Radiomics in Oncology: A Practical Guide.

Radiomics refers to the extraction of mineable data from medical imaging and has been applied within oncology to improve diagnosis, prognostication, and clinical decision support, with the goal of delivering precision medicine. The authors provide a practical approach for successfully implementing a radiomic workflow from planning and conceptualization through manuscript writing. Applications in oncology typically are either classification tasks that involve computing the probability of a sample belonging to a category, such as benign versus malignant, or prediction of clinical events with a time-to-event analysis, such as overall survival. The radiomic workflow is multidisciplinary, involving radiologists and data and imaging scientists, and follows a stepwise process involving tumor segmentation, image preprocessing, feature extraction, model development, and validation. Images are curated and processed before segmentation, which can be performed on tumors, tumor subregions, or peritumoral zones. Extracted features typically describe the distribution of signal intensities and spatial relationship of pixels within a region of interest. To improve model performance and reduce overfitting, redundant and nonreproducible features are removed. Validation is essential to estimate model performance in new data and can be performed iteratively on samples of the dataset (cross-validation) or on a separate hold-out dataset by using internal or external data. A variety of noncommercial and commercial radiomic software applications can be used. Guidelines and artificial intelligence checklists are useful when planning and writing up radiomic studies. Although interest in the field continues to grow, radiologists should be familiar with potential pitfalls to ensure that meaningful conclusions can be drawn. Online supplemental material is available for this article. Published under a CC BY 4.0 license.

Radiomic features of cervical cancer on T2-and diffusion-weighted MRI: Prognostic value in low-volume tumors suitable for trachelectomy.

BACKGROUND: Textural features extracted from MRI potentially provide prognostic information additional to volume for influencing surgical management of cervical cancer. PURPOSE: To identify textural features that differ between cervical tumors above and below the volume threshold of eligibility for trachelectomy and determine their value in predicting recurrence in patients with low-volume tumors. METHODS: Of 378 patients with Stage1-2 cervical cancer imaged prospectively (3T, endovaginal coil), 125 had well-defined, histologically-confirmed squamous or adenocarcinomas with >100 voxels (>0.07 cm3) suitable for radiomic analysis. Regions-of-interest outlined the whole tumor on T2-W images and apparent diffusion coefficient (ADC) maps. Textural features based on grey-level co-occurrence matrices were compared (Mann-Whitney test with Bonferroni correction) between tumors greater (n = 46) or less (n = 79) than 4.19 cm3. Clustering eliminated correlated variables. Significantly different features were used to predict recurrence (regression modelling) in surgically-treated patients with low-volume tumors and compared with a model using clinico-pathological features. RESULTS: Textural features (Dissimilarity, Energy, ClusterProminence, ClusterShade, InverseVariance, Autocorrelation) in 6 of 10 clusters from T2-W and ADC data differed between high-volume (mean ± SD 15.3 ± 11.7 cm3) and low-volume (mean ± SD 1.3 ± 1.2 cm3) tumors. (p < 0.02). In low-volume tumors, predicting recurrence was indicated by: Dissimilarity, Energy (ADC-radiomics, AUC = 0.864); Dissimilarity, ClusterProminence, InverseVariance (T2-W-radiomics, AUC = 0.808); Volume, Depth of Invasion, LymphoVascular Space Invasion (clinico-pathological features, AUC = 0.794). Combining ADC-radiomic (but not T2-radiomic) and clinico-pathological features improved prediction of recurrence compared to the clinico-pathological model (AUC = 0.916, p = 0.006). Findings were supported by bootstrap re-sampling (n = 1000). CONCLUSION: Textural features from ADC maps and T2-W images differ between high- and low-volume tumors and potentially predict recurrence in low-volume tumors.

Growth Trajectories, Breast Size, and Breast-Tissue Composition in a British Prebirth Cohort of Young Women.

