Biomedical subjects

Thomas H Mareci

Publications and source records attributed to Thomas H Mareci.

10 recordsLinked to original sources

PubMed2006

Computational model of interstitial transport in the spinal cord using diffusion tensor imaging.

Local drug delivery methods, including convection-enhanced delivery (CED), are being used to increase distribution in selected regions of nervous tissue. There is a need for 3D models that predict spatial drug distribution within these tissues. A methodology was developed to process magnetic resonance microscopy (MRM) and diffusion tensor imaging (DTI) scans, segment gray and white matter regions, assign tissue transport properties, and model the interstitial transport of macromolecules. Fiber tract orientation was derived from DTI data and used to assign directional dependence of hydraulic conductivity, K, and tracer diffusivity, Dt, transport tensors. Porous media solutions for interstitial fluid pressure, velocity, and albumin distribution were solved using a finite volume method. To test this DTI-based methodology, a rat spinal cord transport model was developed to simulate CED into the dorsal white matter column. Predicted distribution results correspond well with small volume (approximately 1 microl) trends found experimentally, although albumin loss was greater at larger infusion volumes (>2 microl). Simulations were similar to those using fixed transport properties due to the bulk alignment of white matter fibers along the cord axis. These findings help to validate the DTI-based methodology which can be applied to modeling regions where fiber tract organization is more complex, e.g., the brain.

Animals↗

PubMed2006

Structural insights from high-resolution diffusion tensor imaging and tractography of the isolated rat hippocampus.

The hippocampus is a critical structure for learning and memory formation injured by diverse neuropathologies such as epilepsy or Alzheimer's disease. Recently, clinical investigations have attempted to use diffusion tensor MRI as a more specific surrogate marker for hippocampal damage. To first better understand the tissue architecture of healthy hippocampal regions, this study characterized 10 rat hippocampi with diffusion tensor imaging (DTI) at 50-microm in-plane image resolution using a 14.1-T magnet. Chemical fixation of the dissected and straightened rat hippocampus provided a simple, effective way to reduce partial volume effects when segmenting hippocampal regions and improved mean signal-to-noise per unit time (e.g. 50.6+/-4.4 at b=1250 s/mm2 in 27 min). Contrary to previous reports that water diffusion is homogeneous throughout the nervous system, statistically different mean diffusivities were observed (e.g. 0.238+/-0.054 and 0.318+/-0.084 microm2/ms for the molecular and granule cell layers respectively) (ANOVA, P<0.05). Different hippocampal subregions had lower fractional anisotropy than uniformly fibrous structures like corpus callosum because of their complex architecture. DTI-derived color fiber orientation maps and tractography demonstrated most components of the trisynaptic intrahippocampal pathway (e.g. orientations in stratum lacunosum-moleculare were dominated by perforant and Schaffer fibers) and also permitted some assessment of connectivity in the rat hippocampus.

Animals↗

PubMed2006

Resolution of complex tissue microarchitecture using the diffusion orientation transform (DOT).

This article describes an accurate and fast method for fiber orientation mapping using multidirectional diffusion-weighted magnetic resonance (MR) data. This novel approach utilizes the Fourier transform relationship between the water displacement probabilities and diffusion-attenuated MR signal expressed in spherical coordinates. The radial part of the Fourier integral is evaluated analytically under the assumption that MR signal attenuates exponentially. The values of the resulting functions are evaluated at a fixed distance away from the origin. The spherical harmonic transform of these functions yields the Laplace series coefficients of the probabilities on a sphere of fixed radius. Alternatively, probability values can be computed nonparametrically using Legendre polynomials. Orientation maps calculated from excised rat nervous tissue data demonstrate this technique's ability to accurately resolve crossing fibers in anatomical regions such as the optic chiasm. This proposed methodology has a trivial extension to multiexponential diffusion-weighted signal decay. The developed methods will improve the reliability of tractography schemes and may make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Animals↗

PubMed2006

Evolving into epilepsy: Multiscale electrophysiological analysis and imaging in an animal model.

