Double spin-echo sequence for rapid spectroscopic imaging of hyperpolarized 13C

Dynamic nuclear polarization of metabolically active compounds labeled with (13)C has been introduced as a means for imaging metabolic processes in vivo. To differentiate between the injected compound and the various metabolic products, an imaging technique capable of separating the different chemical-shift species must be used. In this paper, the design and testing of a pulse sequence for rapid magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized (13)C is presented. The pulse sequence consists of a small-tip excitation followed by a double spin echo using adiabatic refocusing pulses and a "flyback" echo-planar readout gradient. Key elements of the sequence are insensitivity to calibration of the transmit gain, the formation of a spin echo giving high-quality spectral information, and a small effective tip angle that preserves the magnetization for a sufficient duration. Experiments in vivo showed three-dimensional coverage with excellent spectral quality and SNR.     

Spin tagging for hyperpolarized ¹³C metabolic studies

In studies utilizing pre-polarized (13)C substrates to investigate metabolic activities in vivo, the metabolite signals observed in a region or a voxel contains a mixture of intracellular and extracellular components. This extracellular component arriving via perfusion may confound the measurements of metabolic flux or exchange rates. But if spin tagging is performed on the magnetization of the substrate, it may be possible to measure the signals of the metabolic products in the intracellular space that were derived from the tagged substrate spins locally. In this study, a spin tagging pulse sequence designed for acquiring data from spatially tagged longitudinal magnetization in hyperpolarized (13)C metabolic studies was presented and tested. Using a spectral-spatial RF pulse during the tagging preparation enabled the observation of metabolite signals derived exclusively from the tagged substrate in vivo.     

Slice-selective excitation with B₁⁺-insensitive composite pulses

Spatially selective excitation pulses have been designed to produce uniform flip angles in the presence of the RF and static field inhomogeneities typically encountered in MRI studies of the human brain at 7 T. Pulse designs are based upon non-selective, composite pulses numerically optimized for the desired performance over prescribed ranges of field inhomogeneities. The non-selective pulses are subsequently transformed into spatially selective pulses with the same field-insensitive properties through modification of the spectral composition of the individual sub-pulses which are then executed in conjunction with an oscillating gradient waveform. An in-depth analysis of the performance of these RF pulses is presented in terms of total pulse durations, slice profiles, linearity of in-slice magnetization phase, sensitivity to RF and static field variations, and signal loss due to T(2) effects. Both simulations and measurements in phantoms and in the human brain are used to evaluate pulses with nominal flip angles of 45° and 90°. Target slice thickness in all cases is 2mm. Results indicate that the described class of field-insensitive RF pulses is capable of improving flip-angle uniformity in 7 T human brain imaging. There appears to be a subset of pulses with durations ?10 ms for which non-linearities in the magnetization phase are minimal and signal loss due to T(2) decay is not prohibitive. Such pulses represent practical solutions for achieving uniform flip angles in the presence of the large field inhomogeneities common to high-field human imaging and help to better establish the performance limits of high-field imaging systems with single-channel transmission.     

An improved 3-D Look--Locker imaging method for T(1) parameter estimation

The 3-D Look-Locker (LL) imaging method has been shown to be a highly efficient and accurate method for the volumetric mapping of the spin lattice relaxation time T(1). However, conventional 3-D LL imaging schemes are typically limited to small tip angle RF pulses (5 degrees ), thereby improving the SNR and the accuracy of the method. In phantom studies, a mean T(1) measurement accuracy of less than 2% (0.2-3.1%) using a tip angle of 10 degrees was obtained for a range of T(1) from approximately 300 to 1,700 ms with a measurement time increase of only 15%. This accuracy compares favorably with the conventional 3-D LL method that provided an accuracy between 2.2% and 7.3% using a 5 degrees flip angle.     