Mammographic percent density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations of magnetic resonance imaging (MRI) breast-tissue composition at age 21 years with prospectively collected measurements of body size and composition from birth to early adulthood and markers of puberty (all standardized) in a sample of 500 nulliparous women from a prebirth cohort of children born in Avon, United Kingdom, in 1991-1992 and followed up to 2011-2014. Linear models were fitted to estimate relative change in MRI percent water, which is equivalent to mammographic percent density, associated with a 1-standard-deviation increase in the exposure of interest. In mutually adjusted analyses, MRI percent water was positively associated with birth weight (relative change (RC) = 1.03, 95% confidence interval (CI): 1.00, 1.06) and pubertal height growth (RC = 1.07, 95% CI: 1.02, 1.13) but inversely associated with pubertal weight growth (RC = 0.86, 95% CI: 0.84, 0.89) and changes in dual-energy x-ray absorptiometry percent body fat mass (e.g., for change between ages 11 years and 13.5 years, RC = 0.96, 95% CI: 0.93, 0.99). Ages at thelarche and menarche were positively associated with MRI percent water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role.

Extracranial Soft-Tissue Tumors: Repeatability of Apparent Diffusion Coefficient Estimates from Diffusion-weighted MR Imaging.

Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.

Pre-natal exposures and breast tissue composition: findings from a British pre-birth cohort of young women and a systematic review.

BACKGROUND: Breast density, the amount of fibroglandular tissue in the adult breast for a women's age and body mass index, is a strong biomarker of susceptibility to breast cancer, which may, like breast cancer risk itself, be influenced by events early in life. In the present study, we investigated the association between pre-natal exposures and breast tissue composition. METHODS: A sample of 500 young, nulliparous women (aged approximately 21 years) from a U.K. pre-birth cohort underwent a magnetic resonance imaging examination of their breasts to estimate percent water, a measure of the relative amount of fibroglandular tissue equivalent to mammographic percent density. Information on pre-natal exposures was collected throughout the mothers' pregnancy and shortly after delivery. Regression models were used to investigate associations between percent water and pre-natal exposures. Mediation analysis, and a systematic review and meta-analysis of the published literature, were also conducted. RESULTS: Adjusted percent water in young women was positively associated with maternal height (p for linear trend [p t] = 0.005), maternal mammographic density in middle age (p t = 0.018) and the participant's birth size (p t < 0.001 for birthweight). A 1-SD increment in weight (473 g), length (2.3 cm), head circumference (1.2 cm) and Ponderal Index (4.1 g/cm3) at birth were associated with 3 % (95 % CI 2-5 %), 2 % (95 % CI 0-3 %), 3 % (95 % CI 1-4 %) and 1 % (95 % CI 0-3 %), respectively, increases in mean adjusted percent water. The effect of maternal height on the participants' percent water was partly mediated through birth size, but there was little evidence that the effect of birthweight was primarily mediated via adult body size. The meta-analysis supported the study findings, with breast density being positively associated with birth size. CONCLUSIONS: These findings provide strong evidence of pre-natal influences on breast tissue composition. The positive association between birth size and relative amount of fibroglandular tissue indicates that breast density and breast cancer risk may share a common pre-natal origin.

Detecting microvascular changes in the mouse spleen using optical computed tomography.

Methods of monitoring drug toxicity in off-target organs are very important in the development of effective and safe drugs. Standard 2-D techniques, such as histology, are prone to sampling errors and can miss important information. We demonstrate a novel application of optical computed tomography (CT) imaging to quantitatively assess, in 3-D, the response of adult murine spleen to off-target drug toxicity induced by treatment with the vascular disrupting agent ZD6126. Reconstructed images from optical CT scans sensitive to haemoglobin absorption reveal detailed, high-contrast 3-D maps of splenic structure and microvasculature. A significant difference in total splenic volume was found between vehicle and ZD6126-treated cohorts, with mean volumes of 61±3mm(3) and 44±3mm(3) respectively (both n=3, p=0.05). Textural statistics for each sample were calculated using grey-level co-occurrence matrices (GLCMs). Standard 2-D GLCM analysis was found to be slice-dependent while 3-D GLCM contrast and homogeneity analysis resulted in separation of the vehicle and ZD6126-treated cohorts over a range of length scales.

A scan-specific quality control acquisition for clinical whole-body (WB) MRI protocols.

