Double Wave Vector Research Articles

Microscopic diffusion anisotropy in the human brain: Age-related changes

The fractional anisotropy (FA) that can be derived from diffusion tensor imaging (DTI), is ambiguous because it not only depends on the tissue microstructure but also on the axon or fiber orientation distribution within a voxel. Measures of the microscopic diffusion anisotropy, like the microscopic anisotropy index (MA) that can be determined with so-called double-wave-vector (DWV) or double diffusion encoding (DDE) imaging, are independent of this orientation distribution and, thus, offer a more direct and undisguised access to the tissue structure on a cellular or microscopic scale. In this study, FA and MA measurements were performed in a group of aged (>60y), healthy volunteers and compared to the data obtained recently for a group of young (<33y), healthy volunteers to reveal age-related differences. The coefficients-of-variation (CV) determined for the aged group were considerably lower for MA than for FA in average and in most of the 16 ROIs analyzed due to lower between-subject variations of MA. FA differences between the young and the aged group were in line with previous DTI studies. MA was also decreased in the aged group but in more of the 16 ROIs and with a higher significance. Furthermore, MA differences were also observed in frontal brain regions containing fiber crossings that did not reveal significant FA differences, i.e. MA seems to provide a better sensitivity to detect microstructural changes in such regions. In some non-cortical gray matter structures like the putamen, FA was increased but MA was decreased in the aged group which could indicate a coherent fiber orientation in the aged group related to the loss of crossing or fanning fibers. In conclusion, MA not only could improve the detectability of differences of the tissue microstructure but, in conjunction with FA, could also help to identify the underlying changes.

Studying the extracellular contribution to the double wave vector diffusion-weighted signal

Abstract The use of two independent diffusion periods between excitation and acquisition, known as double wave vector (DWV) diffusion-weighting or double diffusion encoding, was proven to yield structural information that it is otherwise not easily available in vivo. Comparing the signal difference between relative diffusion gradient orientations, the antiparallel-parallel and the parallel-perpendicular differences yield information on pore size and shape, respectively. However, results in vivo provided larger pore sizes than expected for axons in the corticospinal tract. This study exploits DWV sensitivity to pore shape and aims to obtain information on the extracellular contributions to the DWV pore size results presented here. The in vivo DWV experiments resulted in a positive parallel-perpendicular difference which is consistent with an irregularly shaped pore dominating the origin of the signal.

Orientationally invariant metrics of apparent compartment eccentricity from double pulsed field gradient diffusion experiments

Pulsed field gradient diffusion sequences (PFG) with multiple diffusion encoding blocks have been indicated to offer new microstructural tissue information, such as the ability to detect nonspherical compartment shapes in macroscopically isotropic samples, i.e. samples with negligible directional signal dependence on diffusion gradients in standard diffusion experiments. However, current acquisition schemes are not rotationally invariant in the sense that the derived metrics depend on the orientation of the sample, and are affected by the interplay of sampling directions and compartment orientation dispersion when applied to macroscopically anisotropic systems. Here we propose a new framework, the d-PFG 5-design, to enable rotationally invariant estimation of double wave vector diffusion metrics (d-PFG). The method is based on the idea that an appropriate orientational average of the signal emulates the signal from a powder preparation of the same sample, where macroscopic anisotropy is absent by construction. Our approach exploits the theory of exact numerical integration (quadrature) of polynomials on the rotation group, and we exemplify the general procedure with a set consisting of 60 pairs of diffusion wave vectors (the d-PFG 5-design) facilitating a theoretically exact determination of the fourth order Taylor or cumulant expansion of the orientationally averaged signal. The d-PFG 5-design is evaluated with numerical simulations and ex vivo high field diffusion MRI experiments in a nonhuman primate brain. Specifically, we demonstrate rotational invariance when estimating compartment eccentricity, which we show offers new microstructural information, complementary to that of fractional anisotropy (FA) from diffusion tensor imaging (DTI). The imaging observations are supported by a new theoretical result, directly relating compartment eccentricity to FA of individual pores.

