T2 Decay Research Articles

“Perfect echo” INEPT: More efficient heteronuclear polarization transfer by refocusing homonuclear J-coupling interaction

A “perfect echo” based INEPT experiment that demonstrates more efficient heteronuclear polarization transfer over conventional INEPT has been developed. This scheme refocuses the effect of homonuclear 1H–1H J-evolution and simultaneously allows heteronuclear 13C–1H J-evolution to continue during INEPT. This improves one bond heteronuclear polarization transfer efficiency at longer INEPT transfer delays and also enhances the sensitivity of long range INEPT. The refocusing of homonuclear 1H–1H J-coupling could be achieved by doubling the INEPT transfer period leading to a doubling of T2 losses. Therefore, the sensitivity gain is observed when loss of magnetization due to homonuclear 1H–1H J-modulation is more severe than that of T2 decay. However, in general, INEPT transfer period is rather short compared to the longer T2 observed in small molecules. The long range PE-INEPT transfer to carbonyl carbon in beta-butyrolactone, showed much faster build up of C-13 signal than conventional long range INEPT as the long range heteronuclear J-coupling is comparable in magnitude to homonuclear 1H-1H J-coupling in this case. For one bond heteronuclear polarization transfer at shorter delay, PE-INEPT and conventional INEPT displays equal transfer efficiency. Efficient polarization transfer is observed for small molecules dissolved in isotropic as well as weakly aligned media. Further, simulation results obtained using the full propagator and product operator analysis agree well with the experimental observations.

31P magnetic resonance spectroscopy of the breast and the influence of the menstrual cycle

Phosphorus metabolite ratios are potential biomarkers in breast cancer diagnosis and treatment monitoring. Our purpose was to investigate the metabolite ratios phosphomonoester to phosphodiester, phosphoethanolamine (PE) to glycerophosphoethanolamine (GPE), and phosphocholine (PC) to glycerophosphocholine (GPC) in glandular breast tissue, and the potential effect of the menstrual cycle, using (31)P magnetic resonance spectroscopy (MRS) at 7T. Seven women with regular menstrual cycles each underwent four examinations using a 3D (31)P multi-echo magnetic resonance spectroscopic imaging sequence. Peak integrals were assessed using IDL and JMRUI software. First, T2 relaxation times were calculated using multi-echo data pooled across subjects and time points. Subsequent, metabolite ratios were calculated for each phase of the menstrual cycle using the calculated T2 values to account for when combining the free induction decay and all five echoes. The metabolite ratios were calculated both on group level and individually. T2 decay fits resulted in a T2 relaxation time for PE of 154 ms (95 % CI 144-164), for PC of 173 ms (95 % CI 148-205), for Pi of 188 ms (95 % CI 182-193), for GPE of 48 ms (95 % CI 44-53), and for GPC of 23 ms (95 % CI 21-26). The metabolite ratios analyzed on group level showed negligible variation throughout the menstrual cycle. Individual results did show an apparent intra-individual variation; however, not significant due to the measurements' uncertainty. To conclude, phospholipids in glandular tissue as measured with (31)P MRS at 7 T are not significantly affected by the menstrual cycle.

Comparison of myelin water fraction from multiecho T2 decay curve and steady‐state methods

Myelin water fraction is conventionally measured from the T2 decay curve. Recently, a steady-state approach entitled multicomponent-driven equilibrium single pulse observation of T1 /T2 (mcDESPOT) was employed for myelin water fraction mapping. However, no direct comparison between the established multiecho T2 relaxation method and mcDESPOT has been performed. Gradient and spin echo (GRASE) acquired T2 decay curve and mcDESPOT measurements were acquired from 10 healthy volunteers using a 3T MRI. We compared myelin water fraction, transmit radio frequency field (B1 ), and T2 's of intra- and extracellular water obtained from both methods. For all brain regions examined, myelin water fractions from mcDESPOT were significantly higher than those from multiecho GRASE. B1 maps were qualitatively similar between GRASE and mcDESPOT, but multicomponent T2 times were significantly different. To investigate the effect of exchange, mcDESPOT data were analyzed with and without exchange. When exchange was turned off, intra- and extracellular T2 times from mcDESPOT were roughly consistent with GRASE results; however, myelin water fractions derived from mcDESPOT were still significantly higher than those derived from GRASE. Myelin water fraction values derived from mcDESPOT cannot be considered to be equivalent to those derived from T2 decay curve approaches.