Objective.Image quality in whole-body MRI (WB-MRI) may be degraded by faulty radiofrequency (RF) coil elements or mispositioning of the coil arrays. Phantom-based quality control (QC) is used to identify broken RF coil elements but the frequency of these acquisitions is limited by scanner and staff availability. This work aimed to develop a scan-specific QC acquisition and processing pipeline to detect broken RF coil elements, which is sufficiently rapid to be added to the clinical WB-MRI protocol. The purpose of this is to improve the quality of WB-MRI by reducing the number of patient examinations conducted with suboptimal equipment.Approach.A rapid acquisition (14 s additional acquisition time per imaging station) was developed that identifies broken RF coil elements by acquiring images from each individual coil element and using the integral body coil. This acquisition was added to one centre's clinical WB-MRI protocol for one year (892 examinations) to evaluate the effect of this scan-specific QC. To demonstrate applicability in multi-centre imaging trials, the technique was also implemented on scanners from three manufacturers.Main results. Over the course of the study RF coil elements were flagged as potentially broken on five occasions, with the faults confirmed in four of those cases. The method had a precision of 80% and a recall of 100% for detecting faulty RF coil elements. The coil array positioning measurements were consistent across scanners and have been used to define the expected variation in signal.Significance. The technique demonstrated here can identify faulty RF coil elements and positioning errors and is a practical addition to the clinical WB-MRI protocol. This approach was fully implemented on systems from two manufacturers and partially implemented on a third. It has potential to reduce the number of clinical examinations conducted with suboptimal hardware and improve image quality across multi-centre studies.

Curation of myeloma observational study MALIMAR using XNAT: solving the challenges posed by real-world data.

OBJECTIVES: MAchine Learning In MyelomA Response (MALIMAR) is an observational clinical study combining "real-world" and clinical trial data, both retrospective and prospective. Images were acquired on three MRI scanners over a 10-year window at two institutions, leading to a need for extensive curation. METHODS: Curation involved image aggregation, pseudonymisation, allocation between project phases, data cleaning, upload to an XNAT repository visible from multiple sites, annotation, incorporation of machine learning research outputs and quality assurance using programmatic methods. RESULTS: A total of 796 whole-body MR imaging sessions from 462 subjects were curated. A major change in scan protocol part way through the retrospective window meant that approximately 30% of available imaging sessions had properties that differed significantly from the remainder of the data. Issues were found with a vendor-supplied clinical algorithm for "composing" whole-body images from multiple imaging stations. Historic weaknesses in a digital video disk (DVD) research archive (already addressed by the mid-2010s) were highlighted by incomplete datasets, some of which could not be completely recovered. The final dataset contained 736 imaging sessions for 432 subjects. Software was written to clean and harmonise data. Implications for the subsequent machine learning activity are considered. CONCLUSIONS: MALIMAR exemplifies the vital role that curation plays in machine learning studies that use real-world data. A research repository such as XNAT facilitates day-to-day management, ensures robustness and consistency and enhances the value of the final dataset. The types of process described here will be vital for future large-scale multi-institutional and multi-national imaging projects. CRITICAL RELEVANCE STATEMENT: This article showcases innovative data curation methods using a state-of-the-art image repository platform; such tools will be vital for managing the large multi-institutional datasets required to train and validate generalisable ML algorithms and future foundation models in medical imaging. KEY POINTS: • Heterogeneous data in the MALIMAR study required the development of novel curation strategies. • Correction of multiple problems affecting the real-world data was successful, but implications for machine learning are still being evaluated. • Modern image repositories have rich application programming interfaces enabling data enrichment and programmatic QA, making them much more than simple "image marts".

Integrating Artificial Intelligence Tools in the Clinical Research Setting: The Ovarian Cancer Use Case.

Artificial intelligence (AI) methods applied to healthcare problems have shown enormous potential to alleviate the burden of health services worldwide and to improve the accuracy and reproducibility of predictions. In particular, developments in computer vision are creating a paradigm shift in the analysis of radiological images, where AI tools are already capable of automatically detecting and precisely delineating tumours. However, such tools are generally developed in technical departments that continue to be siloed from where the real benefit would be achieved with their usage. Significant effort still needs to be made to make these advancements available, first in academic clinical research and ultimately in the clinical setting. In this paper, we demonstrate a prototype pipeline based entirely on open-source software and free of cost to bridge this gap, simplifying the integration of tools and models developed within the AI community into the clinical research setting, ensuring an accessible platform with visualisation applications that allow end-users such as radiologists to view and interact with the outcome of these AI tools.

