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Studies of restricted diffusion in heterogeneous media containing variations in susceptibility.

Measurements of water self-diffusion in heterogeneous media by pulsed gradient spin-echo methods depend on the precise choice of experimental parameters. This variation may reflect the presence of restricted or anisotropic diffusion, or the presence of intrinsic magnetic field gradients. In experiments at 2.0 T, restricted diffusion effects have been demonstrated in freshly excised tissues with an effective barrier radius of order 10 microns. In samples with intrinsic susceptibility variations such as tissues or gels containing dispersions of iron oxide particles, the reduction of apparent diffusion coefficient with diffusion interval can be used to estimate the degree of heterogeneity of the magnetic field in the sample. The implications of these effects for diffusion-weighted MRI as well as their use to derive novel tissue parameters are discussed.

Acrylic Resins↗

Reduction of flow artifacts in NMR diffusion imaging using view-angle tilted line-integral projection reconstruction.

Most of the diffusion imaging techniques employ strong diffusion gradient pulses of long duration in order to achieve appreciable signal attenuation through the diffusion effect. However, these strong and long gradient pulses make the resultant images extremely sensitive to the motion or flow of the object. Fourier imaging, with which most of the current NMR imaging is performed, is especially sensitive to the fluctuating flow and the images are usually obscured by severe flow artifacts smeared in the phase-encoding direction. In this paper, we have proposed a diffusion imaging technique which reduces the flow artifacts by use of the line-integral projection reconstruction (LPR) imaging method. Furthermore, the inhomogeneity artifacts expected to occur in LPR imaging have been corrected by application of the view-angle tilting technique. The pulse sequence of the view-angle tilted LPR diffusion imaging is designed in such a way that it works for both isotropic and anisotropic diffusion. Experimental results are presented along with the experimental procedures.

Brain↗

Diffusion-weighted MR microscopy with fast spin-echo.

A diffusion-weighted fast spin-echo (FSE) imaging sequence for high-field MR microscopy was developed and experimentally validated in a phantom and in a live rat. Pulsed diffusion gradients were executed before and after the initial 180 degrees pulse in the FSE pulse train. This produced diffusion-related reductions in image signal intensity corresponding to gradient ("b") factors between 1.80 and 1352 s/mm2. The degree of diffusion weighting was demonstrated to be independent of echo train length for experiments using trains up to 16 echoes long. Quantitative measurements on a phantom and on a live rat produced diffusion coefficients consistent with literature values. Importantly, the eight- to 16-fold increase in imaging efficiency with FSE was not accompanied by a significant loss of spatial resolution or contrast. This permits acquisition of in vivo three-dimensional data in time periods that are appropriate for evolving biological processes. The combination of accurate diffusion weighting and high spatial resolution provided by FSE makes the technique particularly useful for MR microscopy.

Animals↗

In vivo measurement of water diffusion in the human heart.

Existing magnetic resonance methods for diffusion imaging, including echo planar, are ineffective in the beating heart due to motion-induced signal attenuation. To overcome this problem, we used a diffusion-weighted stimulated echo-echo planar magnetic resonance imaging sequence. The two lobes of the diffusion-sensitizing gradient were synchronized to the same point in successive cardiac cycles in order to fix the cardiac position and avoid bulk motion effects. The apparent diffusion coefficients (ADCs) of the interventricular septum in 12 healthy subjects for diffusion gradients along the x-, y-, and z-directions were 1.40 +/- 0.27, 1.48 +/- 0.35, and 1.78 +/- 0.27 x 10(-3) mm2/s. The ADCs of the interventricular septum in a second group of 15 healthy subjects for diffusion gradients along the short axis, horizontal and vertical long axes were 0.92 +/- 0.15, 1.50 +/- 0.15, and 1.10 +/- 0.24 x 10(-3) mm2/s. Because the ADCs were less than the measured values for skeletal muscle and their standard deviations were low, it seems unlikely that bulk motion effects made the dominant contribution to the measured myocardial ADC for the interventricular septum, although motion and/or susceptibility artifacts frequently degraded measurements in the free wall of the left ventricle. Additional evidence that ADC was not predominantly determined by wall motion was obtained in a third group of patients with various cardiac abnormalities, in whom there was only a weak correlation between ADC and ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Navigated diffusion imaging of normal and ischemic human brain.

