Automated design of pulse sequences for magnetic resonance fingerprinting using physics-inspired optimization.

Magnetic resonance fingerprinting (MRF) is a method to extract quantitative tissue properties such as [Formula: see text] and [Formula: see text] relaxation rates from arbitrary pulse sequences using conventional MRI hardware. MRF pulse sequences have thousands of tunable parameters, which can be chosen to maximize precision and minimize scan time. Here, we perform de novo automated design of MRF pulse sequences by applying physics-inspired optimization heuristics. Our experimental data suggest that systematic errors dominate over random errors in MRF scans under clinically relevant conditions of high undersampling. Thus, in contrast to prior optimization efforts, which focused on statistical error models, we use a cost function based on explicit first-principles simulation of systematic errors arising from Fourier undersampling and phase variation. The resulting pulse sequences display features qualitatively different from previously used MRF pulse sequences and achieve fourfold shorter scan time than prior human-designed sequences of equivalent precision in [Formula: see text] and [Formula: see text] Furthermore, the optimization algorithm has discovered the existence of MRF pulse sequences with intrinsic robustness against shading artifacts due to phase variation.

Fundamentals of turbulent flow spectrum imaging.

PURPOSE: To introduce a mathematical framework and in-silico validation of turbulent flow spectrum imaging (TFSI) of stenotic flow using phase-contrast MRI, evaluate systematic errors in quantitative turbulence parameter estimation, and propose a novel method for probing the Lagrangian velocity spectra of turbulent flows. THEORY AND METHODS: The spectral response of velocity-encoding gradients is derived theoretically and linked to turbulence parameter estimation including the velocity autocorrelation function spectrum. Using a phase-contrast MRI simulation framework, the encoding properties of bipolar gradient waveforms with identical first gradient moments but different duration are investigated on turbulent flow data of defined characteristics as derived from computational fluid dynamics. Based on theoretical insights, an approach using velocity-compensated gradient waveforms is proposed to specifically probe desired ranges of the velocity autocorrelation function spectrum with increased accuracy. RESULTS: Practical velocity-encoding gradients exhibit limited encoding power of typical turbulent flow spectra, resulting in up to 50% systematic underestimation of intravoxel SD values. Depending on the turbulence level in fluids, the error due to a single encoding gradient spectral response can vary by 20%. When using tailored velocity-compensated gradients, improved quantification of the Lagrangian velocity spectrum on a voxel-by-voxel basis is achieved and used for quantitative correction of intravoxel SD values estimated with velocity-encoding gradients. CONCLUSION: To address systematic underestimation of turbulence parameters using bipolar velocity-encoding gradients in phase-contrast MRI of stenotic flows with short correlation times, tailored velocity-compensated gradients are proposed to improve quantitative mapping of turbulent blood flow characteristics.

A 3D hybrid-shot spiral sequence for hyperpolarized 13C imaging.

PURPOSE: Hyperpolarized imaging experiments have conflicting requirements of high spatial, temporal, and spectral resolution. Spectral-spatial RF excitation has been shown to form an attractive magnetization-efficient method for hyperpolarized imaging, but the optimum readout strategy is not yet known. METHODS: In this work, we propose a novel 3D hybrid-shot spiral sequence which features two constant density regions that permit the retrospective reconstruction of either high spatial or high temporal resolution images post hoc, (adaptive spatiotemporal imaging) allowing greater flexibility in acquisition and reconstruction. RESULTS: We have implemented this sequence, both via simulation and on a preclinical scanner, to demonstrate its feasibility, in both a 1H phantom and with hyperpolarized 13C pyruvate in vivo. CONCLUSIONS: This sequence forms an attractive method for acquiring hyperpolarized imaging datasets, providing adaptive spatiotemporal imaging to ameliorate the conflict of spatial and temporal resolution, with significant potential for clinical translation.

Improved gradient waveforms for oscillating gradient spin-echo (OGSE) diffusion tensor imaging.

