Spin-locking Sequence Research Articles

Spin-lock based fast whole-brain 3D macromolecular proton fraction mapping of relapsing–remitting multiple sclerosis

A sensitive and efficient imaging technique is required to assess the subtle abnormalities occurring in the normal-appearing white matter (NAWM) and normal-appearing grey matter (NAGM) in patients with relapsing–remitting multiple sclerosis (RRMS). In this study, a fast 3D macromolecular proton fraction (MPF) quantification based on spin-lock (fast MPF-SL) sequence was proposed for brain MPF mapping. Thirty-four participants, including 17 healthy controls and 17 RRMS patients were prospectively recruited. We conducted group comparison and correlation between conventional MPF-SL, fast MPF-SL, and DWI, and compared differences in quantified parameters within MS lesions and the regional NAWM, NAGM, and normal-appearing deep grey matter (NADGN). MPF of MS lesions was significantly reduced (7.17% ± 1.15%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} < 0.01) compared to all corresponding normal-appearing regions. MS patients also showed significantly reduced mean MPF values compared with controls in NAGM (4.87% ± 0.38% vs 5.21% ± 0.32%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.01), NAWM (9.49% ± 0.69% vs 10.32% ± 0.59%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} < 0.01) and NADGM (thalamus 5.59% ± 0.67% vs 6.00% ± 0.41%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.04; caudate 5.10% ± 0.55% vs 5.53% ± 0.58%, P\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$P$$\\end{document} = 0.03). MPF and ADC showed abnormalities in otherwise normal appearing close to lesion areas (P < 0.01). In conclusion, time-efficient MPF mapping of the whole brain can be acquired efficiently (< 3 min) using fast MPF-SL. It offers a promising alternative way to detect white matter abnormalities in MS.

Dynamics of Magnetization Under the Spin-Lock Pulse: General Solution of the Bloch Equation

Functional magnetic resonance imaging (fMRI) conventionally relies on hemodynamics response induced some seconds after neural activation. Therefore, the temporal limitations of fMRI is the main challenge and we focused on the spin-lock sequence, which identifies neural magnetic field using magnetic resonance between the spin-lock pulse and the measurement target. This potentially addresses limitations of the traditional fMRI such as low temporal resolution and high static magnetic field. To enhance spin-lock sequences, it is essential to analyze magnetization dynamics during the spin-lock pulse. This study improved our previous proposal by presenting the particular solution of the Bloch equation, which allows us to consider the effect of <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> relaxation. We also confirmed the novel solution with the comparison of numerical simulations without any approximation and discovered that the solution improved accuracy for <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M_y</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M_z</i> . The offset errors for <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M_y</i> and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M_z</i> became smaller than 1 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-5</sup> times to the thermal equilibrium magnetization and the magnitude of errors was reduced to 3.2975 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-3</sup> and 1.3072 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> times compared to our previous proposal. This improvement contributes to acquisition-integrated spin-lock sequences. There are still drawbacks due to the rotating wave approximation in our new proposal, but, it is applicable when the frequency bandwidth of spin-lock resonance is narrow, or the measurement target, such as a steady-state induced response, can be approximated by a single-frequency sine wave.

Fast myocardial T1\u03c1 mapping in mice using k-space weighted image contrast and a Bloch simulation-optimized radial sampling pattern

