MR Susceptibility Separation for Quantifying Lesion Paramagnetic and Diamagnetic Evolution in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) lesion evolution may involve changes in diamagnetic myelin and paramagnetic iron. Conventional quantitative susceptibility mapping (QSM) can provide net susceptibility distribution, but not the discrete paramagnetic and diamagnetic components. PURPOSE: To apply susceptibility separation (χ separation) to follow lesion evolution in MS with comparison to R2 */R2 ' /QSM. STUDY TYPE: Longitudinal, prospective. SUBJECTS: Twenty relapsing-remitting MS subjects (mean age: 42.5 ± 9.4 years, 13 females; mean years of symptoms: 4.3 ± 1.4 years). FIELD STRENGTH/SEQUENCE: Three-dimensional multiple echo gradient echo (QSM and R2 * mapping), two-dimensional dual echo fast spin echo (R2 mapping), T2 -weighted fluid attenuated inversion recovery, and T1-weighted magnetization prepared gradient echo sequences at 3 T. ASSESSMENT: Data were analyzed from two scans separated by a mean interval of 14.4 ± 2.0 months. White matter lesions on fluid-attenuated inversion recovery were defined by an automatic pipeline, then manually refined (by ZZ/AHW, 3/25 years' experience in MRI), and verified by a radiologist (MN, 25 years' experience in MS). Susceptibility separation yielded the paramagnetic and diamagnetic susceptibility content of each voxel. Lesions were classified into four groups based on the variation of QSM/R2 * or separated into positive/negative components from χ separation. STATISTICAL TESTS: Two-sample paired t tests for assessment of longitudinal differences. Spearman correlation coefficients to assess associations between χ separation and R2 */R2 ' /QSM. Significant level: P < 0.005. RESULTS: A total of 183 lesions were quantified. Categorizing lesions into groups based on χ separation demonstrated significant annual changes in QSM//R2 */R2 ' . When lesions were grouped based on changes in QSM and R2 *, both changing in unison yielded a significant dominant paramagnetic variation and both opposing yielded a dominant diamagnetic variation. Significant Spearman correlation coefficients were found between susceptibility-sensitive MRI indices and χ separation. DATA CONCLUSION: Susceptibility separation changes in MS lesions may distinguish and quantify paramagnetic and diamagnetic evolution, potentially providing additional insight compared to R2 * and QSM alone. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Signal-to-noise ratio penalties from a loss of stimulated echoes when using slab-selective excitation in three-dimensional fast spin echo imaging with long echo trains.

Three-dimensional fast spin echo imaging with long echo trains combines high resolution with reasonable acquisition times and reduced specific absorption rate due to low refocusing flip angles. Typically, an entire volume is encoded (nonselective excitation) or localization can be performed with slab select excitation, which uses a long 90° pulse for precise localization, followed by a preliminary nonselective 180° pulse bounded by spoiler gradients to destroy signal outside of the volume of interest. Subsequent flip angles in the train are nonselective and identical between the two methods. The inclusion of the initial selective pulse and spoiler gradients results in a signal-to-noise ratio (SNR) penalty for slab selection, beyond the slice-averaging dependence, arising from a loss of stimulated echoes. SNR differences are explored using Bloch equation simulations of a T2-weighted 96 echo train sequence with varying parameters including T2, T1, and B1+ and compared with phantom and in vivo brain, neck, and knee experiments. In vivo SNR measurements in the three regions showed a maximum decrease of selective SNR by 29% (gastrocnemius muscle), 25% (pons), and 22% (globus pallidus), despite similar experimental parameters to nonselective experiments. Decreased SNR was compounded by B1+ variation affecting prescribed flip angles with further smaller reductions with T2 and T1 times. In conclusion, the elimination of coherences via the preliminary nominal 180° pulse and spoiler gradients in addition to the extended echo timing from the long excitation pulse resulted in a reduction in SNR compared with the nonselective case. Consideration of the required SNR and chosen anatomy as well as sequence restrictions should be weighed before choosing slab-selective excitation.

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.

T2 quantification in brain using 3D fast spin-echo imaging with long echo trains.

