Vijayaraghavan Rajagopal

OpenCMISS: A multi-physics & multi-scale computational infrastructure for the VPH/Physiome project

The VPH/Physiome Project is developing the model encoding standards CellML (cellml.org) and FieldML (fieldml.org) as well as web-accessible model repositories based on these standards (models.physiome.org). Freely available open source computational modelling software is also being developed to solve the partial differential equations described by the models and to visualise results. The OpenCMISS code (opencmiss.org), described here, has been developed by the authors over the last six years to replace the CMISS code that has supported a number of organ system Physiome projects. OpenCMISS is designed to encompass multiple sets of physical equations and to link subcellular and tissue-level biophysical processes into organ-level processes. In the Heart Physiome project, for example, the large deformation mechanics of the myocardial wall need to be coupled to both ventricular flow and embedded coronary flow, and the reaction-diffusion equations that govern the propagation of electrical waves through myocardial tissue need to be coupled with equations that describe the ion channel currents that flow through the cardiac cell membranes. In this paper we discuss the design principles and distributed memory architecture behind the OpenCMISS code. We also discuss the design of the interfaces that link the sets of physical equations across common boundaries (such as fluid-structure coupling), or between spatial fields over the same domain (such as coupled electromechanics), and the concepts behind CellML and FieldML that are embodied in the OpenCMISS data structures. We show how all of these provide a flexible infrastructure for combining models developed across the VPH/Physiome community.

Modeling breast biomechanics for multi-modal image analysis—successes and challenges

Biomechanical modeling of the breast is a burgeoning research field that has potential uses across a wide range of healthcare applications. This review describes recent developments regarding multi‐modal breast image analysis, and outlines some of the key challenges that researchers face in introducing the models into the clinical arena. Deformable breast models have demonstrated capabilities across a wide range of breast cancer diagnoses and treatments. Specific applications include magnetic resonance (MR) image guided surgery, registration of x‐ray and MR images, and breast reduction/augmentation surgery planning. Challenges lie in improving the fidelity of these models, which are presently simplistic and use many unverified parameters. Specific challenges include characterization of individual‐specific mechanical properties of breast tissues, precise representation of loading and boundary constraints during different clinical procedures, and validation of modeling techniques used to represent key mechanical aspects such as the suspensory Coopers ligaments. Scientists must also work towards translating their research tools into the clinical setting by developing efficient tools with user‐friendly interactivity. Widespread adoption of such techniques has the potential to significantly reduce the numbers of misdiagnosed breast cancers and enhance surgical planning for patient treatment. Copyright

Breast lesion co-localisation between X-ray and MR images using finite element modelling

This paper presents a novel X-ray and MR image registration technique based on individual-specific biomechanical finite element (FE) models of the breasts. Information from 3D magnetic resonance (MR) images was registered to X-ray mammographic images using non-linear FE models subject to contact mechanics constraints to simulate the large compressive deformations between the two imaging modalities. A physics-based perspective ray-casting algorithm was used to generate 2D pseudo-X-ray projections of the FE-warped 3D MR images. Unknown input parameters to the FE models, such as the location and orientation of the compression plates, were optimised to provide the best match between the pseudo and clinical X-ray images. The methods were validated using images taken before and during compression of a breast-shaped phantom, for which 12 inclusions were tracked between imaging modalities. These methods were then applied to X-ray and MR images from six breast cancer patients. Error measures (such as centroid and surface distances) of segmented tumours in simulated and actual X-ray mammograms were used to assess the accuracy of the methods. Sensitivity analysis of the lesion co-localisation accuracy to rotation about the anterior-posterior axis was then performed. For 10 of the 12 X-ray mammograms, lesion localisation accuracies of 14 mm and less were achieved. This analysis on the rotation about the anterior-posterior axis indicated that, in cases where the lesion lies in the plane parallel to the mammographic compression plates, that cuts through the nipple, such rotations have relatively minor effects.This has important implications for clinical applicability of this multi-modality lesion registration technique, which will aid in the diagnosis and treatment of breast cancer.

Modelling Prone to Supine Breast Deformation Under Gravity Loading Using Heterogeneous Finite Element Models

Biomechanical models of the breast can be used to co-locate information between the various medical images to identify tumour locations, while also providing the ability to predict their locations during surgical procedures. We have created subject-specific, heterogeneous 3D finite element (FE) models of breast biomechanics to provide the ability to predict breast deformation under different loading conditions. We have verified the applicability of such modelling for simulating the prone to supine reorientation of the breast and obtained good agreement to ground-truth supine images obtained from breast MRI. In particular, we highlight the importance of modelling the pectoral muscles for gravity loading simulations.

