize the relative antibacterial, antiplasmodial, and cytotoxic activities of a series of proline-free and proline-containing model antimicrobial peptides (AMPs) in terms of their structural properties. When compared with proline-free analogs, proline-containing peptides had greater activity against Gram-negative bacteria, two mammalian cancer cell lines, and intraerythrocytic Plasmodium falciparum, which they were capable of killing without causing hemolysis. In contrast, incorporation of proline did not have a consistent effect on peptide activity against Mycobacterium tuberculosis. In membrane-mimicking environments, structures with high α-helix content were adopted by both proline-free and proline-containing peptides. In solution, AMPs generally adopted disordered structures unless their sequences comprised more hydrophobic amino acids or until coordinating phosphate ions were added. Proline-containing peptides resisted ordering induced by either method. The roles of the angle subtended by positively charged amino acids and the positioning of the proline residues were also investigated. Careful positioning of proline residues in AMP sequences is required to enable the peptide to resist ordering and maintain optimal antibacterial activity, whereas varying the angle subtended by positively charged amino acids can attenuate hemolytic potential albeit with a modest reduction in potency. Maintaining conformational flexibility improves AMP potency and selectivity toward bacterial, plasmodial, and cancerous cells while enabling the targeting of intracellular pathogens.
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http://dx.doi.org/10.1074/jbc.M112.359067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464521PMC
October 2012

Localized fibroglandular tissue as a predictor of future tumor location within the breast.

Cancer Epidemiol Biomarkers Prev 2011 Aug 21;20(8):1718-25. Epub 2011 Jun 21.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Mammographic density (MD) is a strong marker of breast cancer risk, but it is unclear whether tumors arise specifically within dense tissue.

Methods: In 231 British women diagnosed with breast cancer after at least one negative annual screening during a mammographic screening trial, we assessed whether tumor location was related to localized MD 5 years prior to diagnosis. Radiologists identified tumor locations on digitised films. We used a validated algorithm to align serial images from the same woman to locate the corresponding point on the prediagnostic film. A virtual 1 cm square grid was overlaid on prediagnostic films and MD calculated for each square within a woman's breast (mean = 271 squares/film). Conditional logistic regression, matching on a woman's breast, was used to estimate the odds of a tumor arising in a square in relation to its prediagnostic square-specific MD.

Results: Median (interquartile range) prediagnostic MD was 98.2% (46.8%-100%) in 1 cm-squares that subsequently contained the tumor and 41.0% (31.5%-53.9%) for the whole breast. The odds of a tumor arising in a 1 cm-square were, respectively, 6.1 (95% CI: 1.9-20.1), 16.6 (5.2-53.2), and 25.5-fold (8.1-80.3) higher for squares in the second, third, and fourth quartiles of prediagnostic MD relative to those in the lowest quartile within that breast (P(trend) < 0.001). The corresponding odds ratios were 2.3 (1.3-4.0), 3.9 (2.3-6.4), and 4.6 (2.8-7.6) if a 3 cm-square grid was used.

Conclusion: Tumors arise predominantly within the radiodense breast tissue.

Impact: Localized MD may be used as a predictor of subsequent tumor location within the breast.
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http://dx.doi.org/10.1158/1055-9965.EPI-11-0423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154655PMC
August 2011

Automated registration of diagnostic to prediagnostic x-ray mammograms: evaluation and comparison to radiologists' accuracy.

Med Phys 2010 Sep;37(9):4530-9

Cancer Research UK Epidemiology and Genetics Group, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.

Purpose: To compare and evaluate intensity-based registration methods for computation of serial x-ray mammogram correspondence.

Methods: X-ray mammograms were simulated from MRIs of 20 women using finite element methods for modeling breast compressions and employing a MRI/x-ray appearance change model. The parameter configurations of three registration methods, affine, fluid, and free-form deformation (FFD), were optimized for registering x-ray mammograms on these simulated images. Five mammography film readers independently identified landmarks (tumor, nipple, and usually two other normal features) on pairs of diagnostic and corresponding prediagnostic digitized images from 52 breast cancer cases. Landmarks were independently reidentified by each reader. Target registration errors were calculated to compare the three registration methods using the reader landmarks as a gold standard. Data were analyzed using multilevel methods.