The dependence of the diffusion tensor on frequency is of great interest in studies of tissue microstructure because it reveals restrictions to the Brownian motion of water molecules caused by cell membranes. Oscillating gradient spin-echo (OGSE) sequences can sample this dependence with gradient shapes for which the power spectrum of the zeroth moment is focused at a target frequency. In order to maintain the total spectral power (ie the b-value), oscillating gradient amplitudes must grow with the frequency squared. For this reason, OGSE applications on clinical MRI scanners are limited to low frequencies, for which it is difficult to obtain a narrow frequency bandwidth of the gradient moment in a useful echo time. In particular, the commonly used pair of single-period trapezoidal-cosine pulses separated by a half-period produces significant side lobes away from the target frequency. To mitigate this effect, improved OGSE waveforms are proposed, which reduce the gap between the two gradient pulses to the minimum duration required for the refocusing RF pulse. Additionally, a slight deviation from the periodicity of the waveforms is proposed in order to permit using the maximum slew rate of the gradient system for all lobes of trapezoidal waveforms while maintaining advantageous spectral properties, which is not the case for the currently used OGSE sequences. Numerical calculations validate these changes, showing that both modifications significantly narrow the gradient moment power spectrum and increase the contribution of its main lobe to the b-value, thus improving the specificity of the measurement. The utility of the new shapes is demonstrated by diffusion tensor measurements of human white matter in vivo over the range of 30-75 Hz with a b-value of nearly 1000 s/mm2 , using a high-performance gradient insert. However, the improvement should increase the sampling precision of OGSE experiments for all gradient systems.

1H/13C/15N triple-resonance experiments for structure determinaton of membrane proteins by oriented-sample NMR.

The benefits of triple-resonance experiments for structure determination of macroscopically oriented membrane proteins by solid-state NMR are discussed. While double-resonance 1H/15N experiments are effective for structure elucidation of alpha-helical domains, extension of the method of oriented samples to more complex topologies and assessing side-chain conformations necessitates further development of triple-resonance (1H/13C/15N) NMR pulse sequences. Incorporating additional spectroscopic dimensions involving 13C spin-bearing nuclei, however, introduces essential complications arising from the wide frequency range of the 1H-13C dipolar couplings and 13C CSA (>20 â€‹kHz), and the presence of the 13C-13C homonuclear dipole-dipole interactions. The recently reported ROULETTE-CAHA pulse sequence, in combination with the selective z-filtering, can be used to evolve the structurally informative 1H-13C dipolar coupling arising from the aliphatic carbons while suppressing the signals from the carbonyl and methyl regions. Proton-mediated magnetization transfer under mismatched Hartman-Hahn conditions (MMHH) can be used to correlate 13C and 15N nuclei in such triple-resonance experiments for the subsequent 15N detection. The recently developed pulse sequences are illustrated for n-acetyl Leucine (NAL) single crystal and doubly labeled Pf1 coat protein reconstituted in magnetically aligned bicelles. An interesting observation is that in the case of 15N-labeled NAL measured at 13C natural abundance, the triple (1H/13C/15N) MMHH scheme predominantly gives rise to long-range intermolecular magnetization transfers from 13C to 15N spins; whereas direct Hartmann-Hahn 13C/15N transfer is entirely intramolecular. The presented developments advance NMR of oriented samples for structure determination of membrane proteins and liquid crystals.

Twice-refocused stimulated echo diffusion imaging: Measuring diffusion time dependence at constant T1 weighting.

