Preoperative Systems for Computer Aided Diagnosis based on Image Registration: Applications to Breast Cancer and Atherosclerosis

Computer Aided Diagnosis (CAD) systems assist clinicians including radiologists and cardiologists to detect abnormalities and highlight conspicuous possible disease. Implementing a pre-operative CAD system contains a framework that accepts related technical as well as clinical parameters as input by analyzing the predefined method and demonstrates the prospective output. In this work we developed the Computer Aided Diagnostic System for biomedical imaging analysis of two applications on Breast Cancer and Atherosclerosis. The aim of the first CAD application is to optimize the registration strategy specifically for Breast Dynamic Infrared Imaging and to make it user-independent. Base on the fact that automated motion reduction in dynamic infrared imaging is on demand in clinical applications, since movement disarranges time-temperature series of each pixel, thus originating thermal artifacts that might bias the clinical decision. All previously proposed registration methods are feature based algorithms requiring manual intervention. We implemented and evaluated 3 different 3D time-series registration methods: 1. Linear affine, 2. Non-linear Bspline, 3. Demons applied to 12 datasets of healthy breast thermal images. The results are evaluated through normalized mutual information with average values of 0.70±0.03, 0.74±0.03 and 0.81±0.09 (out of 1) for Affine, BSpline and Demons registration, respectively, as well as breast boundary overlap and Jacobian determinant of the deformation field. The statistical analysis of the results showed that symmetric diffeomorphic Demons registration method outperforms also with the best breast alignment and non-negative Jacobian values which guarantee image similarity and anatomical consistency of the transformation, due to homologous forces enforcing the pixel geometric disparities to be shortened on all the frames. We propose Demons registration as an effective technique for time-series dynamic infrared registration, to stabilize the local temperature oscillation. The aim of the second implemented CAD application is to assess contribution of calcification in plaque vulnerability and wall rupture and to find its maximum resistance before break in image-based models of carotid artery stenting. The role of calcification inside fibroatheroma during carotid artery stenting operation is controversial in which cardiologists face two major problems during the placement: (i) “plaque protrusion” (i.e. elastic fibrous caps containing early calcifications that penetrate inside the stent); (ii) “plaque vulnerability” (i.e. stiff plaques with advanced calcifications that break the arterial wall or stent). Finite Element Analysis was used to simulate the balloon and stent expansion as a preoperative patient-specific virtual framework. A nonlinear static structural analysis was performed on 20 patients acquired using in vivo MDCT angiography. The Agatston Calcium score was obtained for each patient and subject-specific local Elastic Modulus (EM) was calculated. The in silico results showed that by imposing average ultimate external load of 1.1MPa and 2.3MPa on balloon and stent respectively, average ultimate stress of 55.7±41.2kPa and 171±41.2kPa are obtained on calcifications. The study reveals that a significant positive correlation (R=0.85, p<0.0001) exists on stent expansion between EM of calcification and ultimate stress as well as Plaque Wall Stress (PWS) (R=0.92, p<0.0001), comparing to Ca score that showed insignificant associations with ultimate stress (R=0.44, p=0.057) and PWS (R=0.38, p=0.103), suggesting minor impact of Ca score in plaque rupture. These average data are in good agreement with results obtained by other research groups and we believe this approach enriches the arsenal of tools available for pre-operative prediction of carotid artery stenting procedure in the presence of calcified plaques

An improved model for joint segmentation and registration based on linear curvature smoother

Image segmentation and registration are two of the most challenging tasks in medical imaging. They are closely related because both tasks are often required simultaneously. In this article, we present an improved variational model for a joint segmentation and registration based on active contour without edges and the linear curvature model. The proposed model allows large deformation to occur by solving in this way the difficulties other jointly performed segmentation and registration models have in case of encountering multiple objects into an image or their highly dependence on the initialisation or the need for a pre-registration step, which has an impact on the segmentation results. Through different numerical results, we show that the proposed model gives correct registration results when there are different features inside the object to be segmented or features that have clear boundaries but without fine details in which the old model would not be able to cope. </jats:p

Finite element surface registration incorporating curvature, volume preservation, and statistical model information

We present a novel method for nonrigid registration of 3D surfaces and images. The method can be used to register surfaces by means of their distance images, or to register medical images directly. It is formulated as a minimization problem of a sum of several terms representing the desired properties of a registration result: smoothness, volume preservation, matching of the surface, its curvature, and possible other feature images, as well as consistency with previous registration results of similar objects, represented by a statistical deformation model. While most of these concepts are already known, we present a coherent continuous formulation of these constraints, including the statistical deformation model. This continuous formulation renders the registration method independent of its discretization. The finite element discretization we present is, while independent of the registration functional, the second main contribution of this paper. The local discontinuous Galerkin method has not previously been used in image registration, and it provides an efficient and general framework to discretize each of the terms of our functional. Computational efficiency and modest memory consumption are achieved thanks to parallelization and locally adaptive mesh refinement. This allows for the first time the use of otherwise prohibitively large 3D statistical deformation models

Fast algorithms for biophysically-constrained inverse problems in medical imaging