Interpretability of radiomics models is improved when using feature group selection strategies for predicting molecular and clinical targets in clear-cell renal cell carcinoma: insights from the TRACERx Renal study.

BACKGROUND: The aim of this work is to evaluate the performance of radiomics predictions for a range of molecular, genomic and clinical targets in patients with clear cell renal cell carcinoma (ccRCC) and demonstrate the impact of novel feature selection strategies and sub-segmentations on model interpretability. METHODS: Contrast-enhanced CT scans from the first 101 patients recruited to the TRACERx Renal Cancer study (NCT03226886) were used to derive radiomics classification models to predict 20 molecular, histopathology and clinical target variables. Manual 3D segmentation was used in conjunction with automatic sub-segmentation to generate radiomics features from the core, rim, high and low enhancing sub-regions, and the whole tumour. Comparisons were made between two classification model pipelines: a Conventional pipeline reflecting common radiomics practice, and a Proposed pipeline including two novel feature selection steps designed to improve model interpretability. For both pipelines nested cross-validation was used to estimate prediction performance and tune model hyper-parameters, and permutation testing was used to evaluate the statistical significance of the estimated performance measures. Further model robustness assessments were conducted by evaluating model variability across the cross-validation folds. RESULTS: Classification performance was significant (p < 0.05, H0:AUROC = 0.5) for 11 of 20 targets using either pipeline and for these targets the AUROCs were within ± 0.05 for the two pipelines, except for one target where the Proposed pipeline performance increased by > 0.1. Five of these targets (necrosis on histology, presence of renal vein invasion, overall histological stage, linear evolutionary subtype and loss of 9p21.3 somatic alteration marker) had AUROC > 0.8. Models derived using the Proposed pipeline contained fewer feature groups than the Conventional pipeline, leading to more straightforward model interpretations without loss of performance. Sub-segmentations lead to improved performance and/or improved interpretability when predicting the presence of sarcomatoid differentiation and tumour stage. CONCLUSIONS: Use of the Proposed pipeline, which includes the novel feature selection methods, leads to more interpretable models without compromising prediction performance. TRIAL REGISTRATION: NCT03226886 (TRACERx Renal).

Informatics in radiology: development of a research PACS for analysis of functional imaging data in clinical research and clinical trials.

Picture archiving and communication systems (PACS) provide limited flexibility for the development of novel research methods. By contrast, the research model of data access is more flexible but has vulnerabilities in numerous areas. No single monolithic application can fulfill the diverse and rapidly changing needs of the clinical imaging research community. Instead, the focus should be on the interoperability of preexisting systems. To a large extent, this can be achieved by means of a unified interface for storing and retrieving data. The concept of a research PACS combines the advantages of the clinical and research models of data access while eliminating the disadvantages. A research PACS streamlines the data management process. Instead of a single software program, it consists of a confederation of independent applications brought together by the ability to store and retrieve data in a common database. A prototype research PACS has been developed that is based on the Extensible Neuroimaging Archive Toolkit (XNAT) in association with two new in-house tools: a data selection tool and a data archiving tool. By taking as an example the comparison of regions of interest in multifunctional liver data, it was demonstrated that this framework allows a number of in-house and open-source applications originally designed to work on a stand-alone basis to be integrated into a unified workflow, with minimal redevelopment effort.

Integrating the OHIF Viewer into XNAT: Achievements, Challenges and Prospects for Quantitative Imaging Studies.

