Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy.Magn Key words: diffusion; diffusion-weighted MRI (DWI); diffusion tensor imaging (DTI); white matter; tractographyTissues with regularly ordered microstructure, such as skeletal muscle, spine, tongue, heart, and cerebral white matter, exhibit anisotropic water diffusion due to the alignment of the diffusion compartments in the tissue (1-7). The direction of preferred diffusion, and hence the direction of preferred orientation in the tissue, can be resolved with a method called magnetic resonance (MR) diffusion tensor imaging (DTI) (7), which measures the apparent water self-diffusion tensor under the assumption of Gaussian diffusion. Based on the eigenstructure of the measured diffusion tensor, it is possible to infer the orientation of the diffusion compartments within the voxel so that, for example, the major eigenvector of the diffusion tensor parallels the mean fiber orientation (7), and the minor eigenvector parallels the normal to the mean plane of fiber dispersion (8).The tensor model is incapable, however, of resolving multiple fiber orientations within an individual voxel. This shortcoming of the tensor model stems from the fact that the tensor possesses only a single orientational maximum, i.e., the major eigenvalue of the diffusion tensor (9,10). At the millimeter-scale resolution typical of DTI, the volume of cerebral white matter containing such intravoxel orientational heterogeneity (IVOH) may be considerable given the widespread divergence and convergence of fascicles (11-13). The abundance of IVOH at the millimeter scale can be further appreciated by considering the ubiquity of oblate (pancake-shaped) diffusion tensors in DTI, a hypothesized indicator of IVOH (3,4,8).Given the obstacle that IVOH (particularly fiber crossing (14 -16)) poses to white matter tractography algorithms (14 -20), we sought to determine whether high angular resolution, high b-value diffusion gradient sampling could resolve such intravoxel heterogeneity (9). H...

Methods are presented to map complex fiber architectures in tissues by imaging the 3D spectra of tissue water diffusion with MR. First, theoretical considerations show why and under what conditions diffusion contrast is positive. Using this result, spin displacement spectra that are conventionally phase-encoded can be accurately reconstructed by a Fourier transform of the measured signal's modulus. Second, studies of in vitro and in vivo samples demonstrate correspondence between the orientational maxima of the diffusion spectrum and those of the fiber orientation density at each location. In specimens with complex muscular tissue, such as the tongue, diffusion spectrum images show characteristic local heterogeneities of fiber architectures, including angular dispersion and intersection. Cerebral diffusion spectra acquired in normal human subjects resolve known white matter tracts and tract intersections. Over the past decade, MRI methods have been developed that can nondestructively map the structural anisotropy of fibrous tissues in living systems by mapping the diffusion tensor (DT) of tissue water (for review see Ref. 1). Such methods have been used to elucidate the fiber architecture and functional dynamics of the myocardium (2,3) and skeletal muscle (4). They have also been used in the nervous system to identify and map the trajectories of neural white matter tracts and infer neuroanatomic connectivity (for review see Ref. 5).Notwithstanding this progress, the DT paradigm has notable limitations. Because the distances resolved by MRI are far larger than the diffusion scale, each 3D resolution element (voxel) represents many distinct diffusional environments. This provides a complicated diffusion signal that in general is underspecified by the six degrees of freedom of the DT model. An example of particular interest occurs when a tissue has a composite fiber structure, such that each small region may contain fibers of multiple orientations corresponding to distinct diffusion anisotropies (6).The present study describes a model-free MRI methodology called diffusion spectrum imaging (DSI). This method affords the capacity to resolve intravoxel diffusion heterogeneity of compartments with sufficient angular separation and anisotropy by measuring its diffusion density spectra estimator. In describing this method, we will show that DSI generalizes the analysis of diffusion spectra by demonstrating that the Fourier transform of the diffusion spectrum must be positive. We also discuss how the DSI method encompasses existing alternate analyses of MRI diffusion contrast, and present examples of diffusion contrast in biological tissues analyzed with DSI. THEORY Measuring the Diffusion SpectrumWe consider the classical Stejskal-Tanner experiment (7). It allows the phase-encoding of spin displacements by embedding a strong pulse gradient of duration ␦ and intensity ͉g͉ on each side of the RF-pulse of a conventional spin-echo sequence. In such a manner the MR signal is made proportional to the voxel average (͗ ⅐ ͘) deph...

