Pulse Sequence Design Research Articles

Mathematical optimization of contrast concentration for T1-weighted spoiled gradient echo imaging.

To develop and validate closed form mathematical expressions that predict the optimal contrast agent concentration for the maximum T1-weighted spoiled gradient echo (SGRE) signal. Gadolinium and iron-based contrast agents can have significant transverse relaxivity that leads to signal dropout with increasing contrast agent concentration. A mathematical expression for the "optimal" contrast agent concentration where recovery of longitudinal magnetization is offset by increasing transverse signal decay was derived. Expressions for the maximum possible SGRE signal were also derived. Three phantoms were constructed, each with varying concentrations of one of the following three agents: gadoteridol, gadobenate dimeglumine, and ferumoxytol. After measuring the longitudinal and transverse relaxivity of the three agents, the SGRE signal was measured in the phantoms over a wide range of flip angles and echo times. Excellent qualitative agreement between the SGRE signal behavior, optimal concentration, and optimal flip angle were observed between experimental measurements and theoretical predictions. This work provides validated mathematical expressions for contrast enhanced T1-weighted SGRE imaging and may provide guidance for contrast dosing and injection protocols, as well as for novel pulse sequence design.

Broadband 1H homodecoupled NMR experiments: recent developments, methods and applications.

In recent years, a great interest in the development of new broadband 1H homonuclear decoupled techniques providing simplified JHH multiplet patterns has emerged again in the field of small molecule NMR. The resulting highly resolved 1H NMR spectra display resonances as collapsed singlets, therefore minimizing signal overlap and expediting spectral analysis. This review aims at presenting the most recent advances in pure shift NMR spectroscopy, with a particular emphasis to the Zangger-Sterk experiment. A detailed discussion about the most relevant practical aspects in terms of pulse sequence design, selectivity, sensitivity, spectral resolution and performance is provided. Finally, the implementation of the different reported strategies into traditional 1D and 2D NMR experiments is described while several practical applications are also reviewed.

Pulse sequence programming in a dynamic visual environment: SequenceTree

To describe SequenceTree, an open source, integrated software environment for implementing MRI pulse sequences and, ideally, exporting them to actual MRI scanners. The software is a user-friendly alternative to vendor-supplied pulse sequence design and editing tools and is suited for programmers and nonprogrammers alike. The integrated user interface was programmed using the Qt4/C++ toolkit. As parameters and code are modified, the pulse sequence diagram is automatically updated within the user interface. Several aspects of pulse programming are handled automatically, allowing users to focus on higher-level aspects of sequence design. Sequences can be simulated using a built-in Bloch equation solver and then exported for use on a Siemens MRI scanner. Ideally, other types of scanners will be supported in the future. SequenceTree has been used for 8 years in our laboratory and elsewhere and has contributed to more than 50 peer-reviewed publications in areas such as cardiovascular imaging, solid state and nonproton NMR, MR elastography, and high-resolution structural imaging. SequenceTree is an innovative, open source, visual pulse sequence environment for MRI combining simplicity with flexibility and is ideal both for advanced users and users with limited programming experience.

Analysis on the use of Multi-Sequence MRI Series for Segmentation of Abdominal Organs

Segmentation of abdominal organs from MRI data sets is a challenging task due to various limitations and artefacts. During the routine clinical practice, radiologists use multiple MR sequences in order to analyze different anatomical properties. These sequences have different characteristics in terms of acquisition parameters (such as contrast mechanisms and pulse sequence designs) and image properties (such as pixel spacing, slice thicknesses and dynamic range). For a complete understanding of the data, computational techniques should combine the information coming from these various MRI sequences. These sequences are not acquired in parallel but in a sequential manner (one after another). Therefore, patient movements and respiratory motions change the position and shape of the abdominal organs. In this study, the amount of these effects is measured using three different symmetric surface distance metrics performed to three dimensional data acquired from various MRI sequences. The results are compared to intra and inter observer differences and discussions on using multiple MRI sequences for segmentation and the necessities for registration are presented.

