Fiber Orientation Mapping Research Articles

Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings.

In this article, the underlying theory of clinical diffusion MR imaging, including diffusion tensor imaging (DTI) and fiber tractography, is reviewed. First, a brief explanation of the basic physics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping is provided. This is followed by an overview of the additional information that can be derived from the diffusion tensor, including diffusion anisotropy, color-encoded fiber orientation maps, and 3D fiber tractography. This article provides the requisite background for the second article in this 2-part review to appear next month, which covers the major technical factors that affect image quality in diffusion MR imaging, including the acquisition sequence, magnet field strength, gradient amplitude and slew rate, and multichannel radio-frequency coils and parallel imaging. The emphasis is on optimizing these factors for state-of-the-art DWI and DTI based on the best available evidence in the literature.

Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template

Brain registration to a stereotaxic atlas is an effective way to report anatomic locations of interest and to perform anatomic quantification. However, existing stereotaxic atlases lack comprehensive coordinate information about white matter structures. In this paper, white matter-specific atlases in stereotaxic coordinates are introduced. As a reference template, the widely used ICBM-152 was used. The atlas contains fiber orientation maps and hand-segmented white matter parcellation maps based on diffusion tensor imaging (DTI). Registration accuracy by linear and non-linear transformation was measured, and automated template-based white matter parcellation was tested. The results showed a high correlation between the manual ROI-based and the automated approaches for normal adult populations. The atlases are freely available and believed to be a useful resource as a target template and for automated parcellation methods.

Polarized light imaging of white matter architecture

Polarized light imaging (PLI) is a method to image fiber orientation in gross histological brain sections based on the birefringent properties of the myelin sheaths. The method uses the transmission of polarized light to quantitatively estimate the fiber orientation and inclination angles at every point of the imaged section. Multiple sections can be assembled into a 3D volume, from which the 3D extent of fiber tracts can be extracted. This article describes the physical principles of PLI and describes two major applications of the method: the imaging of white matter orientation of the rat brain and the generation of fiber orientation maps of the human brain in white and gray matter. The strengths and weaknesses of the method are set out.

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-μm 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/mm 2 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 μm 2/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.

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.

Three-dimensional diffusion tensor microscopy of fixed mouse hearts.

The relative utility of 3D, microscopic resolution assessments of fixed mouse myocardial structure via diffusion tensor imaging is demonstrated in this study. Isotropic 100-microm resolution fiber orientation mapping within 5.5 degrees accuracy was achieved in 9.1 hr scan time. Preliminary characterization of the diffusion tensor primary eigenvector reveals a smooth and largely linear angular rotation across the left ventricular wall. Moreover, a higher level of structural hierarchy is evident from the organized secondary and tertiary eigenvector fields. These findings are consistent with the known myocardial fiber and laminar structures reported in the literature and suggest an essential role of diffusion tensor microscopy in developing quantitative atlases for studying the structure-function relationships of mouse hearts.

Determining and visualizing uncertainty in estimates of fiber orientation from diffusion tensor MRI.

Diffusion tensor MRI (DT-MRI) permits determination of the dominant orientation of structured tissue within an image voxel. This has led to the development of 2D graphical methods for representing fiber orientation and DT-MRI "tractography," which aims to reconstruct the 3D trajectories of white matter fasciculi. Most contemporary fiber orientation mapping schemes and tractography algorithms employ the directional information contained in the eigenvectors of the diffusion tensor to approximate white matter fiber orientation. However, while the uncertainty associated with every estimate of an eigenvector has long been recognized, no attempts to quantify this uncertainty in vivo have been reported. Here, a method is proposed for determining confidence intervals in fiber orientation from real DT-MRI data using the bootstrap method. This is used to construct maps of the "cone of uncertainty," allowing simultaneous viewing of fiber orientation and its uncertainty, and to examine the relationship between orientation uncertainty and tissue anisotropy.

In vivo diffusion tensor imaging of human calf muscle.

To investigate a tetrahedral diffusion gradient encoding scheme to measure the diffusion tensor in vivo for human calf muscle. The theoretical TE which maximizes the signal-to-noise ratio (SNR) of the diffusion images was derived for both the orthogonal and tetrahedral sampling strategies and the SNR advantage verified experimentally. A diffusion echo-planar imaging (EPI) sequence was used to image five volunteers. Gradient cycling and geometric averaging was performed to eliminate cross-terms between the imaging and diffusion gradients. Trace diffusion coefficients in human muscle are spatially invariant and have low intersubject variability (<4%). Images of the off-diagonal terms confirm the anisotropy of muscle, and fiber orientation maps were derived from these off-diagonal images. A noninvariant index of anisotropy, A(ratio) (average value: 1.28), was found to be less susceptible to noise than the invariant index. This technique is robust and can be readily implemented on clinical scanners with EPI capabilities.

