Validation of nonrigid image registration using finite-element methods: application to breast MR images

This paper presents a novel method for validation of nonrigid medical image registration. This method is based on the simulation of physically plausible, biomechanical tissue deformations using finite-element methods. Applying a range of displacements to finite-element models of different patient anatomies generates model solutions which simulate gold standard deformations. From these solutions, deformed images are generated with a range of deformations typical of those likely to occur in vivo. The registration accuracy with respect to the finite-element simulations is quantified by co-registering the deformed images with the original images and comparing the recovered voxel displacements with the biomechanically simulated ones. The functionality of the validation method is demonstrated for a previously described nonrigid image registration technique based on free-form deformations using B-splines and normalized mutual information as a voxel similarity measure, with an application to contrast-enhanced magnetic resonance mammography image pairs. The exemplar nonrigid registration technique is shown to be of subvoxel accuracy on average for this particular application. The validation method presented here is an important step toward more generic simulations of biomechanically plausible tissue deformations and quantification of tissue motion recovery using nonrigid image registration. It will provide a basis for improving and comparing different nonrigid registration techniques for a diversity of medical applications, such as intrasubject tissue deformation or motion correction in the brain, liver or heart.     

Nonlinear elastic registration of brain images with tumor pathologyusing a biomechanical model [MRI]

A biomechanical model of the brain is presented, using a finite-element formulation. Emphasis is given to the modeling of the soft-tissue deformations induced by the growth of tumors and its application to the registration of anatomical atlases, with images from patients presenting such pathologies. First, an estimate of the anatomy prior to the tumor growth is obtained through a simulated biomechanical contraction of the tumor region. Then a normal-to-normal atlas registration to this estimated pre-tumor anatomy is applied. Finally, the deformation from the tumor-growth model is applied to the resultant registered atlas, producing an atlas that has been deformed to fully register to the patient images. The process of tumor growth is simulated in a nonlinear optimization framework, which is driven by anatomical features such as boundaries of brain structures. The deformation of the surrounding tissue is estimated using a nonlinear elastic model of soft tissue under the boundary conditions imposed by the skull, ventricles, and the falx and tentorium. A preliminary two-dimensional (2-D) implementation is presented in this paper, and tested on both simulated and patient data. One of the long-term goals of this work is to use anatomical brain atlases to estimate the locations of important brain structures in the brain and to use these estimates in presurgical and radiosurgical planning systems.     

A comparative study of biomechanical simulators in deformable registration of brain tumor images

Simulating the brain tissue deformation caused by tumor growth has been found to aid the deformable registration of brain tumor images. In this paper, we evaluate the impact that different biomechanical simulators have on the accuracy of deformable registration. We use two alternative frameworks for biomechanical simulations of mass effect in 3-D magnetic resonance (MR) brain images. The first one is based on a finite-element model of nonlinear elasticity and unstructured meshes using the commercial software package ABAQUS. The second one employs incremental linear elasticity and regular grids in a fictitious domain method. In practice, biomechanical simulations via the second approach may be at least ten times faster. Landmarks error and visual examination of the coregistered images indicate that the two alternative frameworks for biomechanical simulations lead to comparable results of deformable registration. Thus, the computationally less expensive biomechanical simulator offers a practical alternative for registration purposes.     

Simulation of tissue atrophy using a topology preserving transformation model

We propose a method to simulate atrophy and other similar volumetric change effects on medical images. Given a desired level of atrophy, we find a dense warping deformation that produces the corresponding levels of volumetric loss on the labeled tissue using an energy minimization strategy. Simulated results on a real brain image indicate that the method generates realistic images of tissue loss. The method does not make assumptions regarding the mechanics of tissue deformation, and provides a framework where a pre-specified pattern of atrophy can readily be simulated. Furthermore, it provides exact correspondences between images prior and posterior to the atrophy that can be used to evaluate provisional image registration and atrophy quantification algorithms.     

