Inline dual-echo T2 quantification in brain using a fast mapping reconstruction technique.

T2 mapping from 2D proton density and T2-weighted images (PD-T2) using Bloch equation simulations can be time consuming and introduces a latency between image acquisition and T2 map production. A fast T2 mapping reconstruction method is investigated and compared with a previous modeling approach to reduce computation time and allow inline T2 maps on the MRI console. Brain PD-T2 images from five multiple sclerosis patients were used to compare T2 map reconstruction times between the new subtraction method and the Euclidean norm minimization technique. Bloch equation simulations were used to create the lookup table for decay curve matching in both cases. Agreement of the two techniques used Bland-Altman analysis for investigating individual subsets of data and all image points in the five volumes (meta-analysis). The subtraction method resulted in an average reduction of computation time for single slices from 134 s (minimization method) to 0.44 s. Comparing T2 values between the subtraction and minimization methods resulted in a confidence interval ranging from -0.06 to 0.06 ms (95% of values were within ± 0.06 ms between the techniques). Using identical reconstruction code based on the subtraction method, inline T2 maps were produced from PD-T2 images directly on the scanner console. The excellent agreement between the two methods permits the subtraction technique to be interchanged with the previous method, reducing computation time and allowing inline T2 map reconstruction based on Bloch simulations directly on the scanner.

Quantification of lung water density with UTE Yarnball MRI.

PURPOSE: An efficient Yarnball ultrashort-TE k-space trajectory, in combination with an optimized pulse sequence design and automated image-processing approach, is proposed for fast and quantitative imaging of water density in the lung parenchyma. METHODS: Three-dimensional Yarnball k-space trajectories (TE = 0.07 ms) were designed at 3 T for breath-hold and free-breathing navigator acquisitions targeting the lung parenchyma (full torso spatial coverage) with minimal T1 and T2∗ weighting. A composite of all solid tissues surrounding the lungs (muscle, liver, heart, blood pool) was used for user-independent lung water density signal referencing and B1 -inhomogeneity correction needed for the calculation of relative lung water density images. Sponge phantom experiments were used to validate absolute water density quantification, and relative lung water density was evaluated in 10 healthy volunteers. RESULTS: Phantom experiments showed excellent agreement between sponge wet weight and imaging-derived water density. Breath-hold (13 seconds) and free-breathing (~2 minutes) Yarnball acquisitions in volunteers (2.5-mm isotropic resolution) had negligible artifacts and good lung parenchyma SNR (>10). Whole-lung average relative lung water density values with fully automated analysis were 28.2 ± 1.9% and 28.6 ± 1.8% for breath-hold and free-breathing acquisitions, respectively, with good test-retest reproducibility (intraclass correlation coefficient = 0.86 and 0.95, respectively). CONCLUSIONS: Quantitative lung water density imaging with an optimized Yarnball k-space acquisition approach is possible in a breath-hold or short free-breathing study with automated signal referencing and segmentation.

Three-dimensional Yarnball k-space acquisition for accelerated MRI.

PURPOSE: To introduce an efficient sampling technique named Yarnball, which may serve as a direct alternative to 3D Cones. METHODS: Yarnball evolves through 3D k-space with increasing loop size, and the differential equations defining this flexible trajectory are presented in detail. The sampling efficiencies of Yarnball and 3D Cones were compared through point spread function analysis and simulated imaging (which highlights undersampling in the absence of other scanning effects). The feasibility of Yarnball implementation was demonstrated for fully sampled T1 -weighted images of the human head at 3 T. RESULTS: The mostly large 3D loops of the Yarnball trajectory facilitate rapid sampling under peripheral nerve stimulation constraint, an advantage that increases with readout duration (TRO ). Point spread function analysis yielded 89% (TRO = 2 ms) and 77% (TRO = 10 ms) of Yarnball voxels with magnitude less than 0.01% of the point spread function peak. For 3D Cones, these values were only 52% and 29%. The 3D-Cones technique required 1.4 times (TRO = 2 ms) and 1.8 times (TRO = 10 ms) more trajectories than Yarnball to produce simulated images of a sphere free from undersampling artifact. For a prolate spheroidal (head-like) object, 1.75 times and 2.6 times more trajectories were required for 3D Cones. Yarnball produced 0.72 mm (1/2kmax ) isotropic T1 -weighted human brain images free from undersampling artifact in only 98 seconds at 3 T. CONCLUSION: Yarnball demonstrated greater k-space sampling efficiency than directly comparable 3D Cones, and may have value wherever 3D Cones has been considered. Yarnball may also have value in the context of rapid T1 -weighted brain imaging.