The principal barrier to clinical application of diffusion-weighted MR imaging is the severe image degradation caused by patient motion. One way to compensate for motion effects is the use of a "navigator echo" phase correction scheme. In this work, a modification of this technique is introduced, in which the phase correction step is performed in the frequency domain (i.e., after the readout Fourier transform). This significantly improves the robustness of the navigator echo approach and, when combined with cardiac gating, allows diagnostic quality diffusion-weighted images of the brain to be routinely obtained on standard clinical scanner hardware. The technique was evaluated in phantom studies and in 23 humans (3 normal volunteers and 20 patients). Diffusion anisotropy and apparent diffusion coefficient maps were generated from the image data and showed decreased apparent diffusion in acute stroke lesions and, in several cases, increased apparent diffusion in chronic stroke lesions.

Aged↗

High resolution renal diffusion imaging using a modified steady-state free precession sequence.

A modified steady-state free precession (SSFP) diffusion sequence is proposed for high resolution renal imaging. A pair of bipolar diffusion gradients was used to minimize the errors in measured apparent diffusion coefficient (ADC) caused by variations in T1, T2, and RF flip angle that have been observed with previously employed SSFP diffusion sequences. Motion sensitivity was reduced by the use of compensated gradients, frame-by-frame averaging, and a repetition time of 22 ms, which for a single-acquisition 128 x 128 image requires only 3 s. High resolution was achieved by signal averaging. The modified sequence was applied to in vivo diffusion measurements. In six normal rat kidneys the ADCs (mean +/- SD; x 10(-3) mm2/s) of the cortex, outer medulla, and inner medulla were 2.28 +/- 0.05, 2.38 +/- 0.10, and 2.95 +/- 0.05, respectively. The technique requires relatively large gradients to achieve adequate diffusion weighting.

1-Propanol↗

Apparent diffusion coefficients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance.

The diffusion characteristics of water in brain white matter were studied in patients with benign and secondary progressive multiple sclerosis (MS), and also in normal controls. In the MS patients, both lesions and normal-appearing white matter (NAWM) were examined to assess whether pathological differences might be evident from the diffusion behavior. A volume-selective technique was used to reduce data acquisition time and improve the reliability and precision of the measurements. This also allowed the time-dependence of apparent diffusion coefficients to be assessed. While lesions from both patient groups showed an elevated diffusion coefficient, no differences between the two groups were found. In addition, NAWM was elevated for both patient groups compared with the control group, although this was only statistically significant for patients with a benign disease course. The degree of elevation of the diffusion coefficient within the individual lesions measured was not related to the disability of the patient. Pathological differences between lesions in patients with different disease courses, if they exist, have not been detected in this study of brain water diffusion.

Brain↗

Evidence for the exchange of arterial spin-labeled water with tissue water in rat brain from diffusion-sensitized measurements of perfusion.

The extraction fraction of vascular water in rat brain is investigated by means of diffusion measurements of arterial spin labeled water at varying cerebral blood flow (CBF) values. The apparent diffusion coefficient (ADC) of the difference of the proton magnetization signal in the brain acquired with and without continuous arterial spin labeling is modeled to provide a measure of the amount of arterial water in tissue and vasculature and thus of the extraction fraction. The tissue and vascular portion of the arterial spin labeled water are differentiated based on their diffusion characteristics in a manner analogous to the intravoxel incoherent motion (IVIM) method. The amount of labeled arterial water that exchanges with tissue water is determined by estimating the fraction of the total signal that is associated with the slow-decaying component of a biexponential fit to the normalized difference signal between the magnetization of brain tissue acquired with and without arterial spin labeling. The results indicate that, at normal CBF (1.15 +/- 0.21 ml x g(-1) x min[-1]), about 90% of the arterial spin labeled water diffuses with an ADC of (1.21 +/- 0.37) x 10[-3] mm2 s[-1]), which is equal to tissue. At high CBF, an increasing fraction of the labeling water has a fast-pseudo-diffusion coefficient due to a decrease in water extraction fractions. The results also show that the contribution of vascular water to the measurement of perfusion by techniques that use endogenous water as a tracer can be efficiently eliminated by the use of diffusion sensitizing gradients with small effective b values (b approximately 20 s/mm2), enabling these techniques to monitor true changes in tissue perfusion.

