Diffeomorphic image registration with applications to deformation modelling between multiple data sets

Over last years, the diffeomorphic image registration algorithms have been successfully introduced into the field of the medical image analysis. At the same time, the particular usability of these techniques, in majority derived from the solid mathematical background, has been only quantitatively explored for the limited applications such as longitudinal studies on treatment quality, or diseases progression. The thesis considers the deformable image registration algorithms, seeking out those that maintain the medical correctness of the estimated dense deformation fields in terms of the preservation of the object and its neighbourhood topology, offer the reasonable computational complexity to satisfy time restrictions coming from the potential applications, and are able to cope with low quality data typically encountered in Adaptive Radiotherapy (ART). The research has led to the main emphasis being laid on the diffeomorphic image registration to achieve one-to-one mapping between images. This involves introduction of the log-domain parameterisation of the deformation field by its approximation via a stationary velocity field. A quantitative and qualitative examination of existing and newly proposed algorithms for pairwise deformable image registration presented in this thesis, shows that the log-Euclidean parameterisation can be successfully utilised in the biomedical applications. Although algorithms utilising the log-domain parameterisation have theoretical justification for maintaining diffeomorphism, in general, the deformation fields produced by them have similar properties as these estimated by classical methods. Having this in mind, the best compromise in terms of the quality of the deformation fields has been found for the consistent image registration framework. The experimental results suggest also that the image registration with the symmetrical warping of the input images outperforms the classical approaches, and simultaneously can be easily introduced to most known algorithms. Furthermore, the log-domain implicit group-wise image registration is proposed. By linking the various sets of images related to the different subjects, the proposed image registration approach establishes a common subject space and between-subject correspondences therein. Although the correspondences between groups of images can be found by performing the classic image registration, the reference image selection (not required in the proposed implementation), may lead to a biased mean image being estimated and the corresponding common subject space not adequate to represent the general properties of the data sets. The approaches to diffeomorphic image registration have been also utilised as the principal elements for estimating the movements of the organs in the pelvic area based on the dense deformation field prediction system driven by the partial information coming from the specific type of the measurements parameterised using the implicit surface representation, and recognising facial expressions where the stationary velocity fields are used as the facial expression descriptors. Both applications have been extensively evaluated based on the real representative data sets of three-dimensional volumes and two-dimensional images, and the obtained results indicate the practical usability of the proposed techniques

Image Based Biomarkers from Magnetic Resonance Modalities: Blending Multiple Modalities, Dimensions and Scales.

The successful analysis and processing of medical imaging data is a multidisciplinary work that requires the application and combination of knowledge from diverse fields, such as medical engineering, medicine, computer science and pattern classification. Imaging biomarkers are biologic features detectable by imaging modalities and their use offer the prospect of more efficient clinical studies and improvement in both diagnosis and therapy assessment. The use of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) and its application to the diagnosis and therapy has been extensively validated, nevertheless the issue of an appropriate or optimal processing of data that helps to extract relevant biomarkers to highlight the difference between heterogeneous tissue still remains. Together with DCE-MRI, the data extracted from Diffusion MRI (DWI-MR and DTI-MR) represents a promising and complementary tool. This project initially proposes the exploration of diverse techniques and methodologies for the characterization of tissue, following an analysis and classification of voxel-level time-intensity curves from DCE-MRI data mainly through the exploration of dissimilarity based representations and models. We will explore metrics and representations to correlate the multidimensional data acquired through diverse imaging modalities, a work which starts with the appropriate elastic registration methodology between DCE-MRI and DWI- MR on the breast and its corresponding validation. It has been shown that the combination of multi-modal MRI images improve the discrimination of diseased tissue. However the fusion of dissimilar imaging data for classification and segmentation purposes is not a trivial task, there is an inherent difference in information domains, dimensionality and scales. This work also proposes a multi-view consensus clustering methodology for the integration of multi-modal MR images into a unified segmentation of tumoral lesions for heterogeneity assessment. Using a variety of metrics and distance functions this multi-view imaging approach calculates multiple vectorial dissimilarity-spaces for each one of the MRI modalities and makes use of the concepts behind cluster ensembles to combine a set of base unsupervised segmentations into an unified partition of the voxel-based data. The methodology is specially designed for combining DCE-MRI and DTI-MR, for which a manifold learning step is implemented in order to account for the geometric constrains of the high dimensional diffusion information.The successful analysis and processing of medical imaging data is a multidisciplinary work that requires the application and combination of knowledge from diverse fields, such as medical engineering, medicine, computer science and pattern classification. Imaging biomarkers are biologic features detectable by imaging modalities and their use offer the prospect of more efficient clinical studies and improvement in both diagnosis and therapy assessment. The use of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) and its application to the diagnosis and therapy has been extensively validated, nevertheless the issue of an appropriate or optimal processing of data that helps to extract relevant biomarkers to highlight the difference between heterogeneous tissue still remains. Together with DCE-MRI, the data extracted from Diffusion MRI (DWI-MR and DTI-MR) represents a promising and complementary tool. This project initially proposes the exploration of diverse techniques and methodologies for the characterization of tissue, following an analysis and classification of voxel-level time-intensity curves from DCE-MRI data mainly through the exploration of dissimilarity based representations and models. We will explore metrics and representations to correlate the multidimensional data acquired through diverse imaging modalities, a work which starts with the appropriate elastic registration methodology between DCE-MRI and DWI- MR on the breast and its corresponding validation. It has been shown that the combination of multi-modal MRI images improve the discrimination of diseased tissue. However the fusion of dissimilar imaging data for classification and segmentation purposes is not a trivial task, there is an inherent difference in information domains, dimensionality and scales. This work also proposes a multi-view consensus clustering methodology for the integration of multi-modal MR images into a unified segmentation of tumoral lesions for heterogeneity assessment. Using a variety of metrics and distance functions this multi-view imaging approach calculates multiple vectorial dissimilarity-spaces for each one of the MRI modalities and makes use of the concepts behind cluster ensembles to combine a set of base unsupervised segmentations into an unified partition of the voxel-based data. The methodology is specially designed for combining DCE-MRI and DTI-MR, for which a manifold learning step is implemented in order to account for the geometric constrains of the high dimensional diffusion information

