Breast Cancer: Modelling and Detection

This paper reviews a number of the mathematical models used in cancer modelling and then chooses a specific cancer, breast carcinoma, to illustrate how the modelling can be used in aiding detection. We then discuss mathematical models that underpin mammographic image analysis, which complements models of tumour growth and facilitates diagnosis and treatment of cancer. Mammographic images are notoriously difficult to interpret, and we give an overview of the primary image enhancement technologies that have been introduced, before focusing on a more detailed description of some of our own recent work on the use of physics-based modelling in mammography. This theoretical approach to image analysis yields a wealth of information that could be incorporated into the mathematical models, and we conclude by describing how current mathematical models might be enhanced by use of this information, and how these models in turn will help to meet some of the major challenges in cancer detection

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. We address this by providing an integrated numerical framework that can simulate the therapeutic effects of BCT over the extended period of treatment and recovery. A validated, three-dimensional, multiscale finite element procedure that simulates breast tissue deformations and physiological wound healing is presented. In the proposed methodology, a partitioned, continuum-based mathematical model for tissue recovery and angiogenesis, and breast tissue deformation is considered. The effectiveness and accuracy of the proposed numerical scheme is illustrated through patient-specific representative examples. Wound repair and contraction numerical analyses of real MRI-derived breast geometries are investigated, and the final predictions of the breast shape are validated against post-operative follow-up optical surface scans from four patients. Mean (standard deviation) breast surface distance errors in millimetres of 3.1 (±3.1), 3.2 (±2.4), 2.8 (±2.7) and 4.1 (±3.3) were obtained, demonstrating the ability of the surgical simulation tool to predict, pre-operatively, the outcome of BCT to clinically useful accuracy

A novel model for one-dimensional morphoelasticity. Part I - Theoretical foundations

While classical continuum theories of elasticity and viscoelasticity have long been used to describe the mechanical behaviour of solid biological tissues, they are of limited use for the description of biological tissues that undergo continuous remodelling. The structural changes to a soft tissue associated with growth and remodelling require a mathematical theory of ‘morphoelasticity’ that is more akin to plasticity than elasticity. However, previously-derived mathematical models for plasticity are difficult to apply and interpret in the context of growth and remodelling: many important concepts from the theory of plasticity do not have simple analogues in biomechanics.\ud \ud In this work, we describe a novel mathematical model that combines the simplicity and interpretability of classical viscoelastic models with the versatility of plasticity theory. While our focus here is on one-dimensional problems, our model builds on earlier work based on the multiplicative decomposition of the deformation gradient and can be adapted to develop a three-dimensional theory. The foundation of this work is the concept of ‘effective strain’, a measure of the difference between the current state and a hypothetical state where the tissue is mechanically relaxed. We develop one-dimensional equations for the evolution of effective strain, and discuss a number of potential applications of this theory. One significant application is the description of a contracting fibroblast-populated collagen lattice, which we further investigate in Part II

Biomechanics

Biomechanics is a vast discipline within the field of Biomedical Engineering. It explores the underlying mechanics of how biological and physiological systems move. It encompasses important clinical applications to address questions related to medicine using engineering mechanics principles. Biomechanics includes interdisciplinary concepts from engineers, physicians, therapists, biologists, physicists, and mathematicians. Through their collaborative efforts, biomechanics research is ever changing and expanding, explaining new mechanisms and principles for dynamic human systems. Biomechanics is used to describe how the human body moves, walks, and breathes, in addition to how it responds to injury and rehabilitation. Advanced biomechanical modeling methods, such as inverse dynamics, finite element analysis, and musculoskeletal modeling are used to simulate and investigate human situations in regard to movement and injury. Biomechanical technologies are progressing to answer contemporary medical questions. The future of biomechanics is dependent on interdisciplinary research efforts and the education of tomorrow’s scientists

Creating Collagen 3D Microenvironment by Developing Pneumatic Actuated Soft Micromold (PASMO) for Biological Application

Small volume, high surface area and protective fibulas scaffold of collagen modular microenvironment improves cell viability and proliferation. Therefore, the ability to produce collagen modular microenvironment accurately and reliably is of most importance to the advancement of tissue engineering. Currently, no such fabrication technique exists due to the inherent fragility of collagen. Herein, we report the very first platform that addresses such challenges. Pneumatic actuated soft micro mold (PASMO) composes asymmetric structure, which performs different mechanical properties. PASMO device is classified as particles’ template (top layer), air channel layer (middle layer) and resistance(bottom layer). The major deformation of PASMO is assigned to particles’ template layer because the mechanical property of particles’ template is less than resistance layer. Therefore, the deformation would form on particles’ template to expand and extract microparticles from PASMO device after increasing inner pressure. Soft micro mold with pneumatic extraction actuator not only can produce arbitrary shapes of collagen microstructures precisely but also can encapsulate cells inside without causing damage during the extraction process. MDA-MB-231-GFP encapsulated in collagen microcubes can fully stretch and survive well. Moreover, MDA-MB-231-GFP in collagen microcubes can sense the treatment of Paclitaxel and the size of microcubes changed as following the different concentration of Paclitaxel due to the inhibition of cellar division. Furthermore, creating cancer microenvironment can efficiently localize cancer cells at the specific location so that it minimizes the varieties of experiments. Another application is for cell therapy, like beta cells encapsulation for creating artificial islet. Artificial islets are micro-disk can secrete insulin based on the stimulation of glucose from the surrounding. Blood vessels can successfully form around the implanted artificial islets. This formation of the blood vessel for subcutaneous transplantation not only can regulate the level of glucose in blood but also can simplify surgery to avoid the risk. For multiple locations of implanted artificial islets clusters, blood vessels can also form connections between these two groups