PURPOSE: Diffusion times longer than 50 ms are typically probed with stimulated-echo sequences. Varying the diffusion time in stimulated-echo sequences affects the T1 weighting of subcompartments, complicating the analysis of diffusion time dependence. Although inversion recovery preparation could be used to change the T1 weighting, it cannot ensure equal T1 weighting at arbitrary mixing times. In this article, a sequence that ensures constant T1 weighting over a wide range of diffusion times is presented. METHODS: The proposed sequence features 2 independent longitudinal storage periods: TM1 and TM2 . Diffusion encoding is performed during TM1 , effectively coupling the diffusion time and TM1 . Equal T1 weighting at arbitrary diffusion times is realized by keeping the total mixing time TM1 + TM2 constant. The sequence was compared with conventional stimulated-echo measurements of diffusion in a 2-compartment phantom consisting of distilled water and paraffinum perliquidum. Additionally, in vivo DTI of the brain was carried out for 8 healthy volunteers with diffusion times ranging from 50 to 500 ms. RESULTS: Diffusion time dependence of the axial and radial diffusivity was detected in the brain. Both sequences resulted in almost identical diffusivities in white matter. In regions containing partial volumes of gray and white matter, a dependency on T1 weighting was observed. CONCLUSION: In accordance with previous studies, little variance of T1 values appeared to be present in healthy white matter. However, this is likely different in diseased tissue. Here, the proposed sequence can be effective in differentiating between diffusion time dependence and T1 weighting effects.

Parameter map error due to normal noise and aliasing artifacts in MR fingerprinting.

PURPOSE: To introduce a quantitative tool that enables rapid forecasting of T1 and T2 parameter map errors due to normal and aliasing noise as a function of the MR fingerprinting (MRF) sequence, which can be used in sequence optimization. THEORY AND METHODS: The variances of normal noise and aliasing artifacts in the collected signal are related to the variances in T1 and T2 maps through derived quality factors. This analytical result is tested against the results of a Monte-Carlo approach for analyzing MRF sequence encoding capability in the presence of aliasing noise, and verified with phantom experiments at 3 T. To further show the utility of our approach, our quality factors are used to find efficient MRF sequences for fewer repetitions. RESULTS: Experimental results verify the ability of our quality factors to rapidly assess the efficiency of an MRF sequence in the presence of both normal and aliasing noise. Quality factor assessment of MRF sequences is in agreement with the results of a Monte-Carlo approach. Analysis of MRF parameter map errors from phantom experiments is consistent with the derived quality factors, with T1 (T2 ) data yielding goodness of fit R2 ≥ 0.92 (0.80). In phantom and in vivo experiments, the efficient pulse sequence, determined through quality factor maximization, led to comparable or improved accuracy and precision relative to a longer sequence, demonstrating quality factor utility in MRF sequence design. CONCLUSION: The here introduced quality factor framework allows for rapid analysis and optimization of MRF sequence design through T1 and T2 error forecasting.

Time-optimized 4D phase contrast MRI with real-time convex optimization of gradient waveforms and fast excitation methods.

PURPOSE: To shorten 4D flow acquisitions by shortening TRs with fast RF pulses and gradient waveforms. Real-time convex optimization is used to generate these gradients waveforms on the scanner. THEORY AND METHODS: RF and slab-select waveforms were shortened with a minimum phase SLR excitation and the time-optimal variable-rate selective excitation method. Real-time convex optimization was used to shorten bipolar and spoiler gradients by finding the shortest gradient waveforms that satisfied constraints on scan parameters, gradient hardware, M0 , M1 , and peripheral nerve stimulation. Waveforms were calculated and TE and/or TR values were compared for a range of scan parameters and compared to a conventional 4D flow sequence. The method was tested in flow phantoms, and in the aorta and neurovasculature of volunteers (N = 10). Additionally, eddy current error was measured in a large phantom. RESULTS: TEs and TRs were shortened by 21-32% and 20-34%, respectively, compared to the conventional sequence over a range of scan parameters. Bland-Altman analysis of 2 flow phantom configurations showed flow rate bias of 0.3 mL/s and limits of agreement (LOA) of [-6.9, 7.5] mL/s for a cardiac phantom and a bias of -0.1 mL/s with LOA = [-0.4, 0.2] mL/s for a neuro phantom. Similar agreement was also seen for flow measurements in volunteers (bias = -1.0 and -0.1 mL/s, LOA = [-34.9, 33.0] and [-0.7, 0.6] mL/s). Measured eddy currents were 39% larger with the CVX + mpVERSE method. CONCLUSION: The real-time optimized 4D flow gradients and fast slab-selection excitation methods produced up to 34% faster TRs with excellent flow measurement agreement compared to a conventional 4D flow sequence.

