High-resolution diffusion-weighted 3D MRI, using diffusion-weighted driven-equilibrium (DW-DE) and multishot segmented 3D-SSFP without navigator echoes.

In this work we report on the development of a novel technique for high-resolution diffusion-weighted (DW) MRI based upon 3D steady-state free precession (3D-SSFP). First the 3D-SSFP acquisition was segmented (each segment consisting of a series of RF pulses and gradient-recalled echoes), and then DW-driven equilibrium (DE) was inserted between each segment. The in-plane imaging matrix was typically 256 x 192 or 256 x 160, which resulted in high-resolution DW images. The DW-DE segmented SSFP signal was contaminated by the non-DW magnetization, which recovered and contributed signal during the readout train (T(1) contamination). Center-out slice encoding was used to place the greatest diffusion weighting at the center of k-space. A numerical simulation and supporting experiments were performed to evaluate the relationship of the transverse magnetization to imaging parameters, such as the b-value, echo-train length (ETL), echo-train (group) repetition time (TR(g)), and RF excitation TR (Delta t). Both the numerical simulation and the experiments suggested that the effect of T(1) contamination would be reduced with a longer TR(g), smaller b-value, shorter ETL, and center-out slice phase encoding. Phase errors caused by microscopic motions during the diffusion gradients were converted into amplitude errors by the tip-up pulse at the end of the diffusion-weighting segment. As a result, small bulk motions, such as CSF pulsation, did not cause motion-related ghosting artifacts, which would be typical in images from other multishot DWI techniques. This technique can be used for high-resolution DWI of nonbrain anatomies.     

Boosting the sampling efficiency of q-Ball imaging using multiple wavevector fusion.

q-Ball imaging (QBI) is a high-angular-resolution diffusion imaging (HARDI) method that is capable of resolving complex, subvoxel white matter (WM) architecture. QBI requires time-intensive sampling of the diffusion signal and large diffusion wavevectors. Here we describe a reconstruction scheme for QBI, termed multiple wavevector fusion (MWF), that substantially boosts the sampling efficiency and signal-to-noise ratio (SNR) of QBI. The MWF reconstruction operates by nonlinearly fusing the diffusion signal from separate low and high wavevector acquisitions. The combination of wavevectors provides the benefits of the high SNR of the low wavevector signal and the high angular contrast-to-noise ratio (CNR) and peak separation of the high wavevector signal. The MWF procedure provides a framework for combining diffusion tensor imaging (DTI) and QBI. Numerical simulations show that MWF of DTI and QBI provides a more accurate estimate of the diffusion orientation distribution function (ODF) than QBI alone. The accuracy improvement can be translated into an efficiency gain of 274-377%. An intravoxel peak connectivity metric (IPCM) is presented that calculates the peak connectivity between an ODF and its neighboring voxels. In human WM, MWF reveals more detailed WM architecture than QBI as measured by the IPCM for all sampling schemes presented.     

PROPELLER-EPI with parallel imaging using a circularly symmetric phased-array RF coil at 3.0 T: application to high-resolution diffusion tensor imaging.

A technique integrating multishot periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and parallel imaging is presented for diffusion echo-planar imaging (EPI) at high spatial resolution. The method combines the advantages of parallel imaging to achieve accelerated sampling along the phase-encoding direction, and PROPELLER acquisition to further decrease the echo train length (ETL) in EPI. With an eight-element circularly symmetric RF coil, a parallel acceleration factor of 4 was applied such that, when combined with PROPELLER acquisition, a reduction of geometric distortions by a factor substantially greater than 4 was achieved. The resulting phantom and human brain images acquired with a 256 x 256 matrix and an ETL of only 16 were visually identical in shape to those acquired using the fast spin-echo (FSE) technique, even without field-map corrections. It is concluded that parallel PROPELLER-EPI is an effective technique that can substantially reduce susceptibility-induced geometric distortions at high field strength.     

High-resolution DTI of a localized volume using 3D single-shot diffusion-weighted STimulated echo-planar imaging (3D ss-DWSTEPI).

Diffusion tensor MRI (DTI) using conventional single-shot (SS) 2D diffusion-weighted (DW)-EPI is subject to severe susceptibility artifacts. Multishot DW imaging (DWI) techniques can reduce these distortions, but they generally suffer from artifacts caused by motion-induced phase errors. Parallel imaging can also reduce the distortions if the sensitivity profiles of the receiver coils allow a sufficiently high reduction factor for the desired field of view (FOV). A novel 3D DTI technique, termed 3D single-shot STimulated EPI (3D ss-STEPI), was developed to acquire high-resolution DW images of a localized region. The new technique completes k-space acquisition of a limited 3D volume after a single diffusion preparation. Because the DW magnetization is stored in the longitudinal direction until readout, it undergoes T(1) rather than T(2) decay. Inner volume imaging (IVI) is used to limit the imaging volume. This reduces the time required for EPI readout of each complete k(x)-k(y) plane, and hence reduces T(2)(*) decay during the readout and T(1) decay between the readout of each k(z). 3D ss-STEPI images appear to be free of severe susceptibility and motion artifacts. 3D ss-STEPI allows high-resolution DTI of limited volumes of interest, such as localized brain regions, cervical spinal cord, optic nerve, and other extracranial organs.     