Venous contribution to sodium MRI in the human brain.

PURPOSE: Sodium MRI shows great promise as a marker for cerebral metabolic dysfunction in stroke, brain tumor, and neurodegenerative pathologies. However, cerebral blood vessels, whose volume and function are perturbed in these pathologies, have elevated sodium concentrations relative to surrounding tissue. This study aims to assess whether this fluid compartment could bias measurements of tissue sodium using MRI. METHODS: Density-weighted and B1 corrected sodium MRI of the brain was acquired in 9 healthy participants at 4.7T. Veins were identified using co-registered 1 H T2∗ -weighted images and venous partial volume estimates were calculated by down-sampling the finer spatial resolution venous maps from the T2∗ -weighted images to the coarser spatial resolution of the sodium data. Linear regressions of venous partial volume estimates and sodium signal were performed for regions of interest including just gray matter, just white matter, and all brain tissue. RESULTS: Linear regression demonstrated a significant venous sodium contribution above the underlying tissue signal. The apparent venous sodium concentrations derived from regression were 65.8 ± 4.5 mM (all brain tissue), 71.0 ± 7.4 mM (gray matter), and 55.0 ± 4.7 mM (white matter). CONCLUSION: Although the partial vein linear regression did not yield the expected sodium concentration in blood (~87 mM), likely the result of point spread function smearing, this regression highlights that blood compartments may bias brain tissue sodium signals across neurological conditions where blood volumes may differ.

23Na MRI of human skeletal muscle using long inversion recovery pulses.

23Na inversion recovery (IR) imaging allows for a weighting toward intracellular sodium in the human calf muscle and thus enables an improved analysis of pathophysiological changes of the muscular ion homeostasis. However, sodium signal-to-noise ratio (SNR) is low, especially when using IR sequences. 23Na has a nuclear spin of 3/2 and therefore experiences a strong electrical quadrupolar interaction. This results in very short relaxation times as well as in possible residual quadrupolar splitting. Consequently, relaxation effects during a radiofrequency pulse can no longer be neglected and even allow for increasing SNR as has previously been shown for human brain and knee. The aim of this work was to increase the SNR in 23Na IR imaging of the human calf muscle by using long inversion pulses instead of the usually applied short pulses. First, the influence of the inversion pulse length (1 to 20 ms) on the SNR as well as on image contrast was simulated for different model environments and verified by phantom measurements. Depending on the model environment (agarose 4% and 8%, xanthan 2% and 3%), SNR values increased by a factor of 1.15 up to 1.35, while NaCl solution was successfully suppressed. Thus, image contrast between the non-suppressed model compartments changes with IR pulse length. Finally, in vivo measurements of the human calf muscle of ten healthy volunteers were conducted at 3 Tesla. On average, a 1.4-fold increase in SNR could be achieved by increasing the inversion pulse length from 1 ms to 20 ms, leaving all other parameters - including the scan time - constant. This enables 23Na IR MRI with improved spatial resolution or reduced acquisition time.

Calculating potential error in sodium MRI with respect to the analysis of small objects.

PURPOSE: To facilitate correct interpretation of sodium MRI measurements, calculation of error with respect to rapid signal decay is introduced and combined with that of spatially correlated noise to assess volume-of-interest (VOI) 23 Na signal measurement inaccuracies, particularly for small objects. METHODS: Noise and signal decay-related error calculations were verified using twisted projection imaging and a specially designed phantom with different sized spheres of constant elevated sodium concentration. As a demonstration, lesion signal measurement variation (5 multiple sclerosis participants) was compared with that predicted from calculation. RESULTS: Both theory and phantom experiment showed that VOI signal measurement in a large 10-mL, 314-voxel sphere was 20% less than expected on account of point-spread-function smearing when the VOI was drawn to include the full sphere. Volume-of-interest contraction reduced this error but increased noise-related error. Errors were even greater for smaller spheres (40-60% less than expected for a 0.35-mL, 11-voxel sphere). Image-intensity VOI measurements varied and increased with multiple sclerosis lesion size in a manner similar to that predicted from theory. Correlation suggests large underestimation of 23 Na signal in small lesions. CONCLUSIONS: Acquisition-specific measurement error calculation aids 23 Na MRI data analysis and highlights the limitations of current low-resolution methodologies. Magn Reson Med 79:2968-2977, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Residual quadrupole interaction in brain and its effect on quantitative sodium imaging.

