Improving diffusion MRI using simultaneous multi-slice echo planar imaging.

In diffusion MRI, simultaneous multi-slice single-shot EPI acquisitions have the potential to increase the number of diffusion directions obtained per unit time, allowing more diffusion encoding in high angular resolution diffusion imaging (HARDI) acquisitions. Nonetheless, unaliasing simultaneously acquired, closely spaced slices with parallel imaging methods can be difficult, leading to high g-factor penalties (i.e., lower SNR). The CAIPIRINHA technique was developed to reduce the g-factor in simultaneous multi-slice acquisitions by introducing inter-slice image shifts and thus increase the distance between aliased voxels. Because the CAIPIRINHA technique achieved this by controlling the phase of the RF excitations for each line of k-space, it is not directly applicable to single-shot EPI employed in conventional diffusion imaging. We adopt a recent gradient encoding method, which we termed "blipped-CAIPI", to create the image shifts needed to apply CAIPIRINHA to EPI. Here, we use pseudo-multiple replica SNR and bootstrapping metrics to assess the performance of the blipped-CAIPI method in 3× simultaneous multi-slice diffusion studies. Further, we introduce a novel image reconstruction method to reduce detrimental ghosting artifacts in these acquisitions. We show that data acquisition times for Q-ball and diffusion spectrum imaging (DSI) can be reduced 3-fold with a minor loss in SNR and with similar diffusion results compared to conventional acquisitions.

White matter maturation reshapes structural connectivity in the late developing human brain.

From toddler to late teenager, the macroscopic pattern of axonal projections in the human brain remains largely unchanged while undergoing dramatic functional modifications that lead to network refinement. These functional modifications are mediated by increasing myelination and changes in axonal diameter and synaptic density, as well as changes in neurochemical mediators. Here we explore the contribution of white matter maturation to the development of connectivity between ages 2 and 18 y using high b-value diffusion MRI tractography and connectivity analysis. We measured changes in connection efficacy as the inverse of the average diffusivity along a fiber tract. We observed significant refinement in specific metrics of network topology, including a significant increase in node strength and efficiency along with a decrease in clustering. Major structural modules and hubs were in place by 2 y of age, and they continued to strengthen their profile during subsequent development. Recording resting-state functional MRI from a subset of subjects, we confirmed a positive correlation between structural and functional connectivity, and in addition observed that this relationship strengthened with age. Continuously increasing integration and decreasing segregation of structural connectivity with age suggests that network refinement mediated by white matter maturation promotes increased global efficiency. In addition, the strengthening of the correlation between structural and functional connectivity with age suggests that white matter connectivity in combination with other factors, such as differential modulation of axonal diameter and myelin thickness, that are partially captured by inverse average diffusivity, play an increasingly important role in creating brain-wide coherence and synchrony.

Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers.

MRI tractography is the mapping of neural fiber pathways based on diffusion MRI of tissue diffusion anisotropy. Tractography based on diffusion tensor imaging (DTI) cannot directly image multiple fiber orientations within a single voxel. To address this limitation, diffusion spectrum MRI (DSI) and related methods were developed to image complex distributions of intravoxel fiber orientation. Here we demonstrate that tractography based on DSI has the capacity to image crossing fibers in neural tissue. DSI was performed in formalin-fixed brains of adult macaque and in the brains of healthy human subjects. Fiber tract solutions were constructed by a streamline procedure, following directions of maximum diffusion at every point, and analyzed in an interactive visualization environment (TrackVis). We report that DSI tractography accurately shows the known anatomic fiber crossings in optic chiasm, centrum semiovale, and brainstem; fiber intersections in gray matter, including cerebellar folia and the caudate nucleus; and radial fiber architecture in cerebral cortex. In contrast, none of these examples of fiber crossing and complex structure was identified by DTI analysis of the same data sets. These findings indicate that DSI tractography is able to image crossing fibers in neural tissue, an essential step toward non-invasive imaging of connectional neuroanatomy.

Reduction of eddy-current-induced distortion in diffusion MRI using a twice-refocused spin echo.

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. By adjusting the timing of the diffusion gradients, eddy currents with a single exponential decay constant can be nulled, and eddy currents with similar decay constants can be greatly reduced. This new sequence is demonstrated in phantom measurements and in diffusion anisotropy images of normal human brain.

The influence of brain tissue anisotropy on human EEG and MEG.