Signal and contrast effects due to T2 decay during k-space readout of UTE (ultrashort TE) sequences

In ultrashort TE (UTE) imaging, the short T2 values of the tissues of interest are comparable to the k-space readout duration, which result in significant T2 decay during k-space readout. This decay consequently causes significant effects on signal and contrast in UTE sequences, which we evaluate in this paper using models that incorporate the gradient slew rate slew and maximal constant gradient strength gmax, in conjunction with objects of diameter L. The resulting signal and contrast relationships demonstrate steep signal changes between T2 values of ~50–500μs, corresponding to high T2 weighted contrast in this range. When γ⋅gmax2/(4π⋅slew)>1/(2L), termed the “ramp only” regime, gmax has no significant effect whereas decreasing slew leads to decreases in signal amplitude and shifts the contrast peak to higher T2 values. When γ⋅gmax2/(4π⋅slew)<1/(2L), termed the “mixed gradient” regime, both gmax and slew have significant effects, where decreases in either gmax or slew lead to lower signal amplitudes and shifts the contrast peak to higher T2 values. Under typical scan settings, the “ramp only” regime is usually dominant. Further, we demonstrate an unusual dependence of T2 weighted signal and contrast on object size, whereby objects with smaller values of L demonstrate lower signal amplitudes and peak contrast at higher T2 values, compared to otherwise identical objects with larger L. These results improve understanding of T2 weighted signal and contrast properties in short T2 tissue imaging with UTE.

Spatially resolved measurements of mean spin–spin relaxation time constants

Magnetic Resonance measurements of the T2 distribution have become very common and they are a powerful way to probe microporous fluid bearing solids. While the structure of the T2 distribution, and changes in the structure, are often very informative, it is common to reduce the T2 distribution to a mean numeric quantity in order to provide a quantitative interpretation of the distribution. Magnetic Resonance Imaging measurements of the T2 distribution have recently been introduced, but they are time consuming, especially for 2 and 3 spatial dimensions.In this paper we explore a direct MRI measurement of the arithmetic mean of 1/T2, characterizing the distribution by using the initial slope of the spatially resolved T2 decay in a CPMG prepared Centric Scan SPRITE experiment. The methodology is explored with a test phantom sample and realistic petroleum reservoir core plug samples. The arithmetic mean of 1/T2 is related to the harmonic mean of T2. The mean obtained from the early decay is explored through measurements of uniform saturated core plug samples and by comparison to other means determined from the complete T2 distribution. Complementary data were obtained using SE-SPI T2 distribution MRI measurements.The utility of the arithmetic mean 1/T2 is explored through measurements of centrifuged core plug samples where the T2 distribution varies spatially. The harmonic mean T2 obtained from the early decay was employed to estimate the irreducible water saturation for core plug samples.

Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse

Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the pathways that can be studied are limited by the fast T1 decay of the nuclear spin order. In metabolites containing pairs of coupled nuclear spins-1/2, the spin order may be maintained by exploiting the non-magnetic singlet (spin-0) state of the pair. This may allow preservation of the hyperpolarization in vivo during transport to tissues of interest, such as tumors, or to detect slower metabolic reactions. We show here that in human blood and in a mouse in vivo at millitesla fields the 13C singlet lifetime of [1,2-13C2]pyruvate was significantly longer than the 13C T1, although it was shorter than the T1 at field strengths of several tesla. We also examine the singlet-derived NMR spectrum observed for hyperpolarized [1,2-13C2]lactate, originating from the metabolism of [1,2-13C2]pyruvate. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.