PURPOSE: Three-dimensional fast spin-echo (FSE) sequences commonly use very long echo trains (>64 echoes) and severely reduced refocusing angles. They are increasingly used in brain exams due to high, isotropic resolution and reasonable scan time when using long trains and short interecho spacing. In this study, T2 quantification in 3D FSE is investigated to achieve increased resolution when comparing with established 2D (proton-density dual-echo and multi-echo spin-echo) methods. METHODS: The FSE sequence design was explored to use long echo trains while minimizing T2 fitting error and maintaining typical proton density and T2 -weighted contrasts. Constant and variable flip angle trains were investigated using extended phase graph and Bloch equation simulations. Optimized parameters were analyzed in phantom experiments and validated in vivo in comparison to 2D methods for eight regions of interest in brain, including deep gray-matter structures and white-matter tracts. RESULTS: Phantom and healthy in vivo brain T2 measurements showed that optimized variable echo-train 3D FSE performs similarly to previous 2D methods, while achieving three-fold-higher slice resolution, evident visually in the 3D T2 maps. Optimization resulted in better T2 fitting and compared well with standard multi-echo spin echo (within the 8-ms confidence limits defined based on Bland-Altman analysis). CONCLUSION: T2 mapping using 3D FSE with long echo trains and variable refocusing angles provides T2 accuracy in agreement with 2D methods with additional high-resolution benefits, allowing isotropic views while avoiding incidental magnetization transfer effects. Consequently, optimized 3D sequences should be considered when choosing T2 mapping methods for high anatomic detail.

A method to evaluate body length of live aquatic vertebrates using digital images.

Traditional methods to measure body lengths of aquatic vertebrates rely on anesthetics, and extended handling times. These procedures can increase stress, potentially affecting the animal's welfare after its release. We developed a simple procedure using digital images to estimate body lengths of coastal cutthroat trout (Oncorhynchus clarkii clarkii) and larval coastal giant salamander (Dicamptodon tenebrosus). Images were postprocessed using ImageJ2. We measured more than 900 individuals of these two species from 200 pool habitats along 9.6 river kilometers. The percent error (mean ± SE) of our approach compared to the use of a traditional graded measuring board was relatively small for all length metrics of the two species. Total length of trout was -2.2% ± 1.0. Snout-vent length and total length of larval salamanders was 3.5% ± 3.3 and -0.6% ± 1.7, respectively. We cross-validated our results by two independent observers that followed our protocol to measure the same animals and found no significant differences (p > .7) in body size distributions for all length metrics of the two species. Our procedure provides reliable information of body size reducing stress and handling time in the field. The method is transferable across taxa and the inclusion of multiple animals per image increases sampling efficiency with stored images that can be reviewed multiple times. This practical tool can improve data collection of animal size over large sampling efforts and broad spatiotemporal contexts.

Influence of eddy current, Maxwell and gradient field corrections on 3D flow visualization of 3D CINE PC-MRI data.

PURPOSE: The measurement of velocities based on phase contrast MRI can be subject to different phase offset errors which can affect the accuracy of velocity data. The purpose of this study was to determine the impact of these inaccuracies and to evaluate different correction strategies on three-dimensional visualization. METHODS: Phase contrast MRI was performed on a 3 T system (Siemens Trio) for in vitro (curved/straight tube models; venc: 0.3 m/s) and in vivo (aorta/intracranial vasculature; venc: 1.5/0.4 m/s) data. For comparison of the impact of different magnetic field gradient designs, in vitro data was additionally acquired on a wide bore 1.5 T system (Siemens Espree). Different correction methods were applied to correct for eddy currents, Maxwell terms, and gradient field inhomogeneities. RESULTS: The application of phase offset correction methods lead to an improvement of three-dimensional particle trace visualization and count. The most pronounced differences were found for in vivo/in vitro data (68%/82% more particle traces) acquired with a low venc (0.3 m/s/0.4 m/s, respectively). In vivo data acquired with high venc (1.5 m/s) showed noticeable but only minor improvement. CONCLUSION: This study suggests that the correction of phase offset errors can be important for a more reliable visualization of particle traces but is strongly dependent on the velocity sensitivity, object geometry, and gradient coil design.

Pliocene warmth, polar amplification, and stepped Pleistocene cooling recorded in NE Arctic Russia.

Understanding the evolution of Arctic polar climate from the protracted warmth of the middle Pliocene into the earliest glacial cycles in the Northern Hemisphere has been hindered by the lack of continuous, highly resolved Arctic time series. Evidence from Lake El'gygytgyn, in northeast (NE) Arctic Russia, shows that 3.6 to 3.4 million years ago, summer temperatures were ~8°C warmer than today, when the partial pressure of CO2 was ~400 parts per million. Multiproxy evidence suggests extreme warmth and polar amplification during the middle Pliocene, sudden stepped cooling events during the Pliocene-Pleistocene transition, and warmer than present Arctic summers until ~2.2 million years ago, after the onset of Northern Hemispheric glaciation. Our data are consistent with sea-level records and other proxies indicating that Arctic cooling was insufficient to support large-scale ice sheets until the early Pleistocene.