Creating Collagen 3D Microenvironment by Developing Pneumatic Actuated Soft Micromold (PASMO) for Biological Application

Small volume, high surface area and protective fibulas scaffold of collagen modular microenvironment improves cell viability and proliferation. Therefore, the ability to produce collagen modular microenvironment accurately and reliably is of most importance to the advancement of tissue engineering. Currently, no such fabrication technique exists due to the inherent fragility of collagen. Herein, we report the very first platform that addresses such challenges. Pneumatic actuated soft micro mold (PASMO) composes asymmetric structure, which performs different mechanical properties. PASMO device is classified as particles’ template (top layer), air channel layer (middle layer) and resistance(bottom layer). The major deformation of PASMO is assigned to particles’ template layer because the mechanical property of particles’ template is less than resistance layer. Therefore, the deformation would form on particles’ template to expand and extract microparticles from PASMO device after increasing inner pressure. Soft micro mold with pneumatic extraction actuator not only can produce arbitrary shapes of collagen microstructures precisely but also can encapsulate cells inside without causing damage during the extraction process. MDA-MB-231-GFP encapsulated in collagen microcubes can fully stretch and survive well. Moreover, MDA-MB-231-GFP in collagen microcubes can sense the treatment of Paclitaxel and the size of microcubes changed as following the different concentration of Paclitaxel due to the inhibition of cellar division. Furthermore, creating cancer microenvironment can efficiently localize cancer cells at the specific location so that it minimizes the varieties of experiments. Another application is for cell therapy, like beta cells encapsulation for creating artificial islet. Artificial islets are micro-disk can secrete insulin based on the stimulation of glucose from the surrounding. Blood vessels can successfully form around the implanted artificial islets. This formation of the blood vessel for subcutaneous transplantation not only can regulate the level of glucose in blood but also can simplify surgery to avoid the risk. For multiple locations of implanted artificial islets clusters, blood vessels can also form connections between these two groups

A fibrocontractive mechanochemical model of dermal wound\ud closure incorporating realistic growth factor kinetics

Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: the cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched

Surface and bulk stresses drive morphological changes in fibrous microtissues

Engineered fibrous tissues consisting of cells encapsulated within collagen gels are widely used three-dimensional in vitro models of morphogenesis and wound healing. Although cell-mediated matrix remodeling that occurs within these scaffolds has been extensively studied, less is known about the mesoscale physical principles governing the dynamics of tissue shape. Here, we show both experimentally and by using computer simulations how surface contraction through the development of surface stresses (analogous to surface tension in fluids) coordinates with bulk contraction to drive shape evolution in constrained three-dimensional microtissues. We used microelectromechanical systems technology to generate arrays of fibrous microtissues and robot-assisted microsurgery to perform local incisions and implantation. We introduce a technique based on phototoxic activation of a small molecule to selectively kill cells in a spatially controlled manner. The model simulations, which reproduced the experimentally observed shape changes after surgical and photochemical operations, indicate that fitting of only bulk and surface contractile moduli is sufficient for the prediction of the equilibrium shape of the microtissues. The computational and experimental methods we have developed provide a general framework to study and predict the morphogenic states of contractile fibrous tissues under external loading at multiple length scales.Published versio

Computer graphics simulation of natural mummification by desiccation

© 2020 The Authors. Computer Animation and Virtual Worlds published by John Wiley & Sons, Ltd. Organic bodies are subject to internal processes after death, causing significant structural, and optical changes. Mummification by desiccation leads to volume shrinkage, skin wrinkling, and discoloration. We propose a method to simulate the process of mummification by desiccation and its effects on the corpse's morphology and appearance. The mummifying body is represented by a layered model consisting of a tetrahedral mesh, representing the volume, plus a high resolution triangle surface mesh representing the skin. The finite element method is used to solve the moisture diffusion and the resulting volume deformations. Skin wrinkling is achieved using position based dynamics. In order to model a visually believable reproduction of the skin coloration changes due to mummification, a skin shading approach is used that considers moisture content, hemoglobin content, and oxygen saturation. The main focus of the work in this article is to recreate the appearance changes of mummification by desiccation, which, to the best of our knowledge, has not been attempted before in computer graphics to this level of realism. The suggested approach is able to model changes in the internal structure and the surface appearance of the body which resemble the postmortem processes of natural mummification by desiccation