Exploiting the chemical shift displacement effect in the detection of glutamate and glutamine (Glx) with PRESS

A PRESS (Point RESolved Spectroscopy) sequence for the improved detection of the C2 protons of Glx (glutamate and glutamine) at approximately 3.75ppm is presented in this work. It is shown that for spins like the C2 protons of Glx which are involved solely in weak coupling interactions, the chemical shift displacement effect can be turned to advantage by exploiting PRESS refocusing pulses with bandwidths less than the chemical shift difference between the target spins and the spins to which they are weakly coupled. The narrow-bandwidth PRESS sequence allows refocusing of the J-coupling evolution of the target protons in the voxel of interest independently of echo time yielding signal equivalent to that which can be obtained with a one-pulse acquire sequence (assuming ideal pulses and ignoring T2 relaxation). The total echo time of PRESS was set long enough for the decay of macromolecule signal and the two echo times were empirically optimized so that the Glx signal at 3.75ppm suffered minimal contamination from myo-inositol. The efficacy of the method was verified on phantom solutions of Glx and on brain in vivo.     

Parametric multiecho proton spectroscopic imaging: Application to the rat brain in vivo

A parametric multiecho variant of proton spectroscopic imaging (SI) is presented using a multiecho SI sequence with uniform phase-encoding of all echoes within each echo train. The acquisition of SI data sets at different echo times (TE) increases the amount of information obtained within the same total measuring time as in standard SI measurements. The gain in information can be used: (a) to choose the most appropriate TE for each metabolite signal with respect to T₂, spin coupling, or problems caused by peak overlap; (b) to measure the relaxation time T₂ of metabolite signals with high spatial resolution; or (c) to improve the signal-to-noise ratio for metabolite signals with long T₂ values by adding spectra calculated from consecutive echoes. The method was tested in vivo on healthy rat brain and applied to study metabolic changes in rat brain lesions.     

In vivo lactate editing in single voxel proton spectroscopy and proton spectroscopic imaging by homonuclear polarisation transfer

Volume-selective lactate editing has been performed successfully in vitro and in vivo in the brain on a clinical scanner using a PRESS-based single voxel ¹H spectroscopy and a ¹H spectroscopic imaging sequence. The PRESS sequence was made sensitive to homonuclear polarisation by replacing the standard 180° refocusing pulses with 90° pulses. Two acquisitions were made at a total echo time around 2/J (J is the coupling constant for CH and CH₃ spins in lactate ≈7 Hz) whose individual echo times differed by 5.5 ms. Subtraction of one signal from the other yielded the lactate resonance alone. The technique is an effective method of separating the overlapping signals of lactate and lipids. Furthermore this editing method can be performed without state of the art MRI scanner hardware.     

Phase modulation in dipolar-coupled A2 spin systems: effect of maximum state mixing in H NMR in vivo

Coupling constants of nuclear spin systems can be determined from phase modulation of multiplet resonances. Strongly coupled systems such as citrate in prostatic tissue exhibit a more complex modulation than AX connectivities, because of substantial mixing of quantum states. An extreme limit is the coupling of n isochronous spins (A_n system). It is observable only for directly connected spins like the methylene protons of creatine and phosphocreatine which experience residual dipolar coupling in intact muscle tissue in vivo. We will demonstrate that phase modulation of this “pseudo-strong” system is quite simple compared to those of AB systems. Theory predicts that the spin-echo experiment yields conditions as in the case of weak interactions, in particular, the phase modulation depends linearly on the line splitting and the echo time.     

A matched filter echo summation technique for MRI

A technique is presented to increase the signal-to-noise ratio (SNR) in two-dimensional (2D), phase-encoded imaging at low SNR. The essence of this technique is to combine multiple echoes in the time domain. As analyzed in the paper, phase discrepancies exist among different echoes and may deteriorate the combined echo. In particular, extraneous phase shifts can be created if unshielded gradient coils are used. To overcome these phase discrepancies, a matched filter was derived from the k = 0 component of image. This matched filter has the same phase discrepancies among its echoes as the imaging signal and its magnitude decays with an average T₂. In the echo summation with the matched filter, the phase of the matched filter was subtracted from the imaging signal and the magnitude of the matched filter was used as the weighting function. We have shown that this matched filter echo summation technique has better SNR than the case of 2D, phase-encoded imaging in both simulation and experiment. The SNR improvement is up to 60% in a phantom experiment. This technique is mostly useful in low SNR imaging that requires long imaging time, such as spectroscopic imaging and ¹⁹F imaging.     