Relaxation by amplitude modulation: A rapid T1 measurement method

A novel longitudinal relaxation time (T1 ) measurement method using complex amplitude modulation is presented. The method applies a series of inversion pulses to the imaged region in accordance with a binary modulation sequence. The longitudinal magnetization acquired in a given pulse repetition time (TR) interval is the sum of the individual longitudinal magnetization recovered during each previous TR interval, weighted by T1 decay factors and the combined effect of all the radiofrequency pulses they have experienced. The demodulated signal for each voxel is an exponential curve with a decaying rate determined by T1 and the acquisition flip angle θ. Sequences using a 15-cycle pseudorandom binary code were implemented on Siemens 3T Trio with standard gradient echo readout and multislice gradient echo-planar imaging. The sequences were tested on T1 phantoms and human and compared against inversion recovery method. Our studies on phantoms and a human volunteer show that T1 estimated from this method is very accurate and well reproducible. The average scan time is ∼1.6 s per slice (full k-space gradient echo-planar imaging with matrix size 128 × 128). The current protocol is almost twice as fast as two fastest existing methods. Optimizing protocols and incorporating common acceleration techniques will make it even faster.

In vivo GABA T2 determination with J‐refocused echo time extension at 7 T

A method to measure the T2 relaxation time of GABA with spectral editing techniques is proposed. Spectral editing techniques can be used to unambiguously extract signals of low concentration J-coupled spins such as γ-aminobutyric acid (GABA) from overlapping resonances such as creatine and macromolecules. These sequences, however, generally have fixed and relatively long echo times. Therefore, for the absolute quantification of the edited spectrum, the T2 relaxation time must be taken into account. To measure the T2 relaxation time, the signal intensity has to be obtained at multiple echo times. However, on a coupled spin system such as GABA this is challenging, since the signal intensity of the target resonances is modulated not only by T2 decay but also by the J-coupling, which strongly influences the shapes and amplitudes of the edited signals, depending on the echo time. Here, we propose to refocus the J-modulation of the edited signal at different echo times by using chemical shift selective refocusing. In this way the echo time can be arbitrarily extended while preserving the shape of the edited signal. The method was applied in combination with the MEGA-sLASER editing technique to measure the in vivo T2 relaxation time of GABA (87 ± 11 ms, n = 10) and creatine (109 ± 8 ms, n = 10) at 7 T. The T1 relaxation time of these metabolites in a single subject was also determined (GABA, 1334 ± 158 ms; Cr, 1753 ± 12 ms). The T2 decay curve of coupled spin systems can be sampled in an arbitrary fashion without the need for signal shape correction. Furthermore, the method can be applied with any spectral editing technique. The shortest echo time of the method is limited by the echo time of the spectral editing technique.

Storage of Hydrogen Spin Polarization in Long-Lived 13C2 Singlet Order and Implications for Hyperpolarized Magnetic Resonance Imaging

Hyperpolarized magnetic resonance imaging (MRI) is a powerful technique enabling real-time monitoring of metabolites at concentration levels not accessible by standard MRI techniques. A considerable challenge this technique faces is the T1 decay of the hyperpolarization upon injection into the system under study. Here we show that A(n)A'(n)XX' spin systems such as (13)C2-1,2-diphenylacetylene ((13)C2-DPA) sustain long-lived polarization for both (13)C and (1)H spins with decay constants of almost 4.5 min at high magnetic fields of up to 16.44 T without spin-locking; the T1 of proton polarization is only 3.8 s. Therefore, storage of the proton polarization in a (13)C2-singlet state causes a 69-fold extension of the spin lifetime. Notably, this extension is demonstrated with proton-only pulse sequences, which can be readily implemented on standard clinical scanners.

Optimal variable flip angle schemes for dynamic acquisition of exchanging hyperpolarized substrates

In metabolic MRI with hyperpolarized contrast agents, the signal levels vary over time due to T1 decay, T2 decay following RF excitations, and metabolic conversion. Efficient usage of the nonrenewable hyperpolarized magnetization requires specialized RF pulse schemes. In this work, we introduce two novel variable flip angle schemes for dynamic hyperpolarized MRI in which the flip angle is varied between excitations and between metabolites. These were optimized to distribute the magnetization relatively evenly throughout the acquisition by accounting for T1 decay, prior RF excitations, and metabolic conversion. Simulation results are presented to confirm the flip angle designs and evaluate the variability of signal dynamics across typical ranges of T1 and metabolic conversion. They were implemented using multiband spectral–spatial RF pulses to independently modulate the flip angle at various chemical shift frequencies. With these schemes we observed increased SNR of [1-13C]lactate generated from [1-13C]pyruvate, particularly at later time points. This will allow for improved characterization of tissue perfusion and metabolic profiles in dynamic hyperpolarized MRI.

