Regional flux analysis for discovering and quantifying anatomical changes: An application to the brain morphometry in Alzheimer's disease.

In this study we introduce the regional flux analysis, a novel approach to deformation based morphometry based on the Helmholtz decomposition of deformations parameterized by stationary velocity fields. We use the scalar pressure map associated to the irrotational component of the deformation to discover the critical regions of volume change. These regions are used to consistently quantify the associated measure of volume change by the probabilistic integration of the flux of the longitudinal deformations across the boundaries. The presented framework unifies voxel-based and regional approaches, and robustly describes the volume changes at both group-wise and subject-specific level as a spatial process governed by consistently defined regions. Our experiments on the large cohorts of the ADNI dataset show that the regional flux analysis is a powerful and flexible instrument for the study of Alzheimer's disease in a wide range of scenarios: cross-sectional deformation based morphometry, longitudinal discovery and quantification of group-wise volume changes, and statistically powered and robust quantification of hippocampal and ventricular atrophy.

Toward a comprehensive framework for the spatiotemporal statistical analysis of longitudinal shape data.

This paper proposes an original approach for the statistical analysis of longitudinal shape data. The proposed method allows the characterization of typical growth patterns and subject-specific shape changes in repeated time-series observations of several subjects. This can be seen as the extension of usual longitudinal statistics of scalar measurements to high-dimensional shape or image data. The method is based on the estimation of continuous subject-specific growth trajectories and the comparison of such temporal shape changes across subjects. Differences between growth trajectories are decomposed into morphological deformations, which account for shape changes independent of the time, and time warps, which account for different rates of shape changes over time. Given a longitudinal shape data set, we estimate a mean growth scenario representative of the population, and the variations of this scenario both in terms of shape changes and in terms of change in growth speed. Then, intrinsic statistics are derived in the space of spatiotemporal deformations, which characterize the typical variations in shape and in growth speed within the studied population. They can be used to detect systematic developmental delays across subjects. In the context of neuroscience, we apply this method to analyze the differences in the growth of the hippocampus in children diagnosed with autism, developmental delays and in controls. Result suggest that group differences may be better characterized by a different speed of maturation rather than shape differences at a given age. In the context of anthropology, we assess the differences in the typical growth of the endocranium between chimpanzees and bonobos. We take advantage of this study to show the robustness of the method with respect to change of parameters and perturbation of the age estimates.

LCC-Demons: a robust and accurate symmetric diffeomorphic registration algorithm.

Non-linear registration is a key instrument for computational anatomy to study the morphology of organs and tissues. However, in order to be an effective instrument for the clinical practice, registration algorithms must be computationally efficient, accurate and most importantly robust to the multiple biases affecting medical images. In this work we propose a fast and robust registration framework based on the log-Demons diffeomorphic registration algorithm. The transformation is parameterized by stationary velocity fields (SVFs), and the similarity metric implements a symmetric local correlation coefficient (LCC). Moreover, we show how the SVF setting provides a stable and consistent numerical scheme for the computation of the Jacobian determinant and the flux of the deformation across the boundaries of a given region. Thus, it provides a robust evaluation of spatial changes. We tested the LCC-Demons in the inter-subject registration setting, by comparing with state-of-the-art registration algorithms on public available datasets, and in the intra-subject longitudinal registration problem, for the statistically powered measurements of the longitudinal atrophy in Alzheimer's disease. Experimental results show that LCC-Demons is a generic, flexible, efficient and robust algorithm for the accurate non-linear registration of images, which can find several applications in the field of medical imaging. Without any additional optimization, it solves equally well intra & inter-subject registration problems, and compares favorably to state-of-the-art methods.

Benchmarking framework for myocardial tracking and deformation algorithms: an open access database.