High-resolution isotropic 3D diffusion tensor imaging of the human brain.

High-resolution cardiac-gated 3D diffusion tensor imaging (3D-DTI) is demonstrated in vivo for several areas of the human brain. Anatomical mapping of subcortical white matter (WM), as well as definition and identification of major WM bundles from the brainstem were performed in humans for the first time using this technique. Improved intrinsic signal-to-noise ratio (SNR) and relatively reduced sensitivity to physiological motion (e.g., brain pulsations) with respect to cardiac-gated multislice acquisition are demonstrated. The advantages and weaknesses of this approach are discussed.     

Bandwidth-modulated adiabatic RF pulses for uniform selective saturation and inversion.

Radiofrequency (RF) inversion and saturation pulses with extremely high spatial selectivity and uniform profiles are a requirement for numerous MR techniques, such as pulsed arterial spin labeling and outer volume suppression. Adiabatic pulses used for inversion of longitudinal magnetization are ubiquitous, but the superior selectivity of adiabatic full passages has not been widely exploited for saturation because a simple way of calibrating the amplitude of these subadiabatic pulses is lacking. An analytically derived calibration equation is presented, applicable to a large class of pulses including the hyperbolic secant (HS) pulse and allowing the determination of the precise amplitude required to achieve any effective flip angle. The properties of this calibration are examined, and a highly selective and homogeneous HS saturation pulse is demonstrated. Based on this calibration a new class of RF pulses is developed. These bandwidth-modulated adiabatic selective saturation and inversion (BASSI) RF pulses afford optimal amplitude modulation, achieving uniform profiles at any effective flip angle. BASSI pulses are compared to existing gradient modulated adiabatic pulses in simulations and phantom experiments and shown to be superior in terms of selectivity and homogeneity, while requiring less RF energy. An application of BASSI pulses to pulsed arterial spin labeling is shown.     

Measurement of fiber orientation distributions using high angular resolution diffusion imaging.

High angular resolution measurements of diffusion are used to estimate the angular distribution and diffusion anisotropy of fibers in a voxel. A simple, axially symmetric model of diffusion in white matter fibers is used to relate diffusion measurements to fiber properties. The new technique is called fiber orientation estimated using continuous axially symmetric tensors (FORECAST). It is tested using both numerical simulation and in vivo measurements. The new method agrees with other methods in voxels containing single fibers, but resolves crossing fibers better, at least at the level of diffusion weighting used in this study (tr(b) = 1480 s/mm2). The simplifying assumptions of the model are tested by comparison with the "model-free" q-ball analysis of in vivo data and the results are shown to be in good agreement. The new method addresses the problem of partial volume averaging in diffusion tensor imaging and provides a basis for more reliable estimates of fiber orientation and fractional anisotropy.     

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.     

Q-ball imaging.

Magnetic resonance diffusion tensor imaging (DTI) provides a powerful tool for mapping neural histoarchitecture in vivo. However, DTI can only resolve a single fiber orientation within each imaging voxel due to the constraints of the tensor model. For example, DTI cannot resolve fibers crossing, bending, or twisting within an individual voxel. Intravoxel fiber crossing can be resolved using q-space diffusion imaging, but q-space imaging requires large pulsed field gradients and time-intensive sampling. It is also possible to resolve intravoxel fiber crossing using mixture model decomposition of the high angular resolution diffusion imaging (HARDI) signal, but mixture modeling requires a model of the underlying diffusion process.Recently, it has been shown that the HARDI signal can be reconstructed model-independently using a spherical tomographic inversion called the Funk-Radon transform, also known as the spherical Radon transform. The resulting imaging method, termed q-ball imaging, can resolve multiple intravoxel fiber orientations and does not require any assumptions on the diffusion process such as Gaussianity or multi-Gaussianity. The present paper reviews the theory of q-ball imaging and describes a simple linear matrix formulation for the q-ball reconstruction based on spherical radial basis function interpolation. Open aspects of the q-ball reconstruction algorithm are discussed.     

