A critical analysis of neuroanatomical software protocols reveals clinically relevant differences in parcellation schemes.

A high replicability in region-of-interest (ROI) morphometric or ROI-based connectivity analyses is essential for such methods to provide biomarkers of good health or disease. In this article, we focus on package design, and more specifically on cortical parcellation protocols, for novel insight into their contribution to inter-package differences. A critical analysis of cortical parcellation protocols from FreeSurfer, BrainSuite, BrainVISA and BrainGyrusMapping revealed major limitations. Details of reference populations are generally missing, cortical variability is not always explicitly accounted for and, more importantly, definition of gyral borders can be inconsistent. We recommend that in the package selection process end users incorporate protocol suitability for the ROIs under investigation, with these particular points in mind, as inter-package differences are likely to be significant and the source of incompatibility between studies' results.

Automatic cardiac LV segmentation in MRI using modified graph cuts with smoothness and interslice constraints.

PURPOSE: Magnetic resonance imaging (MRI), specifically late-enhanced MRI, is the standard clinical imaging protocol to assess cardiac viability. Segmentation of myocardial walls is a prerequisite for this assessment. Automatic and robust multisequence segmentation is required to support processing massive quantities of data. METHODS: A generic rule-based framework to automatically segment the left ventricle myocardium is presented here. We use intensity information, and include shape and interslice smoothness constraints, providing robustness to subject- and study-specific changes. Our automatic initialization considers the geometrical and appearance properties of the left ventricle, as well as interslice information. The segmentation algorithm uses a decoupled, modified graph cut approach with control points, providing a good balance between flexibility and robustness. RESULTS: The method was evaluated on late-enhanced MRI images from a 20-patient in-house database, and on cine-MRI images from a 15-patient open access database, both using as reference manually delineated contours. Segmentation agreement, measured using the Dice coefficient, was 0.81±0.05 and 0.92±0.04 for late-enhanced MRI and cine-MRI, respectively. The method was also compared favorably to a three-dimensional Active Shape Model approach. CONCLUSION: The experimental validation with two magnetic resonance sequences demonstrates increased accuracy and versatility.

Manually-parcellated gyral data accounting for all known anatomical variability.

Morphometric brain changes occur throughout the lifetime and are often investigated to understand healthy ageing and disease, to identify novel biomarkers, and to classify patient groups. Yet, to accurately characterise such changes, an accurate parcellation of the brain must be achieved. Here, we present a manually-parcellated dataset of the superior frontal, the supramarginal, and the cingulate gyri of 10 healthy middle-aged subjects along with a fully detailed protocol based on two anatomical atlases. Gyral parcels were hand-drawn then reviewed by specialists blinded from the protocol to ensure consistency. Importantly, we follow a procedure that allows accounting for anatomical variability beyond what is usually achieved by standard analysis packages and avoids mutually referring to neighbouring gyri when defining gyral edges. We also provide grey matter thickness, grey matter volume, and white matter surface area information for each parcel. This dataset and corresponding measurements are useful in assessing the accuracy of equivalent parcels and metrics generated by image analysis tools and their impact on morphometric studies.

An atlas- and data-driven approach to initializing reaction-diffusion systems in computer cardiac electrophysiology.

The cardiac electrophysiology (EP) problem is governed by a nonlinear anisotropic reaction-diffusion system with a very rapidly varying reaction term associated with the transmembrane cell current. The nonlinearity associated with the cell models requires a stabilization process before any simulation is performed. More importantly, when used in a 3-dimensional (3D) anatomy, it is not sufficient to perform this stabilization on the basis of isolated cells only, since the coupling of the different cells through the tissue greatly modulates the dynamics of the system. Therefore, stabilization of the system must be performed on the entire 3D model. This work develops a novel procedure for the initialization of reaction-diffusion systems for numerical simulations of cardiac EP from steady-state conditions. We exploit surface point correspondence to establish volumetric point correspondence. Upon introduction of a new 3D anatomy with surface point correspondence, a prediction of the cell model steady states is derived from the set of earlier biophysical simulations. We show that the prediction error is typically less than 10% for all model variables, with most variables showing even greater accuracy. When initializing simulations with the predicted model states, it is demonstrated that simulation times can be cut by at least two-thirds and potentially more, which saves hours or days of high-performance computing. Overall, these results increase the clinical applicability of detailed computational EP studies on personalized anatomies.