Sodium MRI is particularly interesting given the key role that sodium ions play in cellular metabolism. To measure concentration, images must be free from contrast unrelated to sodium density. However, spin 3/2 NMR is complicated by more than rapid biexponential signal decay. Residual quadrupole interactions (described by frequency ωQ) can reduce Mxy development during RF excitation. Three experiments, each performed on the same four healthy volunteers, demonstrate that residual quadrupole interactions are of concern in quantitative sodium imaging of the brain. The first experiment shows a reliable increase in the rate of excitation 'flipping' (1%-6%), particularly in white matter with tracts running superior-inferior (i.e. parallel to B0). Increased flip-rates imply an associated signal loss and are to be expected when ωQ ~ ω1. The second experiment shows that a prescribed flip-angle decrease from 90° to 20°, with concomitant decrease in TE from 0.25 ms to 0.10 ms and no T1 weighting, results in a 14%-26% saline calibration phantom normalized signal (SN) increase in the white matter regions. The third experiment shows that this (SN) increase is primarily due to a residual quadrupole effect, with a small contribution from T2 weighting. There is an observed deviation from the spin 3/2 biexponential curve, also suggesting ωQ dephasing. Using simulation to explain the results of all three experiments, a model of brain tissue is hypothesized. It includes one pool (50%) with ωQ = 0, and another (50%) in which ωQ has a Gaussian distribution with a standard deviation of 625 Hz. Given the result of the second experiment, it is suggested that the use of reduced flip-angles with large ω1 will provide more accurate measures of sodium concentration than 'standard' methods using 90° pulses. Alternatively, further study of sodium ωQmay provide a means to explore tissue structure and organization.

In vivo double quantum filtered sodium magnetic resonance imaging of human brain.

PURPOSE: Sodium signal from ordered environments can be selectively detected using a double-quantum magic angle (DQ-MA) sequence. This study presents the first DQ-MA sodium images of the human brain and evaluates the effect of preparation time (τ) on the signal. THEORY AND METHODS: Three phantoms of saline, agar gel, and xanthan gum were used to test the correct functioning of the DQ-MA sequence. Five healthy volunteers were imaged using DQ-MA with varying τ to determine the optimal preparation time. DQ-MA images were acquired with 1 or 2 averages and nominal resolution of 15 mm isotropic in 3.5 or 7 min, respectively. In addition, higher nominal resolution (8.4 mm isotropic) DQ-MA images were acquired from another subject in 48 min. Post hoc simulations were performed to explain the effect of τ on imaging results. RESULTS: The DQ-MA sequence generates signal from only the xanthan gum phantom, correctly suppressing signal from environments in which the time-averaged quadrupolar interaction is expected to be zero (saline, agar). This sequence generates signal throughout the brain with maximum detection when τ=3 ms. CONCLUSION: The existence of DQ-MA signal in the human brain indicates the presence of sodium nuclei in ordered environments and provides a novel contrast mechanism.

Exploring and enhancing relaxation-based sodium MRI contrast.

OBJECT: Sodium MRI is typically concerned with measuring tissue sodium concentration. This requires the minimization of relaxation weighting. However, (23)Na relaxation may itself be interesting to explore, given an underlying mechanism (i.e. the electric-quadrupole-moment-electric-field-gradient interaction) that differs from (1)H. A new sodium sequence was developed to enhance (23)Na relaxation contrast without decreasing signal-to-noise ratio. MATERIALS AND METHODS: The new sequence, labeled Projection Acquisition in the steady-state with Coherent MAgNetization (PACMAN), uses gradient refocusing of transverse magnetization following readout, a short repetition time, and a long radiofrequency excitation pulse. It was developed using simulation, verified in model environments (saline and agar), and evaluated in the brain of three healthy adult volunteers. RESULTS: Projection Acquisition in the steady-state with Coherent MAgNetization generates a large positive contrast-to-noise ratio (CNR) between saline and agar, matching simulation-based design. In addition to enhanced CNR between cerebral spinal fluid and brain tissue in vivo, PACMAN develops substantial contrast between gray and white matter. Further simulation shows that PACMAN has a ln(T 2f/T 1) contrast dependence (where T 2f is the fast component of (23)Na T 2), as well as residual quadrupole interaction dependence. CONCLUSION: The relaxation dependence of PACMAN sodium MRI may provide contrast related to macromolecular tissue structure.