In this paper we present a benchmarking framework for the validation of cardiac motion analysis algorithms. The reported methods are the response to an open challenge that was issued to the medical imaging community through a MICCAI workshop. The database included magnetic resonance (MR) and 3D ultrasound (3DUS) datasets from a dynamic phantom and 15 healthy volunteers. Participants processed 3D tagged MR datasets (3DTAG), cine steady state free precession MR datasets (SSFP) and 3DUS datasets, amounting to 1158 image volumes. Ground-truth for motion tracking was based on 12 landmarks (4 walls at 3 ventricular levels). They were manually tracked by two observers in the 3DTAG data over the whole cardiac cycle, using an in-house application with 4D visualization capabilities. The median of the inter-observer variability was computed for the phantom dataset (0.77 mm) and for the volunteer datasets (0.84 mm). The ground-truth was registered to 3DUS coordinates using a point based similarity transform. Four institutions responded to the challenge by providing motion estimates for the data: Fraunhofer MEVIS (MEVIS), Bremen, Germany; Imperial College London - University College London (IUCL), UK; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Inria-Asclepios project (INRIA), France. Details on the implementation and evaluation of the four methodologies are presented in this manuscript. The manually tracked landmarks were used to evaluate tracking accuracy of all methodologies. For 3DTAG, median values were computed over all time frames for the phantom dataset (MEVIS=1.20mm, IUCL=0.73 mm, UPF=1.10mm, INRIA=1.09 mm) and for the volunteer datasets (MEVIS=1.33 mm, IUCL=1.52 mm, UPF=1.09 mm, INRIA=1.32 mm). For 3DUS, median values were computed at end diastole and end systole for the phantom dataset (MEVIS=4.40 mm, UPF=3.48 mm, INRIA=4.78 mm) and for the volunteer datasets (MEVIS=3.51 mm, UPF=3.71 mm, INRIA=4.07 mm). For SSFP, median values were computed at end diastole and end systole for the phantom dataset(UPF=6.18 mm, INRIA=3.93 mm) and for the volunteer datasets (UPF=3.09 mm, INRIA=4.78 mm). Finally, strain curves were generated and qualitatively compared. Good agreement was found between the different modalities and methodologies, except for radial strain that showed a high variability in cases of lower image quality.

A statistical model for quantification and prediction of cardiac remodelling: application to tetralogy of Fallot.

Cardiac remodelling plays a crucial role in heart diseases. Analyzing how the heart grows and remodels over time can provide precious insights into pathological mechanisms, eventually resulting in quantitative metrics for disease evaluation and therapy planning. This study aims to quantify the regional impacts of valve regurgitation and heart growth upon the end-diastolic right ventricle (RV) in patients with tetralogy of Fallot, a severe congenital heart defect. The ultimate goal is to determine, among clinical variables, predictors for the RV shape from which a statistical model that predicts RV remodelling is built. Our approach relies on a forward model based on currents and a diffeomorphic surface registration algorithm to estimate an unbiased template. Local effects of RV regurgitation upon the RV shape were assessed with Principal Component Analysis (PCA) and cross-sectional multivariate design. A generative 3-D model of RV growth was then estimated using partial least squares (PLS) and canonical correlation analysis (CCA). Applied on a retrospective population of 49 patients, cross-effects between growth and pathology could be identified. Qualitatively, the statistical findings were found realistic by cardiologists. 10-fold cross-validation demonstrated a promising generalization and stability of the growth model. Compared to PCA regression, PLS was more compact, more precise and provided better predictions.

LogDemons revisited: consistent regularisation and incompressibility constraint for soft tissue tracking in medical images.