Accelerated point spread function mapping using signal modeling for accurate echo-planar imaging geometric distortion correction.

Echo-planar imaging is a fast and commonly used magnetic resonance imaging technique with applications in diffusion weighted and functional MRI. Fast data acquisition in echo-planar imaging is accomplished by the extended readout, which also introduces sensitivity to off-resonance effects such as amplitude of static (polarizing) field inhomogeneities and eddy-currents. These off-resonance effects produce geometric distortions in the corresponding echo-planar images. To correct for these distortions, an acceleration of point spread function (PSF) acquisition using a special sampling pattern is presented in this work. The proposed technique allows for reliable and fully automated distortion correction of echo-planar images at a field strength of 3 T. Additionally, a new approach to visualize and determine the distortions in a hybrid (x, y, kPSF) three-dimensional space is proposed. The accuracy and robustness of the proposed technique is demonstrated in phantom and in vivo experiments. The accuracy of the presented method here is compared to previous techniques for echo-planar imaging distortion correction such as PLACE.

Three-dimensional arbitrary voxel shapes in spectroscopy with submillisecond TEs.

A novel spectroscopic method for submillisecond TEs and three-dimensional arbitrarily shaped voxels was developed and applied to phantom and in vivo measurements, with additional parallel excitation (PEX) implementation. A segmented spherical shell excitation trajectory was used in combination with appropriate radiofrequency weights for target selection in three dimensions. Measurements in a two-compartment phantom realized a TE of 955 µs, excellent spectral quality and comparable signal-to-noise ratios between accelerated (R = 2) and nonaccelerated modes. The two-compartment model allowed a comparison of the spectral suppression qualities of the method and, although outer volume signals were suppressed by factors of 1434 and 2246 compared with the theoretical unsuppressed case for the clinical and PEX modes, respectively, incomplete suppression of the outer volume (935 cm(3) compared with a target volume of 5.86 cm(3) ) resulted in a spectral contamination of 10.2% and 6.5% compared with the total signal. The method was also demonstrated in vivo in human brain on a clinical system at TE = 935 µs with good signal-to-noise ratio and spatial and spectral selection, and included LCModel relative quantification analysis. Eight metabolites showed significant fitting accuracy, including aspartate, N-acetylaspartylglutamate, glutathione and glutamate.

Selective excitation of two-dimensional arbitrarily shaped voxels with parallel excitation in spectroscopy.

Parallel excitation is being studied intensively for applications in MR imaging and in particular for selecting arbitrary shapes as regions of interest. In this work, parallel excitation was applied to arbitrarily shaped voxel selection in spectroscopy and investigated for different excitation k-space trajectories (radial, rectilinear, and spiral) and acceleration factors. Each trajectory was segmented into multiple excitations to increase the overall bandwidth during target selection. Acceleration by parallel excitation was used to decrease the number of segments. Evaluation of spatial and spectral localization of the target of interest was performed in simulation and phantom experiments, and was compared with the point resolved spectroscopy (PRESS) experiment with standard voxels. The selective excitation experiments demonstrated excellent spatial localization and a broad frequency response, although PRESS was superior in direct comparisons with respect to signal-to-noise ratio (SNR) and outer volume suppression. Extensive SNR variation was observed dependent on trajectory (8%-90%), with the preferred radial case producing approximately 40%-60% SNR of the PRESS case. Accelerated trajectories at R = 4 provided comparable artifact signal and target excitation accuracy compared with their nonaccelerated counterparts; however, further acceleration (R = 8) resulted in increased artifact (33% increase at R = 8).

Difference spectroscopy using PRESS asymmetry: application to glutamate, glutamine, and myo-inositol.

