Sarang C. Joshi

Unbiased diffeomorphic atlas construction for computational anatomy

Construction of population atlases is a key issue in medical image analysis, and particularly in brain mapping. Large sets of images are mapped into a common coordinate system to study intra-population variability and inter-population differences, to provide voxel-wise mapping of functional sites, and help tissue and object segmentation via registration of anatomical labels. Common techniques often include the choice of a template image, which inherently introduces a bias. This paper describes a new method for unbiased construction of atlases in the large deformation diffeomorphic setting. A child neuroimaging autism study serves as a driving application. There is lack of normative data that explains average brain shape and variability at this early stage of development. We present work in progress toward constructing an unbiased MRI atlas of 2 years of children and the building of a probabilistic atlas of anatomical structures, here the caudate nucleus. Further, we demonstrate the segmentation of new subjects via atlas mapping. Validation of the methodology is performed by comparing the deformed probabilistic atlas with existing manual segmentations.

Principal geodesic analysis for the study of nonlinear statistics of shape

A primary goal of statistical shape analysis is to describe the variability of a population of geometric objects. A standard technique for computing such descriptions is principal component analysis. However, principal component analysis is limited in that it only works for data lying in a Euclidean vector space. While this is certainly sufficient for geometric models that are parameterized by a set of landmarks or a dense collection of boundary points, it does not handle more complex representations of shape. We have been developing representations of geometry based on the medial axis description or m-rep. While the medial representation provides a rich language for variability in terms of bending, twisting, and widening, the medial parameters are not elements of a Euclidean vector space. They are in fact elements of a nonlinear Riemannian symmetric space. In this paper, we develop the method of principal geodesic analysis, a generalization of principal component analysis to the manifold setting. We demonstrate its use in describing the variability of medially-defined anatomical objects. Results of applying this framework on a population of hippocampi in a schizophrenia study are presented.

Volumetric transformation of brain anatomy

Presents diffeomorphic transformations of three-dimensional (3-D) anatomical image data of the macaque occipital lobe and whole brain cryosection imagery and of deep brain structures in human brains as imaged via magnetic resonance imagery. These transformations are generated in a hierarchical manner, accommodating both global and local anatomical detail. The initial low-dimensional registration is accomplished by constraining the transformation to be in a low-dimensional basis. The basis is defined by the Greens function of the elasticity operator placed at predefined locations in the anatomy and the eigenfunctions of the elasticity operator. The high-dimensional large deformations are vector fields generated via the mismatch between the template and target-image volumes constrained to be the solution of a Navier-Stokes fluid model. As part of this procedure, the Jacobian of the transformation is tracked, insuring the generation of diffeomorphisms. It is shown that transformations constrained by quadratic regularization methods such as the Laplacian, biharmonic, and linear elasticity models, do not ensure that the transformation maintains topology and, therefore, must only be used for coarse global registration.

Landmark matching via large deformation diffeomorphisms

This paper describes the generation of large deformation diffeomorphisms phi:Omega=[0,1]3<-->Omega for landmark matching generated as solutions to the transport equation dphi(x,t)/dt=nu(phi(x,t),t),epsilon[0,1] and phi(x,0)=x, with the image map defined as phi(.,1) and therefore controlled via the velocity field nu(.,t),epsilon[0,1]. Imagery are assumed characterized via sets of landmarks {xn, yn, n=1, 2, ..., N}. The optimal diffeomorphic match is constructed to minimize a running smoothness cost parallelLnu parallel2 associated with a linear differential operator L on the velocity field generating the diffeomorphism while simultaneously minimizing the matching end point condition of the landmarks. Both inexact and exact landmark matching is studied here. Given noisy landmarks xn matched to yn measured with error covariances Sigman, then the matching problem is solved generating the optimal diffeomorphism phi;(x,1)=integral0(1)nu(phi(x,t),t)dt+x where nu(.)=argmin(nu.)integral1(0) integralOmega parallelLnu(x,t) parallel2dxdt +Sigman=1N[yn-phi(xn,1)] TSigman(-1)[yn-phi(xn,1)]. Conditions for the existence of solutions in the space of diffeomorphisms are established, with a gradient algorithm provided for generating the optimal flow solving the minimum problem. Results on matching two-dimensional (2-D) and three-dimensional (3-D) imagery are presented in the macaque monkey.

Four‐dimensional radiotherapy planning for DMLC‐based respiratory motion tracking

Four-dimensional (4D) radiotherapy is the explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy. Temporal anatomic changes can occur for many reasons, though the focus of the current investigation is respiration motion for lung tumors. The aim of this study was to develop 4D radiotherapy treatment-planning methodology for DMLC-based respiratory motion tracking. A 4D computed tomography (CT) scan consisting of a series of eight 3D CT image sets acquired at different respiratory phases was used for treatment planning. Deformable image registration was performed to map each CT set from the peak-inhale respiration phase to the CT image sets corresponding to subsequent respiration phases. Deformable registration allows the contours defined on the peak-inhale CT to be automatically transferred to the other respiratory phase CT image sets. Treatment planning was simultaneously performed on each of the eight 3D image sets via automated scripts in which the MLC-defined beam aperture conforms to the PTV (which in this case equaled the GTV due to CT scan length limitations) plus a penumbral margin at each respiratory phase. The dose distribution from each respiratory phase CT image set was mapped back to the peak-inhale CT image set for analysis. The treatment intent of 4D planning is that the radiation beam defined by the DMLC tracks the respiration-induced target motion based on a feedback loop including the respiration signal to a real-time MLC controller. Deformation with respiration was observed for the lung tumor and normal tissues. This deformation was verified by examining the mapping of high contrast objects, such as the lungs and cord, between image sets. For the test case, dosimetric reductions for the cord, heart, and lungs were found for 4D planning compared with 3D planning. 4D radiotherapy planning for DMLC-based respiratory motion tracking is feasible and may offer tumor dose escalation and/or a reduction in treatment-related complications. However, 4D planning requires new planning tools, such as deformable registration and automated treatment planning on multiple CT image sets.