Non-linear image registration is a standard approach to track soft tissues in medical images. By estimating spatial transformations between images, visible structures can be followed over time. For clinical applications the model of transformation must be consistent with the properties of the biological tissue, such as incompressibility. LogDemons is a fast non-linear registration algorithm that provides diffusion-like diffeomorphic transformations parameterised by stationary velocity fields. Yet, its use for tissue tracking has been limited because of the ad-hoc Gaussian regularisation that prevents implementing other transformation models. In this paper, we propose a mathematical formulation of demons regularisation that fits into LogDemons framework. This formulation enables to ensure volume-preserving deformations by minimising the energy functional directly under the linear divergence-free constraint, yielding little computational overhead. Tests on synthetic incompressible fields showed that our approach outperforms the original logDemons in terms of incompressible deformation recovery. The algorithm showed promising results on one patient for the automatic recovery of myocardium strain from cardiac anatomical and 3D tagged MRI.

Computation of a probabilistic statistical shape model in a maximum-a-posteriori framework.

OBJECTIVES: When analyzing shapes and shape variabilities, the first step is bringing those shapes into correspondence. This is a fundamental problem even when solved by manually determining exact correspondences such as landmarks. We developed a method to represent a mean shape and a variability model for a training data set based on probabilistic correspondence computed between the observations. METHODS: First, the observations are matched on each other with an affine transformation found by the Expectation-Maximization Iterative-Closest-Points (EM-ICP) registration. We then propose a maximum-a-posteriori (MAP) framework in order to compute the statistical shape model (SSM) parameters which result in an optimal adaptation of the model to the observations. The optimization of the MAP explanation is realized with respect to the observation parameters and the generative model parameters in a global criterion and leads to very efficient and closed-form solutions for (almost) all parameters. RESULTS: We compared our probabilistic SSM to a SSM based on one-to-one correspondences and the PCA (classical SSM). Experiments on synthetic data served to test the performances on non-convex shapes (15 training shapes) which have proved difficult in terms of proper correspondence determination. We then computed the SSMs for real putamen data (21 training shapes). The evaluation was done by measuring the generalization ability as well as the specificity of both SSMs and showed that especially shape detail differences are better modeled by the probabilistic SSM (Hausdorff distance in generalization ability Re approximately 25% smaller). CONCLUSIONS: The experimental outcome shows the efficiency and advantages of the new approach as the probabilistic SSM performs better in modeling shape details and differences.

An augmented reality system for liver thermal ablation: design and evaluation on clinical cases.

We present in this paper an augmented reality guidance system for liver thermal ablation in interventional radiology. To show the relevance of our methodology, the system is incrementally evaluated on an abdominal phantom and then on patients in the operating room. The system registers in a common coordinate system a preoperative image of the patient and the position of the needle that the practitioner manipulates. The breathing motion uncertainty is taken into account with a respiratory gating technique: the preoperative image and the guidance step are synchronized on expiratory phases. In order to fulfil the real-time constraints, we have developed and validated algorithms that automatically process and extract feature points. Since the guidance interface is also a major component of the system effectiveness, we validate the overall targeting accuracy on an abdominal phantom. This experiment showed that a practitioner can reach a predefined target with an accuracy of 2mm with an insertion time below one minute. Finally, we propose a passive evaluation protocol of the overall system in the operating room during five interventions on patients. These experiments show that the system can provide a guidance information during expiratory phases with an error below 5mm.

Geometric variability of the scoliotic spine using statistics on articulated shape models.

This paper introduces a method to analyze the variability of the spine shape and of the spine shape deformations using articulated shape models. The spine shape was expressed as a vector of relative poses between local coordinate systems of neighboring vertebrae. Spine shape deformations were then modeled by a vector of rigid transformations that transforms one spine shape into another. Because rigid transformations do not naturally belong to a vector space, conventional mean and covariance could not be applied. The Fréchet mean and a generalized covariance were used instead. The spine shapes of a group of 295 scoliotic patients were quantitatively analyzed as well as the spine shape deformations associated with the Cotrel-Dubousset corrective surgery (33 patients), the Boston brace (39 patients), and the scoliosis progression without treatment (26 patients). The variability of intervertebral poses was found to be inhomogeneous (lumbar vertebrae were more variable than the thoracic ones) and anisotropic (with maximal rotational variability around the coronal axis and maximal translational variability along the axial direction). Finally, brace and surgery were found to have a significant effect on the Fréchet mean and on the generalized covariance in specific spine regions where treatments modified the spine shape.