Volumetric intraoperative brain deformation compensation: model development and phantom validation

During neurosurgery, nonrigid brain deformation may affect the reliability of tissue localization based on preoperative images. To provide accurate surgical guidance in these cases, preoperative images must be updated to reflect the intraoperative brain. This can be accomplished by warping these preoperative images using a biomechanical model. Due to the possible complexity of this deformation, intraoperative information is often required to guide the model solution. In this paper, a linear elastic model of the brain is developed to infer volumetric brain deformation associated with measured intraoperative cortical surface displacement. The developed model relies on known material properties of brain tissue, and does not require further knowledge about intraoperative conditions. To provide an initial estimation of volumetric model accuracy, as well as determine the model's sensitivity to the specified material parameters and surface displacements, a realistic brain phantom was developed. Phantom results indicate that the linear elastic model significantly reduced localization error due to brain shift, from > 16 mm to under 5 mm, on average. In addition, though in vivo quantitative validation is necessary, preliminary application of this approach to images acquired during neocortical epilepsy cases confirms the feasibility of applying the developed model to in vivo data.     

Biomechanical modeling of the human head for physically based, nonrigid image registration

The accuracy of image-guided neurosurgery generally suffers from brain deformations due to intraoperative changes. These deformations cause significant changes of the anatomical geometry (organ shape and spatial interorgan relations), thus making intraoperative navigation based on preoperative images error prone. In order to improve the navigation accuracy, we developed a biomechanical model of the human head based on the finite element method, which can be employed for the correction of preoperative images to cope with the deformations occurring during surgical interventions. At the current stage of development, the two-dimensional (2-D) implementation of the model comprises two different materials, though the theory holds for the three-dimensional (3-D) case and is capable of dealing with an arbitrary number of different materials. For the correction of a preoperative image, a set of homologous landmarks must be specified which determine correspondences. These correspondences can be easily integrated into the model and are maintained throughout the computation of the deformation of the preoperative image. The necessary material parameter values have been determined through a comprehensive literature study. Our approach has been tested for the case of synthetic images and yields physically plausible deformation results. Additionally, we carried out registration experiments with a preoperative MR image of the human head and a corresponding postoperative image simulating an intraoperative image. We found that our approach yields good prediction results, even in the case when correspondences are given in a relatively small area of the image only.     

Multiscale modeling for image analysis of brain tumor studies

Image-based modeling of tumor growth combines methods from cancer simulation and medical imaging. In this context, we present a novel approach to adapt a healthy brain atlas to MR images of tumor patients. In order to establish correspondence between a healthy atlas and a pathologic patient image, tumor growth modeling in combination with registration algorithms is employed. In a first step, the tumor is grown in the atlas based on a new multiscale, multiphysics model including growth simulation from the cellular level up to the biomechanical level, accounting for cell proliferation and tissue deformations. Large-scale deformations are handled with an Eulerian approach for finite element computations, which can operate directly on the image voxel mesh. Subsequently, dense correspondence between the modified atlas and patient image is established using nonrigid registration. The method offers opportunities in atlas-based segmentation of tumor-bearing brain images as well as for improved patient-specific simulation and prognosis of tumor progression.     

A framework for predictive modeling of anatomical deformations

A framework for modeling and predicting anatomical deformations is presented, and tested on simulated images. Although a variety of deformations can be modeled in this framework, emphasis is placed on surgical planning, and particularly on modeling and predicting changes of anatomy between preoperative and intraoperative positions, as well as on deformations induced by tumor growth. Two methods are examined. The first is purely shape-based and utilizes the principal modes of co-variation between anatomy and deformation in order to statistically represent deformability. When a patient's anatomy is available, it is used in conjunction with the statistical model to predict the way in which the anatomy will/can deform. The second method is related, and it uses the statistical model in conjunction with a biomechanical model of anatomical deformation. It examines the principal modes of co-variation between shape and forces, with the latter driving the biomechanical model, and thus predicting deformation. Results are shown on simulated images, demonstrating that systematic deformations, such as those resulting from change in position or from tumor growth, can be estimated very well using these models. Estimation accuracy will depend on the application, and particularly on how systematic a deformation of interest is.     