Purpose: XNAT is an informatics software platform to support imaging research, particularly in the context of large, multicentre studies of the type that are essential to validate quantitative imaging biomarkers. XNAT provides import, archiving, processing and secure distribution facilities for image and related study data. Until recently, however, modern data visualisation and annotation tools were lacking on the XNAT platform. We describe the background to, and implementation of, an integration of the Open Health Imaging Foundation (OHIF) Viewer into the XNAT environment. We explain the challenges overcome and discuss future prospects for quantitative imaging studies. Materials and methods: The OHIF Viewer adopts an approach based on the DICOM web protocol. To allow operation in an XNAT environment, a data-routing methodology was developed to overcome the mismatch between the DICOM and XNAT information models and a custom viewer panel created to allow navigation within the viewer between different XNAT projects, subjects and imaging sessions. Modifications to the development environment were made to allow developers to test new code more easily against a live XNAT instance. Major new developments focused on the creation and storage of regions-of-interest (ROIs) and included: ROI creation and editing tools for both contour- and mask-based regions; a "smart CT" paintbrush tool; the integration of NVIDIA's Artificial Intelligence Assisted Annotation (AIAA); the ability to view surface meshes, fractional segmentation maps and image overlays; and a rapid image reader tool aimed at radiologists. We have incorporated the OHIF microscopy extension and, in parallel, introduced support for microscopy session types within XNAT for the first time. Results: Integration of the OHIF Viewer within XNAT has been highly successful and numerous additional and enhanced tools have been created in a programme started in 2017 that is still ongoing. The software has been downloaded more than 3700 times during the course of the development work reported here, demonstrating the impact of the work. Conclusions: The OHIF open-source, zero-footprint web viewer has been incorporated into the XNAT platform and is now used at many institutions worldwide. Further innovations are envisaged in the near future.

Gross tumour volume radiomics for prognostication of recurrence & death following radical radiotherapy for NSCLC.

Recurrence occurs in up to 36% of patients treated with curative-intent radiotherapy for NSCLC. Identifying patients at higher risk of recurrence for more intensive surveillance may facilitate the earlier introduction of the next line of treatment. We aimed to use radiotherapy planning CT scans to develop radiomic classification models that predict overall survival (OS), recurrence-free survival (RFS) and recurrence two years post-treatment for risk-stratification. A retrospective multi-centre study of >900 patients receiving curative-intent radiotherapy for stage I-III NSCLC was undertaken. Models using radiomic and/or clinical features were developed, compared with 10-fold cross-validation and an external test set, and benchmarked against TNM-stage. Respective validation and test set AUCs (with 95% confidence intervals) for the radiomic-only models were: (1) OS: 0.712 (0.592-0.832) and 0.685 (0.585-0.784), (2) RFS: 0.825 (0.733-0.916) and 0.750 (0.665-0.835), (3) Recurrence: 0.678 (0.554-0.801) and 0.673 (0.577-0.77). For the combined models: (1) OS: 0.702 (0.583-0.822) and 0.683 (0.586-0.78), (2) RFS: 0.805 (0.707-0.903) and 0·755 (0.672-0.838), (3) Recurrence: 0·637 (0.51-0.·765) and 0·738 (0.649-0.826). Kaplan-Meier analyses demonstrate OS and RFS difference of >300 and >400 days respectively between low and high-risk groups. We have developed validated and externally tested radiomic-based prediction models. Such models could be integrated into the routine radiotherapy workflow, thus informing a personalised surveillance strategy at the point of treatment. Our work lays the foundations for future prospective clinical trials for quantitative personalised risk-stratification for surveillance following curative-intent radiotherapy for NSCLC.

Spatial patterns of tumour growth impact clonal diversification in a computational model and the TRACERx Renal study.

Genetic intra-tumour heterogeneity fuels clonal evolution, but our understanding of clinically relevant clonal dynamics remain limited. We investigated spatial and temporal features of clonal diversification in clear cell renal cell carcinoma through a combination of modelling and real tumour analysis. We observe that the mode of tumour growth, surface or volume, impacts the extent of subclonal diversification, enabling interpretation of clonal diversity in patient tumours. Specific patterns of proliferation and necrosis explain clonal expansion and emergence of parallel evolution and microdiversity in tumours. In silico time-course studies reveal the appearance of budding structures before detectable subclonal diversification. Intriguingly, we observe radiological evidence of budding structures in early-stage clear cell renal cell carcinoma, indicating that future clonal evolution may be predictable from imaging. Our findings offer a window into the temporal and spatial features of clinically relevant clonal evolution.

"Real-world" radiomics from multi-vendor MRI: an original retrospective study on the prediction of nodal status and disease survival in breast cancer, as an exemplar to promote discussion of the wider issues.