Animals↗

A simplified method to measure the diffusion tensor from seven MR images.

Analytical expressions of the diffusion tensor of water, D, and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2, maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications.

Animals↗

In vivo diffusion tensor imaging of the human prostate.

This study demonstrates the feasibility of in vivo prostate diffusion tensor imaging (DTI) in human subjects. We implemented an EPI-based diffusion-weighted (DW) sequence with seven-direction diffusion gradient sensitization, and acquired DT images from six subjects using cardiac gating with a phased-array prostate surface coil operating in a linear mode. We calculated two indices to quantify diffusion anisotropy. The direction of the eigenvector corresponding to the leading eigenvalue was displayed by means of a color-coding scheme. The average diffusion values of the prostate peripheral zone (PZ) and central gland (CG) were 1.95 +/- 0.08 x 10(-3) mm2 s and 1.53 +/- 0.34 x 10(-3) mm2 s, respectively. The average fractional anisotropy (FA) values for the PZ and CG were 0.46 +/- 0.04 and 0.40 +/- 0.08, respectively. The diffusion ellipsoid in prostate tissue was anisotropic and approximated a prolate model, as shown in the color maps of the anisotropy. Consistent with the tissue architecture, the prostate fiber orientations were predominantly in the superior-inferior (SI) direction for both the PZ and CG. This study shows the feasibility of in vivo DTI and establishes normative DT values for six subjects.

Anisotropy↗

Reduction of noise in diffusion tensor images using anisotropic smoothing.

To improve the accuracy of tissue structural and architectural characterization with diffusion tensor imaging, a novel smoothing technique is developed for reducing noise in diffusion tensor images. The technique extends the traditional anisotropic diffusion filtering method by allowing isotropic smoothing within homogeneous regions and anisotropic smoothing along structure boundaries. This is particularly useful for smoothing diffusion tensor images in which direction information contained in the tensor needs to be restored following noise corruption and preserved around tissue boundaries. The effectiveness of this technique is quantitatively studied with experiments on simulated and human in vivo diffusion tensor data. Illustrative results demonstrate that the anisotropic smoothing technique developed can significantly reduce the impact of noise on the direction as well as anisotropy measures of the diffusion tensor images.

Algorithms↗

Mapping complex tissue architecture with diffusion spectrum magnetic resonance imaging.

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. Finally, the relation between the presented model-free imaging technique and other available diffusion MRI schemes is discussed.

Algorithms↗

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.

Algorithms↗

Echoplanar diffusion tensor imaging of the lower leg musculature using eddy current nulled stimulated echo preparation.

A sequence for echoplanar diffusion tensor imaging of musculature was developed using a stimulated echo preparation. The strategy was optimized in order to obtain reliable diffusion tensor data in a short measuring time. Image distortion problems due to eddy currents arising from long-lasting diffusion sensitizing gradients could be overcome by insertion of additional gradient pulses in the TM interval of the stimulated echo preparation. In contrast to former approaches with similar intention, the proposed strategy does not influence the stimulated echo signal itself and does not lead to prolonged echo time as in the case of spin echo methods. Phantom measurements were performed to compare eddy current induced distortion effects in diffusion weighted images. The diffusion tensor in the musculature of the lower leg was investigated in four healthy subjects and maps of the trace and the three eigenvalues of the diffusion tensor, fractional anisotropy maps, and angle maps were calculated.

Diffusion Magnetic Resonance Imaging↗

Measurement of xenon diffusing capacity in the rat lung by hyperpolarized 129Xe MRI and dynamic spectroscopy in a single breath-hold.