Registration of 3-D intraoperative MR images of the brain using a finite-element biomechanical model

We present a new algorithm for the nonrigid registration of three-dimensional magnetic resonance (MR) intraoperative image sequences showing brain shift. The algorithm tracks key surfaces of objects (cortical surface and the lateral ventricles) in the image sequence using a deformable surface matching algorithm. The volumetric deformation field of the objects is then inferred from the displacements at the boundary surfaces using a linear elastic biomechanical finite-element model. Two experiments on synthetic image sequences are presented, as well as an initial experiment on intraoperative MR images showing brain shift. The results of the registration algorithm show a good correlation of the internal brain structures after deformation, and a good capability of measuring surface as well as subsurface shift. We measured distances between landmarks in the deformed initial image and the corresponding landmarks in the target scan. Cortical surface shifts of up to 10 mm and subsurface shifts of up to 6 mm were recovered with an accuracy of 1 mm or less and 3 mm or less respectively.     

Fast LV motion estimation using subspace approximation techniques

Cardiac motion estimation is very important in understanding cardiac dynamics and in noninvasive diagnosis of heart disease. Magnetic resonance (MR) imaging tagging is a technique for measuring heart deformations. In cardiac tagged MR images, a set of dark lines are noninvasively encoded within myocardial tissue providing the means for measurement of deformations of the heart. The points along tag lines measured in different frames and in different directions carry important information for determining the three-dimensional nonrigid movement of left ventricle. However, these measurements are sparse and, therefore, multidimensional interpolation techniques are needed to reconstruct a dense displacement field. In this paper, a novel subspace approximation technique is used to accomplish this task. We formulate the displacement estimation as a variational problem and then project the solution into spline subspaces. Efficient numerical methods are derived by taking advantages of B-spline properties. The proposed technique significantly improves our previous results reported in [3] with respect to computational time. The method is applied to a temporal sequence of two-dimensional images and is validated with simulated and in vivo heart data.     

Three-dimensional anatomical model-based segmentation of MR brainimages through principal axes registration

Model-based segmentation and analysis of brain images depends on anatomical knowledge which may be derived from conventional atlases. Classical anatomical atlases are based on the rigid spatial distribution provided by a single cadaver. Their use to segment internal anatomical brain structures in a high-resolution MR brain image does not provide any knowledge about the subject variability, and therefore they are not very efficient in analysis. The authors present a method to develop three-dimensional computerized composite models of brain structures to build a computerized anatomical atlas. The composite models are developed using the real MR brain images of human subjects which are registered through the principal axes transformation. The composite models provide probabilistic spatial distributions, which represent the variability of brain structures and can be easily updated for additional subjects. The authors demonstrate the use of such a composite model of ventricular structure to help segmentation of the ventricles and cerebrospinal fluid of MR brain images. Here, a composite model of ventricles using a set of 22 human subjects is developed and used in a model-based segmentation of ventricles, sulci, and white matter lesions. To illustrate the clinical usefulness, automatic volumetric measurements on ventricular size and cortical atrophy for an additional eight alcoholics and 10 normal subjects were made. The volumetric quantitative results indicated regional brain atrophy in chronic alcoholics     

MCG simulations with a realistic heart-torso model

Magnetocardiograms (MCGs) simulated high-resolution heart-torso model of an adult subject were compared with measured MCGs acquired from the same individual. An exact match of the measured and simulated MCGs was not found due to the uncertainties in tissue conductivities and cardiac source positions. However, general features of the measured MCGs were reasonably represented by the simulated data for most, but not all of the channels. This suggests that the model accounts for the most important mechanisms underlying the genesis of MCGs and may be useful for cardiac magnetic field modeling under normal and diseased states. MCGs were simulated with a realistic finite-element heart-torso model constructed from segmented magnetic resonance images with 19 different tissue types identified. A finite-element model was developed from the segmented images. The model consists of 2.51 million brick-shaped elements and 2.58 million nodes, and has a voxel resolution of 1.56×1.56×3 mm. Current distributions inside the torso and the magnetic fields and MCGs at the gradiometer coil locations were computed. MCGs were measured with a Philips twin Dewar first-order gradiometer SQUID-system consisting of 31 channels in one tank and 19 channels in the other     