Clinical evaluation of a respiratory gated guidance system for liver punctures.

We have previously proposed a computer guidance system for liver punctures designed for intubated (free breathing) patients. The lack of accuracy reported (1 cm) was mostly due to the breathing motion that was not taken into account. In this paper we modify our system to synchronise the guidance information on the expiratory phases of the patient and present an evaluation on 6 patients of our respiratory gated system. Firstly, we show how a specific choice of patient allows us to rigorously and passively evaluate the system accuracy. Secondly, we demonstrate that our system can provide a guidance information with an error below 5 mm during expiratory phases.

Grid-enabling medical image analysis.

Grids have emerged as a promising technology to handle the data and compute intensive requirements of many application areas. Digital medical image processing is a promising application area for grids. Given the volume of data, the sensitivity of medical information, and the joint complexity of medical datasets and computations expected in clinical practice, the challenge is to fill the gap between the grid middleware and the requirements of clinical applications. The research project AGIR (Grid Analysis of Radiological Data) presented in this paper addresses this challenge through a combined approach: on one hand, leveraging the grid middleware through core grid medical services which target the requirements of medical data processing applications; on the other hand, grid-enabling a panel of applications ranging from algorithmic research to clinical applications.

The Healthgrid White Paper.

Over the last four years, a community of researchers working on Grid and High Performance Computing technologies started discussing the barriers and opportunities that grid technologies must face and exploit for the development of health-related applications. This interest lead to the first Healthgrid conference, held in Lyon, France, on January 16th-17th, 2003, with the focus of creating increased awareness about the possibilities and advantages linked to the deployment of grid technologies in health, ultimately targeting the creation of a European/international grid infrastructure for health. The topics of this conference converged with the position of the eHealth division of the European Commission, whose mandate from the Lisbon Meeting was "To develop an intelligent environment that enables ubiquitous management of citizens' health status, and to assist health professionals in coping with some major challenges, risk management and the integration into clinical practice of advances in health knowledge." In this context "Health" involves not only clinical procedures but covers the whole range of information from molecular level (genetic and proteomic information) over cells and tissues, to the individual and finally the population level (social healthcare). Grid technology offers the opportunity to create a common working backbone for all different members of this large "health family" and will hopefully lead to an increased awareness and interoperability among disciplines. The first HealthGrid conference led to the creation of the Healthgrid association, a non-profit research association legally incorporated in France but formed from the broad community of European researchers and institutions sharing expertise in health grids. After the second Healthgrid conference, held in Clermont-Ferrand on January 29th-30th, 2004, the need for a "white paper" on the current status and prospective of health grids was raised. Over fifty experts from different areas of grid technologies, eHealth applications and the medical world were invited to contribute to the preparation of this document.

A Grid service for the interactive use of a parallel non-rigid registration algorithm of medical images.

OBJECTIVE: The goal of this work is to improve the usability of a non-rigid registration software for medical images. METHOD: We have built a registration grid service in order to use the interactivity of a visualization workstation and the computing power of a cluster. On the user side, the system is composed of a graphical interface that interacts in a complex and fluid manner with the registration software running on a remote cluster. CONCLUSION: Although the transmission of images back and forth between the computer running the user interface and the cluster running the registration service adds to the total registration time, it provides a user-friendly way of using the registration software without heavy infrastructure investments in hospitals. The system exhibits good performances even if the user is connected to the grid service through a low throughput network such as a wireless network interface or ADSL.

Riemannian elasticity: a statistical regularization framework for non-linear registration.