Results: Between-reader variability varied with landmark (p < 0.01) and screen (p = 0.03), with between-reader mean distance (mm) in point location on the diagnostic/prediagnostic images of 2.50 (95% CI 1.95, 3.15)/2.84 (2.24, 3.55) for nipples and 4.26 (3.43, 5.24)/4.76 (3.85, 5.84) for tumors. Registration accuracy was sensitive to the type of landmark and the amount of breast density. For dense breasts (> or = 40%), the affine and fluid methods outperformed FFD. For breasts with lower density, the affine registration surpassed both fluid and FFD. Mean accuracy (mm) of the affine registration varied between 3.16 (95% CI 2.56, 3.90) for nipple points in breasts with density 20%-39% and 5.73 (4.80, 6.84) for tumor points in breasts with density < 20%.

Conclusions: Affine registration accuracy was comparable to that between independent film readers. More advanced two-dimensional nonrigid registration algorithms were incapable of increasing the accuracy of image alignment when compared to affine registration.
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http://dx.doi.org/10.1118/1.3457470DOI Listing
September 2010

African American English dialect and performance on nonword spelling and phonemic awareness tasks.

Am J Speech Lang Pathol 2007 May;16(2):157-68

Communication Sciences and Disorders, University of South Florida, 4202 East Fowler Avenue, PCD 1017, Tampa, FL 33620-8150, USA.

Purpose: To evaluate the role of dialect on phonemic awareness and nonword spelling tasks. These tasks were selected for their reliance on phonological and orthographic processing, which may be influenced by dialect use.

Method: Eighty typically developing African American children in Grades 1 and 3 were first screened for dialect use and then completed a standardized test of phonological processing and a nonword spelling measure. The influence of dialect was analyzed in both experimental tasks, followed by a qualitative analysis of dialect use in nonword spellings.

Results: Dialect density measures based solely on the use of African American English (AAE) phonological features explained few differences in phonological processing scores. In contrast, correlations indicated that children with higher dialect densities produced more nonword spelling errors influenced by AAE, an effect most evident in Grade 3. Qualitative analyses revealed AAE phonological features occurring in many of the misspelled nonwords.

Conclusion: After Grade 2, nonword spelling may be more sensitive to the effects of dialect variation than are phonemic awareness tasks. It is suggested that spelling may be a more sensitive clinical indicator of difficulties in integrating the phonological and orthographic information needed for fluent decoding skill.
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http://dx.doi.org/10.1044/1058-0360(2007/020)DOI Listing
May 2007

Scaffolds for Learning to Read in an Inclusion Classroom.

Lang Speech Hear Serv Sch 2000 Jul;31(3):265-279

Rutgers, The State University of New Jersey, New Brunswick.

Purpose: This article describes a study on the scaffolding of learning to read in a primary-level, continuous-progress, inclusion classroom that stressed a critical thinking curriculum and employed a collaborative teaching model. Two emergent reading groups were the focus of study-one group that was taught by a general educator and the other by a special educator. The primary purposes were to discern the teachers' discourse patterns in order to define whether scaffolding sequences were more directive or more supportive and the degree to which these sequences represented differentiated instruction for children with a language learning disability (LLD).

Method: Two students with an LLD and two younger, typically developing peers were videotaped in their emergent reading groups during an 8-week period. The distribution, types, and functions of teacher scaffolding sequences were examined.

Results: Both team members primarily used directive scaffolding sequences, suggesting that the assistance provided to children emphasized only direct instruction (skill learning) and not analytical thinking concerning phonemegrapheme relationships (strategy learning). Distribution of scaffolding sequence types directed to the four students indicated that the two children with an LLD were receiving reading instruction that was undifferentiated from the two typically developing, younger children.

Clinical Implications: In order for children with an LLD to benefit from inclusion, explicit, systematic, and intensive instruction in phonological awareness and spelling-sound relationships should be implemented within the context of multilevel instruction that balances skill- and strategy-based learning.
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http://dx.doi.org/10.1044/0161-1461.3103.265DOI Listing
July 2000
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