Large angle spin-echo imaging

A study was undertaken to assess the use of excitation flip angles greater than 90° for T₁ weighted spin-echo (SE) imaging with a single 180° refocusing pulse and short TR values. Theoretical predictions of signal intensity for SE images with excitation pulse angles of 90–180° were calculated based on the Bloch equations and then measured experimentally from MR images of MnCl₂ phantoms of various concentrations. Liver signal-to-noise ratios (SNR) and liver-spleen contrast-to-noise ratios (CNR) were measured from breathhold MR images of the upper abdomen in 16 patients using 90 and 110° excitation flip angles. The theoretical predictions showed significant improvements in SNR with excitation flip angles >90°, which were more pronounced at small TR values. The phantom studies showed reasonably good agreement with the theoretical predictions in correlating the excitation pulse angle with signal intensity. In the human imaging studies, the 110° excitation pulse angle resulted in a 7.4% (p < .01) increase in liver SNR and an 8.2% (p = .2) increase in liver-spleen CNR compared to the 90° pulse angle at TR = 275 ms. Increased signal intensity resulting from the use of large flip angle excitation pulses with a single echo SE pulse sequence was predicted and confirmed experimentally in phantoms and humans.     

RF pulse concatenation for spatially selective inversion

It is shown that spatially selective inversion and saturation can be achieved by concatenation of RF pulses with lower flip angles. A concatenation rule which enables global doubling of the flip angle of any given excitation pulse applied to initial z magnetization is proposed. In this fashion, the selectivity of the single pulse is preserved, making the high selectivity achievable in the low flip-angle regime available for inversion and large flip-angle saturation purposes. The profile quality achievable with exemplary concatenated pulses is investigated in comparison with adiabatic inversion. It is verified that by using concatenated inversion in the transfer insensitive labeling technique (TILT), the MT artifact is suppressed. Copyright 2000 Academic Press.     

Maximizing MR signal for 2D UTE slice selection in the presence of rapid transverse relaxation

Ultrashort TE (UTE) sequences allow direct visualization of tissues with very short T2 relaxation times, such as tendons, ligaments, menisci, and cortical bone. In this work, theoretical calculations, simulations, and phantom studies, as well as in vivo imaging were performed to maximize signal-to-noise ratio (SNR) for slice selective RF excitation for 2D UTE sequences. The theoretical calculations and simulations were based on the Bloch equations, which lead to analytic expressions for the optimal RF pulse duration and amplitude to maximize magnetic resonance signal in the presence of rapid transverse relaxation. In steady state, it was found that the maximum signal amplitude was not obtained at the classical Ernst angle, but at an either lower or higher flip angle, depending on whether the RF pulse duration or amplitude was varied, respectively.     

Signal intensities in FLASH-EPI-hybrid sequences.

Theoretical considerations on the signal-to-noise ratio (SNR) in FLASH-EPI-Hybrid imaging were published previously. The purpose of this work was to investigate in vivo the signal intensities in Hybrid images as a function of sequence specific parameters. In detail, the SNR as a function of the number of echoes m per RF excitation, the excitation flip angle alpha, and the dependence on the tissue relaxation times T1 and T2* were studied. In eight healthy subjects brain and abdominal Hybrid images were acquired where m and alpha were changed independently. Signal intensities in human brain, liver, and kidney were evaluated for each Hybrid experiment. Additionally, T1 and T2* values of these tissue types were quantified to allow for a comparison with the theory. An excellent agreement between calculated and measured signal behavior was found. The theory was therefore validated in vivo and can thus be used to optimize the signal-to-noise in Hybrid experiments.     

High-flip-angle slice-selective parallel RF transmission with 8 channels at 7 T

At high magnetic field, B(1)(+) non-uniformity causes undesired inhomogeneity in SNR and image contrast. Parallel RF transmission using tailored 3D k-space trajectory design has been shown to correct for this problem and produce highly uniform in-plane magnetization with good slice selection profile within a relatively short excitation duration. However, at large flip angles the excitation k-space based design method fails. Consequently, several large-flip-angle parallel transmission designs have recently been suggested. In this work, we propose and demonstrate a large-flip-angle parallel excitation design for 90 degrees and 180 degrees spin-echo slice-selective excitations that mitigate severe B(1)(+) inhomogeneity. The method was validated on an 8-channel transmit array at 7T using a water phantom with B(1)(+) inhomogeneity similar to that seen in human brain in vivo. Slice-selective excitations with parallel RF systems offer means to implement conventional high-flip excitation sequences without a severe pulse-duration penalty, even at very high B(0) field strengths where large B(1)(+) inhomogeneity is present.     