Statistically-driven 3D fiber reconstruction and denoising from multi-slice cardiac DTI using a Markov random field model.

The construction of subject-specific dense and realistic 3D meshes of the myocardial fibers is an important pre-requisite for the simulation of cardiac electrophysiology and mechanics. Current diffusion tensor imaging (DTI) techniques, however, provide only a sparse sampling of the 3D cardiac anatomy based on a limited number of 2D image slices. Moreover, heart motion affects the diffusion measurements, thus resulting in a significant amount of noisy fibers. This paper presents a Markov random field (MRF) approach for dense reconstruction of 3D cardiac fiber orientations from sparse DTI 2D slices. In the proposed MRF model, statistical constraints are used to relate the missing and the known fibers, while a consistency term is encoded to ensure that the obtained 3D meshes are locally continuous. The validation of the method using both synthetic and real DTI datasets demonstrates robust fiber reconstruction and denoising, as well as physiologically meaningful estimations of cardiac electrical activation.

Estimation of trabecular bone parameters in children from multisequence MRI using texture-based regression.

PURPOSE: This paper presents a statistical approach for the prediction of trabecular bone parameters from low-resolution multisequence magnetic resonance imaging (MRI) in children, thus addressing the limitations of high-resolution modalities such as HR-pQCT, including the significant exposure of young patients to radiation and the limited applicability of such modalities to peripheral bones in vivo. METHODS: A statistical predictive model is constructed from a database of MRI and HR-pQCT datasets, to relate the low-resolution MRI appearance in the cancellous bone to the trabecular parameters extracted from the high-resolution images. The description of the MRI appearance is achieved between subjects by using a collection of feature descriptors, which describe the texture properties inside the cancellous bone, and which are invariant to the geometry and size of the trabecular areas. The predictive model is built by fitting to the training data a nonlinear partial least square regression between the input MRI features and the output trabecular parameters. RESULTS: Detailed validation based on a sample of 96 datasets shows correlations >0.7 between the trabecular parameters predicted from low-resolution multisequence MRI based on the proposed statistical model and the values extracted from high-resolution HRp-QCT. CONCLUSIONS: The obtained results indicate the promise of the proposed predictive technique for the estimation of trabecular parameters in children from multisequence MRI, thus reducing the need for high-resolution radiation-based scans for a fragile population that is under development and growth.

An Algorithm for the Segmentation of Highly Abnormal Hearts Using a Generic Statistical Shape Model.

Statistical shape models (SSMs) have been widely employed in cardiac image segmentation. However, in conditions that induce severe shape abnormality and remodeling, such as in the case of pulmonary hypertension (PH) or hypertrophic cardiomyopathy (HCM), a single SSM is rarely capable of capturing the anatomical variability in the extremes of the distribution. This work presents a new algorithm for the segmentation of severely abnormal hearts. The algorithm is highly flexible, as it does not require a priori knowledge of the involved pathology or any specific parameter tuning to be applied to the cardiac image under analysis. The fundamental idea is to approximate the gross effect of the abnormality with a virtual remodeling transformation between the patient-specific geometry and the average shape of the reference model (e.g., average normal morphology). To define this mapping, a set of landmark points are automatically identified during boundary point search, by estimating the reliability of the candidate points. With the obtained transformation, the feature points extracted from the patient image volume are then projected onto the space of the reference SSM, where the model is used to effectively constrain and guide the segmentation process. The extracted shape in the reference space is finally propagated back to the original image of the abnormal heart to obtain the final segmentation. Detailed validation with patients diagnosed with PH and HCM shows the robustness and flexibility of the technique for the segmentation of highly abnormal hearts of different pathologies.

Patient-Specific Biomechanical Modeling of Bone Strength Using Statistically-Derived Fabric Tensors.