Image distortion due to field gradient eddy currents can create image artifacts in diffusion-weighted MR images. These images, acquired by measuring the attenuation of NMR signal due to directionally dependent diffusion, have recently been shown to be useful in the diagnosis and assessment of acute stroke and in mapping of tissue structure. This work presents an improvement on the spin-echo (SE) diffusion sequence that displays less distortion and consequently improves image quality. Adding a second refocusing pulse provides better image quality with less distortion at no cost in scanning efficiency or effectiveness, and allows more flexible diffusion gradient timing. Multidirectional diffusion sequences (1-3) have recently been shown to be useful in the diagnosis and assessment of acute stroke and in mapping of tissue structure (4 -10). These methods apply gradient pulses at higher intensity and with longer duration than in any other well known MRI sequence, resulting in comparatively large and persistent eddy currents. Use of the spin-echo (SE) diffusion sequence with an echo planar (EP) readout combines atypically large eddy currents with an eddy current-sensitive EP readout, causing spatial distortion dependent on the direction of the applied diffusion gradient. Misregistration artifacts result when directional diffusion is calculated from multiple images with differing gradient directions.Each on and off field gradient transition produces eddy currents to some degree. If the eddy current (and its associated magnetic field) decays to an inconsequential value between the time of the applied field gradient transition and the image readout, a spatially dependent change in image phase will result with no discernible distortion. Since diffusion encoding relies on the attenuation of the image magnitude, a change in image phase does not change the diffusion measurement as long as the phase gradient per pixel is small (11). However, when the eddy current decays slowly, so that a residual field remains during the image readout, the field behaves like an additional spatial encoding gradient field and causes distortion of the image.While the usual SE diffusion sequence, introduced by Stejkal and Tanner (12), uses a single refocusing RF pulse, many SE diffusion sequence variants can be created using multiple refocusing pulses. SEs result from any combination of refocusing pulses that returns the spins' phase evolution to the origin in classical phase space (13). Using more than one refocusing pulse permits variable intervals between the pulses, requiring only that the spins' alternating defocusing and refocusing times sum equally at the time of the intended SE. This flexibility in timing adds utility when used for diffusion imaging.Since the on and off field gradient transitions produce equal and opposite eddy currents, the shorter the time between on and off transitions, the less decay of the residual fields during the gradient pulse and the more complete the fields' cancellation. Toward this end, a reduction of distor...

While functional brain imaging methods can locate the cortical regions subserving particular cognitive functions, the connectivity between the functional areas of the human brain remains poorly understood. Recently, investigators have proposed a method to image neural connectivity noninvasively using a magnetic resonance imaging method called diffusion tensor imaging (DTI). DTI measures the molecular diffusion of water along neural pathways. Accurate reconstruction of neural connectivity patterns from DTI has been hindered, however, by the inability of DTI to resolve more than a single axon direction within each imaging voxel. Here, we present a novel magnetic resonance imaging technique that can resolve multiple axon directions within a single voxel. The technique, called q-ball imaging, can resolve intravoxel white matter fiber crossing as well as white matter insertions into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber architecture eliminates a key obstacle to mapping neural connectivity in the human brain noninvasively.

Different aspects of hyperacute cerebral ischemia are depicted at DW and HW imaging before infarction is depicted at conventional MR or CT. These techniques may improve stroke diagnosis and may contribute to advances in treatment.

The aim of this study was to implement a quantitative in vivo cardiac diffusion tensor imaging (DTI) technique that was robust, reproducible, and feasible to perform in patients with cardiovascular disease. A stimulated-echo single-shot echo-planar imaging (EPI) sequence with zonal excitation and parallel imaging was implemented, together with a novel modification of the prospective navigator (NAV) technique combined with a biofeedback mechanism. Ten volunteers were scanned on two different days, each time with both multiple breath-hold (MBH) and NAV multislice protocols. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) fiber maps were created. Comparison of initial and repeat scans showed good reproducibility for both MBH and NAV techniques for FA (P > 0.22), MD (P > 0.15), and HA (P > 0.28). Comparison of MBH and NAV FA (FAMBHday1 = 0.60 ± 0.04, FANAVday1 = 0.60 ± 0.03, P = 0.57) and MD (MDMBHday1 = 0.8 ± 0.2 × 1023 mm2/s, MDNAVday1 = 0.9 ± 0.2 × 10−3 mm2/s, P = 0.07) values showed no significant differences, while HA values (HAMBHday1Endo = 22 ± 10°, HAMBHday1Mid-Endo = 20 ± 6°, HAMBHday1Mid-Epi = −1 ± 6°, HAMBHday1Epi = 17 ± 6°, HANAVday1Endo = 7 ± 7°, HAMBHday1Mid-Endo = 13 ± 8°, HAMBHday1Epi = −2 ± 7°, HAMBHday1Epi −14 ± 6°,) were significantly different. The scan duration was 20% longer with the NAV approach. Currently, the MBH approach is the more robust in normal volunteers. While the NAV technique still requires resolution of some bulk motion sensitivity issues, these preliminary experiments show its potential for in vivo clinical cardiac diffusion tensor imaging and for delivering high-resolution in vivo 3D DTI tractography of the heart.

Background-Diffusion tensor magnetic resonance imaging (DT-MRI) provides a means for nondestructive characterization of myocardial architecture. We used DT-MRI to investigate changes in direction-dependent water diffusivity to reflect alterations in tissue integrity (trace apparent diffusion coefficients [ADCs] and fractional anisotropy [FA]), as well as indicators of remodeling of fiber helix angles, in patients after myocardial infarction. Methods and Results-Thirty-seven patients (35 men, 2 women; median age, 59) after acute myocardial infarction (median interval from onset, 26 days) were enrolled. DT-MRI was performed at the midventricular level to measure trace ADC, FA, and helix angles of myofibers. Helix angles were grouped into left-handed helical fibers, circumferential fibers, and right-handed helical fibers. Measurements were correlated with viability and regional wall motion assessed by contrast-delay-enhancement and cine MRI, respectively. The infarct zone showed significantly increased trace ADC and decreased FA than the remote zone.

Gray matter is mildly anisotropic in normal and early ischemic states. However, early white matter ischemia is associated with not only changes in trace ADC values but also significant changes in the anisotropy, or shape, of the water self-diffusion tensor.