PurposeT1ρ dispersion quantification can potentially be used as a cardiac magnetic resonance index for sensitive detection of myocardial fibrosis without the need of contrast agents. However, dispersion quantification is still a major challenge, because T1ρ mapping for different spin lock amplitudes is a very time consuming process. This study aims to develop a fast and accurate T1ρ mapping sequence, which paves the way to cardiac T1ρ dispersion quantification within the limited measurement time of an in vivo study in small animals.MethodsA radial spin lock sequence was developed using a Bloch simulation-optimized sampling pattern and a view-sharing method for image reconstruction. For validation, phantom measurements with a conventional sampling pattern and a gold standard sequence were compared to examine T1ρ quantification accuracy. The in vivo validation of T1ρ mapping was performed in N = 10 mice and in a reproduction study in a single animal, in which ten maps were acquired in direct succession. Finally, the feasibility of myocardial dispersion quantification was tested in one animal.ResultsThe Bloch simulation-based sampling shows considerably higher image quality as well as improved T1ρ quantification accuracy (+ 56%) and precision (+ 49%) compared to conventional sampling. Compared to the gold standard sequence, a mean deviation of − 0.46 ± 1.84% was observed. The in vivo measurements proved high reproducibility of myocardial T1ρ mapping. The mean T1ρ in the left ventricle was 39.5 ± 1.2 ms for different animals and the maximum deviation was 2.1% in the successive measurements. The myocardial T1ρ dispersion slope, which was measured for the first time in one animal, could be determined to be 4.76 ± 0.23 ms/kHz.ConclusionThis new and fast T1ρ quantification technique enables high-resolution myocardial T1ρ mapping and even dispersion quantification within the limited time of an in vivo study and could, therefore, be a reliable tool for improved tissue characterization.

Low-field fMRI using spin-lock sequences: the influence of MRI noise on magnetic field detection

Low-field fMRI using spin-lock sequences: the influence of MRI noise on magnetic field detection

Noise influence in MRI measurements of neuromagnetic fields using spin-lock sequence

Noise influence in MRI measurements of neuromagnetic fields using spin-lock sequence

Noise influence in MRI measurements of neuromagnetic fields using spin-lock sequence

Noise influence in MRI measurements of neuromagnetic fields using spin-lock sequence

Low-field fMRI using spin-lock sequences: the influence of MRI noise on magnetic field detection

Low-field fMRI using spin-lock sequences: the influence of MRI noise on magnetic field detection

Neural magnetic field dependent fMRI toward direct functional connectivity measurements: A phantom study

Recently, the main issue in neuroscience has been the imaging of the functional connectivity in the brain. No modality that can measure functional connectivity directly, however, has been developed yet. Here, we show the novel MRI sequence, called the partial spinlock sequence toward direct measurements of functional connectivity. This study investigates a probable measurement of phase differences directly associated with functional connectivity. By employing partial spinlock imaging, the neural magnetic field might influence the magnetic resonance signals. Using simulation and phantom studies to model the neural magnetic fields, we showed that magnetic resonance signals vary depending on the phase of an externally applied oscillating magnetic field with non-right flip angles. These results suggest that the partial spinlock sequence is a promising modality for functional connectivity measurements.

Spin-lock imaging of early tissue pH changes in ischemic rat brain.

We have previously reported that the dispersion of spin-lattice relaxation rates in the rotating frame (R1ρ ) of tissue water protons at high field can be dominated by chemical exchange contributions. Ischemia in brain causes changes in tissue pH, which in turn may affect proton exchange rates. Amide proton transfer (APT, a form of chemical exchange saturation transfer) has been shown to be sensitive to chemical exchange rates and able to detect pH changes non-invasively following ischemic stroke. However, the specificity of APT to pH changes is decreased because of the influence of several other factors that affect magnetization transfer. R1ρ is less influenced by such confounding factors and thus may be more specific for detecting variations in pH. Here, we applied a spin-locking sequence to detect ischemic stroke in animal models. Although R1ρ images acquired with a single spin-locking amplitude (ω1 ) have previously been used to assess stroke, here we use ΔR1ρ , which is the difference in R1ρ values acquired with two different locking fields to emphasize selectively the contribution of chemical exchange effects. Numerical simulations with different exchange rates and measurements of tissue homogenates with different pH were performed to evaluate the specificity of ΔR1ρ to detect tissue acidosis. Spin-lock and APT data were acquired on five rat brains after ischemic strokes induced via middle cerebral artery occlusions. Correlations between these data were analyzed at different time points after the onset of stroke. The results show that ΔR1ρ (but not R1ρ acquired with a single ω1 ) was significantly correlated with APT metrics consistent with ΔR1ρ varying with pH.

Non-invasive T1ρ mapping of the human cartilage response to loading and unloading.