Evaluation of B0-inhomogeneity correction for triple-quantum-filtered sodium MRI of the human brain at 4.7 T.

Off-resonance can result in signal loss on triple-quantum-filtered (TQF) sodium images. Three correction methods have been proposed to mitigate this problem, but their effectiveness and necessity has not yet been evaluated for human brain. This evaluation is warranted given the doubling or quadrupling of scan length without the expected signal-to-noise ratio (SNR) benefit. First, simulations and agar gel experiments showed that the off-resonance effects on signal loss were asymmetric about on-resonance. Second, the two scan length doubling correction methods were tested for two sets of TQF acquisition parameters in 10 healthy volunteers at 4.7 Tesla. Using only manual shimming on the sodium signal and a 3-pulse TQF sequence with an optimal preparation time value of 6 ms, the majority of brain tissue voxels (87-94% depending on sequence parameters) experienced B0 inhomogeneity amounting to less than 10% signal losses. Relative signal intensities of 0.96 ± 0.04 and 0.98 ± 0.02 were measured in these voxels relative to on-resonant voxels for SNR-optimized and standard TQF parameters. The remaining brain voxels in regions with known susceptibility problems suffered more substantial signal losses, which were partially recovered with the correction methods. At field strengths below 4.7T, at similar ranges of offset frequencies at higher fields and in typical volunteers, B0 correction appears unnecessary for TQF analysis in most of the brain. In many cases where regions with known susceptibility issues are not of concern, a doubling of scan time may be better spent to either improve SNR or spatial resolution in the TQF sodium images.

Triple-quantum-filtered sodium imaging of the human brain at 4.7 T.

The limited signal-to-noise ratio of triple-quantum-filtered MRI of sodium is a major hurdle for its application clinically. Although it has been shown that short 90° radiofrequency pulses in combination with sufficiently long repetition time for full T(1) recovery (labelled "standard" parameters) produce the maximum signal through the triple-quantum-filter, and in this work, simulation and images of agar phantoms and human brain demonstrate that the use of longer radiofrequency pulses and reduced repetition time (optimized parameters to accommodate more averages for a constant specific absorption rate, reducing noise variance for a given scan length) results in signal-to-noise ratio improvement (22 ± 5% in brain tissue of five healthy volunteers--images created in 11 min with nominal resolution of 8.4 mm isotropic). However, residual intensity was observed in the ventricular space on triple-quantum-filtered images acquired with either optimized or standard parameters, contrary to the expectation of complete single-quantum signal suppression. Further simulation and experimentation suggest that this is likely due to the combination of triple-quantum-passed signal from surrounding brain tissue being spatially smeared into the ventricular space and single-quantum-signal breakthrough from sodium nuclei in the fluid space. It is shown that the latter can be eliminated with judicious first flip angle selection.

Signal-to-noise optimization for sodium MRI of the human knee at 4.7 Tesla using steady state.

Sodium magnetic resonance imaging of knee cartilage is a possible diagnostic method for osteoarthritis, but low signal-to-noise ratio yields low spatial resolution images and long scan times. For a given scan time, a steady-state approach with reduced repetition time and increased averaging may improve signal-to-noise ratio and hence attainable resolution. However, repetition time reduction results in increased power deposition, which must be offset with increased radiofrequency pulse length and/or reduced flip angle to maintain an acceptable specific absorption rate. Simulations varying flip angle, repetition time, and radiofrequency pulse length were performed for constant power deposition corresponding to ∼6 W/kg over the human knee at 4.7 T. For 10% agar, simulation closely matched experiment. For healthy human knee cartilage, a 37% increase in signal-to-noise ratio was predicted for steady-state over "fully relaxed" parameters while a 29% ± 4% increase was determined experimentally (n=10). Partial volume of cartilage with synovial fluid, inaccurate relaxation parameters used in simulation, and/or quadrupolar splitting may be responsible for this disagreement. Excellent quality sodium images of the human knee were produced in 9 mins at 4.7 T using the signal-to-noise ratio enhancing steady-state technique.

Assessment of averaging spatially correlated noise for 3-D radial imaging.