Low trauma fractures are amongst the most frequently encountered problems in the clinical assessment and treatment of bones, with dramatic health consequences for individuals and high financial costs for health systems. Consequently, significant research efforts have been dedicated to the development of accurate computational models of bone biomechanics and strength. However, the estimation of the fabric tensors, which describe the microarchitecture of the bone, has proven to be challenging using in vivo imaging. On the other hand, existing research has shown that isotropic models do not produce accurate predictions of stress states within the bone, as the material properties of the trabecular bone are anisotropic. In this paper, we present the first biomechanical study that uses statistically-derived fabric tensors for the estimation of bone strength in order to obtain patient-specific results. We integrate a statistical predictive model of trabecular bone microarchitecture previously constructed from a sample of ex vivo micro-CT datasets within a biomechanical simulation workflow. We assess the accuracy and flexibility of the statistical approach by estimating fracture load for two different databases and bone sites, i.e., for the femur and the T12 vertebra. The results obtained demonstrate good agreement between the statistically-driven and micro-CT-based estimates, with concordance coefficients of 98.6 and 95.5% for the femur and vertebra datasets, respectively.

Statistical estimation of femur micro-architecture using optimal shape and density predictors.

The personalization of trabecular micro-architecture has been recently shown to be important in patient-specific biomechanical models of the femur. However, high-resolution in vivo imaging of bone micro-architecture using existing modalities is still infeasible in practice due to the associated acquisition times, costs, and X-ray radiation exposure. In this study, we describe a statistical approach for the prediction of the femur micro-architecture based on the more easily extracted subject-specific bone shape and mineral density information. To this end, a training sample of ex vivo micro-CT images is used to learn the existing statistical relationships within the low and high resolution image data. More specifically, optimal bone shape and mineral density features are selected based on their predictive power and used within a partial least square regression model to estimate the unknown trabecular micro-architecture within the anatomical models of new subjects. The experimental results demonstrate the accuracy of the proposed approach, with average errors of 0.07 for both the degree of anisotropy and tensor norms.

A framework for optimal kernel-based manifold embedding of medical image data.

Kernel-based dimensionality reduction is a widely used technique in medical image analysis. To fully unravel the underlying nonlinear manifold the selection of an adequate kernel function and of its free parameters is critical. In practice, however, the kernel function is generally chosen as Gaussian or polynomial and such standard kernels might not always be optimal for a given image dataset or application. In this paper, we present a study on the effect of the kernel functions in nonlinear manifold embedding of medical image data. To this end, we first carry out a literature review on existing advanced kernels developed in the statistics, machine learning, and signal processing communities. In addition, we implement kernel-based formulations of well-known nonlinear dimensional reduction techniques such as Isomap and Locally Linear Embedding, thus obtaining a unified framework for manifold embedding using kernels. Subsequently, we present a method to automatically choose a kernel function and its associated parameters from a pool of kernel candidates, with the aim to generate the most optimal manifold embeddings. Furthermore, we show how the calculated selection measures can be extended to take into account the spatial relationships in images, or used to combine several kernels to further improve the embedding results. Experiments are then carried out on various synthetic and phantom datasets for numerical assessment of the methods. Furthermore, the workflow is applied to real data that include brain manifolds and multispectral images to demonstrate the importance of the kernel selection in the analysis of high-dimensional medical images.

A Predictive Model of Vertebral Trabecular Anisotropy From Ex Vivo Micro-CT.

Spine-related disorders are amongst the most frequently encountered problems in clinical medicine. For several applications such as 1) to improve the assessment of the strength of the spine, as well as 2) to optimize the personalization of spinal interventions, image-based biomechanical modeling of the vertebrae is expected to play an important predictive role. However, this requires the construction of computational models that are subject-specific and comprehensive. In particular, they need to incorporate information about the vertebral anisotropic micro-architecture, which plays a central role in the biomechanical function of the vertebrae. In practice, however, accurate personalization of the vertebral trabeculae has proven to be difficult as its imaging in vivo is currently infeasible. Consequently, this paper presents a statistical approach for accurate prediction of the vertebral fabric tensors based on a training sample of ex vivo micro-CT images. To the best of our knowledge, this is the first predictive model proposed and validated for vertebral datasets. The method combines features selection and partial least squares regression in order to derive optimal latent variables for the prediction of the fabric tensors based on the more easily extracted shape and density information. Detailed validation with 20 ex vivo T12 vertebrae demonstrates the accuracy and consistency of the approach for the personalization of trabecular anisotropy.