Towards perfect NMR: Spin-echo versus perfect-echo building blocks.

The development of new tools to improve the quality of nuclear magnetic resonance (NMR) spectra is a challenging task. The concept of "perfect NMR" includes the design of robust pulse sequences that allow an investigator to obtain undistorted pure in-phase signals, with pure absorption lineshapes that are free of phase anomalies derived from undesired J modulations. Here, alternative NMR building blocks to the spin-echo that are based on a general double SE module, known as a perfect-echo, are reviewed. Several implementations to minimize/remove unwanted dispersive contributions in homonuclear and heteronuclear NMR experiments are described and illustrated with some examples of broad interest for small molecules.

Encoding and readout strategies in magnetic resonance elastography.

Magnetic resonance elastography (MRE) has evolved significantly since its inception. Advances in motion-encoding gradient design and readout strategies have led to improved encoding and signal-to-noise ratio (SNR) efficiencies, which in turn allow for higher spatial resolution, increased coverage, and/or shorter scan times. The purpose of this review is to summarize MRE wave-encoding and readout approaches in a unified mathematical framework to allow for a comparative assessment of encoding and SNR efficiency of the various methods available. Besides standard full- and fractional-wave-encoding approaches, advanced techniques including flow compensation, sample interval modulation and multi-shot encoding are considered. Signal readout using fast k-space trajectories, reduced field of view, multi-slice, and undersampling techniques are summarized and put into perspective. The review is concluded with a foray into displacement and diffusion encoding as alternative and/or complementary techniques.

High-resolution reduced field of view diffusion tensor imaging using spatially selective RF pulses.

PURPOSE: Diffusion tensor imaging (DTI) plays a vital role in identifying white matter fiber bundles. Achievable imaging resolution and imaging time demands remain the major challenges in detecting small fiber bundles with current clinical DTI sequences. METHODS: A novel reduced field of view ultra-high-resolution DTI technique named eZOOM (elliptically refocused zonally oblique multislice) was developed. A small circular disk was imaged using spatially selective radiofrequency (RF) pulses, reducing the imaging matrix size. The frequency profile of the spectral-spatial refocusing RF pulse provided intrinsic fat suppression, eliminating the need for fat saturation pulses. RESULTS: Multislice DTI at a resolution of 0.35 × 0.35 mm in a celery fiber phantom was successfully performed by scanning an 8-cm field of view at 3T. An adequate diffusion-to-noise ratio (DNR >20) was achieved for a 25-min acquisition using a direct-sampling RF receiver. Human subjects (n = 7) were scanned at resolutions of 0.47 × 0.47 mm having a DNR <20 within a 75-min scanning time, requiring further enhancements to increase the signal-to-noise ratio. CONCLUSIONS: The new eZOOM-DTI method offers multislice DTI at ultra-high imaging resolutions substantially exceeding those available with current echo-planar DTI techniques. Parallel and fast spin echo methods can be combined with eZOOM to improve SNR and DNR in humans.

Review of oxygen-enhanced lung mri: Pulse sequences for image acquisition and T1 measurement.

Oxygen-enhanced MR imaging (OE-MRI) is a special proton imaging technique that can be performed without modifying the scanner hardware. Many fundamental studies have been conducted following the initial reporting of this technique in 1996, illustrating the high potential for its clinical application. This review aims to summarise and analyse current pulse sequences and T1 measurement methods for OE-MRI, including fundamental theories, existing pulse sequences applied to OE-MRI acquisition and T1 mapping. Wash-in and wash-out time identify lung function and are sensitive to ventilation; thus, dynamic OE-MRI is also discussed in this review. We compare OE-MRI with the primary competitive technique, hyperpolarised gas MRI. Finally, an overview of lower-field applications of OE-MRI is highlighted, as relatively recent publications demonstrated positive results. Lower-field OE-MRI, which is lower than 1.5 T, could be an alternative modality for detecting lung diseases. This educational review is aimed at researchers who want a quick summary of the steps needed to perform pulmonary OE-MRI with a particular focus on sequence design, settings, and quantification methods.

