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.     

Lactate quantification by means of press spectroscopy—Influence of refocusing pulses and timing scheme

The quantitative assessment of lactic acid in tissue is an important goal for in vivo volume-selective NMR spectroscopy to aid in the noninvasive diagnosis of oxygen deficiency or other metabolic disorders. PRESS localized ¹H spectra provide comparatively high signal-to-noise ratio from small volume elements in a single acquisition mode. The quantification of lactate after multipulse excitation is not trivial due to the J-coupling characteristics which do not occur for the substances serving as references. The influence of the timing scheme and of the quality of the refocusing pulses was systematically evaluated for the lactate resonances by volume-selective measurements. Gaussian pulses, Hanning-filtered sinc pulses, and numerically optimized RE-BURP-pulses were applied for refocusing the magnetization in the PRESS sequence and the effects on the lactate AX₃ spin system were compared. For these pulses, sequence parameters are presented providing high sensitivity to lactate signals. Timing schemes are shown which provide good quantification of lactate, even in cases with B₁-inhomogeneities or slight misadjustment of the transmitter amplitude. The combination of both echo times in the double-echo sequences clearly influences the signal characteristics of lactate at overall echo times near TE = 145 and 290 ms, which may result in pure in-phase magnetization for this weakly coupled homonuclear system. Numerically optimized refocusing pulses (RE-BURP) provided up to 50% higher signal ratio of the methyl protons of lactate to uncoupled nuclei than the often used Hanning-filtered sinc pulses.     

Proton Spectroscopy of Human Brain with Very Short Echo Time Using High Gradient Amplitudes

In localized proton magnetic resonance spectroscopy very short echo times (TE) are achieved to diminish signal loss due to T₂ relaxation and to avoid phase distortions due to J-coupling. A sequence for single volume spectroscopy in human brain is described with a TE as low as 5 ms. Examinations were performed on a 1.5 T whole-body imager with actively shielded gradients. A self-designed stimulated echo acquisition mode (STEAM) sequence with very high amplitude spoiling gradients of 24 mT/m was used to take advantage of the whole potential of the gradient system. Optimization of TE was carried out by controlling spectral quality and localization in both phantom and volunteer measurements. Proton spectra of human brain were acquired in 21 healthy volunteers. Spectra of occipital white matter, parieto-occipital grey/white matter, and cerebellum revealed none or only small eddy current distortions at a TE of 5 ms. The volume of interest was 8–12 ml, repetition time was 1.5 s, and mixing time was 5 ms. Peak ratios of major metabolites referring to creatine were estimated and the relative standard deviations were calculated to determine interindividual reproducibility. The relative standard deviation of myo-inositol ranged from 6% to 11% within these brain regions whereas for glutamine and glutamate 7% to 16% were found.     

Quantitative Evaluation of the Lactate Signal Loss and Its Spatial Dependence in PRESS Localized H NMR Spectroscopy

Localized ¹H NMR spectroscopy using the 90°−t₁−180°−t₁+t₂−180°−t₂−Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t₁ and t₂. The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t₁=t₂) at an echo time of 2/J (290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX₃ spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3, …, we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.     

Quantification of slow flow using FAIR

Phase contrast (PC)-based MRI methods are considered to be the most accurate approach for spatially resolved flow quantification, but the measurement of very slow velocities requires signal detection at long echo times and the application of strong field gradients. On the other hand, measurements based on time-of-flight or inflow effects can be conducted at short echo times and without flow-encoding gradients. A method for imaging flow at velocities of the order of 0.1 mm/s is presented and validated here. It consists of measuring the apparent spin-lattice relation rate (R₁*) of the flowing fluid using magnetization preparation by alternating slice-selective and nonselective inversion pulses (FAIR or flow-sensitive alternating inversion recovery) and a fast gradient-echo detection sequence. This method is appropriate for the quantitative imaging of slow flow at low Reynolds numbers in fluids where the T₂ values are too short to allow sensitive flow measurements by phase contrast-based methods.     