Implementation and assessment of diffusion-weighted partial Fourier readout-segmented echo-planar imaging

Single-shot echo-planar imaging has been used widely in diffusion magnetic resonance imaging due to the difficulties in correcting motion-induced phase corruption in multishot data. Readout-segmented EPI has addressed the multishot problem by introducing a two-dimensional nonlinear navigator correction with online reacquisition of uncorrectable data to enable acquisition of high-resolution diffusion data with reduced susceptibility artifact and T*(2) blurring. The primary shortcoming of readout-segmented EPI in its current form is its long acquisition time (longer than similar resolution single-shot echo-planar imaging protocols by approximately the number of readout segments), which limits the number of diffusion directions. By omitting readout segments at one side of k-space and using partial Fourier reconstruction, readout-segmented EPI imaging times could be reduced. In this study, the effects of homodyne and projection onto convex sets reconstructions on estimates of the fractional anisotropy, mean diffusivity, and diffusion orientation in fiber tracts and raw T(2)- and trace-weighted signal are compared, along with signal-to-noise ratio results. It is found that projections onto convex sets reconstruction with 3/5 segments in a 2 mm isotropic diffusion tensor image acquisition and 9/13 segments in a 0.9 × 0.9 × 4.0 mm(3) diffusion-weighted image acquisition provide good fidelity relative to the full k-space parameters. This allows application of readout-segmented EPI to tractography studies, and clinical stroke and oncology protocols.     

High-resolution DTI with 2D interleaved multislice reduced FOV single-shot diffusion-weighted EPI (2D ss-rFOV-DWEPI).

Diffusion tensor MRI (DTI), using single-shot 2D diffusion weighted-EPI (2D ss-DWEPI), is limited to intracranial (i.c.) applications far from the sinuses and bony structures, due to the severe geometric distortions caused by significant magnetic field inhomogeneities at or near the tissue-air or tissue-bone interfaces. Reducing these distortions in single-shot EPI by shortening the readout period generally requires a reduced field of view (and the potential of wraparound artifact) in the phase-encoding direction and/or reduced spatial resolution. To resolve the problem, a novel 2D reduced FOV single-shot diffusion-weighted EPI (2D ss-rFOV-DWEPI) pulse sequence applicable for high resolution diffusion-weighted MRI of local anatomic regions, such as brainstem, cervical spinal cord, and optic nerve, has been developed. In the proposed technique, time-efficient interleaved acquisition of multiple slices with a limited FOV was achieved by applying an even number of refocusing 180 degrees pulses with the slice-selection gradient applied in the phase-encoding direction. The two refocusing pulses used for each slice acquisition were separated by a short time interval (typically less than 45 ms) required for the 2D EPI echotrain acquisition. The new technique can be useful for high resolution DTI of various anatomies, such as localized brain structures, cervical spinal cord, optic nerve, heart, or other extra-cerebral organ, where conventional 2D ss-DWEPI is limited in usage due to the severity of image distortions.     

Q-ball reconstruction of multimodal fiber orientations using the spherical harmonic basis.

Diffusion tensor imaging (DTI) accurately delineates white matter pathways when the Gaussian model of diffusion is valid. However, DTI yields erroneous results when diffusion takes on a more complex distribution, as is the case in the brain when fiber tracts cross. High angular resolution diffusion imaging (HARDI) overcomes this limitation of DTI by more fully characterizing the angular dependence of intravoxel diffusion. Among the various HARDI methods that have been proposed, QBI offers advantages such as linearity, model independence, and relatively easy implementation. In this work, reconstruction of the q-ball orientation distribution function (ODF) is reformulated in terms of spherical harmonic basis functions, yielding an analytic solution with useful properties of a frequency domain representation. The harmonic basis is parsimonious for typical b-values, which enables the ODF to be synthesized from a relatively small number of noisy measurements and thus brings the technique closer to clinical feasibility from the standpoint of total imaging time. The proposed method is assessed using Monte Carlo computer simulations and compared with conventional q-ball reconstruction using spherical RBFs. In vivo results from 3T whole-brain HARDI of adult volunteers are also provided to verify the underlying mathematical theory.     

Characterizing non-Gaussian diffusion by using generalized diffusion tensors.

Diffusion tensor imaging (DTI) is known to have a limited capability of resolving multiple fiber orientations within one voxel. This is mainly because the probability density function (PDF) for random spin displacement is non-Gaussian in the confining environment of biological tissues and, thus, the modeling of self-diffusion by a second-order tensor breaks down. The statistical property of a non-Gaussian diffusion process is characterized via the higher-order tensor (HOT) coefficients by reconstructing the PDF of the random spin displacement. Those HOT coefficients can be determined by combining a series of complex diffusion-weighted measurements. The signal equation for an MR diffusion experiment was investigated theoretically by generalizing Fick's law to a higher-order partial differential equation (PDE) obtained via Kramers-Moyal expansion. A relationship has been derived between the HOT coefficients of the PDE and the higher-order cumulants of the random spin displacement. Monte-Carlo simulations of diffusion in a restricted environment with different geometrical shapes were performed, and the strengths and weaknesses of both HOT and established diffusion analysis techniques were investigated. The generalized diffusion tensor formalism is capable of accurately resolving the underlying spin displacement for complex geometrical structures, of which neither conventional DTI nor diffusion-weighted imaging at high angular resolution (HARD) is capable. The HOT method helps illuminate some of the restrictions that are characteristic of these other methods. Furthermore, a direct relationship between HOT and q-space is also established.