Two-component diffusion tensor MRI of isolated perfused hearts.

Nonmonoexponential MR diffusion decay behavior has been observed at high diffusion-weighting strengths for cell aggregates and tissues, including the myocardium; however, implications for myocardial MR diffusion tensor imaging are largely unknown. In this study, a slow-exchange-limit, two-component diffusion tensor model was fitted to diffusion-weighted images obtained in isolated, perfused rat hearts. Results indicate that there are at least two distinct components of anisotropic diffusion, characterized by a "fast" component whose principal diffusivity is comparable to that of the perfusate, and a highly anisotropic "slow" component. It is speculated that the two components correspond to tissue compartments and have a general agreement with the orientations of anisotropy, or fiber orientations, in the myocardium. Moreover, consideration of previous studies of myocardial diffusion suggests that the presently observed fast component may likely be dominated by diffusion in the vascular space, whereas the slow component may include the intracellular and interstitial compartments. The implications of the results for myocardial fiber orientation mapping and limitations of the current two-component model used are also discussed.

Demonstration of Primary and Secondary Muscle Fiber Architecture of the Bovine Tongue by Diffusion Tensor Magnetic Resonance Imaging

The myoarchitecture of the tongue is comprised of a complex array of muscle fiber bundles, which form the structural basis for lingual deformations during speech and swallowing. We used magnetic resonance imaging of the water diffusion tensor to display the primary and secondary fiber architectural attributes of the excised bovine tongue. Fiber orientation mapping provides a subdivision of the tongue into its principal intrinsic and extrinsic muscular components. The anterior tongue consists of a central region of orthogonally oriented intrinsic fibers surrounded by an axially oriented muscular sheath. The posterior tongue consists principally of a central region of extrinsic fibers, originating at the inferior surface and projecting in a fan-like manner in the superior, lateral, and posterior directions, and lateral populations of extrinsic fibers directed posterior-inferior and posterior-superior. Analysis of cross-fiber anisotropy indicates a basic contrast of design between the extrinsic and the intrinsic fibers. Whereas the extrinsic muscles exhibit a uniaxial architecture typical of skeletal muscle, the intrinsic core muscles, comprised of the verticalis and the transversus muscles, show strong cross-fiber anisotropy. This pattern is consistent with the theory that the tongue's core functions as a muscular hydrostat in that conjoint contraction of the transverse and vertical fibers enable the tissue to expand at right angles to these fibers. These findings suggest that three-dimensional analysis of diffusion tensor magnetic resonance imaging provides a structural basis for understanding the micromechanics of the mammalian tongue.

Quantitative estimation of 3-D fiber course in gross histological sections of the human brain using polarized light

Series of polarized light images can be used to achieve quantitative estimates of the angles of inclination ( z-direction) and direction (in xy-plane) of central nervous fibers in histological sections of the human brain. (1) The corpus callosum of a formalin-fixed human brain was sectioned at different angles of inclination of nerve fibers and at different thicknesses of the samples. The minimum, and maximum intensities, and their differences revealed a linear relationship to the angle of inclination of fibers. It was demonstrated that sections with a thickness of 80–120 μm are best suited for estimating the angle of inclination. (2) Afterwards the optic tracts of eight formalin-fixed human brains were sliced at different angles of fiber inclination at 100 μm. Measurements of intensity in 30 pixels in each section were used to calculate a linear function of calibration. The maximum intensities and the differences between maximum and minimum values measured with two polars only were best suited for estimation of fiber inclination. (3) Gross histological brain slices of formalin-fixed human brains were digitized under azimuths from 0 to 80° using two polars only. These sequences were used to estimate the inclination of fibers (in z-direction). The same slices were digitized under azimuths from 0 to 160° in steps of 20° using a quarter wave plate additionally. These sequences were used to estimate the direction of the fibers in xy-direction. The method can be used to produce maps of fiber orientation in gross histological sections of the human brain similar to the fiber orientation maps derived by diffusion weighted magnetic resonance imaging.

MR Color Mapping of Myelin Fiber Orientation

Diffusion of water in brain white matter has been shown to be anisotropic: Water mobility is lower when measured perpendicular to the fiber direction rather than parallel to it. This feature was used to produce images of the myelin fiber orientation. Coronal and sagittal MR diffusion images were obtained in volunteers using an echo-planar imaging sequence sensitized to molecular diffusion in perpendicular directions. Color-coded images of myelin orientation were then generated by combining these images together. The orientation of the white matter tracts was found to be in excellent agreement with known anatomy. Myelin fiber orientation mapping may offer a new perspective to evaluate white matter disorders.