To define the physiological response to sequential loading and unloading in histologically intact human articular cartilage using serial T1ρ mapping, as T1ρ is considered to indicate the tissue's macromolecular content. 18 macroscopically intact cartilage-bone samples were obtained from the central lateral femoral condyles of 18 patients undergoing total knee replacement. Serial T1ρ mapping was performed on a clinical 3.0-T MRI system using a modified prostate coil. Spin-lock multiple gradient-echo sequences prior to, during and after standardized indentation loading (displacement controlled, strain 20%) were used to obtain seven serial T1ρ maps: unloaded (δ0), quasi-statically loaded (indentation1-indentation3) and under subsequent relaxation (relaxation1-relaxation3). After manual segmentation, zonal and regional regions-of-interest were defined. ROI-specific relative changes were calculated and statistically assessed using paired t-tests. Histological (Mankin classification) and biomechanical (unconfined compression) evaluations served as references. All samples were histologically and biomechanically grossly intact (Mankin sum: 1.8±1.2; Young's Modulus: 0.7±0.4MPa). Upon loading, T1ρ consistently increased throughout the entire sample thickness, primarily subpistonally (indentation1 [M±SD]: 9.5±7.8% [sub-pistonal area, SPA] vs 4.2±5.8% [peri-pistonal area, PPA]; P<0.001). T1ρ further increased with ongoing loading (indentation3: 14.1±8.1 [SPA] vs 7.7±5.9% [PPA]; P<0.001). Even upon unloading (i.e., relaxation), T1ρ persistently increased in time. Serial T1ρ-mapping reveals distinct and complex zonal and regional changes in articular cartilage as a function of loading and unloading. Thereby, longitudinal adaptive processes in hyaline cartilage become evident, which may be used for the tissue's non-invasive functional characterization by T1ρ.

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Two metrics of contrast based on R1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Off-resonance effects in 14N NQR signals from the pulsed spin-locking (PSL) and three-pulse echo sequence; a study for monoclinic TNT

In NQR detection applications signal averaging by the summation of rapidly regenerated signals from multiple pulse sequences of the pulsed spin-locking (PSL) type is often used to improve sensitivity. It is important to characterise and if possible minimise PSL sequence off-resonance effects since they can make it difficult to optimise detection performance. We illustrate this with measurements of the variation of the decay time T2e and the amplitude of PSL signal trains with pulse spacing and excitation offset frequency for the 870kHz ν+14N NQR line of monoclinic TNT under carefully stabilised temperature conditions. We have also carried out a similar study of signals from monoclinic TNT and 1H-1,2,3-triazole generated by a three-pulse echo sequence and the results are shown to agree well with a theoretical treatment appropriate to polycrystalline NQR samples such as TNT for which spin I=1, asymmetry parameter η≠0 and T1≫T2. Based on this theory we derive simple models for calculating TNT PSL signal trains and hence the pulse spacing and off-resonance dependence of signal amplitude and T2e which we compare to our experimental data. We discuss the influence of PSL echo summation on off-resonance effects in detected signal intensity and show how a phase-alternated multiple pulse sequence can be used in combination with the PSL sequence to eliminate variation in detection performance due to off-resonance effects.

Measurement of regional cerebral glucose uptake by magnetic resonance spin-lock imaging

PurposeThe regional uptake of glucose in rat brain in vivo was measured at high resolution using spin-lock magnetic resonance imaging after infusion of the glucose analogue 2-deoxy-d-glucose (2DG). Previous studies of glucose metabolism have used 13C-labeled 2DG and NMR spectroscopy, 18F-labeled fluorodeoxyglucose (FDG) and PET, or chemical exchange saturation transfer (CEST) MRI, all of which have practical limitations. Our goal was to explore the ability of spin-lock sequences to detect specific chemically-exchanging species in vivo and to compare the effects of 2DG in brain tissue on CEST images. MethodsNumerical simulations of R1p and CEST contrasts for a variety of sample parameters were performed to evaluate the potential specificity of each method for detecting the exchange contributions of 2DG. Experimental measurements were made in tissue phantoms and in rat brain in vivo which demonstrated the ability of spin-lock sequences for detecting 2DG. ResultsR1p contrast acquired with appropriate spin-lock sequences can isolate the contribution of exchanging protons in 2DG in vivo and appears to have better sensitivity and more specificity to 2DG–water exchange effects than CEST. ConclusionSpin-lock imaging provides a novel approach to the detection and measurement of glucose uptake in brain in vivo.