NMR-based diffusion pore imaging by double wave vector measurements

One main interest of nuclear magnetic resonance (NMR) diffusion experiments is the investigation of boundaries such as cell membranes hindering the diffusion process. NMR diffusion measurements allow collecting the signal from the whole sample. This mainly eliminates the problem of vanishing signal at increasing resolution. It has been a longstanding question if, in principle, the exact shape of closed pores can be determined by NMR diffusion measurements. In this work, we present a method using short diffusion gradient pulses only, which is able to reveal the shape of arbitrary closed pores without relying on a priori knowledge. In comparison to former approaches, the method has reduced demands on relaxation times due to faster convergence to the diffusion long-time limit and allows for a more flexible NMR sequence design, because, e.g., stimulated echoes can be used.

Towards compartment size estimation in vivo based on double wave vector diffusion weighting

It has been shown that double wave vector diffusion weighting, which employs two gradient pulse pairs of independent directions, can provide information about tissue structure that is not easily available otherwise, such as cell size or shape in a tissue sample. One approach to measure cell size is based on the signal difference between parallel and antiparallel gradient orientations at small mixing times between the two diffusion weightings. A major difficulty for in vivo application is the small size of the signal difference if clinical MR systems with limited gradient hardware are employed. In this study, the method is applied to human brain tissue in vivo, using whole-body gradients. Data are reported for the corticospinal tracts. The characteristics of the observed signal difference between parallel and antiparallel gradient orientations are consistent with both analytical and numerical predictions. As an estimate of pore size, the resulting mean squared radius of gyration of the pores amounts to approximately 4 µm(2) . An analysis that accounts for the finite values of gradient pulse duration and diffusion time yields a volume contribution-weighted mean pore diameter of 13 μm if a cylindrical pore shape is assumed. The results demonstrate that the technique can be applied in vivo.

Detection of microscopic diffusion anisotropy on a whole‐body MR system with double wave vector imaging

Double-wave-vector diffusion-weighting experiments can detect diffusion anisotropy on a microscopic level which, e.g., could distinguish lower fiber densities from reduced fiber coherence. The underlying signal difference between parallel and orthogonal wave vector orientations has been observed on vertical-bore MR systems (≥500 mT m(-1) ); however, numerical simulations reveal that it is expected to be considerably reduced for typical whole-body MR gradient pulse durations. Here, pig spinal cord tissue and a reference fluid phantom were investigated on a 3 T clinical MR system (40 mT m(-1) ). By averaging over different absolute wave vector orientations, signal variations caused by experimental imperfections like background gradient fields and eddy currents were minimized and a rotationally invariant anisotropy measure could be assessed. A significant microscopic anisotropy was observed in gray and white matter tissue even in the plane perpendicular to the cord which is consistent with previous vertical-bore experiments. Thus, it is demonstrated that double-wave-vector experiments can investigate the microscopic anisotropy on whole-body MR systems.

The displacement correlation tensor: Microstructure, ensemble anisotropy and curving fibers

Experiments with multiple diffusion wave vectors are known to carry more information than what is available from standard diffusion experiments. Here we consider a special case of this class of pulse sequences, the double wave vector diffusion experiment, and use the cumulant expansion of the signal to introduce the displacement correlation tensor. We discuss its physical interpretation and properties, noting in particular that its short time behavior allows determination of the surface to volume ratio of the pore space. We present a general expression for the displacement correlation tensor, and provide explicit expressions for a few model geometries. We then show that the scatter matrix characterizing the orientation distribution of an ensemble of cylinders is simply related to the displacement correlation tensor. This result is generalized to ensembles of pores with arbitrary shapes allowing a precise formulation of the influence of microstructural and ensemble anisotropy on the double wave vector diffusion signal in the Gaussian phase approximation. Finally, as a new application of the double wave vector diffusion signal, we analyze its behavior in a curving fiber, and suggest that the displacement correlation tensor may be used to estimate sub-voxel fiber curvature and deflection angle. The theoretical results are corroborated by computer simulations.