Analysis of local projected current density from one component of magnetic flux density in MREIT

Magnetic resonance electrical impedance tomography is a new modality capable of imaging the static electrical conductivity of an object by measuring Bz data, a component of the magnetic flux density B = (Bx, By, Bz), perturbed by an external injection current. In an imaging area, the current density J induced by the external injection current can be uniquely decomposed into a recoverable component JP and an invisible component from the measured Bz data. In the case of in vivo animal and human imaging experiments, the imaging area frequently includes local defective regions with a low signal-to-noise ratio. As a result, the measured Bz data in the defective regions include serious noise due to rapid T2 decay, a small amount of internal current density and weak MR signals. In this paper, we propose an algorithm to reconstruct a recoverable current density from the measured Bz data in a local region avoiding the defective regions. We estimate the L2-norm of the difference between the induced internal current density J and the locally recovered from the measured Bz data in the local region . The difference only depends on the z-components of J and J0 and the values of Bx and By on the boundary , where J0 is the background current density by the injected current. Numerical simulations and phantom experiments demonstrate that the proposed method directly reconstructs a local current density avoiding noise effects in defective regions.

Sideband separation experiments in NMR with phase incremented echo train acquisition

A general approach for enhancing sensitivity of nuclear magnetic resonance sideband separation experiments, such as Two-Dimensional One Pulse (TOP), Magic-Angle Turning (MAT), and Phase Adjust Spinning Sidebands (PASS) experiments, with phase incremented echo-train acquisition (PIETA) is described. This approach is applicable whenever strong inhomogeneous broadenings dominate the unmodulated frequency resonances, such as in non-crystalline solids or in samples with large residual frequency anisotropy. PIETA provides significant sensitivity enhancements while also eliminating spectral artifacts would normally be present with Carr-Purcell-Meiboom-Gill acquisition. Additionally, an intuitive approach is presented for designing and processing echo train acquisition magnetic resonance experiments on rotating samples. Affine transformations are used to relate the two-dimensional signals acquired in TOP, MAT, and PASS experiments to a common coordinate system. Depending on sequence design and acquisition conditions two significant artifacts can arise from truncated acquisition time and discontinuous damping in the T2 decay. Here we show that the former artifact can always be eliminated through selection of a suitable affine transformation, and give the conditions in which the latter can be minimized or removed entirely.

Temporal phase correction of multiple echo T2 magnetic resonance images

Typically, magnetic resonance imaging (MRI) analysis is performed on magnitude data, and multiple echo T2 data consist of numerous images of the same slice taken with different echo spacing, giving voxel-wise temporal sampling of the noise as the signals decay according to T2 relaxation. Magnitude T2 decay data has Rician distributed noise which is characterized by a change in the noise distribution from Gaussian, through a transitional region, to Rayleigh as the signal to noise ratio decreases with increasing echo time. Non-Gaussian noise distributions may produce errors in the commonly applied non-negative least squares (NNLS) algorithm that is used to assess multiple echo decays for compartmentalized water environments through the creation of T2 distributions. Typically, Gaussian noise is sought by performing spatial-based phase correction on the MRI data however, these methods cannot capitalize on the temporal information available from multiple echo T2 acquisitions. Here we describe a temporal phase correction (TPC) algorithm that utilizes the temporal noise information available in multiple echo T2 acquisitions to put the relevant decay information in the Real portion of the decay data and leave only noise in the Imaginary portion. We apply this TPC algorithm to create real-valued multiple echo T2 data from human subjects measured at 1.5T. We show that applying TPC causes changes in the T2 distribution estimates; notably the possible resolution of separate extracellular and intracellular water environments, and the disappearance of the commonly labeled cerebrospinal fluid peak, which might be an artefact observed in many previously published multiple echo T2 analyses.