The influence of gray and white matter tissue anisotropy on the human electroencephalogram (EEG) and magnetoencephalogram (MEG) was examined with a high resolution finite element model of the head of an adult male subject. The conductivity tensor data for gray and white matter were estimated from magnetic resonance diffusion tensor imaging. Simulations were carried out with single dipoles or small extended sources in the cortical gray matter. The inclusion of anisotropic volume conduction in the brain was found to have a minor influence on the topology of EEG and MEG (and hence source localization). We found a major influence on the amplitude of EEG and MEG (and hence source strength estimation) due to the change in conductivity and the inclusion of anisotropy. We expect that inclusion of tissue anisotropy information will improve source estimation procedures.

Conductivity tensor mapping of the human brain using diffusion tensor MRI.

Knowledge of the electrical conductivity properties of excitable tissues is essential for relating the electromagnetic fields generated by the tissue to the underlying electrophysiological currents. Efforts to characterize these endogenous currents from measurements of the associated electromagnetic fields would significantly benefit from the ability to measure the electrical conductivity properties of the tissue noninvasively. Here, using an effective medium approach, we show how the electrical conductivity tensor of tissue can be quantitatively inferred from the water self-diffusion tensor as measured by diffusion tensor magnetic resonance imaging. The effective medium model indicates a strong linear relationship between the conductivity and diffusion tensor eigenvalues (respectively, final sigma and d) in agreement with theoretical bounds and experimental measurements presented here (final sigma/d approximately 0.844 +/- 0.0545 S small middle dots/mm(3), r(2) = 0.945). The extension to other biological transport phenomena is 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.

Fiber crossing in human brain depicted with diffusion tensor MR imaging.

Human white matter fiber crossings were investigated with use of the full eigenstructure of the magnetic resonance diffusion tensor. Intravoxel fiber dispersions were characterized by the plane spanned by the major and medium eigenvectors and depicted with three-dimensional graphics. This method improves the analysis of fiber orientations, beyond the principal fiber directions, to a broader range of complex fiber architectures.

Myocardial fiber shortening in humans: initial results of MR imaging.

PURPOSE: To use diffusion-sensitive magnetic resonance (MR) imaging to obtain images of fiber orientation in vivo and to map fiber shortening in humans by means of integrating such data with strain images. MATERIALS AND METHODS: Images of fiber shortening for midventricular short-axis sections were acquired in eight healthy subjects. Fiber orientation maps obtained by means of diffusion-sensitive MR imaging were coregistered with systolic strain maps obtained by means of velocity-sensitive MR imaging. Fiber shortening was quantified by use of the component of systolic strain in the fiber direction. RESULTS: The results were reproducible among subjects and were consistent with published values. MR imaging of myocardial fibers showed axisymmetric progression of fiber angles from -90 degrees epicardially to +90 degrees endocardially, with maxima near 0 degrees. Fiber shortening (mean, 0.12 +/- 0.01 [SD]) was more uniform than radial, circumferential, longitudinal, or cross-fiber strain or any principal strain. Fiber orientation coincided with the direction of maximum contraction epicardially, with that of minimum contraction endocardially, and varied between these extremes linearly with wall depth (r = 0.6). CONCLUSION: Registered diffusion and strain MR imaging can be used quantitatively to map fiber orientation and its relations to myocardial deformation in humans.

Human acute cerebral ischemia: detection of changes in water diffusion anisotropy by using MR imaging.

PURPOSE: To (a) determine the optimal choice of a scalar metric of anisotropy and (b) determine by means of magnetic resonance imaging if changes in diffusion anisotropy occurred in acute human ischemic stroke. MATERIALS AND METHODS: The full diffusion tensor over the entire brain was measured. To optimize the choice of a scalar anisotropy metric, the performances of scalar indices in simulated models and in a healthy volunteer were analyzed. The anisotropy, trace apparent diffusion coefficient (ADC), and eigenvalues of the diffusion tensor in lesions and contralateral normal brain were compared in 50 patients with stroke. RESULTS: Changes in anisotropy in patients were quantified by using fractional anisotropy because it provided the best performance in terms of contrast-to-noise ratio as a function of signal-to-noise ratio in simulations. The anisotropy of ischemic white matter decreased (P = .01). Changes in anisotropy in ischemic gray matter were not significant (P = .63). The trace ADC decreased for ischemic gray matter and white matter (P < .001). The first and second eigenvalues decreased in both ischemic gray and ischemic white matter (P < .001). The third eigenvalue decreased in ischemic gray (P = .001) and white matter (P = .03). CONCLUSION: 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.

Biomechanical basis for lingual muscular deformation during swallowing.