Orientational analysis of the Achilles tendon and enthesis using an ultrashort echo time spectroscopic imaging sequence

Tendons and entheses are magnetic resonance (MR) “invisible” when imaged with conventional clinical pulse sequences. When the highly ordered, collagen-rich fibers in tendons and entheses are placed at the magic angle, dipolar interactions are decreased and their T2s are often considerably increased. The bulk magnetic susceptibility of tendons and entheses also varies with orientation to B₀, leading to a direction-dependent resonance frequency shift. Ultrashort echo time (UTE) sequences with a minimum TE of 8 μs provide high signal from both tendons and entheses. The combination of a UTE sequence with an interleaved undersampled variable TE acquisition scheme provides a new approach for fast spectroscopic imaging of short T2 tissues. This UTE spectroscopic imaging (UTESI) technique provides quantitative information including T2?, chemical shift and resonance frequency shift due to bulk susceptibility effect. In this article, the orientational effects on tendons and entheses were investigated using a UTESI sequence on a clinical 3-T scanner. T2? was found to increase fivefold for tendons and twofold for entheses due to the magic angle effect. A resonance frequency shift up to 1.2 ppm was observed for both tendons and entheses due to the bulk susceptibility effect when their orientation was changed from 0° to 90° relative to B₀.     

Identification of patients with hereditary haemochromatosis by magnetic resonance imaging and spectroscopic relaxation time measurements

A total of 4302 healthy blood donors were screened for elevated serum ferritin and transferrin saturation. Fifteen had increased serum ferritin at a follow-up examination. Five relatives of these donors also entered the study. Eleven patients had elevated liver iron concentrations, while five had normal liver iron concentrations. The R₂ relaxation rate in the liver was first measured with a conventional multi-spin-echo imaging sequence, and then by a volume-selective spectroscopic multi-spin-echo sequence, in order to achieve a minimum echo time of 4 msec. No correlation was found between the relaxation rate R₂ and the liver iron concentration, when R₂ was calculated from the imaging data. Multi-exponential transverse relaxation could be resolved when the spectroscopic sequence was used. A strong correlation between the initial slope of the relaxation curve and the liver iron concentration was found (r = 0.90, p < 0.001). Signal intensity ratios between liver and muscle were calculated from the first three echoes in the multi-echo imaging sequence, and from a gradient echo sequence. A strong correlation between the logarithm of the signal intensity ratios and the liver iron concentration was found. Although both spectroscopic T₂ relaxation time measurements and signal intensity ratios could be used to quantify liver iron concentration, the gradient echo imaging seemed to be the best choice. Gradient echo imaging could be performed during a single breath hold, so motion artifacts could be avoided. The accuracy of liver iron concentration estimates from signal intensity ratios in the gradient echo images was about 35%.     

Electron spin-echo experiments in photo-excited triplet states in an external magnetic field

Electron spin-echo experiments in the photo-excited triplet states of quinoxaline-d₆ and naphthalene-d₈ at 1·2 K in an external magnetic field are presented. These include two-pulse Hahn echoes, three-pulse stimulated echoes and Carr-Purcell pulse-echo trains. The decay of the Hahn and stimulated echoes as a function of pulse interval yields measures of the spin relaxation times. Furthermore, the Hahn echo is used to obtain E.P.R. line shapes and the dynamics of the triplet sublevel populations. The angular dependence of the Hahn echo is also investigated. The Hahn echo decay time and decay modulation suggest the kind of role played by nuclear spins in the loss of electron spin phase coherence. Some promising characteristics of the pulse method are discussed.     

B1-insensitive Hadamard spectroscopic imaging technique

A B₁-insensitive Hadamard spectroscopic imaging technique for multivolume localization is presented and tested experimentally. This technique can give localized spectroscopic information from n regions of interest by n scans using homogeneous or inhomogeneous coils, such as surface coils. The B₁ insensitivity is achieved by using RF pulses which invert spins adiabatically at several well-defined slices simultaneously. We show how any adiabatic pulse can be modified such that it can invert spins at one or several desired frequency bands simultaneously. With the modified adiabatic pulses, B₁-insensitive Hadamard spectroscopic imaging experiments of any order can be performed.     