T 2 relaxometry measurements in low spatial frequency brain regions differ between fast spin-echo and multiple-echo spin-echo sequences

Dual-echo fast spin-echo (FSE) sequences are used in T2 relaxometry studies of neurological disorders because of shorter clinical scanning times and protocol simplicity. However, FSE sequences have possible spatial frequency-dependent effects, and derived T2 values may include errors that depend on the spatial frequency characteristics of the brain region of interest. Dual-echo FSE and multi-echo spin-echo (MESE) sequences were acquired in nine subjects. The T2 decay curves for FSE and MESE sequences were estimated and percent error maps were generated. T2 error values were obtained along each patient's corticospinal tract (CST). Whole-brain white matter (WM) and gray matter (GM) T2 error values were also obtained. The paired t test was performed to evaluate differences in T2 values in the CST between FSE and MESE sequences. Histograms of error values in CST and in whole-brain WM and GM structures revealed systematic errors in FSE sequences. Significant differences (P < 0.001) in CST T2 values were also observed between FSE and MESE sequences. Our findings indicate that T2 values derived from FSE sequences are prone to large errors, even in low spatial frequency regions such as the CST, when compared to MESE sequences. Future studies should be aware of this limitation of FSE sequences.

Density weighted turbo spin echo imaging

To optimize the spatial response function (SRF) while maintaining optimal signal to noise ratio (SNR) in T2 weighted turbo spin echo (TSE) imaging by prospective density weighting. Density weighting optimizes the SRF by sampling the k-space with variable density without the need of retrospective filtering, which would typically result in nonoptimal SNR. For TSE, the T2 decay needs to be considered when calculating an optimized sampling pattern. Simulations were carried out and T2 weighted in vivo TSE measurements were performed on a 3 Tesla MRI system. To evaluate the SNR, reversed centric density weighted and retrospectively filtered Cartesian acquisitions with identical measurement parameters and SRFs were compared with TE(eff) = 90 ms and a density weighted k-space sampling optimized to yield a Kaiser function for SRF side lobe suppression for white matter. Density weighting of a reversed centric reordering scheme resulted in an SNR increase of (43 ± 13)% compared with the Cartesian acquisition with retrospective filtering while maintaining comparable contrast behavior. Density weighting is applicable to TSE imaging and results in significantly increased SNR. The gain can be used to shorten the measurement time, which suggests applying density weighting in both time and SNR constrained MRI.

Combined parallel and partial fourier MR reconstruction for accelerated 8-channel hyperpolarized carbon-13 in vivo magnetic resonance Spectroscopic imaging (MRSI).

To implement and evaluate combined parallel magnetic resonance imaging (MRI) and partial Fourier acquisition and reconstruction for rapid hyperpolarized carbon-13 ((13) C) spectroscopic imaging. Short acquisition times mitigate hyperpolarized signal losses that occur due to T1 decay, metabolism, and radiofrequency (RF) saturation. Human applications additionally require rapid imaging to permit breath-holding and to minimize the effects of physiologic motion. Numerical simulations were employed to validate and characterize the reconstruction. In vivo MR spectroscopic images were obtained from a rat following injection of hyperpolarized (13) C pyruvate using an 8-channel array of carbon-tuned receive elements. For small spectroscopic matrix sizes, combined parallel imaging and partial Fourier undersampling resulted primarily in decreased spatial resolution, with relatively less visible spatial aliasing. Parallel reconstruction qualitatively restored lost image detail, although some pixel spectra had persistent numerical error. With this technique, a 30 × 10 × 16 matrix of 4800 3D MR spectroscopy imaging voxels from a whole rat with isotropic 8 mm(3) resolution was acquired within 11 seconds. Parallel MRI and partial Fourier acquisitions can provide the shorter imaging times and wider spatial coverage that will be necessary as hyperpolarized (13) C techniques move toward human clinical applications.