Patient-Specific Modeling of Breast Biomechanics with Applications to Breast Cancer Detection and Treatment

There are many challenges clinicians are faced with when diagnosing and treating breast cancer. Biomechanical modeling of the breast is a field of research that aims to assist clinicians by providing a physics based approach to addressing some of these challenges. This review describes the state of the art in the field, from aiding co-location of information between various medical imaging modalities used to identify tumours; to providing the ability to predict the location of these tumors during different biopsy or surgical procedures; to aiding temporal registration of follow-up medical images used to review the progress of suspicious lesions and therefore evaluate effectiveness of breast cancer treatments; to aiding implant selection for breast augmentation procedures and the subsequent prediction of the resulting appearance following such procedures. Significant technical challenges remain in terms of improving the accuracy of such biomechanical models. These include the precise determination and application of loading and boundary constraints applied during different clinical procedures, and accurate characterization of individual-specific mechanical properties of the different breast tissues. In addition to these more technical challenges, a number of practical challenges exist when translating biomechanical models from research based environments into clinical workflows, which demand general applicability, and ease and speed of use. This review outlines such challenges and provides an overview of the steps researchers are taking to address them. Once these challenges have been met, there is potential for extending the use of biomechanics to simulate more complex clinical procedures, from modeling needle insertions into breast tissue during real-time biopsy procedures, to simulating and predicting the outcome of different surgical procedures such as tumorectomies. Clinical adoption of such state-of-the-art modeling techniques has significant potential for reducing the number of misdiagnosed breast cancers while also helping improve clinical treatment of patients.

Computational modeling of the breast during mammography for tumor tracking

Mammography is currently recognized as the gold standard for screening and diagnosis of breast cancer. A number of non-rigid registration algorithms have been used to track regions of interest across 2D mammographic images (cranio-caudal and mediolateral-oblique views). However, such techniques typically rely solely on the image properties A modeling framework is presented to potentially improve tumor tracking by constraining the image registration using physical laws of soft tissue mechanics. A simplified phantom model was constructed using an incompressible, homogeneous and isotropic silicon gel, modeled as a hyperelastic neo-Hookean material. The material constant was estimated using a nonlinear least-squares optimization technique to minimize errors between predicted displacements of material points in a large deformation finite element (FE) model and the corresponding experimentally observed displacements under gravity loading. The gel phantom was compressed between two plates to mimic a typical mammographic procedure and the deformed surfaces were scanned. Contact constraints were used to simulate compression in the FE model and the predicted displacements agreed well with the experimentally observed deformation. We also found that the effects of gravity markedly affected the accuracy of the compression model results. We conclude that modeling the soft tissue mechanics of the breast can provide a useful tool for tracking possible tumors from the compressed state (during mammography) to other configurations for further examination.

Correlation of Breast Image Alignment using Biomechanical Modelling

Breast cancer is one of the most common causes of cancer death among women around the world. Researchers have found that a combination of imaging modalities (such as x-ray mammography, magnetic resonance, and ultrasound) leads to more effective diagnosis and management of breast cancers because each imaging modality displays different information about the breast tissues. In order to aid clinicians in interpreting the breast images from different modalities, we have developed a computational framework for generating individual-specific, 3D, finite element (FE) models of the breast. Medical images are embedded into this model, which is subsequently used to simulate the large deformations that the breasts undergo during different imaging procedures, thus warping the medical images to the deformed views of the breast in the different modalities. In this way, medical images of the breast taken in different geometric configurations (compression, gravity, etc.) can be aligned according to physically feasible transformations. In order to analyse the accuracy of the biomechanical model predictions, squared normalised cross correlation (NCC2) was used to provide both local and global comparisons of the model-warped images with clinical images of the breast subject to different gravity loaded states. The local comparison results were helpful in indicating the areas for improvement in the biomechanical model. To improve the modelling accuracy, we will need to investigate the incorporation of breast tissue heterogeneity into the model and altering the boundary conditions for the breast model. A biomechanical image registration tool of this kind will help radiologists to provide more reliable diagnosis and localisation of breast cancer.