An electromechanical model of the heart for image analysis and simulation

This paper presents a new three-dimensional electromechanical model of the two cardiac ventricles designed both for the simulation of their electrical and mechanical activity, and for the segmentation of time series of medical images. First, we present the volumetric biomechanical models built. Then the transmembrane potential propagation is simulated, based on FitzHugh-Nagumo reaction-diffusion equations. The myocardium contraction is modeled through a constitutive law including an electromechanical coupling. Simulation of a cardiac cycle, with boundary conditions representing blood pressure and volume constraints, leads to the correct estimation of global and local parameters of the cardiac function. This model enables the introduction of pathologies and the simulation of electrophysiology interventions. Moreover, it can be used for cardiac image analysis. A new proactive deformable model of the heart is introduced to segment the two ventricles in time series of cardiac images. Preliminary results indicate that this proactive model, which integrates a priori knowledge on the cardiac anatomy and on its dynamical behavior, can improve the accuracy and robustness of the extraction of functional parameters from cardiac images even in the presence of noisy or sparse data. Such a model also allows the simulation of cardiovascular pathologies in order to test therapy strategies and to plan interventions.     

ORBIT: a multiresolution framework for deformable registration of brain tumor images

A deformable registration method is proposed for registering a normal brain atlas with images of brain tumor patients. The registration is facilitated by first simulating the tumor mass effect in the normal atlas in order to create an atlas image that is as similar as possible to the patient's image. An optimization framework is used to optimize the location of tumor seed as well as other parameters of the tumor growth model, based on the pattern of deformation around the tumor region. In particular, the optimization is implemented in a multiresolution and hierarchical scheme, and it is accelerated by using a principal component analysis (PCA)-based model of tumor growth and mass effect, trained on a computationally more expensive biomechanical model. Validation on simulated and real images shows that the proposed registration framework, referred to as ORBIT (optimization of tumor parameters and registration of brain images with tumors), outperforms other available registration methods particularly for the regions close to the tumor, and it has the potential to assist in constructing statistical atlases from tumor-diseased brain images.      

Volume conduction in an anatomically based surface EMG model

A finite-element model to simulate surface electromyography (EMG) in a realistic human upper arm is presented. The model is used to explore the effect of limb geometry on surface-detected muscle fiber action potentials. The model was based on magnetic resonance images of the subject's upper arm and includes both resistive and capacitive material properties. To validate the model geometry, experimental and simulated potentials were compared at different electrode sites during the application of a subthreshold sinusoidal current source to the skin surface. Of the material properties examined, the closest approximation to the experimental data yielded a mean root-mean-square (rms) error of the normalized surface potential of 18% or 27%, depending on the site of the applied source. Surface-detected action potentials simulated using the realistic volume conductor model and an idealized cylindrical model based on the same limb geometry were then compared. Variation in the simulated limb geometry had a considerable effect on action potential shape. However, the rate of decay of the action potential amplitude with increasing distance from the fiber was similar in both models. Inclusion of capacitive material properties resulted in temporal low-pass filtering of the surface action potentials. This effect was most pronounced in the end-effect components of action potentials detected at locations far from the active fiber. It is concluded that accurate modeling of the limb geometry, asymmetry, tissue capacitance and fiber curvature is important when the specific action potential shapes are of interest. However, if the objective is to examine more qualitative features of the surface EMG signal, then an idealized volume conductor model with appropriate tissue thicknesses provides a close approximation.     

An adaptive-focus statistical shape model for segmentation and shape modeling of 3-D brain structures

This paper presents a deformable model for automatically segmenting brain structures from volumetric magnetic resonance (MR) images and obtaining point correspondences, using geometric and statistical information in a hierarchical scheme. Geometric information is embedded into the model via a set of affine-invariant attribute vectors, each of which characterizes the geometric structure around a point of the model from a local to a global scale. The attribute vectors, in conjunction with the deformation mechanism of the model, warranty that the model not only deforms to nearby edges, as is customary in most deformable surface models, but also that it determines point correspondences based on geometric similarity at different scales. The proposed model is adaptive in that it initially focuses on the most reliable structures of interest, and gradually shifts focus to other structures as those become closer to their respective targets and, therefore, more reliable. The proposed techniques have been used to segment boundaries of the ventricles, the caudate nucleus, and the lenticular nucleus from volumetric MR images.     