Impact of T2 decay on carotid artery wall thickness measurements

To investigate the impact of T2 relaxation of the carotid wall on measurements of its thickness. The common carotid artery wall was imaged using a spin echo sequence acquired at four echo times (17 ms to 68 ms) in 65 participants as part of VALIDATE study. Images were acquired transverse to the artery 1.5 cm proximal to the flow divider. Mean wall thickness, mean wall signal intensity, lumen area, and outer wall area were measured for each echo. Contours were also traced on the image from the fourth echo and then propagated to the images from the preceding echoes. This was repeated using the image from the first echo. Mean wall signal intensity measurements at the four echo times were fit to a mono-exponential decay curve to derive the mean T2 relaxation time for each set of contours. Mean wall thickness decreased with increasing echo time, with an average thickness reduction of 8.6% between images acquired at the first and last echo times (TE) (0.93 mm at TE 17 ms versus 0.85 mm at TE 68 ms, P < 0.001). Average T2 relaxation time of the carotid wall decreased by 3% when the smaller contours from the last echo were used, which excluded the outer-most layer (54.3 ± 7.6 ms versus 52.7 ± 6.6 ms, P = 0.03). Carotid wall thickness measurements decrease with echo time as expected by the fast T2 relaxation time of the outer-most layer, namely the adventitia. A short echo time is needed for thickness measurements to include adventitia, which plays an important role in plaque development.

Measuring Biexponential Transverse Relaxation of the ASL Signal at 9.4 T to Estimate Arterial Oxygen Saturation and the Time of Exchange of Labeled Blood Water into Cortical Brain Tissue

The transverse decay of the arterial spin labeling (ASL) signal was measured at four inflow times in the rat brain cortex at 9.4 T. Biexponential T2 decay was observed that appears to derive from different T2 values associated with labeled water in the intravasculature (IV) and extravascular (EV) compartments. A two compartment biexponential model was used to assess the relative contribution of the IV and EV compartments to the ASL signal, without assuming a value for T2 of labeled blood water in the vessels. This novel methodology was applied to estimate the exchange time of blood water into EV tissue space and the oxygen saturation of blood on the arterial side of the vasculature. The mean exchange time of labeled blood water was estimated to be 370±40 ms. The oxygen saturation of the arterial side of the vasculature was significantly less than 100% (∼85%), which may have implications for quantitative functional magnetic resonance imaging studies where the arterial oxygen saturation is frequently assumed to be 100%.

A Robust Ultrashort TE (UTE) Imaging Method With Corrected k-Space Trajectory by Using Parametric Multiple Function Model of Gradient Waveform

Ultra-short TE (UTE) sequences with radial sampling make it possible to visualize tissues with very short T2 decay times. The UTE sequence acquires an echo signal from the central to the outer parts of k-space and is very sensitive to small trajectory errors. Therefore, k-space errors caused by imperfections in the gradient system performance, such as gradient delay and waveform distortion, must be corrected. During normal clinical use, these errors must be corrected to account for any gradient strength, or image obliquity. Because of time limitation on clinical examination, a simple, robust, and time-efficient correction method for use with UTE is needed. We demonstrated image degradation due to k-space errors by simulation and found that uncontrolled gradient time delays were the dominant cause of image degradation. They could be corrected by using a pre-scan calibration that works by comparison of half and full echo signals. Further improvements in image quality were achieved by using a one-time calibration of gradient waveform approximations that were built from multiple exponential functions and were used during image reconstruction. We have developed a robust UTE correction method that consists of a gradient waveform approximation that follows a short pre-scan for estimating gradient time delay errors.

A rapid method for direct detection of metabolic conversion and magnetization exchange with application to hyperpolarized substrates

In this work, we present a new MR spectroscopy approach for directly observing nuclear spins that undergo exchange, metabolic conversion, or, generally, any frequency shift during a mixing time. Unlike conventional approaches to observe these processes, such as exchange spectroscopy (EXSY), this rapid approach requires only a single encoding step and thus is readily applicable to hyperpolarized MR in which the magnetization is not replenished after T1 decay and RF excitations. This method is based on stimulated-echoes and uses phase-sensitive detection in conjunction with precisely chosen echo times in order to separate spins generated during the mixing time from those present prior to mixing. We are calling the method Metabolic Activity Decomposition Stimulated-echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as applied it in vivo to normal mice and a transgenic prostate cancer mouse model for observing pyruvate–lactate conversion, which has been shown to be elevated in numerous tumor types. In this application, it provides an improved measure of cellular metabolism by separating [1-13C]-lactate produced in tissue by metabolic conversion from [1-13C]-lactate that has flowed into the tissue or is in the blood. Generally, MAD-STEAM can be applied to any system in which spins undergo a frequency shift.