Determination of transverse relaxation rates in systems with scalar-coupled spins: The role of antiphase coherences

Homogeneous line-widths that arise from transverse relaxation tend to be masked by B0 field inhomogeneity and by multiplets due to homonuclear J-couplings. Besides well-known spin-locking sequences that lead to signals that decay with a rate R1ρ without any modulations, alternative experiments allow one to determine the transverse relaxation rates R2 in systems with scalar-coupled spins. We evaluate three recent strategies by experiment and simulation: (i) moderate-amplitude SITCOM-CPMG sequences (Dittmer and Bodenhausen, 2006 [2]), (ii) multiple-quantum filtered (MQF) sequences (Barrère et al., 2011 [4]) and (iii) PROJECT sequences (Aguilar et al., 2012 [5]). Experiments where the J-evolution is suppressed by spin-locking measure the pure relaxation rate R2(Ix) of an in-phase component. Experiments based on J-refocusing yield a mixture of in-phase rates R2(Ix) and antiphase rates R2(2IySz), where the latter are usually faster than the former. Moderate-amplitude SITCOM-CPMG and PROJECT methods can be applied to systems with many coupled spins, but applications of MQF sequences are limited to two-spin systems since modulations in larger systems can only partly be suppressed.

Contributions of chemical exchange to T1ρ dispersion in a tissue model

Variations in T(1ρ) with locking-field strength (T(1ρ) dispersion) may be used to estimate proton exchange rates. We developed a novel approach utilizing the second derivative of the dispersion curve to measure exchange in a model system of cross-linked polyacrylamide gels. These gels were varied in relative composition of comonomers, increasing stiffness, and in pH, modifying exchange rates. Magnetic resonance images were recorded with a spin-locking sequence as described by Sepponen et al. These measurements were fit to a mono-exponential decay function yielding values for T(1ρ) at each locking-field measured. These values were then fit to a model by Chopra et al. for estimating exchange rates. For low stiffness gels, the calculated exchange values increased by a factor of 4 as pH increased, consistent with chemical exchange being the dominant contributor to T(1ρ) dispersion. Interestingly, calculated chemical exchange rates also increased with stiffness, likely due to modified side-chain exchange kinetics as the composition varied. This article demonstrates a new method to assess the structural and chemical effects on T(1ρ) relaxation dispersion with a suitable model. These phenomena may be exploited in an imaging context to emphasize the presence of nuclei of specific exchange rates, rather than chemical shifts.

Spin diffusion in multiple pulse spin-locking in solids containing paramagnetic impurities

Spin diffusion and spin–lattice relaxation in solids containing paramagnetic impurities under influence of a multiple-pulse spin-locking radio-frequency sequence are studied theoretically and experimentally. The diffusion equation obtained provides a clue for determination of the time dependent magnetization. The spin–lattice relaxation time is calculated as a function of the correlation time and multiple-pulse field parameters. From the experimental data the spin diffusion coefficient, the radius of the spin diffusion barrier, and the correlation time for very slow molecular motion in polycrystalline (C 2F) n system are estimated and found to be D ∼ 7.1 × 10 − 12 cm 2 / s , r c ∼ 4.8 × 10 − 10 m , and τ c ∼ 10.2 μ s , respectively.