NMR Methods for the Study of Instrinsically Disordered Proteins Structure, Dynamics, and Interactions: General Overview and Practical Guidelines.

Thanks to recent improvements in NMR instrumentation, pulse sequence design, and sample preparation, a panoply of new NMR tools has become available for atomic resolution characterization of intrinsically disordered proteins (IDPs) that are optimized for the particular chemical and spectroscopic properties of these molecules. A wide range of NMR observables can now be measured on increasingly complex IDPs that report on their structural and dynamic properties in isolation, as part of a larger complex, or even inside an entire living cell. Herein we present basic NMR concepts, as well as optimised tools available for the study of IDPs in solution. In particular, the following sections are discussed hereafter: a short introduction to NMR spectroscopy and instrumentation (Sect. 3.1), the effect of order and disorder on NMR observables (Sect. 3.2), particular challenges and bottlenecks for NMR studies of IDPs (Sect. 3.3), 2D HN and CON NMR experiments: the fingerprint of an IDP (Sect. 3.4), tools for overcoming major bottlenecks of IDP NMR studies (Sect. 3.5), 13C detected experiments (Sect. 3.6), from 2D to 3D: from simple snapshots to site-resolved characterization of IDPs (Sect. 3.7), sequential NMR assignment: 3D experiments (Sect. 3.8), high-dimensional NMR experiments (nD, with n>3) (Sect. 3.9) and conclusions and perspectives (Sect. 3.10).

Various diffusion magnetic resonance imaging techniques for pancreatic cancer.

Pancreatic cancer is one of the most common malignant tumors and remains a treatment-refractory cancer with a poor prognosis. Currently, the diagnosis of pancreatic neoplasm depends mainly on imaging and which methods are conducive to detecting small lesions. Compared to the other techniques, magnetic resonance imaging (MRI) has irreplaceable advantages and can provide valuable information unattainable with other noninvasive or minimally invasive imaging techniques. Advances in MR hardware and pulse sequence design have particularly improved the quality and robustness of MRI of the pancreas. Diffusion MR imaging serves as one of the common functional MRI techniques and is the only technique that can be used to reflect the diffusion movement of water molecules in vivo. It is generally known that diffusion properties depend on the characterization of intrinsic features of tissue microdynamics and microstructure. With the improvement of the diffusion models, diffusion MR imaging techniques are increasingly varied, from the simplest and most commonly used technique to the more complex. In this review, the various diffusion MRI techniques for pancreatic cancer are discussed, including conventional diffusion weighted imaging (DWI), multi-b DWI based on intra-voxel incoherent motion theory, diffusion tensor imaging and diffusion kurtosis imaging. The principles, main parameters, advantages and limitations of these techniques, as well as future directions for pancreatic diffusion imaging are also discussed.

Diffusion on a molecular scale as observed using PGSE NMR

For half a century, pulsed‐gradient Spin‐Echo NMR based on the Stejskal–Tanner equation has been used to infer Fick's‐Law diffusion coefficients of solutes in simple liquids and complex fluids. The decades since the original papers have seen vast advances in instrument technology and pulse sequence design, all leading to improved measurements of diffusion coefficients. However, just as the last half‐century has brought major advances in instrument technology, so also it has also brought major advances in scientific understanding of diffusion on molecular distance and time scales. This article discusses implications of these advances in molecular hydrodynamics for the interpretation of PGSE NMR attenuation curves. The results here are particularly significant for studies on complex fluid systems that have relaxations on the time and distance scales that are observed in PGSE NMR experiments. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 43A: 1–15, 2015.

Towards Understanding Protein Disorder In-Cell.

Investigating the activity and structure of cellular biochemical machinery at atomic resolution has been a point of paramount significance for understanding health and disease over the decades. The underlying molecular mechanisms are primarily studied in vitro. Nuclear magnetic resonance (NMR) is a technique that allows to look into cells and study proteins and other constituents, thanks to careful experimental design and technological advances (spectrometer sensitivity and pulse sequence design). Here we outline current applications of the technique and propose a realistic future for the field.