Equi-ripple design of quadratic-phase RF pulses

An improved strategy for the design of quadratic-phase RF pulses with high selectivity and broad bandwidths using the Shinnar-Le Roux (SLR) transformation is proposed. Unlike previous implementations, the required quadratic-phase finite impulse response (FIR) filters are generated using the complex Remez exchange algorithm, which ensures an equi-ripple deviation from the ideal response function. It is argued analytically that quadratic-phase pulses are near-optimal in terms of minimising the B1-amplitude for a given bandwidth and flip angle. Furthermore, several parameter relations are derived, providing practical design guidelines. The effectiveness of the proposed design method is demonstrated by examples of excitation and saturation pulses applied in vitro and in vivo.     

On the use of steady-state signal equations for 2D TrueFISP imaging

To explain the signal behavior in 2D-TrueFISP imaging, a slice excitation profile should be considered that describes a variation of effective flip angles and magnetization phases after excitation. These parameters can be incorporated into steady-state equations to predict the final signal within a pixel. The use of steady-state equations assumes that excitation occurs instantaneously, although in reality this is a nonlinear process. In addition, often the flip angle variation within the slice excitation profile is solely considered when using steady-state equations, while TrueFISP is especially known for its sensitivity to phase variations. The purpose of this study was therefore to evaluate the precision of steady-state equations in calculating signal intensities in 2D TrueFISP imaging. To that end, steady-state slice profiles and corresponding signal intensities were calculated as function of flip angle, RF phase advance and pulse shape. More complex Bloch simulations were considered as a gold standard, which described every excitation within the sequence until steady state was reached. They were used to analyze two different methods based on steady-state equations. In addition, measurements on phantoms were done with corresponding imaging parameters. Although the Bloch simulations described the steady-state slice profile formation better than methods based on steady-state equations, the latter performed well in predicting the steady-state signal resulting from it. In certain cases the phase variation within the slice excitation profile did not even have to be taken into account.     

Spectrally-Presaturated Modulation (SPM): An efficient fat suppression technique for STEAM-based cardiac imaging sequences

Stimulated-echo acquisition mode (STEAM) is a key pulse sequences in MRI in general, and in cardiac imaging in particular. Fat suppression is an important feature in cardiac imaging to improve visualization and eliminate off-resonance and chemical-shift artifacts. Nevertheless, fat suppression comes at the expense of reduced temporal resolution and signal-to-noise ratio (SNR). The purpose of this study is to develop an efficient fat suppression method (Spectrally-Presaturated Modulation) for STEAM-based sequences to enable imaging with high temporal-resolution, high SNR, and no increase in scan time. The developed method is based on saturating the fat magnetization prior to applying STEAM modulation; therefore, only the water-content of the tissues is modulated by the sequence, resulting in fat-suppressed images without the need to run the fat suppression module during image acquisition. The potential significance of the proposed method is presented in two STEAM-based cardiac MRI applications: complementary spatial-modulation of magnetization (CSPAMM), and black-blood cine imaging. Phantom and in vivo experiments are conducted to evaluate the developed technique and compare it to the commonly implemented chemical-shift selective (CHESS) and water-excitation using spectral-spatial selective pulses (SSSP) fat suppression techniques. The results from the phantom and in vivo experiments show superior performance of the proposed method compared to the CHESS and SSSP techniques in terms of temporal resolution and SNR. In conclusion, the developed fat suppression technique results in enhanced image quality of STEAM-based images, especially in cardiac applications, where high temporal-resolution is imperative for accurate measurement of functional parameters and improved performance of image analysis algorithms.     