Hydrophobic Side Chain Dynamics of a Glutamate Receptor Ligand Binding Domain

Ionotropic glutamate receptors are ligand-gated ion channels that mediate much of the fast excitatory neurotransmission in the central nervous system. The extracellular ligand binding core (S1S2) of the GluR2 subtype of ionotropic glutamate receptors can be produced as a soluble protein with properties essentially identical to the corresponding domain in the intact, membrane-bound protein. Using a variety of biophysical techniques, much has been learned about the structure and dynamics of S1S2 and the relationship between its ligand-induced conformational changes and the function of the receptor. It is clear that dynamic processes are essential to the function of ionotropic glutamate receptors. We have isotopically labeled side chain methyls of GluR2 S1S2 and used NMR spectroscopy to study their dynamics on the ps-ns and mus-ms time scales. Increased disorder is seen in regions that are part of the key dimer interface in the intact protein. When glutamate is bound, the degree of ps-ns motion is less than that observed with other ligands, suggesting that the physiological agonist binds to a preformed binding site. At the slower time scales, the degree of S1S2 flexibility induced by ligand binding is greatest for willardiine partial agonists, least for antagonists, and intermediate for full agonists. Notable differences among bound ligands are in the region of the protein that forms a hinge between two lobes that close upon agonist binding, and along the beta-sheet in Lobe 2. These motions provide clues as to the functional properties of partial agonists and to the conformational changes associated with lobe closure and channel activation.

A new assignment technique of 2D‐NMR spectra by spin‐lock sequence to a tripeptide containing tryptophan in water

We developed a new assignment technique of tryptophan residues using pulsed field gradient TOCSY-ROESY (PFG-TORO) and pulsed field gradient TOCSY-ROESY-TOCSY (PFG-TOROTO) techniques in water. Connectivity from betaH to zeta2H (H-7) via epsilon1H (H-1) and delta1H (H-2) in the TORO spectrum and from betaH to zeta3H (H-5) and eta2H (H-6) via epsilon1H (H-1) and delta1H (H-2) in the TOROTO spectrum could be able to assign each of the protons of the indole rings.

Inhibition of Neuronal Nicotinic Acetylcholine Receptor Subtypes by α-Conotoxin GID and Analogues

alpha-Conotoxins are small disulfide-rich peptides from the venom of the Conus species that target the nicotinic acetylcholine receptor (nAChR). They are valuable pharmacological tools and also have potential therapeutic applications particularly for the treatment of chronic pain. alpha-Conotoxin GID is isolated from the venom of Conus geographus and has an unusual N-terminal tail sequence that has been shown to be important for binding to the alpha4beta2 subtype of the nAChR. To date, only four conotoxins that inhibit the alpha4beta2 subtype have been characterized, but they are of considerable interest as it is the most abundant nAChR subtype in the mammalian brain and has been implicated in a range of diseases. In this study, analysis of alanine-scan and truncation mutants of GID reveals that a conserved proline in alpha-conotoxins is important for activity at the alpha7, alpha3beta2, and alpha4beta2 subtypes. Although the proline residue was the most critical residue for activity at the alpha3beta2 subtype, Asp(3), Arg(12), and Asn(14) are also critical at the alpha7 subtype. Interestingly, very few of the mutations tested retained activity at the alpha4beta2 subtype indicating a tightly defined binding site. This lack of tolerance to sequence variation may explain the lack of selective ligands discovered for the alpha4beta2 subtype to date. Overall, our findings contribute to the understanding of the structure-activity relationships of alpha-conotoxins and may be beneficial for the ongoing attempts to exploit modulators of the neuronal nAChRs as therapeutic agents.

Relaxation during spin-lock spin-echo pulse sequence in N14 nuclear quadrupole resonance

In this work, we investigate off-resonance effect on the (14)N nuclear quadrupole resonance magnetization decay during the spin-lock spin-echo pulse sequence (SLSE). The compound chosen for this study is paranitrotoluene with a single (14)N site, which represents a suitable simplified model for the explosive trinitrotoluene with six nonequivalent (14)N sites. We find that the quasi-steady state magnetization exhibits dips at particular frequency offsets and more interestingly that its decay rate T(2 eff) (-1) exhibits similar dips (slower decay) at the same frequency offsets. The coexistence of dips is very important for applications where the primary use of the SLSE sequence is to increase the signal-to-noise ratio, as longer sampling times compensate for small magnetization values. A theory explaining both observations is presented which includes homonuclear dipolar interactions and spin coupling to the lattice. We show that the homonuclear dipolar interaction contributes only 20% to the total magnetization decay rate, while spin-lattice coupling is the dominant mechanism.