In inter-subject registration, one often lacks a good model of the transformation variability to choose the optimal regularization. Some works attempt to model the variability in a statistical way, but the re-introduction in a registration algorithm is not easy. In this paper, we interpret the elastic energy as the distance of the Green-St Venant strain tensor to the identity, which reflects the deviation of the local deformation from a rigid transformation. By changing the Euclidean metric for a more suitable Riemannian one, we define a consistent statistical framework to quantify the amount of deformation. In particular, the mean and the covariance matrix of the strain tensor can be consistently and efficiently computed from a population of non-linear transformations. These statistics are then used as parameters in a Mahalanobis distance to measure the statistical deviation from the observed variability, giving a new regularization criterion that we called the statistical Riemannian elasticity. This new criterion is able to handle anisotropic deformations and is inverse-consistent. Preliminary results show that it can be quite easily implemented in a non-rigid registration algorithms.

A complete augmented reality guidance system for liver punctures: first clinical evaluation.

We provided in an augmented reality guidance system for liver punctures, which has been validated on a static abdominal phantom. In this paper, we report the first in vivo experiments. We developed a strictly passive protocol to directly evaluate our system on patients. We show that the system algorithms work efficiently and we highlight the clinical constraints that we had to overcome (small operative field, weight and sterility of the tracked marker attached to the needle...). Finally, we investigate to what extent breathing motion can be neglected for free breathing patient. Results show that the guiding accuracy, close to 1 cm, is sufficient for large targets only (above 3 cm of diameter) when the breathing motion is neglected. In the near future, we aim at validating our system on smaller targets using a respiratory gating technique.

Deformable biomechanical models: application to 4D cardiac image analysis.

This article describes a methodology for creating a generic volumetric biomechanical model from different image modalities and segmenting time series of medical images using this model. The construction of such a generic model consists of three stages: geometric meshing, non-rigid deformation of the mesh in images of various modalities, and image-to-mesh information mapping through rasterization. The non-rigid deformation stage, which relies on a combination of global and local deformations, can then be used to segment time series of images, e.g. cine MRI or gated SPECT cardiac images. We believe that this type of deformable biomechanical model can play an important role in the extraction of useful quantitative local parameters of cardiac function. The biomechanical model of the heart will be coupled with an electrical model of another collaborative project in order to simulate and analyze a larger class of pathologies.

Rigid registration of 3-D ultrasound with MR images: a new approach combining intensity and gradient information.

We present a new image-based technique to rigidly register intraoperative three-dimensional ultrasound (US) with preoperative magnetic resonance (MR) images. Automatic registration is achieved by maximization of a similarity measure which generalizes the correlation ratio, and whose novelty is to incorporate multivariate information from the MR data (intensity and gradient). In addition, the similarity measure is built upon a robust intensity-based distance measure, which makes it possible to handle a variety of US artifacts. A cross-validation study has been carried out using a number of phantom and clinical data. This indicates that the method is quite robust and that the worst registration errors are of the order of the MR image resolution.

A geometric algorithm to find small but highly similar 3D substructures in proteins.

MOTIVATION: Most biological actions of proteins depend on some typical parts of their three-dimensional structure, called 3D motifs. It is desirable to find automatically common geometric substructures between proteins to discover similarities in new structures or to model precisely a particular motif. Most algorithms for structural comparison of proteins deal with large (fold) similarities. Here, we focus on small but precise similarities. RESULTS: We propose a new 3D substructure matching algorithm based on geometric hashing techniques. The key feature of the method is the introduction of a 3D reference frame attached to each residue. This allows us to reduce drastically the complexity of the recognition. Our experimental results confirm the validity of the approach and allow us to find smaller similarities than previous methods. AVAILABILITY: The program uses commercial libraries and thus cannot be completely freely distributed. It can be found at ftp://www.inria.fr in the directory epidaure/Outgoing/xpennec/Prospect, but it requires a key to be run, available by request to xavier.pennec@sophia.inria.fr CONTACT: Xavier.Pennec@sophia.inria.fr; Nicholas.Ayache@sophia.inria.fr