A framework for the merging of pre-existing and correspondenceless 3D statistical shape models.

The construction of statistical shape models (SSMs) that are rich, i.e., that represent well the natural and complex variability of anatomical structures, is an important research topic in medical imaging. To this end, existing works have addressed the limited availability of training data by decomposing the shape variability hierarchically or by combining statistical and synthetic models built using artificially created modes of variation. In this paper, we present instead a method that merges multiple statistical models of 3D shapes into a single integrated model, thus effectively encoding extra variability that is anatomically meaningful, without the need for the original or new real datasets. The proposed framework has great flexibility due to its ability to merge multiple statistical models with unknown point correspondences. The approach is beneficial in order to re-use and complement pre-existing SSMs when the original raw data cannot be exchanged due to ethical, legal, or practical reasons. To this end, this paper describes two main stages, i.e., (1) statistical model normalization and (2) statistical model integration. The normalization algorithm uses surface-based registration to bring the input models into a common shape parameterization with point correspondence established across eigenspaces. This allows the model fusion algorithm to be applied in a coherent manner across models, with the aim to obtain a single unified statistical model of shape with improved generalization ability. The framework is validated with statistical models of the left and right cardiac ventricles, the L1 vertebra, and the caudate nucleus, constructed at distinct research centers based on different imaging modalities (CT and MRI) and point correspondences. The results demonstrate that the model integration is statistically and anatomically meaningful, with potential value for merging pre-existing multi-modality statistical models of 3D shapes.

Effect of statistically derived fiber models on the estimation of cardiac electrical activation.

Myocardial fiber orientation plays a critical role in the electrical activation and subsequent contraction of the heart. To increase the clinical potential of electrophysiological (EP) simulation for the study of cardiac phenomena and the planning of interventions, accurate personalization of the fibers is a necessary yet challenging task. Due to the difficulties associated with the in vivo imaging of cardiac fiber structure, researchers have developed alternative techniques to personalize fibers. Thus far, cardiac simulation was performed mainly based on rule-based fiber models. More recently, there has been a significant interest in data-driven and statistically derived fiber models. In particular, our predictive method in [1] allows us to estimate the unknown subject-specific fiber orientation based on the more easily available shape information. The aim of this work is to estimate the effect of using such statistical predictive models for the estimation of cardiac electrical activation times and patterns. To this end, we perform EP simulations based on a database of ten canine ex vivo diffusion tensor imaging (DTI) datasets that include normal and failing cases. To assess the strength of the fiber models under varying conditions, we consider both sinus rhythm and biventricular pacing simulations. The results show that 1) the statistically derived fibers improve the estimation of the local activation times by an average of 53.7% over traditional rule-based models, and that 2) the obtained electrical activations are consistently similar to those of the DTI-based fibers.

Reconstruction of coronary trees from 3DRA using a 3D+t statistical cardiac prior.

A 3D+t description of the coronary tree is important for diagnosis of coronary artery disease and therapy planning. In this paper, we propose a method for finding 3D+t points on coronary artery tree given tracked 2D+t point locations in X-ray rotational angiography images. In order to cope with the ill-posedness of the problem, we use a bilinear model of ventricle as a spatio-temporal constraint on the nonrigid structure of the coronary artery. Based on an energy minimization formulation, we estimate i) bilinear model parameters, ii) global rigid transformation between model and X-ray coordinate systems, and iii) correspondences between 2D coronary artery points on X-ray images and 3D points on bilinear model. We validated the algorithm using a software coronary artery phantom.

Statistical personalization of ventricular fiber orientation using shape predictors.

This paper presents a predictive framework for the statistical personalization of ventricular fibers. To this end, the relationship between subject-specific geometry of the left (LV) and right ventricles (RV) and fiber orientation is learned statistically from a training sample of ex vivo diffusion tensor imaging datasets. More specifically, the axes in the shape space which correlate most with the myocardial fiber orientations are extracted and used for prediction in new subjects. With this approach and unlike existing fiber models, inter-subject variability is taken into account to generate latent shape predictors that are statistically optimal to estimate fiber orientation at each individual myocardial location. The proposed predictive model was applied to the task of personalizing fibers in 10 canine subjects. The results indicate that the ventricular shapes are good predictors of fiber orientation, with an improvement of 11.4% in accuracy over the average fiber model.