Any measurement of signal intensity obtained from an image will be corrupted by noise. If the measurement is from one voxel, an error bound associated with noise can be assigned if the standard deviation of noise in the image is known. If voxels are averaged together within a region of interest (ROI) and the image noise is uncorrelated, the error bound associated with noise will be reduced in proportion to the square root of the number of voxels in the ROI. However, when 3-D-radial images are created the image noise will be spatially correlated. In this paper, an equation is derived and verified with simulated noise for the computation of noise averaging when image noise is correlated, facilitating the assessment of noise characteristics for different 3-D-radial imaging methodologies. It is already known that if the radial evolution of projections are altered such that constant sampling density is produced in k-space, the signal-to-noise ratio (SNR) inefficiency of standard radial imaging (SR) can effectively be eliminated (assuming a uniform transfer function is desired). However, it is shown in this paper that the low-frequency noise power reduction of SR will produce beneficial (anti-) correlation of noise and enhanced noise averaging characteristics. If an ROI contains only one voxel a radial evolution altered uniform k-space sampling technique such as twisted projection imaging (TPI) will produce an error bound ~35% less with respect to noise than SR, however, for an ROI containing 16 voxels the SR methodology will facilitate an error bound ~20% less than TPI. If a filtering transfer function is desired, it is shown that designing sampling density to create the filter shape has both SNR and noise correlation advantages over sampling k-space uniformly. In this context SR is also beneficial. Two sets of 48 images produced from a saline phantom with sodium MRI at 4.7T are used to experimentally measure noise averaging characteristics of radial imaging and good agreement with theory is obtained.

Relationship between sodium intensity and perfusion deficits in acute ischemic stroke.

PURPOSE: To assess the relationship between sodium signal intensity changes and oligemia, measured with perfusion-weighted imaging (PWI), in ischemic stroke patients. MATERIALS AND METHODS: Nine ischemic stroke patients (55 ± 13 years), four with follow-up scans, underwent sodium and proton imaging 4-32 hours after symptom onset. Relative sodium intensity was calculated as the ratio of signal intensities in core (identified as hypertintense lesions on diffusion-weighted imaging [DWI]) or putative penumbra (PWI-DWI mismatch) to contralateral homologous regions. RESULTS: Sodium intensity increases in the core were not correlated with the severity of hypoperfusion, measured with either cerebral blood flow (rho = 0.157; P = 0.61) or cerebral blood volume (rho = -0.234; P = 0.44). In contrast, relative sodium intensity was not elevated (4-7 hours 0.96 ± 0.07; 17-32 hours 1.00 ± 0.07) in PWI-DWI mismatch regions. CONCLUSION: Sodium signal intensity cannot be predicted by the degree of hypoperfusion acutely. Sodium intensity also remains unchanged in PWI-DWI mismatch tissue, indicating preservation of ionic homeostasis. Sodium magnetic resonance imaging (MRI), in conjunction with PWI and DWI, may permit identification of patients with viable tissue, despite an unknown symptom onset time.

Sodium imaging intensity increases with time after human ischemic stroke.

OBJECTIVE: Establishing time of onset is important in acute stroke management. Current imaging modalities do not allow determination of stroke onset time. Although correlations between sodium magnetic resonance imaging signal intensity within ischemic lesions and time of onset have been shown in animal models, the relation to onset time has not been established in human stroke. Utilizing high-quality sodium images, we tested the hypothesis that sodium signal intensity increases with time from symptom onset in human ischemic stroke. METHODS: Twenty-one stroke patients (63 +/- 15 years old) were scanned 4 to 104 hours after symptom onset. Follow-up images were obtained in 10 patients at 23 to 161 hours after onset, yielding a total of 32 time points. A standard stroke imaging protocol was acquired at 1.5 Tesla, followed by sodium magnetic resonance imaging at 4.7 Tesla. Relative sodium signal intensity within each lesion was measured with respect to the contralateral side. RESULTS: The sodium image quality was sufficient to visualize each acute lesion (lesion volume range, 1.7-217cm(3)). Relative sodium signal intensity increased nonlinearly over time after stroke onset. Sodium images acquired within 7 hours (n = 5) demonstrated a relative increase in lesion intensity of 10% or less, whereas the majority beyond 9 hours demonstrated increases of 23% or more, with an eventual leveling at 69 +/- 18%. INTERPRETATION: Increases of sodium signal intensity within the ischemic lesion are related to time after stroke onset. Thus, noninvasive imaging of sodium may be a novel metabolic biomarker related to stroke progression. Ann Neurol 2009;66:55-62.

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study.

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).