A New Two-Dimensional Pulse Sequence for T2* Measurements of Protons in C Isotopomers

A new two-dimensional pulse sequence for T₂* measurement of protons directly coupled to ¹³C spins is proposed. The sequence measures the tranverse relaxation time of heteronuclear proton single-quantum coherence under conditions of free precession and is therefore well suited to evaluate relaxation losses of proton magnetization during preparation delays of heteronuclear pulse experiments in analytical NMR. The relevant part of the pulse sequence can be inserted as a “building block” into any direct or inverse detecting H,C correlation pulse sequence if proton spin–spin relaxation is to be investigated. In this contribution, the building block is inserted into a HETCOR as well as into a HMQC pulse sequence. Experimental results for the HETCOR-based sequence are given.     

Application of biselective refocusing soft pulses to the simplification of heteronuclear correlation spectra

The biselective spin echo technique allows the signals of coupled proton pairs to be extracted from crowded liquid state proton NMR spectra. Its use as a preparation sequence in heteronuclear chemical shift correlation experiments requires the removal of the heteronuclear coupling interaction during the biselective echo time. The discrimination between coupled and uncoupled protons signals is achieved by double quantum filtration, which delivers antiphase magnetization states. The latter are not directly compatible with the design of an HSQC-like pulse sequence. The conversion of antiphase to in-phase magnetization states by a second biselective echo sequence solves this problem. The optimization of spin echo delays is also discussed. Lastly, the article presents modified HSQC and HMBC pulses sequences in which information is obtained solely for the biselectively selected proton pairs. A peracetylated trisaccharide was used as a test molecule.     

Single-Pulse Echo and Its Secondary Signals in Two-Level Spin Systems

The dependences of the amplitudes of single- and two-pulse spin echoes and their secondary signals in NMR (protons of glycerin in an inhomogeneous magnetic field) in the exciting-pulse repetition period T _r have been compared. The difference in origin of the primary and secondary signals of a single-pulse echo in a two-level spin system has been confirmed. It is shown that only a primary single-pulse echo observed when T _r > T ₁ (T ₁ is the spin lattice relaxation time) results from single-pulse excitation. The secondary single-pulse echo signals are observed for T _r < T ₁ and are due to the multiphase formation mechanism. The results obtained for magnetically ordered substances are analyzed. Based on these data, it was inferred earlier that primary and secondary single-pulse echo signals were formed by one and the same multiphase mechanism.     

RF Gradient BIRD/TANGO Sequence to Eliminate Uncoupled Magnetization

A modification of the BIRD and TANGO sequences is presented which employs radiofrequency field gradients to eliminate the net magnetization from uncoupled spins, while completely preserving coupled magnetization. The standard BIRD and TANGO sequences cause selective nutation of protons directly bound to a coupling partner, while returning uncoupled magnetization to +z. These sequences lend themselves naturally to modification using RF gradients, which require no increase in pulse-sequence complexity while providing substantial suppression of uncoupled resonances and elimination of typical antiphase and multiple-quantum error terms that arise from improperly set pulse lengths or delays. In the RF-gradient BIRD/TANGO sequence, the uncoupled magnetization is dephased in a plane orthogonal to the RF axis, while the desired signal components are refocused, effectively in a rotary echo. The sequence has applications to solvent suppression and selective isotopomer excitation. It is demonstrated for selective excitation of the satellites in a sample of chloroform, yielding suppression of the uncoupled magnetization by a factor of approximately 800.     