We present algorithms and software for parameter estimation for forward and inverse tumor growth problems and diffeomorphic image registration. Our methods target the following scenarios: automatic image registration of healthy images to tumor bearing medical images and parameter estimation/calibration of tumor models. This thesis focuses on robust and scalable algorithms for these problems. Although the proposed framework applies to many problems in oncology, we focus on primary brain tumors and in particular low and high-grade gliomas. For the tumor model, the main quantity of interest is the extent of tumor infiltration into the brain, beyond what is visible in imaging. The inverse tumor problem assumes that we have patient images at two (or more) well-separated times so that we can observe the tumor growth. Also, the inverse problem requires that the two images are segmented. But in a clinical setting such information is usually not available. In a typical case, we just have multimodal magnetic resonance images with no segmentation. We address this lack of information by solving a coupled inverse registration and tumor problem. The role of image registration is to find a plausible mapping between the patient's tumor-bearing image and a normal brain (atlas), with known segmentation. Solving this coupled inverse problem has a prohibitive computational cost, especially in 3D. To address this challenge we have developed novel schemes, scaled up to 200K cores. Our main contributions is the design and implementation of fast solvers for these problems. We also study the performance for the tumor parameter estimation and registration solvers and their algorithmic scalability. In particular, we introduce the following novel algorithms: An adjoint formulation for tumor-growth problems with/without mass-effect; The first parallel 3D Newton-Krylov method for large diffeomorphic image registration; A novel parallel semi-Lagrangian algorithm for solving advection equations in image registration and its parallel implementation on shared and distributed memory architectures; and Accelerated FFT (AccFFT), an open-source parallel FFT library for CPU and GPUs scaled up to 131,000 cores with optimized kernels for computing spectral operators. The scientific outcomes of this thesis, has appeared in the proceedings of three ACM/IEEE SCxy conferences (two best student paper finalist, and one ACM SRC gold medal), two journal papers, two papers in review, four papers in preparation (coupling, mass effect, segmentation, and multi-species tumor model), and seven conference presentations.Computational Science, Engineering, and Mathematic

A novel variational model for image registration using Gaussian curvature

Image registration is one important task in many image processing applications. It aims to align two or more images so that useful information can be extracted through comparison, combination or superposition. This is achieved by constructing an optimal trans- formation which ensures that the template image becomes similar to a given reference image. Although many models exist, designing a model capable of modelling large and smooth deformation field continues to pose a challenge. This paper proposes a novel variational model for image registration using the Gaussian curvature as a regulariser. The model is motivated by the surface restoration work in geometric processing [Elsey and Esedoglu, Multiscale Model. Simul., (2009), pp. 1549-1573]. An effective numerical solver is provided for the model using an augmented Lagrangian method. Numerical experiments can show that the new model outperforms three competing models based on, respectively, a linear curvature [Fischer and Modersitzki, J. Math. Imaging Vis., (2003), pp. 81- 85], the mean curvature [Chumchob, Chen and Brito, Multiscale Model. Simul., (2011), pp. 89-128] and the diffeomorphic demon model [Vercauteren at al., NeuroImage, (2009), pp. 61-72] in terms of robustness and accuracy.Comment: 23 pages, 5 figures. Key words: Image registration, Non-parametric image registration, Regularisation, Gaussian curvature, surface mappin

Patch-based nonlinear image registration for gigapixel whole slide images

Producción CientíficaImage registration of whole slide histology images allows the fusion of fine-grained information-like different immunohistochemical stains-from neighboring tissue slides. Traditionally, pathologists fuse this information by looking subsequently at one slide at a time. If the slides are digitized and accurately aligned at cell level, automatic analysis can be used to ease the pathologist's work. However, the size of those images exceeds the memory capacity of regular computers. Methods: We address the challenge to combine a global motion model that takes the physical cutting process of the tissue into account with image data that is not simultaneously globally available. Typical approaches either reduce the amount of data to be processed or partition the data into smaller chunks to be processed separately. Our novel method first registers the complete images on a low resolution with a nonlinear deformation model and later refines this result on patches by using a second nonlinear registration on each patch. Finally, the deformations computed on all patches are combined by interpolation to form one globally smooth nonlinear deformation. The NGF distance measure is used to handle multistain images. Results: The method is applied to ten whole slide image pairs of human lung cancer data. The alignment of 85 corresponding structures is measured by comparing manual segmentations from neighboring slides. Their offset improves significantly, by at least 15%, compared to the low-resolution nonlinear registration. Conclusion/Significance: The proposed method significantly improves the accuracy of multistain registration which allows us to compare different antibodies at cell level

TFMLAB: A MATLAB toolbox for 4D traction force microscopy

Article number 100723We present TFMLAB, a MATLAB software package for 4D (x;y;z;t) Traction Force Microscopy (TFM). While various TFM computational workflows are available in the literature, open-source programs that are easy to use by researchers with limited technical experience and that can analyze 4D in vitro systems do not exist. TFMLAB integrates all the computational steps to compute active cellular forces from confocal microscopy images, including image processing, cell segmentation, image alignment, matrix displacement measurement and force recovery. Moreover, TFMLAB eases usability by means of interactive graphical user interfaces. This work describes the package's functionalities and analyzes its performance on a real TFM caseKU Leuven 1S68818NFonds Wetenschappelijk Onderzoek (FWO) V413019NFonds Wetenschappelijk Onderzoek (FWO) G085018NCambridge Conservation Initiative (CCI) 2014TC16RFCB046Ministerio de Educación, Cultura y Deporte de España CAS17/00096Ministerio de Economía y Competitividad de España (MINECO) PGC2018-097257-B-C31Consejo Europeo de Investigación 308223KU Leuven C14/17/111Fonds Wetenschappelijk Onderzoek (FWO)/Hercules G0H6316