Steady-state free precession with hyperpolarized 3He: experiments and theory

The magnetization response of hyperpolarized 3He gas to a steady-state free precession (SSFP) sequence was simulated using matrix product operators. The simulations included the effects of flip angle (alpha), sequence timings, resonant frequency, gas diffusion coefficient, imaging gradients, T1 and T2. Experiments performed at 1.5 T, on gas phantoms and with healthy human subjects, confirm the predicted theory, and indicate increased SNR with SSFP through use of higher flip angles when compared to optimized spoiled gradient echo (SPGR). Simulations and experiments show some compromise to the SNR and some point spread function broadening at high alpha due to the incomplete refocusing of transverse magnetization, caused by diffusion dephasing from the readout gradient. Mixing of gas polarization levels by diffusion between slices is also identified as a source of signal loss in SSFP at higher alpha through incomplete refocusing. Nevertheless, in the sample experiments, a SSFP sequence with an optimized flip angle of alpha=20 degrees, and 128 sequential phase encoding views, showed a higher SNR when compared to SPGR (alpha=7.2 degrees) with the same bandwidth. Some of the gas sample experiments demonstrated a transient signal response that deviates from theory in the initial phase. This was identified as being caused by radiation damping interactions between the large initial transverse magnetization and the high quality factor (Q=250) birdcage resonator. In 3He NMR experiments, performed without imaging gradients, diffusion dephasing can be mitigated, and the effective T2 is relatively long (1 s). Under these circumstances the SSFP sequence behaves like a CPMG sequence with sinalpha/2 weighting of SNR. Experiments and simulations were also performed to characterize the off-resonance behaviour of the SSFP HP 3He signal. Characteristic banding artifacts due to off-resonance harmonic beating were observed in some of the in vivo SSFP images, for instance in axial slices close to the diaphragm where B0 inhomogeneity is highest. Despite these artifacts, a higher SNR was observed with SSFP in vivo when compared to the SPGR sequence. The trends predicted by theory of increasing SSFP SNR with increasing flip angle were observed in the range alpha=10-20 degrees without compromise to image quality through blurring caused by excessive k-space filtering.     

Spectroscopic imaging of the brain with phased-array coils at 3.0 T

The goal of this study was to develop and evaluate high-resolution magnetic resonance spectroscopic imaging (MRSI) utilizing the gains in signal-to-noise ratio (SNR) provided by combining higher magnetic field with high-sensitivity phased-array (PA) coils. We investigated the maximum improvement in spatial resolution as small as 0.09 cm(3) for brain MRSI while maintaining adequate SNR and acquisition time. The use of low peak power, dual-band spectral-spatial pulses was also investigated for application to 3 T MRSI of the brain using the body coil for radiofrequency excitation and PA coils for signal reception.     

Partial angle inversion recovery (PAIR) MR imaging: spin-echo and snapshot implementation.

The effects of varying the inversion or excitation RF pulse flip angles on image contrast and imaging time have been investigated in IR imaging theoretically, with phantoms and with normal volunteers. Signal intensity in an IR pulse sequence as a function of excitation, inversion and refocusing pulse flip angles was calculated from the solution to the Bloch equations and was utilized to determine the contrast behavior of a lesion/liver model. Theoretical and experimental results were consistent with each other. With the TI chosen to suppress the fat signal, optimization of the excitation pulse flip angle results in an increase in lesion/liver contrast or allows reduction in imaging time which, in turn, can be traded for an increased number of averages. This, in normal volunteers, improved spleen/liver contrast-to-noise ratio (9.0 vs. 5.7, n = 8, p less than 0.01) and suppressed respiratory ghosts by 33% (p less than 0.01). Reducing or increasing the inversion pulse from 180 degrees results in shorter TI needed to null the signal from the tissue of interest. Although this decreases the contrast-to-noise ratio, it can substantially increase the number of sections which can be imaged per given TR in conventional IR imaging or during breathold in the snapshot IR (turboFLASH) technique. Thus, the optimization of RF pulses is useful in obtaining faster IR images, increasing the contrast and/or increasing the number of imaging planes.     

A Near-Resonance Solution to the Bloch Equations and Its Application to RF Pulse Design

A near-resonance expansion of the solution to the Bloch equations in the presence of a radiofrequency (RF) pulse is presented in this paper. The first-order approximation explicitly demonstrates the nonlinear nature of the Bloch equations and precisely relates the excitation profile with the RF pulse when the flip angle is less than π/2. As an application of this solution, we present a procedure for designing RF pulses to generate symmetric excitation profiles with arbitrary shapes for new encoding approaches such as wavelet encoding.     