Epilepsy research for the design of seizure detection/prediction neuroprosthetics has been faced with the search for electrophysiologic control parameters that can be used to infer the epileptic state of the animal and be leveraged at a later time to deliver neurotherapeutic feedback. The analysis presented here uses multi-microelectrode array technology to provide an electrophysiologic quantification of a hippocampal neural ensemble during the latent period of epileptogenesis. Through the use of signal processing system identification methodologies, we were able to assess the spatial and temporal interrelations of ensembles of hippocampal neurons and relate them to the evolution of the epileptic condition. High-field magnetic resonance (MR) imaging was used to determine the location of electrode placement and to evaluate hippocampal pyramidal cell structural damage. Long-term single unit activity analysis suggests that hippocampal neurons in both CA1-2 and dentate regions increase the number of occurrences and duration of their bursting activity after injury to the contra-lateral hippocampus. The trends inferred from both single neuron and ensemble analysis suggests that the evolution into epilepsy is not abrupt but modulates gradually from the time of injury.

Action Potentials↗

PubMed2005

Generalized scalar measures for diffusion MRI using trace, variance, and entropy.

This paper details the derivation of rotationally invariant scalar measures from higher-rank diffusion tensors (DTs) and functions defined on a unit sphere. This was accomplished with the use of an expression that generalizes the evaluation of the trace operator to tensors of arbitrary rank, and even to functions whose domains are the unit sphere. It is shown that the mean diffusivity is invariant to the selection of tensor rank for the model used. However, this rank invariance does not apply to the anisotropy measures. Therefore, a variance-based, general anisotropy measure is proposed. Also an information theoretical parametrization of anisotropy is introduced that is frequently more consistent with the meaning attributed to anisotropy. We accomplished this by associating anisotropy with the amount of orientational information present in the data, regardless of the imaging technique used. Using a simplified model of fibrous tissue, we simulated anisotropy values with varying orientational complexity and tensor models. Simulations suggested that a lower-rank tensor model may produce artificially low anisotropy values in voxels with complex structure. This was confirmed with a spin-echo experiment performed on an excised rat brain.

Animals↗

PubMed2005

Fast orientation mapping from HARDI.

This paper introduces a new, accurate and fast method for fiber orientation mapping using high angular resolution diffusion imaging (HARDI) data. The approach utilizes the Fourier relationship between the water displacement probabilities and diffusion attenuated magnetic resonance (MR) signal expressed in spherical coordinates. The Laplace series coefficients of the water displacement probabilities are evaluated at a fixed distance away from the origin. The computations take under one minute for most three-dimensional datasets. We present orientation maps computed from excised rat optic chiasm, brain and spinal cord images. The developed method will improve the reliability of tractography schemes and make it possible to correctly identify the neural connections between functionally connected regions of the nervous system.

Algorithms↗

PubMed2005

Evaluation of the pathologic characteristics of excitotoxic spinal cord injury with MR imaging.

BACKGROUND AND PURPOSE: Although high-resolution MR imaging is a valuable diagnostic tool, in vivo MR imaging has not yet been compared with in vitro MR imaging and histologic techniques following experimental spinal cord injury (SCI). The goal of the present study was to evaluate the feasibility of using in vivo MR imaging, in vitro MR imaging, and histologic techniques to study pathologic changes associated with excitotoxic SCI at a single time point. These results are important for future research using in vivo MR imaging to study the temporal profile of pathologic changes following SCI. METHODS: Rats received intraspinal injections of quisqualic acid at the T12-L2 spinal level. In vivo T1- and T2-weighted and dynamic contrast-enhanced MR images were collected 17-24 days postinjury. Once completed, spinal cords were removed and in vitro MR microscopy and histologic assessment were performed. MR images were collected using 4.7-T (in vivo) and 14.1-T magnets (in vitro). RESULTS: Pathologic changes--including hemorrhage, neuronal loss, cavities, and central canal expansion--were visible in T2-weighted in vivo MR images. Evaluation of the blood-spinal cord barrier after injury with contrast agent enhancement showed no disruption at the time points evaluated. In vitro MR images and histologic evaluation confirmed pathologic details observed in vivo. CONCLUSION: Results show that high-resolution in vivo MR imaging has the potential to be used in studying the progression of pathologic changes at multiple time points following SCI. This strategy may provide a way of studying structure-function relationships between therapeutic interventions and different pathologic characteristics of the injured spinal cord.