Our goal was to quantify intramural mechanics in the tongue through an assessment of local strain during the physiological phases of swallowing. Subjects were imaged with an ultrafast gradient echo magnetic resonance imaging (MRI) pulse sequence after the application of supersaturated magnetized bands in the x and y directions. Local strain was defined through deformation of discrete triangular elements defined by these bands and was depicted graphically either as color-coded two-dimensional strain maps or as three-dimensional octahedra whose axes correspond to the principal strains for each element. During early accommodation, the anterior tongue showed positive strain (expansive) in the anterior-posterior direction (x), whereas the middle tongue showed negative strain (contractile) in the superior-inferior direction (y). During late accommodation, the anterior tongue displayed increased positive x-direction and y-direction strain, whereas the posterior tongue displayed increased negative y-direction strain. These findings were consistent with contraction of the anterior-located intrinsic muscles and the posterior-located genioglossus and hyoglossus muscles. During propulsion, posterior displacement of the tongue was principally associated with positive strain directed in the x and y directions. These findings were consistent with posterior passive stretch in the midline due to contraction of the laterally inserted styloglossus muscle, as well as contraction of the posterior located transversus muscle. We conclude that MRI of lingual deformation during swallowing resolves the synergistic contractions of the intrinsic and extrinsic muscle groups.

Cardiac diffusion tensor MRI in vivo without strain correction.

Cardiac diffusion MRI with diffusion encoding that spans a cardiac cycle is complicated by myocardial strains. This paper presents a method to obtain accurate diffusion data without strain correction. Owing to the synchrony of normal cardiac motion, there are time points in the cardiac cycle, "sweet spots," when the cardiac configuration approximates its temporal mean. If the diffusion is encoded then, the net effect of strain on the observed diffusion approximates zero. To test this, MRI diffusion and strain-rate movies are performed on cyclically deformed gel phantoms and in five normal subjects. In phantoms, the sweet spots predicted from the strain time curves agree with the times when the observed diffusion equals the true diffusion. In humans, the strain prediction of the sweet spots and the locations determined by the diffusion trace show a high correlation, r = 0.99. In all subjects, diffusion MRI presents a fiber orientation pattern comparable to that obtained from a stationary specimen. Magn Reson Med 42:393-403, 1999.

Intramural mechanics of the human tongue in association with physiological deformations.

Contraction of the tongue musculature during speech and swallowing is associated with characteristic patterns of tissue deformation. In order to quantify local deformation (strain) in the human tongue, we used a non-invasive NMR tagging technique that represents tissue as discrete deforming elements. Subjects were studied with a fast gradient echo pulse sequence (TR,TE 2.3/0.8 ms, slice thickness 10 mm, and effective spatial resolution 1.3x1.3 mm). Individual elements were defined by selectively supersaturating bands of magnetic spills in resting tongue tissue along the antero-posterior and superior inferior directions of the mid-sagittal plane, resulting in a rectilinear square grid. Axial and shear strains relative to the rest condition were determined for each clement and represented by two-dimensional surface strain maps. During forward protrusion, the anterior tongue underwent positive antero posterior strain (elongation) (maximum 200%) and symmetrical negative medial lateral and superior inferior strain (contraction). During sagittal curl directed to the hard palate, the tongue exhibited positive asymmetrical antero posterior strain (maximum 160%) that increased radially as a function of distance from the center of curvature (r = 0.9216, p<0.0005), and commensurate negative strain in the medial lateral direction. Similarly, the magnitude of anterior posterior strain during left-directed tongue curl was proportional to the distance from the curved inner surface (r = O.8978, p<0.0005). We conclude that the regulation of tongue position for the motions studied was related to regional activation of the intrinsic lingual musculature.

Determination of lingual myoarchitecture in whole tissue by NMR imaging of anisotropic water diffusion.

The muscular anatomy of the tongue consists of a complex three-dimensional array of fibers, which together produce the variations of shape and position necessary for deglutition. To define the myoarchitecture of the intact mammalian tongue, we have utilized NMR techniques to assess the location and orientation of muscle fiber bundles through measurement of the direction-specific diffusional properties of water molecules. Whole sheep tongues were excised and imaged with a slice-selective stimulated-echo diffusion sequence in the midline sagittal plane, and three-dimensional diffusion tensors were determined for each voxel. The derived diffusion tensors were depicted graphically as octahedra whose long axes indicate local muscle fiber orientation. Two distinct groups of midline fibers were identified: 1) in-plane sagittal fibers originating in the posteroinferior region of the tongue, radiating with a fanlike projection anteriorly and superiorly and merging with vertically oriented fibers, and 2) cross-plane (transverse) fibers, oriented at right angles to the vertically aligned fibers, predominantly in the anterior and superior regions of the tongue. Regional comparison of diffusion anisotropy revealed uniform and parallel alignment (high anisotropy) in the posteroinferior region of the tongue, corresponding to the base of the genioglossus, and less uniform, orthogonally aligned fibers (low anisotropy) in the anterosuperior region of the tongue, corresponding to the core intrinsic muscles. These data indicate that lingual myoarchitecture, determined through direction-dependent mobility of water molecules, can be depicted as discrete regions of muscle fibers, whose orientation and extent of diffusion anisotropy predict local contractility.