BACKGROUND: Most MRI radiomics studies to date, even multi-centre ones, have used "pure" datasets deliberately accrued from single-vendor, single-field-strength scanners. This does not reflect aspirations for the ultimate generalisability of AI models. We therefore investigated the development of a radiomics signature from heterogeneous data originating on six different imaging platforms, for a breast cancer exemplar, in order to provide input into future discussions of the viability of radiomics in "real-world" scenarios where image data are not controlled by specific trial protocols but reflective of routine clinical practice. METHODS: One hundred fifty-six patients with pathologically proven breast cancer underwent multi-contrast MRI prior to neoadjuvant chemotherapy and/or surgery. From these, 92 patients were identified for whom T2-weighted, diffusion-weighted and contrast-enhanced T1-weighted sequences were available, as well as key clinicopathological variables. Regions-of-interest were drawn on the above image types and, from these, semantic and calculated radiomics features were derived. Classification models using a variety of methods, both with and without recursive feature elimination, were developed to predict pathological nodal status. Separately, we applied the same methods to analyse the information carried by the radiomic features regarding the originating scanner type and field strength. Repeated, ten-fold cross-validation was employed to verify the results. In parallel work, survival modelling was performed using random survival forests. RESULTS: Prediction of nodal status yielded mean cross-validated AUC values of 0.735 ± 0.15 (SD) for clinical variables alone, 0.673 ± 0.16 (SD) for radiomic features only, and 0.764 ± 0.16 (SD) for radiomics and clinical features together. Prediction of scanner platform from the radiomics features yielded extremely high values of AUC between 0.91 and 1 for the different classes examined indicating the presence of confounding features for the nodal status classification task. Survival analysis, gave out-of-bag prediction errors of 19.3% (clinical features only), 36.9-51.8% (radiomic features from different combinations of image contrasts), and 26.7-35.6% (clinical plus radiomics features). CONCLUSIONS: Radiomic classification models whose predictive ability was consistent with previous single-vendor, single-field strength studies have been obtained from multi-vendor, multi-field-strength data, despite clear confounding information being present. However, our sample size was too small to obtain useful survival modelling results.

Dose response of three-dimensional silicone-based radiochromic dosimeters for photon irradiation in the presence of a magnetic field.

The magnetic field in magnetic resonance imaging guided radiotherapy (MRgRT) delivery systems influences charged-particle trajectories and hence the three-dimensional (3D) radiation dose distributions. This study investigated the dose-response as well as dose-rate and fractionation dependencies of silicone-based 3D radiochromic dosimeters for photon irradiation in a magnetic field using a 0.35 T MRgRT system. We found a linear dose response up to 22.6 Gy and no significant dose-rate dependency as a function of depth. A difference in optical response was observed for dosimeters irradiated in a single compared to multiple fractions. The dosimeter showed clinical potential for verification of MRgRT delivery.

Circulating Growth and Sex Hormone Levels and Breast Tissue Composition in Young Nulliparous Women.

BACKGROUND: Endogenous hormones are associated with breast cancer risk, but little is known about their role on breast tissue composition, a strong risk predictor. This study aims to investigate the relationship between growth and sex hormone levels and breast tissue composition in young nulliparous women. METHODS: A cross-sectional study of 415 young (age ∼21.5 years) nulliparous women from an English prebirth cohort underwent a MRI examination of their breasts to estimate percent-water (a proxy for mammographic percent density) and provided a blood sample to measure plasma levels of growth factors (insulin-like growth factor-I, insulin-like growth factor-II, insulin growth factor-binding protein-3, growth hormone) and, if not on hormonal contraception (n = 117) sex hormones (dehydroepiandrosterone, androstenedione, testosterone, estrone, estadiol, sex hormone-binding globulin, prolactin). Testosterone (n = 330) and sex hormone-binding globulin (n = 318) were also measured at age 15.5 years. Regression models were used to estimate the relative difference (RD) in percent-water associated with one SD increment in hormone levels. RESULTS: Estradiol at age 21.5 and sex hormone-binding globulin at age 21.5 were positively associated with body mass index (BMI)-adjusted percent-water [RD (95% confidence interval (CI)): 3% (0%-7%) and 3% (1%-5%), respectively]. There was a positive nonlinear association between androstenedione at age 21.5 and percent-water. Insulin-like growth factor-I and growth hormone at age 21.5 were also positively associated with BMI-adjusted percent-water [RD (95% CI): 2% (0%-4%) and 4% (1%-7%), respectively]. CONCLUSIONS: The findings suggest that endogenous hormones affect breast tissue composition in young nulliparous women. IMPACT: The well-established associations of childhood growth and development with breast cancer risk may be partly mediated by the role of endogenous hormones on breast tissue composition.