Double-wave-vector diffusion-weighting experiments with multiple concatenations at long mixing times

MR sequences where two diffusion-weighting periods are applied successively in a single acquisition seem to be a promising tool for the investigation of tissue structure on a microscopic level such as the characterization of the compartment size or eccentricity measures of pores. However, the application of such double-wave-vector (DWV) experiments on whole-body MR systems is hampered by the long gradient pulses required that have been shown to reduce the signal modulation. In this work, it is demonstrated that involving multiple concatenations of the two diffusion-weighting periods can ameliorate this problem in experiments with long mixing times between the two wave vectors. The recently presented tensor equation is extended to multiple concatenations. As confirmed by Monte-Carlo simulations, this model shows a good approximation of the signals observed for typical whole-body gradient pulse durations and the derived anisotropy measures are obtained with good accuracy. Most importantly, the signal modulation is increased with multiple concatenations because shorter gradient pulses can be used to achieve the desired diffusion-weighting. Thus, the multiple concatenation approach may help to improve the applicability and reliability of DWV measurements with long mixing times on standard whole-body MR systems.

A tensor model and measures of microscopic anisotropy for double-wave-vector diffusion-weighting experiments with long mixing times

Experiments with two diffusion-weighting periods applied successively in a single experiment, so-called double-wave-vector (DWV) diffusion-weighting experiments, are a promising tool for the investigation of material or tissue structure on a microscopic level, e.g. to determine cell or compartment sizes or to detect pore or cell anisotropy. However, the theoretical descriptions presented so far for experiments that aim to investigate the microscopic anisotropy with a long mixing time between the two diffusion weightings, are limited to certain wave vector orientations, specific pore shapes, and macroscopically isotropic samples. Here, the signal equations for fully restricted diffusion are re-investigated in more detail. A general description of the signal behavior for arbitrary wave vector directions, pore or cell shapes, and orientation distributions of the pores or cells is obtained that involves a fourth-order tensor approach. From these equations, a rotationally invariant measure of the microscopic anisotropy, termed MA, is derived that yields information complementary to that of the (macroscopic) anisotropy measures of standard diffusion-tensor acquisitions. Furthermore, the detailed angular modulation for arbitrary cell shapes with an isotropic orientation distribution is derived. Numerical simulations of the MR signal with a Monte-Carlo algorithms confirm the theoretical considerations. The extended theoretical description and the introduction of a reliable measure of the microscopic anisotropy may help to improve the applicability and reliability of corresponding experiments.

A tensor approach to double wave vector diffusion-weighting experiments on restricted diffusion

Previously, it has been shown theoretically that in case of restricted diffusion, e.g. within isolated pores or cells, a measure of the pore size, the mean radius of gyration, can be estimated from double wave vector diffusion-weighting experiments. However, these results are based on the assumption of an isotropic orientation distribution of the pores or cells which hampers the applicability to samples with anisotropic or unknown orientation distributions, such as biological tissue. Here, the theoretical considerations are re-investigated and generalized in order to describe the signal dependency for arbitrary orientation distributions. The second-order Taylor expansion of the signal delivers a symmetric rank-2 tensor with six independent elements if the two wave vectors are concatenated to a single six-element vector. With this tensor approach the signal behavior for arbitrary wave vectors and orientation distributions can be described as is demonstrated by numerical simulations. The rotationally invariant trace of the tensor represents a pore size measure and can be determined from three orthogonal directions with parallel and antiparallel orientation of the two wave vectors. Thus, the presented tensor approach may help to improve the applicability of double wave vector diffusion-weighting experiments to determine pore or cell sizes, in particular in biological tissue.

Compartment size estimation with double wave vector diffusion‐weighted imaging

Double wave vector diffusion weighting uses gradients along two different directions between excitation and acquisition. It has been shown theoretically that for restricted diffusion the signal amplitude in such an experiment can depend on the angle between the two gradient vectors. The highest amplitude is obtained with antiparallel orientation, and the amplitude difference between parallel and antiparallel gradient orientations depends on the compartment size. The validity of this description is experimentally tested for water between polymer beads, for radish, and for porcine spinal cord, using a clinical MR system with limited gradient strength. The results indicate that the phenomenon is observable; however, the size of the signal difference is considerably diminished when compared with theory. This is attributed to violations of the approximating conditions underlying the theoretical description and to free diffusion contributions. It is concluded that the effect could successfully be used as a basis for developing a new noninvasive method for assessing cell size.