Lj Laura Astola

Measures for pathway analysis in brain white matter using diffusion tensor images

In this paper we discuss new measures for connectivity analysis of brain white matter, using MR diffusion tensor imaging. Our approach is based on Riemannian geometry, the viability of which has been demonstrated by various researchers in foregoing work. In the Riemannian framework bundles of axons are represented by geodesics on the manifold. Here we do not discuss methods to compute these geodesics, nor do we rely on the availability of geodesics. Instead we propose local measures which are directly computable from the local DTI data, and which enable us to preselect viable or exclude uninteresting seed points for the potentially time consuming extraction of geodesics. If geodesics are available, our measures can be readily applied to these as well. We consider two types of geodesic measures. One pertains to the connectivity saliency of a geodesic, the second to its stability with respect to local spatial perturbations. For the first type of measure we consider both differential as well as integral measures for characterizing a geodesics saliency either locally or globally. (In the latter case one needs to be in possession of the geodesic curve, in the former case a single tangent vector suffices.) The second type of measure is intrinsically local, and turns out to be related to a well known tensor in Riemannian geometry.

A New Tensorial Framework for Single-Shell High Angular Resolution Diffusion Imaging

Single-shell high angular resolution diffusion imaging data (HARDI) may be decomposed into a sum of eigenpolynomials of the Laplace-Beltrami operator on the unit sphere. The resulting representation combines the strengths hitherto offered by higher order tensor decomposition in a tensorial framework and spherical harmonic expansion in an analytical framework, but removes some of the conceptual weaknesses of either. In particular it admits analytically closed form expressions for Tikhonov regularization schemes and estimation of an orientation distribution function via the Funk-Radon Transform in tensorial form, which previously required recourse to spherical harmonic decomposition. As such it provides a natural point of departure for a Riemann-Finsler extension of the geometric approach towards tractography and connectivity analysis as has been stipulated in the context of diffusion tensor imaging (DTI), while at the same time retaining the natural coarse-to-fine hierarchy intrinsic to spherical harmonic decomposition.

Finsler Geometry on Higher Order Tensor Fields and Applications to High Angular Resolution Diffusion Imaging

We study three dimensional volumes of higher order tensors, using Finsler geometry. The application considered here is in medical image analysis, specifically High Angular Resolution Diffusion Imaging (HARDI) [1] of the brain. We want to find robust ways to reveal the architecture of the neural fibers in brain white matter. In Diffusion Tensor Imaging (DTI), the diffusion of water is modeled with a symmetric positive definite second order tensor, based on the assumption that there exists one dominant direction of fibers restricting the thermal motion of water molecules, leading naturally to a Riemannian framework. HARDI may potentially overcome the shortcomings of DTI by allowing multiple relevant directions, but invalidates the Riemannian approach. Instead Finsler geometry provides the natural geometric generalization appropriate for multi-fiber analysis. In this paper we provide the exact criterion to determine whether a field of spherical functions has a Finsler structure. We also show a fiber tracking method in Finsler setting. Our model also incorporates a scale parameter, which is beneficial in view of the noisy nature of the data. We demonstrate our methods on analytic as well as real HARDI data.

A Riemannian Scalar Measure for Diffusion Tensor Images

We study a well-known scalar quantity in differential geometry, the Ricci scalar, in the context of Diffusion Tensor Imaging (DTI). We explore the relation between the Ricci scalar and the two most popular scalar measures in DTI: Mean Diffusivity and Fractional Anisotropy. We discuss results of computing the Ricci scalar on synthetic as well as real DTI data.

Parameter estimation in tree graph metabolic networks

We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis–Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings.

Modified geodesic ray-tracing for diffusion tensor imaging

In this paper we develop a modified ray-tracing algorithm for geodesic tractography in the context of brain Diffusion Tensor Imaging (DTI). Our technique is based on computing multi-valued geodesics connecting two given points and tracking the evolution of adjacent geodesics. In order to do so we introduce a new Riemannian metric given by the adjugate sharpened diffusion tensor, combined with a constraint on the tracts outcome based on the geodesic deviation. We present tractography results, and compare our method with the existing ray-tracing approach and deterministic streamlining. Our preliminary results show an improved performance of modified ray-tracing regarding false positive fibers. We also show experiments on subcortical short association U-fibers, whose reconstruction is well-known to be hard in a DTI setting.

Stain separation in digital bright field histopathology

Digital pathology employs images that were acquired by imaging thin tissue samples through a microscope. The preparation of a sample from a biopt to the glass slide entering the imaging device is done manually introducing large variability in the samples to be imaged. For visible contrast it is necessary to stain the samples prior to imaging. Different stains attach to different compounds elucidating the different cellular structures. Towards automatic analysis and for visual comparability there is a need to standardize the images to obtain consistent appearances regardless of the potential differences in sample preparation. A standard approach is to unmix the the various stains computationally, normalize each separate stain image and to recombine these. This paper describes a modification to a standard blind method for stain normalization. The performance is quantified in terms of annotated expert data. Theoretical analysis is presented to rationalize the new approach.

A simplified algorithm for inverting higher order diffusion tensors

In Riemannian geometry, a distance function is determined by an inner product on the tangent space. In Riemann-Finsler geometry, this distance function can be determined by a norm. This gives more freedom on the form of the so-called indicatrix or the set of unit vectors. This has some interesting applications, e.g., in medical image analysis, especially in diffusion weighted imaging (DWI). An important application of DWI is in the inference of the local architecture of the tissue, typically consisting of thin elongated structures, such as axons or muscle fibers, by measuring the constrained diffusion of water within the tissue. From high angular resolution diffusion imaging (HARDI) data, one can estimate the diffusion orientation distribution function (dODF), which indicates the relative diffusivity in all directions and can be represented by a spherical polynomial. We express this dODF as an equivalent spherical monomial (higher order tensor) to directly generalize the (second order) diffusion tensor approach. To enable efficient computation of Riemann-Finslerian quantities on diffusion weighted (DW)-images, such as the metric/norm tensor, we present a simple and efficient algorithm to invert even order spherical monomials, which extends the familiar inversion of diffusion tensors, i.e., symmetric matrices.