De novo NMR pulse sequence design using Monte-Carlo optimization techniques.

Separated Local Field (SLF) experiments have been routinely used for measuring 1H-15N heteronuclear dipolar couplings in oriented-sample solid-state NMR for structure determination of proteins. In the on-going pursuit of designing better-performing SLF pulse sequences (e.g. by increasing the number of subdwells, and varying the rf amplitudes and phases), analytical treatment of the relevant average Hamiltonian terms may become cumbersome and/or nearly impossible. Numerical simulations of NMR experiments using GPU processors can be employed to rapidly calculate spectra for moderately sized spin systems, which permit an efficient numeric optimization of pulse sequences by the Monte Carlo Simulated Annealing protocol. In this work, a computational strategy was developed to find the optimal phases and timings that substantially improve the 1H-15N dipolar linewidths over a broad range of dipolar couplings as compared to SAMPI4. More than 100 pulse sequences were developed de novo and tested on an N-acetyl Leucine crystal. Seventeen distinct pulse sequences were shown to produce sharper mean linewidths than SAMPI4. Overall, these pulse sequences have more variable parameters (involving non-quadrature phases) and do not involve symmetry between the odd and even dwells, which would likely preclude their rigorous analytical treatment. The top performing pulse sequence, termed ROULETTE-1, has 18% sharper mean linewidths than SAMPI4 when run on an N-acetyl Leucine crystal. This sequence was also shown to be robust over a broad range of 1H carrier frequencies and various crystal orientations. The performance of such an optimized pulse sequence was also illustrated on 15N Leucine-labeled Pf1 coat protein reconstituted in magnetically aligned bicelles. For the optimized pulse sequence the mean peak width was 14% sharper than SAMPI4, which in turn yielded a better signal to noise ratio, 20:1 vs. 17:1. This method is potentially extendable to de novo development of a variety of NMR experiments.

Computer-generated pulse sequences for 1H-15N and 1Hα-13Cα separated local-field experiments.

High-resolution separated local field (SLF) experiments are employed in oriented-sample solid state NMR to measure angular-dependent heteronuclear dipolar couplings for structure determination. While traditionally these experiments have been designed analytically by determining cycles of pulses with specific phases and durations to achieve cancellation of the homonuclear dipolar terms in the average Hamiltonian, recent work has introduced a computational approach to optimizing linewidths of the 1H-15N dipolar resonances. Accelerated by GPU processors, a computer algorithm searches for the optimal parameters by simulating numerous 1H-15N NMR spectra. This approach, termed ROULETTE, showed promising results by developing a new pulse sequence (ROULETTE-1.0) exhibiting 18% sharper mean linewidths than SAMPI4 for an N-acetyl Leucine (NAL) crystal. Herein, we expand on this previous work to improve the performance of the 1H-15N SLF experiment and extend the work beyond the original approach to new SLF experiments. The new algorithm, in addition to finding pulse durations and phases, now searches for the optimal on/off application scheme of radio frequency irradiation on each channel. This constitutes true de novo optimization, effectively optimizing every aspect of a pulse sequence instead of just phases and durations. With an improved ROULETTE algorithm, we have found a new 1H-15N pulse sequence, termed ROULETTE-2.0, yielding 32% sharper mean linewidths than SAMPI4 for NAL crystal at 500 MHz 1H frequency. Whereas both SAMPI4 and ROULETTE-1.0 have a window where the rf power on the I-channel is turned off, the new pulse sequence is entirely windowless. Furthermore, the reliability of the algorithm has been greatly improved in terms of avoiding false positives, i.e. well-performing pulse sequences in silica that fail to render narrow resonances in experiment. The program has been extended to the 13Cα-1Hα SLF experiments, using a 6 subdwell architecture similar to the 1H-15N optimization. Compared to the PISEMA pulse sequence, the mean 13Cα-1Hα linewidth is 17% sharper for the new pulse sequence, termed ROULETTE-CAHA. In addition to superior performance, the work demonstrates the broad applicability of the algorithm and its adaptability to different NMR experiments and spin systems.