Retrospective correction for T1-weighting bias in T2 values obtained with various spectroscopic spin-echo acquisition schemes

Localized tissue transverse relaxation time (T₂) is obtained by fitting a decaying exponential to the signals from several spin-echo experiments at different echo times (TE). Unfortunately, time constraints in magnetic resonance spectroscopy (MRS) often mandate in vivo acquisition schemes at short repetition times (TR), that is, comparable with the longitudinal relaxation constant (T₁). This leads to different T₁-weighting of the signals at each TE. Unaccounted for, this varying weighting causes systematic underestimation of the T₂'s, sometimes by as mush as 30%. In this article, we (i) analyze the phenomenon for common MRS spin-echo T₂ acquisition schemes; (ii) propose a general post hoc T₁-bias correction for any (TR, TE) combination; (iii) show that approximate knowledge of T₁ is sufficient, since a 20% uncertainty in T₁ leads to under 3% bias in T₂; and consequently, (iv) efficient, precision-optimized short TR spin-echo T₂ measurement protocols can be designed and used without risk of accuracy loss. Tables of correction for single-refocusing (conventional) spin-echo and double refocusing, such as, PRESS acquisitions, are provided.     

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.     

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.     

Quantitation of phosphorus metabolites in newborn human brain using internal water as reference standard

A new method for noninvasive, in vivo quantitation of cerebral phosphorus (³¹P) metabolites is described. The technique employs point-resolved spectroscopy (PRESS) to obtain both ³¹P-metabolite and proton (¹H) water spectra: brain water is used as an internal concentration reference. Spin-spin relaxation times (T₂s) of cerebral ³¹P metabolites are much longer than the minimum echo time (TE) usable on a spectrometer equipped with actively shielded gradient coils. With short-TE (≈10 ms) ³¹P PRESS, T₂ relaxation is minimal and phase modulation of the nucleotide triphosphate (NTP) multiplets can be accounted for. ¹H water spectra were acquired using several TEs so that extra- and intracellular water signals could be separated from that due to cerebrospinal fluid. Prior calibration of the ³¹P and ¹H spectrometer channels and an assumed brain-water concentration enabled estimations of metabolite concentrations. Using this method, mean ³¹P metabolite concentrations in the brains of eight normal infants of gestational plus postnatal age 34 to 39 wk were: phosphomonoester (PME) 5.6 (SD 0.9); inorganic phosphate 1.4 (0.4); mobile phosphodiester 2.3 (0.6); phosphocreatine 2.9 (0.3); nucleotide triphosphate 2.8 (0.6); and total mobile phosphate 21.4 (2.8) mmol/kg wet.     

A phase rotation scheme for achieving very short echo times with localized stimulated echo spectroscopy

In a single-voxel stimulated echo localization sequence in magnetic resonance spectroscopy, magnetic field gradients are inserted within the echo time (TE) to filter signals generated through coherence pathways other than that leading to the stimulated echo. There is a significant penalty for these gradients as they increase the minimum TE, thereby leading to significant signal loss from spin-spin relaxation and phase distortions in coupled spin systems. Here, an RF phase rotation technique is described for a stimulated echo localization sequence that allows removal of the gradients in the TE intervals and, subsequently, reduction of the minimum TE to only 6 ms. Experiments carried out on six healthy volunteers on a 1.5-T whole-body MR system show a significant signal increase in the metabolite concentrations when measured with a 6-ms TE (N-acetyl-aspartate, 12%, P=.002; creatine, 15%, P=.04; and glutamate+glutamine, 92%, P=.02) compared to concentrations measured with data collected at TEs of 15 and 20 ms.     

Relaxation Model and Mapping of Magnetic Field Gradients in MRI

The purpose of the work is development of algorithms for separate mapping of T ₂ relaxation time and gradients, using gradient recalled echo (GRE) sequence. Application of three-dimensional (3D) model of gradients and their volumetric averaging within a voxel lead to analytical model of relaxation function, which is consistent with experimental data for both regular macroscopic and randomized micro- and mesoscopic gradients. The model is verified by fitting into experimental data obtained on specially made phantoms. Verification of algorithms is completed by comparing gradient maps obtained on specially made cylindrical phantoms with theoretical maps of their exact 3D electro-dynamic solutions. Analytical model of relaxation function proved to be in good agreement with experimental relaxation curves. On the basis of this model, fast and unambiguous fittingless algorithms were developed. Gradient maps measured on special cylindrical phantoms are in good qualitative agreement with theory. 3D statistical model and fittingless algorithms provide the basis for separating the GRE signal into two meaningful parameters—T ₂ and gradients, thus doubling information from magnetic resonance imaging.     