Animals↗

PubMed2004

Patterns of gene expression reveal a temporally orchestrated wound healing response in the injured spinal cord.

Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex and evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after a clinically relevant SCI and (2) test the consistency of transcript expression after SCI in two genetically and immunologically diverse rat strains characterized by differences in T cell competence and associated inflammatory responses. By interrogating Affymetrix U34A rat genome GeneChip microarrays, we defined the transcriptional expression patterns in midcervical contusion lesion sites between 1 and 90 d postinjury of athymic nude (AN) and Sprague Dawley (SD) strains. Stringent statistical analyses detected significant changes in 3638 probe sets, with 80 genes differing between the AN and SD groups. Subsequent detailed functional categorization of these transcripts unveiled an overall tissue remodeling response that was common to both strains. The functionally organized gene profiles were temporally distinct and correlated with repair indices observed microscopically and by magnetic resonance microimaging. Our molecular and anatomical observations have identified a novel, longitudinal perspective of the post-SCI response, namely, that of a highly orchestrated tissue repair and remodeling repertoire with a prominent cutaneous wound healing signature that is conserved between two widely differing rat strains. These results have significant bearing on the continuing development of cellular and pharmacological therapeutics directed at tissue rescue and neuronal regeneration in the injured spinal cord.

Algorithms↗

PubMed2004

A constrained variational principle for direct estimation and smoothing of the diffusion tensor field from complex DWI.

In this paper, we present a novel constrained variational principle for simultaneous smoothing and estimation of the diffusion tensor field from complex valued diffusion-weighted images (DWI). The constrained variational principle involves the minimization of a regularization term of L(P) norms, subject to a nonlinear inequality constraint on the data. The data term we employ is the original Stejskal-Tanner equation instead of the linearized version usually employed in literature. The complex valued nonlinear form leads to a more accurate (when compared to the linearized version) estimate of the tensor field. The inequality constraint requires that the nonlinear least squares data term be bounded from above by a known tolerance factor. Finally, in order to accommodate the positive definite constraint on the diffusion tensor, it is expressed in terms of Cholesky factors and estimated. The constrained variational principle is solved using the augmented Lagrangian technique in conjunction with the limited memory quasi-Newton method. Experiments with complex-valued synthetic and real data are shown to depict the performance of our tensor field estimation and smoothing algorithm.

Algorithms↗

PubMed2003

Generalized diffusion tensor imaging and analytical relationships between diffusion tensor imaging and high angular resolution diffusion imaging.

A new method for mapping diffusivity profiles in tissue is presented. The Bloch-Torrey equation is modified to include a diffusion term with an arbitrary rank Cartesian tensor. This equation is solved to give the expression for the generalized Stejskal-Tanner formula quantifying diffusive attenuation in complicated geometries. This makes it possible to calculate the components of higher-rank tensors without using the computationally-difficult spherical harmonic transform. General theoretical relations between the diffusion tensor (DT) components measured by traditional (rank-2) DT imaging (DTI) and 3D distribution of diffusivities, as measured by high angular resolution diffusion imaging (HARDI) methods, are derived. Also, the spherical tensor components from HARDI are related to the rank-2 DT. The relationships between higher- and lower-rank Cartesian DTs are also presented. The inadequacy of the traditional rank-2 tensor model is demonstrated with simulations, and the method is applied to excised rat brain data collected in a spin-echo HARDI experiment.

Animals↗