Spin echo SPI methods for quantitative analysis of fluids in porous media

Fluid density imaging is highly desirable in a wide variety of porous media measurements. The SPRITE class of MRI methods has proven to be robust and general in their ability to generate density images in porous media, however the short encoding times required, with correspondingly high magnetic field gradient strengths and filter widths, and low flip angle RF pulses, yield sub-optimal S/N images, especially at low static field strength. This paper explores two implementations of pure phase encode spin echo 1D imaging, with application to a proposed new petroleum reservoir core analysis measurement.In the first implementation of the pulse sequence, we modify the spin echo single point imaging (SE-SPI) technique to acquire the k-space origin data point, with a near zero evolution time, from the free induction decay (FID) following a 90° excitation pulse. Subsequent k-space data points are acquired by separately phase encoding individual echoes in a multi-echo acquisition. T₂ attenuation of the echo train yields an image convolution which causes blurring. The T₂ blur effect is moderate for porous media with T₂ lifetime distributions longer than 5 ms. As a robust, high S/N, and fast 1D imaging method, this method will be highly complementary to SPRITE techniques for the quantitative analysis of fluid content in porous media.In the second implementation of the SE-SPI pulse sequence, modification of the basic measurement permits fast determination of spatially resolved T₂ distributions in porous media through separately phase encoding each echo in a multi-echo CPMG pulse train. An individual T₂ weighted image may be acquired from each echo. The echo time (TE) of each T₂ weighted image may be reduced to 500 μs or less. These profiles can be fit to extract a T₂ distribution from each pixel employing a variety of standard inverse Laplace transform methods. Fluid content 1D images are produced as an essential by product of determining the spatially resolved T₂ distribution. These 1D images do not suffer from a T₂ related blurring.The above SE-SPI measurements are combined to generate 1D images of the local saturation and T₂ distribution as a function of saturation, upon centrifugation of petroleum reservoir core samples. The logarithm mean T₂ is observed to shift linearly with water saturation. This new reservoir core analysis measurement may provide a valuable calibration of the Coates equation for irreducible water saturation, which has been widely implemented in NMR well logging measurements.     

Absolute Quantification Using Turbo Spectroscopic Imaging in Multiple Sclerosis Patients

One of the drawbacks of scanning patients using multiple-voxel spectroscopic imaging is the long acquisition time. This is especially true when one is interested in obtaining absolute metabolite concentrations which requires acquisition of unsuppressed water spectra in addition to the suppressed spectra. In our experiment, turbo spectroscopic imaging (TSI) method with acquisition of three echoes per excitation was applied to reduce scanning time without lowering the spatial resolution. In 15 relapsing-remitting multiple sclerosis patients (mean age 37.07 years, mean disease duration 7.67 years), an MRSI scan at the level of centrum semiovale was obtained. The scan time was approximately 7 min including the unsuppressed spectra. Tissue water was used as an internal concentration reference to obtain absolute metabolite concentrations of N-acetyl-aspartate (NAA), creatine (Cr), and choline (Cho). The peak areas were corrected for differences in transversal and longitudinal relaxation times and a water concentration of 55.5 M was assumed. A three-dimensional high-resolution T ₁ scan was acquired and used to segment tissue in gray matter (GM), white matter (WM), and cerebrospinal fluid using FSL’S FAST segmentation method (a software library of the automated segmentation tool by the Center of Functional MRI of the Brain, Oxford, UK). Finally, a regression analysis was employed to address the metabolite concentrations and ratios in GM and WM, respectively. Our study shows that the metabolite concentrations (NAA, Cho, Cr) and metabolite ratios (NAA/Cr and Cho/Cr) in GM and WM obtained using the methods discussed earlier are comparable to the results found in other studies of similar patient groups. It also shows that TSI method can be used to obtain the absolute metabolite ratios in a reasonable scan time.     

MSE-MRI sequence optimisation for measurement of bi- and tri-exponential T2 relaxation in a phantom and fruit

The transverse relaxation signal from vegetal cells can be described by multi-exponential behaviour, reflecting different water compartments. This multi-exponential relaxation is rarely measured by conventional MRI imaging protocols; mono-exponential relaxation times are measured instead, thus limiting information about of the microstructure and water status in vegetal cells. In this study, an optimised multiple spin echo (MSE) MRI sequence was evaluated for assessment of multi-exponential transverse relaxation in fruit tissues. The sequence was designed for the acquisition of a maximum of 512 echoes. Non-selective refocusing RF pulses were used in combination with balanced crusher gradients for elimination of spurious echoes. The study was performed on a bi-compartmental phantom with known T₂ values and on apple and tomato fruit. T₂ decays measured in the phantom and fruit were analysed using bi- and tri-exponential fits, respectively. The MRI results were compared with low field non-spatially resolved NMR measurements performed on the same samples.     

