The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

Background: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk.

Methods: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data.

Nonrigid reconstruction of 3D breast surfaces with a low-cost RGBD camera for surgical planning and aesthetic evaluation.

Accounting for 26% of all new cancer cases worldwide, breast cancer remains the most common form of cancer in women. Although early breast cancer has a favourable long-term prognosis, roughly a third of patients suffer from a suboptimal aesthetic outcome despite breast conserving cancer treatment. Clinical-quality 3D modelling of the breast surface therefore assumes an increasingly important role in advancing treatment planning, prediction and evaluation of breast cosmesis.

Electromagnetic tracking in image-guided laparoscopic surgery: Comparison with optical tracking and feasibility study of a combined laparoscope and laparoscopic ultrasound system.

Purpose: In image-guided laparoscopy, optical tracking is commonly employed, but electromagnetic (EM) systems have been proposed in the literature. In this paper, we provide a thorough comparison of EM and optical tracking systems for use in image-guided laparoscopic surgery and a feasibility study of a combined, EM-tracked laparoscope and laparoscopic ultrasound (LUS) image guidance system.

Methods: We first assess the tracking accuracy of a laparoscope with two optical trackers tracking retroreflective markers mounted on the shaft and an EM tracker with the sensor embedded at the proximal end, using a standard evaluation plate.

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.

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.

Multiscale biphasic modelling of peritumoural collagen microstructure: The effect of tumour growth on permeability and fluid flow.

We present an in-silico model of avascular poroelastic tumour growth coupled with a multiscale biphasic description of the tumour-host environment. The model is specified to in-vitro data, facilitating biophysically realistic simulations of tumour spheroid growth into a dense collagen hydrogel. We use the model to first confirm that passive mechanical remodelling of collagen fibres at the tumour boundary is driven by solid stress, and not fluid pressure.

Mammographic density and ageing: A collaborative pooled analysis of cross-sectional data from 22 countries worldwide.

Background: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known.

Methods And Findings: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD).

Breast MRI segmentation for density estimation: Do different methods give the same results and how much do differences matter?

Purpose: To compare two methods of automatic breast segmentation with each other and with manual segmentation in a large subject cohort. To discuss the factors involved in selecting the most appropriate algorithm for automatic segmentation and, in particular, to investigate the appropriateness of overlap measures (e.g.

Automated Classification of Breast Cancer Stroma Maturity From Histological Images.

Objective: The tumor microenvironment plays a crucial role in regulating tumor progression by a number of different mechanisms, in particular, the remodeling of collagen fibers in tumor-associated stroma, which has been reported to be related to patient survival. The underlying motivation of this work is that remodeling of collagen fibers gives rise to observable patterns in hematoxylin and eosin (H&E) stained slides from clinical cases of invasive breast carcinoma that the pathologist can label as mature or immature stroma. The aim of this paper is to categorise and automatically classify stromal regions according to their maturity and show that this classification agrees with that of skilled observers, hence providing a repeatable and quantitative measure for prognostic studies.

3D volume reconstruction from serial breast specimen radiographs for mapping between histology and 3D whole specimen imaging.

Purpose: In breast imaging, radiological in vivo images, such as x-ray mammography and magnetic resonance imaging (MRI), are used for tumor detection, diagnosis, and size determination. After excision, the specimen is typically sliced into slabs and a small subset is sampled. Histopathological imaging of the stained samples is used as the gold standard for characterization of the tumor microenvironment.

Microstructural models for diffusion MRI in breast cancer and surrounding stroma: an ex vivo study.

The diffusion signal in breast tissue has primarily been modelled using apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM) and diffusion tensor (DT) models, which may be too simplistic to describe the underlying tissue microstructure. Formalin-fixed breast cancer samples were scanned using a wide range of gradient strengths, durations, separations and orientations. A variety of one- and two-compartment models were tested to determine which best described the data.

Mammographic density assessed on paired raw and processed digital images and on paired screen-film and digital images across three mammography systems.

Background: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types.

Methods: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds.

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.

Multiscale Mechano-Biological Finite Element Modelling of Oncoplastic Breast Surgery-Numerical Study towards Surgical Planning and Cosmetic Outcome Prediction.

Surgical treatment for early-stage breast carcinoma primarily necessitates breast conserving therapy (BCT), where the tumour is removed while preserving the breast shape. To date, there have been very few attempts to develop accurate and efficient computational tools that could be used in the clinical environment for pre-operative planning and oncoplastic breast surgery assessment. Moreover, from the breast cancer research perspective, there has been very little effort to model complex mechano-biological processes involved in wound healing.

Low-cost surface reconstruction for aesthetic results assessment and prediction in breast cancer surgery.