Spin-echo attenuation by diffusion in nonuniform field gradients

The diffusion-dependent decay of spin-echo signals from samples distributed over non-uniform field gradients is analyzed. This decay deviates from the linear semilogarithmic dependencies on t³ or t obtained, respectively, in Hahn spin-echo or Carr-Purcell echo trains from spins in constant field gradients. It is demonstrated here that when the average diffusion distance is small compared to the spatial variation of the gradient, the spin-echo decay can be modeled by a simple superposition of signals from a large number of microdomains, each characterized by a different gradient. This is illustrated by two examples, a water sample in a deliberately created quadratic variation of the external field, and a saturated water/ sand mixture with large internal field gradients.     

Quantitative evaluation of the lactate signal loss and its spatial dependence in press localized (1)H NMR spectroscopy

Localized (1)H NMR spectroscopy using the 90 degrees -t(1)-180 degrees -t(1)+t(2)-180 degrees -t(2)-Acq. PRESS sequence can lead to a signal loss for the lactate doublet compared with signals from uncoupled nuclei which is dependent on the choice of t(1) and t(2). The most striking signal loss of up to 78% of the total signal occurs with the symmetrical PRESS sequence (t(1)=t(2)) at an echo time of 2/J (approximately 290 ms). Calculations have shown that this signal loss is related to the pulse angle distributions produced by the two refocusing pulses which leads to the creation of single quantum polarization transfer (PT) as well as to not directly observable states (NDOS) of the lactate AX(3) spin system: zero- and multiple-quantum coherences, and longitudinal spin orders. In addition, the chemical shift dependent voxel displacement (VOD) leads to further signal loss. By calculating the density operator for various of the echo times TE=n/J, n=1, 2, 3,..., we calculated quantitatively the contributions of these effects to the signal loss as well as their spatial distribution. A maximum signal loss of 75% can be expected from theory for the symmetrical PRESS sequence and TE=2/J for Hamming filtered sinc pulses, whereby 47% are due to the creation of NDOS and up to 28% arise from PT. Taking also the VOD effect into account (2 mT/m slice selection gradients, 20-mm slices) leads to 54% signal loss from NDOS and up to 24% from PT, leading to a maximum signal loss of 78%. Using RE-BURP pulses with their more rectangular pulse angle distributions reduces the maximum signal loss to 44%. Experiments at 1.5 T using a lactate solution demonstrated a maximum lactate signal loss for sinc pulses of 82% (52% NDOS, 30% PT) at TE=290 ms using the symmetrical PRESS sequence. The great signal loss and its spatial distribution is of importance for investigations using a symmetrical PRESS sequence at TE=2/J.     

Functional MRI Using Spin Lock Editing Preparation Pulses

A novel approach for detecting blood oxygenation level-dependent (BOLD) signals in the brain is investigated using spin locking (SL) pulses to selectively edit the effects of extravascular diffusion in field gradients from different sized vascular structures. We show that BOLD effects from diffusion amongst susceptibility gradients will contribute significantly not only to transverse relaxation rates (R₂* and R₂) but also to R_1ρ, the rate of longitudinal relaxation in the rotating frame. Similar to the ability of 180-degree pulses to refocus static dephasing effects in a spin echo, moderately strong SL pulses can also reduce contributions of diffusion in large-scale gradients and the choice of SL amplitude can be used to selectively emphasize smaller scale inhomogeneities (such as microvasculature) and to drastically reduce the influence of larger structures (such as veins). Moreover, measurements over a range of locking fields can be used to derive estimates of the spatial scales of intrinsic gradients. The method was used to detect BOLD activation in human visual cortex. Eight healthy young adults were imaged at 3 T using a single-slice, SL-prepped turbo spin echo (TSE) sequence with spin-lock amplitudes ω₁ = 80 Hz and 400 Hz, along with conventional T₂*-weighted and T₂-prepped sequences. The BOLD signal varied from 1.1 ± 0.4 % (ω₁ = 80 Hz) to 0.7 ± 0.2 % (at 400 Hz), whereas the T₂-weighted sequence measured 1.3 ± 0.3 % and the T₂* sequence measured 1.9 ± 0.3 %. This new R_1ρ functional contrast can be made selectively sensitive to intrinsic gradients of different spatial scales, thereby increasing the spatial specificity of the evoked response.     

Short echo time proton spectroscopy of the brain in healthy volunteers using an insert gradient head coil

An insert gradient head coil with built-in X, Y, and Z gradients was used for localized proton spectroscopy in the brain of healthy volunteers, using short echo time stimulated echo acquisition mode (STEAM) sequences. Volume of interest size was 3.4 ml, repetition time was 6.0 s, and echo times were 10 and 20 ms, respectively. Good quality proton spectra with practically no eddy current artefacts were acquired allowing observation of strongly coupled compounds, and compounds with short T₂ relaxation times. The gradient head coil thus permits further studies of compounds such as glutamine/glutamate and myo-inositols. These compounds were more prominent within grey matter than within white matter. Rough estimations of metabolite concentrations using water as an internal standard were in good agreement with previous reports.     