Comparison and validation of tissue modelization and statistical classification methods in T1-weighted MR brain images

This paper presents a validation study on statistical nonsupervised brain tissue classification techniques in magnetic resonance (MR) images. Several image models assuming different hypotheses regarding the intensity distribution model, the spatial model and the number of classes are assessed. The methods are tested on simulated data for which the classification ground truth is known. Different noise and intensity nonuniformities are added to simulate real imaging conditions. No enhancement of the image quality is considered either before or during the classification process. This way, the accuracy of the methods and their robustness against image artifacts are tested. Classification is also performed on real data where a quantitative validation compares the methods' results with an estimated ground truth from manual segmentations by experts. Validity of the various classification methods in the labeling of the image as well as in the tissue volume is estimated with different local and global measures. Results demonstrate that methods relying on both intensity and spatial information are more robust to noise and field inhomogeneities. We also demonstrate that partial volume is not perfectly modeled, even though methods that account for mixture classes outperform methods that only consider pure Gaussian classes. Finally, we show that simulated data results can also be extended to real data.     

Mammogram registration: a phantom-based evaluation of compressed breast thickness variation effects

The temporal comparison of mammograms is complex; a wide variety of factors can cause changes in image appearance. Mammogram registration is proposed as a method to reduce the effects of these changes and potentially to emphasize genuine alterations in breast tissue. Evaluation of such registration techniques is difficult since ground truth regarding breast deformations is not available in clinical mammograms. In this paper, we propose a systematic approach to evaluate sensitivity of registration methods to various types of changes in mammograms using synthetic breast images with known deformations. As a first step, images of the same simulated breasts with various amounts of simulated physical compression have been used to evaluate a previously described nonrigid mammogram registration technique. Registration performance is measured by calculating the average displacement error over a set of evaluation points identified in mammogram pairs. Applying appropriate thickness compensation and using a preferred order of the registered images, we obtained an average displacement error of 1.6 mm for mammograms with compression differences of 1-3 cm. The proposed methodology is applicable to analysis of other sources of mammogram differences and can be extended to the registration of multimodality breast data.     

A unifying framework for partial volume segmentation of brain MR images

Accurate brain tissue segmentation by intensity-based voxel classification of magnetic resonance (MR) images is complicated by partial volume (PV) voxels that contain a mixture of two or more tissue types. In this paper, we present a statistical framework for PV segmentation that encompasses and extends existing techniques. We start from a commonly used parametric statistical image model in which each voxel belongs to one single tissue type, and introduce an additional downsampling step that causes partial voluming along the borders between tissues. An expectation-maximization approach is used to simultaneously estimate the parameters of the resulting model and perform a PV classification. We present results on well-chosen simulated images and on real MR images of the brain, and demonstrate that the use of appropriate spatial prior knowledge not only improves the classifications, but is often indispensable for robust parameter estimation as well. We conclude that general robust PV segmentation of MR brain images requires statistical models that describe the spatial distribution of brain tissues more accurately than currently available models.     

Simultaneous multi-scale registration using large deformation diffeomorphic metric mapping

In the framework of large deformation diffeomorphic metric mapping (LDDMM), we present a practical methodology to integrate prior knowledge about the registered shapes in the regularizing metric. Our goal is to perform rich anatomical shape comparisons from volumetric images with the mathematical properties offered by the LDDMM framework. We first present the notion of characteristic scale at which image features are deformed. We then propose a methodology to compare anatomical shape variations in a multi-scale fashion, i.e., at several characteristic scales simultaneously. In this context, we propose a strategy to quantitatively measure the feature differences observed at each characteristic scale separately. After describing our methodology, we illustrate the performance of the method on phantom data. We then compare the ability of our method to segregate a group of subjects having Alzheimer's disease and a group of controls with a classical coarse to fine approach, on standard 3D MR longitudinal brain images. We finally apply the approach to quantify the anatomical development of the human brain from 3D MR longitudinal images of pre-term babies. Results show that our method registers accurately volumetric images containing feature differences at several scales simultaneously with smooth deformations.