Fusing correspondenceless 3D point distribution models.

This paper presents a framework for the fusion of multiple point distribution models (PDMs) with unknown point correspondences. With this work, models built from distinct patient groups and imaging modalities can be merged, with the aim to obtain a PDM that encodes a wider range of anatomical variability. To achieve this, two technical challenges are addressed in this work. Firstly, the model fusion must be carried out directly on the corresponding means and eigenvectors as the original data is not always available and cannot be freely exchanged across centers for various legal and practical reasons. Secondly, the PDMs need to be normalized before fusion as the point correspondence is unknown. The proposed framework is validated by integrating statistical models of the left and right ventricles of the heart constructed from different imaging modalities (MRI and CT) and with different landmark representations of the data. The results show that the integration is statistically and anatomically meaningful and that the quality of the resulting model is significantly improved.

Interventional endocardial motion estimation from electroanatomical mapping data: application to scar characterization.

Scar presence and its characteristics play a fundamental role in several cardiac pathologies. To accurately define the extent and location of the scar is essential for a successful ventricular tachycardia ablation procedure. Nowadays, a set of widely accepted electrical voltage thresholds applied to local electrograms recorded are used intraoperatively to locate the scar. Information about cardiac mechanics could be considered to characterize tissues with different viability properties. We propose a novel method to estimate endocardial motion from data obtained with an electroanatomical mapping system together with the endocardial geometry segmented from preoperative 3-D magnetic resonance images, using a statistical atlas constructed with bilinear models. The method was validated using synthetic data generated from ultrasound images of nine volunteers and was then applied to seven ventricular tachycardia patients. Maximum bipolar voltages, commonly used to intraoperatively locate scar tissue, were compared to endocardial wall displacement and strain for all the patients. The results show that the proposed method allows endocardial motion and strain estimation and that areas with low-voltage electrograms also present low strain values.

A high-resolution atlas and statistical model of the human heart from multislice CT.

Atlases and statistical models play important roles in the personalization and simulation of cardiac physiology. For the study of the heart, however, the construction of comprehensive atlases and spatio-temporal models is faced with a number of challenges, in particular the need to handle large and highly variable image datasets, the multi-region nature of the heart, and the presence of complex as well as small cardiovascular structures. In this paper, we present a detailed atlas and spatio-temporal statistical model of the human heart based on a large population of 3D+time multi-slice computed tomography sequences, and the framework for its construction. It uses spatial normalization based on nonrigid image registration to synthesize a population mean image and establish the spatial relationships between the mean and the subjects in the population. Temporal image registration is then applied to resolve each subject-specific cardiac motion and the resulting transformations are used to warp a surface mesh representation of the atlas to fit the images of the remaining cardiac phases in each subject. Subsequently, we demonstrate the construction of a spatio-temporal statistical model of shape such that the inter-subject and dynamic sources of variation are suitably separated. The framework is applied to a 3D+time data set of 138 subjects. The data is drawn from a variety of pathologies, which benefits its generalization to new subjects and physiological studies. The obtained level of detail and the extendability of the atlas present an advantage over most cardiac models published previously.

Predictive modeling of cardiac fiber orientation using the Knutsson mapping.

The construction of realistic subject-specific models of the myocardial fiber architecture is relevant to the understanding and simulation of the electromechanical behavior of the heart. This paper presents a statistical approach for the prediction of fiber orientation from myocardial morphology based on the Knutsson mapping. In this space, the orientation of each fiber is represented in a continuous and distance preserving manner, thus allowing for consistent statistical analysis of the data. Furthermore, the directions in the shape space which correlate most with the myocardial fiber orientations are extracted and used for subsequent prediction. With this approach and unlike existing models, all shape information is taken into account in the analysis and the obtained latent variables are statistically optimal to predict fiber orientation in new datasets. The proposed technique is validated based on a sample of canine Diffusion Tensor Imaging (DTI) datasets and the results demonstrate marked improvement in cardiac fiber orientation modeling and prediction.