Application of double spin echo spiral chemical shift imaging to rapid metabolic mapping of hyperpolarized [1-¹³C]-pyruvate

Undersampled spiral CSI (spCSI) using a free induction decay (FID) acquisition allows sub-second metabolic imaging of hyperpolarized 13C. Phase correction of the FID acquisition can be difficult, especially with contributions from aliased out-of-phase peaks. This work extends the spCSI sequence by incorporating double spin echo radiofrequency (RF) pulses to eliminate the need for phase correction and obtain high quality spectra in magnitude mode. The sequence also provides an added benefit of attenuating signal from flowing spins, which can otherwise contaminate signal in the organ of interest. The refocusing pulses can potentially lead to a loss of hyperpolarized magnetization in dynamic imaging due to flow of spins through the fringe field of the RF coil, where the refocusing pulses fail to provide complete refocusing. Care must be taken for dynamic imaging to ensure that the spins remain within the B?-homogeneous sensitive volume of the RF coil.     

Rapid determination of the RF pulse flip angle and spin-lattice relaxation time for materials imaging

For samples with T1s longer than 10s, calibration of the RF probe and a measurement of T1 can be very time-consuming. A technique is proposed for use in imaging applications where one wishes to rapidly obtain information about the RF flip angle and sample T1 prior to imaging. The flip angle measurement time is less than 1s for a single scan. Prior knowledge of the RF flip angle is not required for the measurement of T1. The resulting time savings in measuring the values of flip angle and T1 are particularly significant in the case of samples with very long T1 and short T2*. An imaging extension of the technique provides RF flip angle mapping without the need for incrementing the pulse duration, i.e., RF mapping can be performed at fixed RF amplifier output.     

“FLIPSY”—A New Solvent-Suppression Sequence for Nonexchanging Solutes Offering Improved Integral Accuracy Relative to 1D NOESY

A new method of solvent suppression is described, based on presaturation in combination with volume selection; the name “FLIPSY” is proposed for this sequence. A low-flip-angle pulse is used for excitation, immediately followed by two 180° pulses, each of which is independently phase cycled through Exorcycle. The phase-cycled inversion pulses achieve volume selection in a way similar to the widely used 1D NOESY sequence, thereby largely eliminating any residual “hump” signal from the solvent. The two 180° pulses combine to produce a net 360° rotation forzmagnetization and either a 180° or a 360° rotation for transverse magnetization, depending on the step in the phase cycle. This allows the overall flip angle of the sequence to be controlled by adjusting the length of the initial excitation pulse. It is demonstrated that this property allows one to choose freely a suitable compromise between signal strength and integral accuracy when using FLIPSY, just as when using single-pulse excitation. Such a choice cannot be made when using 1D NOESY, since the effective flip angle in that experiment is always 90°. The application of FLIPSY to recording LC-NMR spectra is demonstrated.     

SAR reduced pulse sequences

Three techniques were considered for reducing the RF (radiofrequency) power deposition in the body while maintaining scan time efficiency: reducing the RF peak amplitude while increasing the pulse width, substituting gradient echoes for spin echoes, and reducing the flip angle of the phase reversal pulse. The use of gradient echoes was found to be the most efficient means to reduce the power delivered to the patient and to obtain rapid data acquisition. The effect upon SAR (specific absorption rate) and SNR (signal-to-noise ratio) was demonstrated on a phantom when the phase reversal pulse was reduced from the standard 180 degrees to 90 degrees. Data in the body indicated a fairly constant SNR down to a refocusing flip angle between 110 degrees and 135 degrees. An initial clinical evaluation was performed at three institutions using the method of reducing the flip angle of the phase reversal pulse. The scan with theta = 120 degrees was rated by readers in a blinded study as having acceptable diagnostic image quality while the 135 degrees scan had comparable image quality to a conventional 90 degrees - 180 degrees pulse sequence. The use of reduced phase reversal pulses was seen as an efficient protocol to obtain T1-weighted images at rapid data rates while reducing the power delivered to the body by about 40%.