We used the dual capability of hyperpolarized 129Xe for spectroscopy and imaging to develop new measures of xenon diffusing capacity in the rat lung that (analogously to the diffusing capacity of carbon monoxide or DLCO) are calculated as a product of total lung volume and gas transfer rate constants divided by the pressure gradient. Under conditions of known constant pressure breath-hold, the volume is measured by hyperpolarized 129Xe MRI, and the transfer rate is measured by dynamic spectroscopy. The new quantities (xenon diffusing capacity in lung parenchyma (DLXeLP)), xenon diffusing capacity in RBCs (DLXeRBC), and total lung xenon diffusing capacity (DLXe)) were measured in six normal rats and six rats with lung inflammation induced by instillation of fungal spores of Stachybotrys chartarum. DLXeLP, DLXeRBC, and DLXe were 56 +/- 10 ml/min/mmHg, 64 +/- 35 ml/min/mmHg, and 29 +/- 9 ml/min/mmHg, respectively, for normal rats, and 27 +/- 9 ml/min/mmHg, 42 +/- 27 ml/min/mmHg, and 16 +/- 7 ml/min/mmHg, respectively, for diseased rats. Lung volumes and gas transfer times for LP (TtrLP) were 16 +/- 2 ml and 22 +/- 3 ms, respectively, for normal rats and 12 +/- 2 ml and 35 +/- 8 ms, respectively, for diseased rats. Xenon diffusing capacities may be useful for measuring changes in gas exchange associated with inflammation and other lung diseases.

Animals↗

Water diffusion heterogeneity index in the human brain is insensitive to the orientation of applied magnetic field gradients.

The alpha diffusion-weighted imaging (DWI) method was developed to study heterogeneous water diffusion in the human brain using magnetic resonance imaging (MRI). An advantage of this model is that it does not require an assumption about the shape of the intravoxel distribution of apparent diffusion rates, and it has a calculable relationship to this distribution. The alpha-DWI technique is useful for detecting microstructural tissue changes associated with brain tumor invasion, and may be useful for directing therapy to invading tumor cells. In previous work, alpha-DWI was performed with magnetic field gradients applied along a single direction in order to avoid artificially introducing a source of heterogeneity to the decay. However, it is known that restricted diffusion is anisotropic in the brain, and the alpha-DWI method must take this into account to be complete. In this work the relationship between the applied magnetic field gradients and the fitted stretched-exponential model parameters was studied in the human brain. It was found the distributed diffusion coefficient (DDC) varies with the direction of applied gradients, while the heterogeneity index alpha is relatively direction-insensitive. It is proposed that in clinical use, maps of alpha can be created using diffusion-weighting gradients applied in a single direction that reflect the tissue heterogeneity.

Algorithms↗

Diffusion-weighted imaging in tissues: theoretical models.

Typical diffusion measurements use Stejskal-Tanner pulsed gradient spin echo sequences to provide information about the average diffusion and displacement profiles of particles in a sample. To derive structural information, a measured displacement profile has to be related by means of a model to the physical and geometrical properties of the tissue, such as diffusion coefficients and shapes of semi-permeable membranes of compartments in the system. The behavior of the NMR signal and the measured ADC are greatly affected by the cellular architecture of a tissue, mainly because cellular membranes are relatively impermeable to water. For long diffusion times, and small signal attenuations, ADC is relatively insensitive to how it is measured. In general, however, ADC values are not readily interpreted unless the measuring conditions are specified in detail. For given measuring conditions, ADC depends on intra- and extracellular diffusion coefficients, membrane permeabilities, cell sizes and the cellular volume fraction. If intra- and extracellular T2 relaxation rates are different enough, ADC may also depend on the relaxation properties of the system and the echo time. An improved understanding of the precise influence of these factors has been obtained by detailed consideration of theoretical and computer models that can be related to experimental data in simple systems. Further refinements of such models should advance our understanding of water diffusion in tissues.

Body Water↗

Diffusion NMR spectroscopy.

MR offers unique tools for measuring molecular diffusion. This review focuses on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasively quantitate the translational displacement of endogenous metabolites in intact mammalian tissues. Most of the metabolites that are observed by in vivo MRS are predominantly located in the intracellular compartment. DW-MRS is of fundamental interest because it enables one to probe the in situ status of the intracellular space from the diffusion characteristics of the metabolites, while at the same time providing information on the intrinsic diffusion properties of the metabolites themselves. Alternative techniques require the introduction of exogenous probe molecules, which involves invasive procedures, and are also unable to measure molecular diffusion in and throughout intact tissues. The length scale of the process(es) probed by MR is in the micrometer range which is of the same order as the dimensions of many intracellular entities. DW-MRS has been used to estimate the dimensions of the cellular elements that restrict intracellular metabolite diffusion in muscle and nerve tissue. In addition, it has been shown that DW-MRS can provide novel information on the cellular response to pathophysiological changes in relation to a range of disorders, including ischemia and excitotoxicity of the brain and cancer.

Animals↗