The high incidence and low mortality of breast cancer surgery has led to an increasing emphasis on the cosmetic outcome of surgical treatment. Advances in aesthetic evaluation, as well as surgical planning and outcome prediction, have been investigated by using geometrically precise 3D modelling of the breast surface prior to surgery and after the procedure. However, existing solutions are based on expensive site specific setups and remain weakly validated.

A review of biomechanically informed breast image registration.

Breast radiology encompasses the full range of imaging modalities from routine imaging via x-ray mammography, magnetic resonance imaging and ultrasound (both two- and three-dimensional), to more recent technologies such as digital breast tomosynthesis, and dedicated breast imaging systems for positron emission mammography and ultrasound tomography. In addition new and experimental modalities, such as Photoacoustics, Near Infrared Spectroscopy and Electrical Impedance Tomography etc, are emerging. The breast is a highly deformable structure however, and this greatly complicates visual comparison of imaging modalities for the purposes of breast screening, cancer diagnosis (including image guided biopsy), tumour staging, treatment monitoring, surgical planning and simulation of the effects of surgery and wound healing etc.

International Consortium on Mammographic Density: Methodology and population diversity captured across 22 countries.

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide.

Symmetric Biomechanically Guided Prone-to-Supine Breast Image Registration.

Prone-to-supine breast image registration has potential application in the fields of surgical and radiotherapy planning, image guided interventions, and multi-modal cancer diagnosis, staging, and therapy response prediction. However, breast image registration of three dimensional images acquired in different patient positions is a challenging problem, due to large deformations induced to the soft breast tissue caused by the change in gravity loading. We present a symmetric, biomechanical simulation based registration framework which aligns the images in a central, virtually unloaded configuration.

Multiscale modelling of solid tumour growth: the effect of collagen micromechanics.

Here we introduce a model of solid tumour growth coupled with a multiscale biomechanical description of the tumour microenvironment, which facilitates the explicit simulation of fibre-fibre and tumour-fibre interactions. We hypothesise that such a model, which provides a purely mechanical description of tumour-host interactions, can be used to explain experimental observations of the effect of collagen micromechanics on solid tumour growth. The model was specified to mouse tumour data, and numerical simulations were performed.

An Inverse Finite Element u/p-Formulation to Predict the Unloaded State of In Vivo Biological Soft Tissues.

Physically realistic patient-specific biomechanical modelling is of paramount importance for many medical applications, where the geometry of tissues or organs is usually constructed from in vivo images. However, it is common for such biological structures to correspond to a deformed state due to being under external loadings. This necessitates the determination of the stress distribution of the known deformed state through an inverse analysis approach.

NiftySim: A GPU-based nonlinear finite element package for simulation of soft tissue biomechanics.

Purpose: NiftySim, an open-source finite element toolkit, has been designed to allow incorporation of high-performance soft tissue simulation capabilities into biomedical applications. The toolkit provides the option of execution on fast graphics processing unit (GPU) hardware, numerous constitutive models and solid-element options, membrane and shell elements, and contact modelling facilities, in a simple to use library.

Methods: The toolkit is founded on the total Lagrangian explicit dynamics (TLEDs) algorithm, which has been shown to be efficient and accurate for simulation of soft tissues.

MRI to X-ray mammography intensity-based registration with simultaneous optimisation of pose and biomechanical transformation parameters.

Determining corresponding regions between an MRI and an X-ray mammogram is a clinically useful task that is challenging for radiologists due to the large deformation that the breast undergoes between the two image acquisitions. In this work we propose an intensity-based image registration framework, where the biomechanical transformation model parameters and the rigid-body transformation parameters are optimised simultaneously. Patient-specific biomechanical modelling of the breast derived from diagnostic, prone MRI has been previously used for this task.

A nonlinear biomechanical model based registration method for aligning prone and supine MR breast images.

Preoperative diagnostic magnetic resonance (MR) breast images can provide good contrast between different tissues and 3-D information about suspicious tissues. Aligning preoperative diagnostic MR images with a patient in the theatre during breast conserving surgery could assist surgeons in achieving the complete excision of cancer with sufficient margins. Typically, preoperative diagnostic MR breast images of a patient are obtained in the prone position, while surgery is performed in the supine position.

Establishing spatial correspondence for the analysis of images from highly deforming anatomy.

This invited presentation summarizes recent advances in the incorporation of knowledge of the geometry, tissue mechanical properties and imaging characteristics in establishing spatial correspondence between multiple images of highly deforming, soft tissue structures. Spatial correspondence is used to aid diagnosis and in the extraction of quantitative parameters for disease detection, monitoring disease progression and assessing therapeutic response. The work is illustrated through clinical examples of multi-modal imaging of the breast, assessment of small bowel motility and polyp detection in the large bowel.