Morphometry of in vivo human white matter association pathways with diffusion-weighted magnetic resonance imaging.

The precise characterization of cortical connectivity is important for the understanding of brain morphological and functional organization. Such connectivity is conveyed by specific pathways or tracts in the white matter. Diffusion-weighted magnetic resonance imaging detects the diffusivity of water molecules in three dimensions. Diffusivity is anisotropic in oriented tissues such as fiber tracts. In the present study, we used this method to map (in terms of orientation, location, and size) the "stem" (compact portion) of the principal association, projection, and commissural white matter pathways of the human brain in vivo, in 3 normal subjects. In addition, its use in clinical neurology is illustrated in a patient with left inferior parietal lobule embolic infarction in whom a significant reduction in relative size of the stem of the left superior longitudinal fasciculus was observed. This represents an important method for the characterization of major association pathways in the living human that are not discernible by conventional magnetic resonance imaging. In the clinical domain, this method will have a potential impact on the understanding of the diseases that involve white matter such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, head injury, and spinal cord injury.

Imaging myocardial fiber architecture in vivo with magnetic resonance.

Methods are presented to image the fiber architecture of the human myocardium in vitro and in vivo. NMR images are obtained of the diffusion anisotropy tensor, indicative of local myofiber orientation. Studies of cardiac necropsy specimens demonstrate classic features of ventricular myoarchitecture including the continuous endocardial to epicardial variation of fiber helix angles (angles to the ventricular circumferential direction) of approximately +1.3 to -1.3 radians. Cross-fiber anisotropy is also observed. In the beating heart, NMR diffusion data must be corrected for the effects of myocardial deformation during the cardiac cycle. This correction can be performed using an independent MRI method to map the strain-rate tensor field of the myocardium through time. Combining fiber orientation with local myocardial strain rate, local rates of myocardial fiber shortening may be computed.

Intramural mechanics in hypertrophic cardiomyopathy: functional mapping with strain-rate MR imaging.

PURPOSE: To characterize systolic and diastolic intramural mechanics in hypertrophic cardiomyopathy (HCM) with a new metric of contractile activity. MATERIALS AND METHODS: Eleven healthy subjects and eight patients with HCM underwent velocity-encoded echo-planar magnetic resonance (MR) imaging (6-8-frame gated breath-hold movies, 3 x 3-mm resolution). A scalar strain rate (SR) parameter was compared with wall thickness and symptoms. RESULTS: The normal pattern of SR included regional uniformity, a monotonically increasing subepicardial to subendocardial gradient, and minimum transmural shear rate. In HCM, heterogeneity of SRs increased in diastole. Regional diastolic SR correlated with regional wall thickness (r = .785, P = .0001). Interobserver global SR assignment agreed in seven of eight patients. All four patients with New York Heart Association class 1 disease had a low global SR deficit score, whereas three of four patients with class 2 or 3 disease had a high SR deficit score (Spearman r = .775, P = .187). CONCLUSION: SR characterization may provide an objective measure of disease course in HCM.

Motionless movies of myocardial strain-rates using stimulated echoes.

We present methods to acquire and analyze NMR movies of myocardial strain rates in which cardiac motion is suppressed and the histories of strain rates are accurately defined for each voxel of myocardial tissue. By means of stimulated echoes, the myocardial strain-rate tensor is phase-encoded at progressive delays in the cardiac cycle while the slice-select and spatial encoding of the image acquisition are performed at a constant cardiac delay. In these data, every image shows the identical myocardial tissue, and the anatomic configuration of the heart appears motionless. The myocardial strain-rate data, however, indicate the state of motion which existed in this slice at the time of the velocity phase-encoding, and these data evolve with the progressive delay as a movie. Using echo-planar MRI, motionless movies of myocardial strain rate of four to eight cardiac delays are obtained in a breath-hold. As an application, a quantitative characterization of cardiac mechanical synchrony is accomplished by principal component analysis (PCA) of the time series of strain rates.

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)