Deformable M-Reps for 3D Medical Image Segmentation

M-reps (formerly called DSLs) are a multiscale medial means for modeling and rendering 3D solid geometry. They are particularly well suited to model anatomic objects and in particular to capture prior geometric information effectively in deformable models segmentation approaches. The representation is based on figural models, which define objects at coarse scale by a hierarchy of figures—each figure generally a slab representing a solid region and its boundary simultaneously. This paper focuses on the use of single figure models to segment objects of relatively simple structure.A single figure is a sheet of medial atoms, which is interpolated from the model formed by a net, i.e., a mesh or chain, of medial atoms (hence the name m-reps), each atom modeling a solid region via not only a position and a width but also a local figural frame giving figural directions and an object angle between opposing, corresponding positions on the boundary implied by the m-rep. The special capability of an m-rep is to provide spatial and orientational correspondence between an object in two different states of deformation. This ability is central to effective measurement of both geometric typicality and geometry to image match, the two terms of the objective function optimized in segmentation by deformable models. The other ability of m-reps central to effective segmentation is their ability to support segmentation at multiple levels of scale, with successively finer precision. Objects modeled by single figures are segmented first by a similarity transform augmented by object elongation, then by adjustment of each medial atom, and finally by displacing a dense sampling of the m-rep implied boundary. While these models and approaches also exist in 2D, we focus on 3D objects.The segmentation of the kidney from CT and the hippocampus from MRI serve as the major examples in this paper. The accuracy of segmentation as compared to manual, slice-by-slice segmentation is reported.

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus

&NA; Article abstract— Objective To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. Background HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. Methods MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. Results Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. Conclusions Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.

Riemannian geometry for the statistical analysis of diffusion tensor data

The tensors produced by diffusion tensor magnetic resonance imaging (DT-MRI) represent the covariance in a Brownian motion model of water diffusion. Under this physical interpretation, diffusion tensors are required to be symmetric, positive-definite. However, current approaches to statistical analysis of diffusion tensor data, which treat the tensors as linear entities, do not take this positive-definite constraint into account. This difficulty is due to the fact that the space of diffusion tensors does not form a vector space. In this paper we show that the space of diffusion tensors is a type of curved manifold known as a Riemannian symmetric space. We then develop methods for producing statistics, namely averages and modes of variation, in this space. We show that these statistics preserve natural geometric properties of the tensors, including the constraint that their eigenvalues be positive. The symmetric space formulation also leads to a natural definition for interpolation of diffusion tensors and a new measure of anisotropy. We expect that these methods will be useful in the registration of diffusion tensor images, the production of statistical atlases from diffusion tensor data, and the quantification of the anatomical variability caused by disease. The framework presented in this paper should also be useful in other applications where symmetric, positive-definite tensors arise, such as mechanics and computer vision.

Principal Geodesic Analysis on Symmetric Spaces: Statistics of Diffusion Tensors

Diffusion tensor magnetic resonance imaging (DT-MRI) is emerging as an important tool in medical image analysis of the brain. However, relatively little work has been done on producing statistics of diffusion tensors. A main difficulty is that the space of diffusion tensors, i.e., the space of symmetric, positive-definite matrices, does not form a vector space. Therefore, standard linear statistical techniques do not apply. We show that the space of diffusion tensors is a type of curved manifold known as a Riemannian symmetric space. We then develop methods for producing statistics, namely averages and modes of variation, in this space. In our previous work we introduced principal geodesic analysis, a generalization of principal component analysis, to compute the modes of variation of data in Lie groups. In this work we expand the method of principal geodesic analysis to symmetric spaces and apply it to the computation of the variability of diffusion tensor data. We expect that these methods will be useful in the registration of diffusion tensor images, the production of statistical atlases from diffusion tensor data, and the quantification of the anatomical variability caused by disease.

Statistical methods in computational anatomy

This paper reviews recent developments by the Washington/Brown groups for the study of anatomical shape in the emerging new discipline of computational anatomy. Parametric representations of anatomical variation for computational anatomy are reviewed, restricted to the assumption of small deformations. The generation of covariance operators for probabilistic measures of anatomical variation on coordinatized submanifolds is formulated as an empirical procedure. Populations of brains are mapped to common coordinate systems, from which template coordinate systems are constructed which are closest to the population of anatomies in a minimum distance sense. Variation of several one-, two and three-dimensional manifolds, i.e. sulci, surfaces and brain volumes are examined via Gaussian measures with mean and covariances estimated directly from maps of templates to targets. Methods are presented for estimating the covariances of vector fields from a family of empirically generated maps, posed as generalized spectrum estimation indexed over the submanifolds. Covariance estimation is made parametric, analogous to autoregressive modelling, by introducing small deformation linear operators for constraining the spectrum of the fields.