A simple, clinically viable technique utilizing PRESS and strong coupling properties is presented for discrimination of coupled brain metabolites. The method relies on signal variation due to alteration of inter-echo timings (PRESS asymmetry) while maintaining a constant total echo time. Spin response of singlets and weakly coupled spins is unchanged due to PRESS asymmetry, allowing difference spectroscopy to detect unobstructed strongly coupled resonances. No changes to the standard PRESS sequence are required except variation of inter-echo timings. The procedure is illustrated for the separate detection of glutamate from glutamine and the detection of myo-inositol in simulation, phantom, and in vivo experiments at 4.7 T. The subtraction yields calculated from the simulation were 53% for glutamate and 75% for myo-inositol, and a resultant contribution of 96% glutamate to the total glutamate/glutamine multiplet in the 2.04-2.14 ppm range. To extend the treatment to other field strengths and metabolites, an analytical approximation based on a strongly coupled AB system was used to model individual spin groups. Subtraction spectroscopy yields for different combinations of coupling parameters were calculated for the detection of various strongly coupled metabolites at common clinical field strengths. The approximation also predicts adequate glutamate/glutamine discrimination at 3.0 T using the difference spectroscopy method.

Field strength dependence of PRESS timings for simultaneous detection of glutamate and glutamine from 1.5 to 7T.

An optimization of the PRESS sequence for magnetic resonance spectroscopy is presented to simultaneously detect the important brain metabolites of glutamate (Glu) and glutamine (Gln) at field strengths of 1.5, 3, 4.7, and 7T. Standard, clinical examinations typically use short echo times which in general are not ideal for the separation of Glu and Gln. The optimization procedure is based on numerical product operator simulations to produce yield and overlap measurements for all possible practical choices of PRESS inter-echo timings. The simulations illustrate the substantial modulations in Glu and Gln with field strength. At all field strengths, the optimized timings demonstrate a significant reduction in overlap compared to short echo PRESS, while maintaining a high metabolite signal, with Glu and Gln yields >90% when excluding T2 relaxation losses. Minimal overlap was attained at 7T (0.3% Gln contamination in the Glu signal), and 4.7T (1.2%). The optimized timings were applied in vivo on healthy volunteers at field strengths of 1.5 and 4.7T.

Spectral editing of weakly coupled spins using variable flip angles in PRESS constant echo time difference spectroscopy: application to GABA.

A general in vivo magnetic resonance spectroscopy editing technique is presented to detect weakly coupled spin systems through subtraction, while preserving singlets through addition, and is applied to the specific brain metabolite gamma-aminobutyric acid (GABA) at 4.7 T. The new method uses double spin echo localization (PRESS) and is based on a constant echo time difference spectroscopy approach employing subtraction of two asymmetric echo timings, which is normally only applicable to strongly coupled spin systems. By utilizing flip angle reduction of one of the two refocusing pulses in the PRESS sequence, we demonstrate that this difference method may be extended to weakly coupled systems, thereby providing a very simple yet effective editing process. The difference method is first illustrated analytically using a simple two spin weakly coupled spin system. The technique was then demonstrated for the 3.01 ppm resonance of GABA, which is obscured by the strong singlet peak of creatine in vivo. Full numerical simulations, as well as phantom and in vivo experiments were performed. The difference method used two asymmetric PRESS timings with a constant total echo time of 131 ms and a reduced 120 degrees final pulse, providing 25% GABA yield upon subtraction compared to two short echo standard PRESS experiments. Phantom and in vivo results from human brain demonstrate efficacy of this method in agreement with numerical simulations.

Strongly coupled versus uncoupled spin response to radio frequency interference effects: application to glutamate and glutamine in spectroscopic imaging.

It is well known that comparable radio frequency (RF) wavelengths and human head dimensions at high fields can lead to an inhomogeneous RF field when using standard RF transmission. However, the impact of RF inhomogeneity on potential differences in quantification between coupled and uncoupled spins at longer echo times has not been investigated thoroughly. The consequence of this RF interference on metabolite quantification in spectroscopic imaging at 4.7 T was investigated for the strongly coupled spin systems of glutamate and glutamine at an echo time of 120 ms, and compared with the singlet response of choline. These effects were studied using a single-voxel PRESS sequence (alpha-2alpha-2alpha) with varying flip angle (alpha) from 90 degrees to 65 degrees in simulation, phantom, and in vivo experiments. Phantom metabolite yield decreased to 57% for choline and 27% for glutamate/glutamine in agreement with the simulations. Even a minor reduction from alpha = 85 degrees to 80 degrees produced a large difference between coupled and uncoupled yields, with a reduction of 7% for choline and 17% for glutamate/glutamine. Anecdotal in vivo spectroscopic imaging studies show similar trends, with large differences between choline and glutamate/glutamine yield over a small, 2.2 cm, region. These results demonstrate severe effects on metabolite yield due to RF variation between strongly coupled and uncoupled spin systems at long echo time, which complicates metabolite quantification.