CPMG echo amplitudes with arbitrary refocusing angle: explicit expressions, asymptotic behavior, approximations

Exact explicit analytical expression for echoes in the Carr–Purcell–Meiboom–Gill sequence with arbitrary excitation and refocusing angles and resonance offset of RF pulses was obtained, employing the generating functions formalism developed earlier by authors. Asymptotic form and analytical approximation for echoes were derived in an elegant way and analyzed in details. In particular, it was shown that depending on T₁, T₂ and parameters of the pulse sequence, oscillatory behavior of echoes can take place. Accuracy of asymptotic forms and approximations were tested by comparison with exactly calculated echo amplitudes. Besides, it was shown, that the generating function approach can be applied to the consideration of terminated pulse sequences, when after-pulses echoes are registered.     

Anomalous pulse angle dependence of the single and double quantum echoes in a photoinduced spin-correlated coupled radical pair

In this work the response of a spin-correlated coupled radical pair to the sequence flash-t-P _ζ-τ-P _2ζ-T is investigated. For the theoretical analysis, the density operator formalism is used. Analytical expressions are derived for the electron spin single (SQ ESE) and double-quantum echoes (DQ ESE) as a function of pulse flip angle and singlet-triplet mixing angle. To illustrate the theoretical results, computer simulations are presented. In the limit of weak coupling, the “out-of-phase” SQ ESE is shown to be of a pure two-spin order having the maximal amplitude for the flip angle of 65.9°. The echo following the Hahn sequence vanishes in the same limit. This confirms the theoretical result already presented in the literature. However, the more general analysis shows that outside the weak coupling approximation the Hahn echo is of purely one-spin order, whereas the echo following the flash-t-P _ζ-τ-P _2ζ-t sequence has its maximal amplitude for the flip angle of 75° and the singlet-triplet mixing angle of 27°. The “in-phase” single- and double-quantum echoes are shown to vanish due to averaging out, within the electron spin resonance spectrometer deadtime, of contributions modulated with the sum and difference of the zero-quantum beat frequency and the frequency due to the spin-spin interaction within the pair. The calculated out-of-phase DQ ESE signal is inverted with respect to the out-of-phase SQ ESE and has only the half of its amplitude. The DQ ESE vanishes for the Hahn sequence. The echo has maximal amplitude in the weak-coupling limit for the flip angle of 65.9°. In contradiction to the analytical result previously published, the out-of-phase DQ ESE does not vanish for long τ and large zero-quantum-beat frequency.     

Combination of magic-echo and single-point imaging techniques for solid-state MRI

Due to reduced molecular motion the transverse relaxation timeT ₂ in solid materials is typically shorter by a factor of 10³ to 10⁵ in comparison to those in liquids, resulting in a large intrinsic nuclear magnetic resonance line-width that can be well above 20 kHz. Therefore high-resolution solid-state magnetic resonance imaging requires either very strong gradients or special line-narrowing techniques. Single-point imaging (SPI) is a successful pure phase encoding sequence in imaging soft-solid materials; however, when used to study rigid solid materials it still suffers from a very long acquisition time and large gradients. On the other hand, magic echo is a technique that can be used to effectively refocus dipolar interaction, thus achieving a line narrowing. Therefore, the aim of this work is to improve the signal intensity with the combination of the magic echo technique and the SPI sequence. In this paper first applications and a comparison of the SPI sequence with a combination of the magic echo and the SPI sequence to image structures of solid-state materials are presented.     

Improved proton spectroscopic U-FLARE imaging for the detection of coupled resonances in the rat brain in vivo

Modifications of the pulse sequence for spectroscopic U-FLARE imaging are discussed to detect not only the predominant singlet signals of N-acetylaspartate, total creatine, and choline containing compounds or the doublet signal of lactate, but also the coupled resonances of glutamate, glutamine, taurine and myo-inositol. Effective homonuclear decoupling is achieved by use of constant time chemical shift encoding. A maximum signal-to-noise ratio (SNR) can be obtained for a certain coupled resonance of interest by optimizing the evolution period t(c) of the J modulated spin echo. Good reproducibility and a high SNR were achieved by combining several methods for water suppression and by using the displaced variant of U-FLARE. Measurements of a 3 mm slice of the rat brain were performed in vivo within 4 min, giving a nominal voxel size of 1.5 x 1.5 x 3.0 mm3 or 1.5 x 0.75 x 3.0 mm3. Thus, optimized spectroscopic U-FLARE is a powerful tool for proton spectroscopic imaging with high spectral, spatial and temporal resolution.