The history of MR imaging as seen through the pages of radiology.

The first reports in Radiology pertaining to magnetic resonance (MR) imaging were published in 1980, 7 years after Paul Lauterbur pioneered the first MR images and 9 years after the first human computed tomographic images were obtained. Historical advances in the research and clinical applications of MR imaging very much parallel the remarkable advances in MR imaging technology. These advances can be roughly classified into hardware (eg, magnets, gradients, radiofrequency [RF] coils, RF transmitter and receiver, MR imaging-compatible biopsy devices) and imaging techniques (eg, pulse sequences, parallel imaging, and so forth). Image quality has been dramatically improved with the introduction of high-field-strength superconducting magnets, digital RF systems, and phased-array coils. Hybrid systems, such as MR/positron emission tomography (PET), combine the superb anatomic and functional imaging capabilities of MR imaging with the unsurpassed capability of PET to demonstrate tissue metabolism. Supported by the improvements in hardware, advances in pulse sequence design and image reconstruction techniques have spurred dramatic improvements in imaging speed and the capability for studying tissue function. In this historical review, the history of MR imaging technology and developing research and clinical applications, as seen through the pages of Radiology, will be considered.

Exploiting flow to control the in vitro spatiotemporal distribution of microbubble-seeded acoustic cavitation activity in ultrasound therapy

Focused ultrasound and microbubbles have been extensively used to generate therapeutic bioeffects. Despite encouraging in vivo results, there remains poor control of the magnitude and spatial distribution of these bioeffects due to the limited ability of conventional pulse shapes and sequences to control cavitation dynamics. Thus current techniques are restricted by an efficacy-safety trade-off. The primary aim of the present study was to incorporate the presence of flow in the design of new short pulse sequences, which can more uniformly distribute the cavitation activity. Microbubbles flowing (fluid velocity: 10 mm s−1) through a 300 μm tube were sonicated with a focused 0.5 MHz transducer while acoustic emissions were captured with an inserted focused 7.5 MHz passive cavitation detector. The two foci were co-axially aligned and their focal points were overlapped. Whereas conventional sequences are composed of a long burst (>10 000 cycles) emitted at a low burst repetition frequency (<10 Hz), we decomposed this burst into short pulses by adding intervals to facilitate inter-pulse microbubble movement. To evaluate how this sequence influenced cavitation distribution, we emitted short pulses (peak-rarefactional pressure (PRP): 40–366 kPa, pulse length (PL): 5–25 cycles) at high pulse repetition frequencies (PRF: 0.625–10 kHz) for a burst length of 100 ms. Increased cavitation persistence, implied by the duration of the microbubble acoustic emissions, was a measure of improved distribution due to the presence of flow. Sonication at lower acoustic pressures, longer pulse intervals and lower PLs improved the spatial distribution of cavitation. Furthermore, spectral analysis of the microbubble emissions revealed that the improvement at low pressures is due to persisting stable cavitation. In conclusion, new short-pulse sequences were shown to improve spatiotemporal control of acoustic cavitation dynamics during physiologically relevant flow. This could lead to adjustable distribution of the generated in vivo bioeffect and therefore efficient and safe treatment of a wide range of pathologies.