Molecular Diffusion in NMR Microscopy

The signal-to-noise ratio and the T₂ contrast in ¹H NMR microscopy are strongly affected by self-diffusion effects. Here, we investigate the free diffusion of water within imaging gradients. As a result we obtain an apparent relaxation time T₂ which in NMR microscopy is at least one order of magnitude smaller than the true T₂ value of water in the object. This apparent T₂ relaxation is considerably reduced by improving spatial resolution. We conclude that quantitative true T₂ values cannot be calculated from series of images with increasing echo time. Furthermore, from the knowledge of the apparent T₂, an optimum short echo time can be found in order to maximize signal-to-noise ratio. Our theoretical findings are confirmed by phantom experiments at 11.75 T field strength.     

Multifrequency photon echo generated by extremely short pulses

A photon echo in a multilevel quantum medium excited by two extremely short pulses with durations of less than one period of oscillation of the light is investigated theoretically. It is shown thatQ echo signals (Q is the number of allowed transitions) can form at each frequency of the allowed transitions, and the number of echo responses for all the allowed transitions equalsQ ². Of these,Q(Q?1) signals are separated in both time and space. The otherQ echo signals of all the allowed frequencies all arise at the time 2τ ₂₁ (τ ₂₁ is the time interval between application of the first and second pulses to the medium) and are collinear with one another.     

Structural Analysis of Relaxation Curves in MRI

In magnetic resonance imaging, the gradient recalled echo sequence preserves information about spatial heterogeneities of magnetic field within a voxel, providing additional opportunity for classification of biological tissues. All the information, composed of physically meaningful parameters, like proton density, spin–spin relaxation time T ₂, gradients of magnetic field and spin–spin relaxation, effective relaxation time \(T_{2}^{*}\), and many others, is encoded in the shape of a relaxation curve, which is more complicated than a pure monoexponent, traditionally observed in spin echo sequences. The previous work [A. Protopopov, Appl. Magn. Reason. 48, 255-274 (2017)], introduced the theory and basic algorithms for separation of those parameters. The present work further expands this theory to the case of spin–spin relaxation gradients, improves reliability of the algorithms, introduces physical explanation of the phenomenon previously known as “multiexponentiality”, and presents new validation of the algorithms on volunteers. The entire approach may be named the structural analysis of relaxation curves.     

Spectra of multiquantum echo signals from quadrupole nuclei with half-integral spin in magnetically ordered materials

The numerical simulation of two-pulse echo signals at times 2τ, 4τ, and 6τ for the I=5/2 spin and at time 2τ, 4τ, and 8τ for the I=7/2 spin (τ is the time interval between exciting pulses) is carried out. It is shown that a delay by 2τ in the moment of formation of the echo results in the disappearance of extreme quadrupole satellites in the NMR spectrum obtained by recording the frequency dependence of the echo amplitude. The echoes at the maximum possible time of formation (2I+1)τ are only observed at the frequency of the purely magnetic spectroscopic transition $ \pm \frac{1}{2} \rightleftarrows \mp \frac{1}{2}$ ; no such echoes are observed at the quadrupole satellite frequencies. The computations are compared with the experimental results obtained for the ⁵⁵Mn nuclei (spin I=5/2) in the perovskite GdCu₃Mn₄O₁₂ and the spinel Li_0.5Fe_2.5O₄: Mn.     

Effect of the amplitude of excitation pulses on the shape of photon-echo signals in two-level systems

It is theoretically established that multiple photon-echo signals reflect the oscillatory structure of the primary echo signal, which arises under the conditions of collinear excitation of two-level active centers by laser pulses having the same width but different amplitudes. It is shown that the oscillatory structure of the primary photon echo exists within the intervals (?t ₁, t ₁) and (?2t ₁, 2t ₁), where t ₁ is the pulse width. It is found that, when the pulse width is of the same order of magnitude as the delay between the pulses and the amplitudes of the excitation pulses obey certain relations, the oscillatory structure of the primary photon-echo signal becomes asymmetric. In the mode of quadratic detection of the primary photon-echo signal, the asymmetric oscillatory structure of the primary echo manifests itself as a manifold of isolated signals (multiple photon echoes), with the time intervals between these signals being equal to the pulse width.