TRASE 1D sequence performance in imperfect B1 fields.

Transmit Array Spatial Encoding (TRASE) is an MRI technique that uses radio-frequency (RF) magnetic field (B1) phase gradients for spatial encoding. A TRASE pulse sequence consists of a long echo train in which each echo samples a different k-space point. Due to the need for accurate refocusing, TRASE imaging performance depends on |B1| homogeneity. Although the CPMG echo train is often relied on to provide immunity against B1 flip angle errors, this does not apply to TRASE echo trains. Due to the spatially dependent B1 phases involved in TRASE imaging, the CPMG condition, where all spins flip about the y-axis in the rotating frame, can only be achieved at one single location within the sample. Moreover, CPMG only preserves one component of the transverse magnetization, the y-component, whereas TRASE requires both components to be retained. Here we investigate the performance of a set of variants of a 1-dimensional (1D) TRASE sequence under conditions of |B1| errors. We varied the B1 transmit pulse RF waveform phases in an effort to optimize the TRASE imaging point spread function (PSF). The performance of 256 sequence variants, including those previously reported in the literature was studied. Both Bloch equation simulations and experimental confirmations were completed. Off-resonance (B0 inhomogeneity) effects were not considered so that the effects of B1 inhomogeneity alone could be understood. Results show that, using optimum transmit pulse phases, high quality image encoding is achievable over ∼90% of the Nyquist field-of-view (FOV) for a practically realizable variation in B1 amplitude (Δ|B1|⩽±11%). This improves significantly upon the performance of a previously-reported sequence which generated ∼75% usable FOV within the Nyquist FOV.

Pulseq-Graphical Programming Interface: Open source visual environment for prototyping pulse sequences and integrated magnetic resonance imaging algorithm development.

PURPOSE: To provide a single open-source platform for comprehensive MR algorithm development inclusive of simulations, pulse sequence design and deployment, reconstruction, and image analysis. METHODS: We integrated the "Pulseq" platform for vendor-independent pulse programming with Graphical Programming Interface (GPI), a scientific development environment based on Python. Our integrated platform, Pulseq-GPI, permits sequences to be defined visually and exported to the Pulseq file format for execution on an MR scanner. For comparison, Pulseq files using either MATLAB only ("MATLAB-Pulseq") or Python only ("Python-Pulseq") were generated. We demonstrated three fundamental sequences on a 1.5 T scanner. Execution times of the three variants of implementation were compared on two operating systems. RESULTS: In vitro phantom images indicate equivalence with the vendor supplied implementations and MATLAB-Pulseq. The examples demonstrated in this work illustrate the unifying capability of Pulseq-GPI. The execution times of all the three implementations were fast (a few seconds). The software is capable of user-interface based development and/or command line programming. CONCLUSION: The tool demonstrated here, Pulseq-GPI, integrates the open-source simulation, reconstruction and analysis capabilities of GPI Lab with the pulse sequence design and deployment features of Pulseq. Current and future work includes providing an ISMRMRD interface and incorporating Specific Absorption Ratio and Peripheral Nerve Stimulation computations.

Direct imaging of functional networks.

In blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI), current methods typically acquire ∼ 500,000 imaging voxels at each time point, and then use computer algorithms to reduce this data to the coefficients of a few hundred parcels or networks. This suggests that the amount of relevant information present in the fMRI signal is relatively small, and presents an opportunity to greatly improve the speed and signal to noise ratio (SNR) of the fMRI process. In this work, a theoretical framework is presented for calculating the coefficients of functional networks directly from highly undersampled fMRI data. Using predefined functional parcellations or networks and a compact k-space trajectory that samples data at optimal spatial scales, the problem of estimating network coefficients is reformulated to allow for direct least squares estimation, without Fourier encoding. By simulation, this approach is shown to allow for acceleration of the imaging process under ideal circumstances by nearly three orders of magnitude.