Investigating the effect of a magnetic field on dose distributions at phantom-air interfaces using PRESAGE® 3D dosimeter and Monte Carlo simulations.

Dosimetric quality assurance (QA) of the new Elekta Unity (MR-linac) will differ from the QA performed of a conventional linac due to the constant magnetic field, which creates an electron return effect (ERE). In this work we aim to validate PRESAGE® dosimetry in a transverse magnetic field, and assess its use to validate the research version of the Monaco TPS of the MR-linac. Cylindrical samples of PRESAGE® 3D dosimeter separated by an air gap were irradiated with a cobalt-60 unit, while placed between the poles of an electromagnet at 0.5 T and 1.5 T. This set-up was simulated in EGSnrc/Cavity Monte Carlo (MC) code and relative dose distributions were compared with measurements using 1D and 2D gamma criteria of 3% and 1.5 mm. The irradiation conditions were adapted for the MR-linac and compared with Monaco TPS simulations. Measured and EGSnrc/Cavity simulated profiles showed good agreement with a gamma passing rate of 99.9% for 0.5 T and 99.8% for 1.5 T. Measurements on the MR-linac also compared well with Monaco TPS simulations, with a gamma passing rate of 98.4% at 1.5 T. Results demonstrated that PRESAGE® can accurately measure dose and detect the ERE, encouraging its use as a QA tool to validate the Monaco TPS of the MR-linac for clinically relevant dose distributions at tissue-air boundaries.

Characterization of a parallel-beam CCD optical-CT apparatus for 3D radiation dosimetry.

3D measurement of optical attenuation is of interest in a variety of fields of biomedical importance, including spectrophotometry, optical projection tomography (OPT) and analysis of 3D radiation dosimeters. Accurate, precise and economical 3D measurements of optical density (OD) are a crucial step in enabling 3D radiation dosimeters to enter wider use in clinics. Polymer gels and Fricke gels, as well as dosimeters not based around gels, have been characterized for 3D dosimetry over the last two decades. A separate problem is the verification of the best readout method. A number of different imaging modalities (magnetic resonance imaging (MRI), optical CT, x-ray CT and ultrasound) have been suggested for the readout of information from 3D dosimeters. To date only MRI and laser-based optical CT have been characterized in detail. This paper describes some initial steps we have taken in establishing charge coupled device (CCD)-based optical CT as a viable alternative to MRI for readout of 3D radiation dosimeters. The main advantage of CCD-based optical CT over traditional laser-based optical CT is a speed increase of at least an order of magnitude, while the simplicity of its architecture would lend itself to cheaper implementation than both MRI and laser-based optical CT if the camera itself were inexpensive enough. Specifically, we study the following aspects of optical metrology, using high quality test targets: (i) calibration and quality of absorbance measurements and the camera requirements for 3D dosimetry; (ii) the modulation transfer function (MTF) of individual projections; (iii) signal-to-noise ratio (SNR) in the projection and reconstruction domains; (iv) distortion in the projection domain, depth-of-field (DOF) and telecentricity. The principal results for our current apparatus are as follows: (i) SNR of optical absorbance in projections is better than 120:1 for uniform phantoms in absorbance range 0.3 to 1.6 (and better than 200:1 for absorbances 1.0 to 3.5 with the test target and a novel absorbance range extension method), (ii) the spatial resolution is shown to be at worst 0.5 mm (and often better than this) with an associated DOF of 8 cm, (iii) the SNR of uniform phantoms in reconstruction domain is above 80:1 (one standard deviation) over an absorbance dynamic range of 0.3 to 1.6, (iv) the apparatus is telecentric and without distortion. Finally, a sample scan and reconstruction of a scan of a PRESAGE dosimeter are shown, demonstrating the capabilities of the apparatus.