A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer

Model-driven registration for multi-parametric renal MRI

The use of MR imaging biomarkers is a promising technique that may assist towards faster prognosis and more accurate diagnosis of diseases like diabetic kidney disease (DKD). The quantification of MR Imaging renal biomarkers from multiparametric MRI is a process that requires a physiological model to be fitted on the data. This process can provide accurate estimates only under the assumption that there is pixelto-pixel correspondence between images acquired over different time points. However, this is rarely the case due to motion artifacts (breathing, involuntary muscle relaxation) introduced during the acquisition. Hence, it is of vital importance for a biomarkers quantification pipeline to include a motion correctionstep in order to properly align the images and enable a more accurate parameter estimation. This study aims in testing whether a Model Driven Registration (MDR), which integrates physiological models in the registration process itself, can serve as a universal solution for the registration of multiparametric renal MRI. MDR is compared with a state-of-the-art model-free motion correction approach for multiparametric MRI, that minimizes a Principal Components Analysis based metric, performing a groupwise registration. The results of the two methods are compared on T1, DTI and DCE-MRI data for a small cohort of 10 DKD patients, obtained from BEAt-DKD project’s digital database. The majority of the evaluation metrics used to compare the two methods indicated that MDR achieved better registration results, while requiring significantly lower computational times. In conclusion, MDR could be considered as the method of choice for motion correction of multiparametric quantitative renal MRI

Proceedings of the Second International Workshop on Mathematical Foundations of Computational Anatomy (MFCA'08) - Geometrical and Statistical Methods for Modelling Biological Shape Variability

International audienceThe goal of computational anatomy is to analyze and to statistically model the anatomy of organs in different subjects. Computational anatomic methods are generally based on the extraction of anatomical features or manifolds which are then statistically analyzed, often through a non-linear registration. There are nowadays a growing number of methods that can faithfully deal with the underlying biomechanical behavior of intra-subject deformations. However, it is more difficult to relate the anatomies of different subjects. In the absence of any justified physical model, diffeomorphisms provide a general mathematical framework that enforce topological consistency. Working with such infinite dimensional space raises some deep computational and mathematical problems, in particular for doing statistics. Likewise, modeling the variability of surfaces leads to rely on shape spaces that are much more complex than for curves. To cope with these, different methodological and computational frameworks have been proposed (e.g. smooth left-invariant metrics, focus on well-behaved subspaces of diffeomorphisms, modeling surfaces using courants, etc.) The goal of the Mathematical Foundations of Computational Anatomy (MFCA) workshop is to foster the interactions between the mathematical community around shapes and the MICCAI community around computational anatomy applications. It targets more particularly researchers investigating the combination of statistical and geometrical aspects in the modeling of the variability of biological shapes. The workshop aims at being a forum for the exchange of the theoretical ideas and a source of inspiration for new methodological developments in computational anatomy. A special emphasis is put on theoretical developments, applications and results being welcomed as illustrations. Following the very successful first edition of this workshop in 2006 (see http://www.inria.fr/sophia/asclepios/events/MFCA06/), the second edition was held in New-York on September 6, in conjunction with MICCAI 2008. Contributions were solicited in Riemannian and group theoretical methods, Geometric measurements of the anatomy, Advanced statistics on deformations and shapes, Metrics for computational anatomy, Statistics of surfaces. 34 submissions were received, among which 9 were accepted to MICCAI and had to be withdrawn from the workshop. Each of the remaining 25 paper was reviewed by three members of the program committee. To guaranty a high level program, 16 papers only were selected

Longitudinal analysis of extreme prematurity: a neuroimage investigation of early brain development

Brain development is a complex process, and disruptions from its normal course may affect the later neurological outcome of an individual. Preterm infants are at higher risk of disability, since a substantial part of brain development happens outside the mother’s womb, making it vulnerable to a range of insults. Understanding the early brain development during the preterm period is of critical importance and magnetic resonance imaging (MRI) allows us to investigate this. Methodologically, this is a challenging task, as classical approaches of studying longitudinal development over this period do not cope with the large changes taking place. This thesis focuses on the development of tools to study the changes in cortical folding, shape of different brain structures and microstructural changes over the preterm period from longitudinal data of extremely preterm-born infants. It describes a tissue segmentation pipeline, optimised on a postmortem fetal dataset, and then focuses on finding longitudinal correspondences between the preterm and termequivalent brain regions and structures in extremely preterm-born infants using MRI. Three novel registration techniques are proposed for longitudinal registration of this challenging data. These are based on matching the spectral components associated with either the cortical surfaces, diffusion tensor images, or both. These allow us to quantify longitudinal changes in different brain regions and structures. We investigated changes in cortical folding of different lobes, microstructural changes and tracts in the white matter, cortical thickness and changes in cortical fractional anisotropy and mean diffusivity. We used cortical surface registration to look at shape differences between controls and extremely preterm-born young adults to gain an insight into the long-term impact of prematurity. This research may contribute to the development of early biomarkers for predicting the neurological outcome of preterm infants and illuminate our understanding of brain development during this crucial period