Dynamical decoupling design for identifying weakly coupled nuclear spins in a bath

Identifying weakly coupled nuclear spins around single electron spins is a key step toward implementing quantum information processing using coupled electron-nuclei spin systems or sensing like single-spin nuclear magnetic resonance detection using diamond defect spins. Dynamical decoupling control of the center electron spin with periodic pulse sequences [e.g., the Carre-Purcell-Meiboom-Gill (CPMG) sequence] has been successfully used to identify single nuclear spins and to resolve structure of nuclear spin clusters. Here, we design a type of pulse sequence by replacing the repetition unit (a single $\ensuremath{\pi}$ pulse) of the CPMG sequence with a group of nonuniformly spaced $\ensuremath{\pi}$ pulses. Using the nitrogen-vacancy center system in diamond, we theoretically demonstrate that the designed pulse sequence improves the resolution of nuclear spin noise spectroscopy, and more information about the surrounding nuclear spins is extracted. The principle of dynamical decoupling design proposed in this paper is useful in many systems (e.g., defect spin qubit in solids, trapped ion, and superconducting qubit) for high-resolution noise spectroscopy.

Neuronal or hemodynamic? Grappling with the functional MRI signal.

Magnetic resonance imaging (MRI) and functional MRI (fMRI) continue to advance because creative physicists, engineers, neuroscientists, clinicians, and physiologists find new ways for extracting more information from the signal. Innovations in pulse sequence design, paradigm design, and processing methods have advanced the field and firmly established fMRI as a cornerstone for understanding the human brain. In this article, the field of fMRI is described through consideration of the central problem of separating hemodynamic from neuronal information. Discussed here are examples of how pulse sequences, activation paradigms, and processing methods are integrated such that novel, high-quality information can be obtained. Examples include the extraction of information such as activation onset latency, metabolic rate, neuronal adaptation, vascular patency, vessel diameter, vigilance, and subvoxel activation. Experimental measures include time series latency, hemodynamic shape, MR phase, multivoxel patterns, ratios of activation-related R2* to R2, metabolic rate changes, fluctuation correlations and frequencies, changes in fluctuation correlations and frequencies over time, resting correlation states, echo time dependence, and more.

High performance MRI simulations of motion on multi-GPU systems.

BackgroundMRI physics simulators have been developed in the past for optimizing imaging protocols and for training purposes. However, these simulators have only addressed motion within a limited scope. The purpose of this study was the incorporation of realistic motion, such as cardiac motion, respiratory motion and flow, within MRI simulations in a high performance multi-GPU environment.MethodsThree different motion models were introduced in the Magnetic Resonance Imaging SIMULator (MRISIMUL) of this study: cardiac motion, respiratory motion and flow. Simulation of a simple Gradient Echo pulse sequence and a CINE pulse sequence on the corresponding anatomical model was performed. Myocardial tagging was also investigated. In pulse sequence design, software crushers were introduced to accommodate the long execution times in order to avoid spurious echoes formation.The displacement of the anatomical model isochromats was calculated within the Graphics Processing Unit (GPU) kernel for every timestep of the pulse sequence. Experiments that would allow simulation of custom anatomical and motion models were also performed. Last, simulations of motion with MRISIMUL on single-node and multi-node multi-GPU systems were examined.ResultsGradient Echo and CINE images of the three motion models were produced and motion-related artifacts were demonstrated. The temporal evolution of the contractility of the heart was presented through the application of myocardial tagging. Better simulation performance and image quality were presented through the introduction of software crushers without the need to further increase the computational load and GPU resources. Last, MRISIMUL demonstrated an almost linear scalable performance with the increasing number of available GPU cards, in both single-node and multi-node multi-GPU computer systems.ConclusionsMRISIMUL is the first MR physics simulator to have implemented motion with a 3D large computational load on a single computer multi-GPU configuration. The incorporation of realistic motion models, such as cardiac motion, respiratory motion and flow may benefit the design and optimization of existing or new MR pulse sequences, protocols and algorithms, which examine motion related MR applications.

The role of level anti-crossings in nuclear spin hyperpolarization

Nuclear spin hyperpolarization is an important resource for increasing the sensitivity of NMR spectroscopy and MRI. Signal enhancements can be as large as 3–4 orders of magnitude. In hyperpolarization experiments, it is often desirable to transfer the initial polarization to other nuclei of choice, either protons or insensitive nuclei such as 13C and 15N. This situation arises primarily in Chemically Induced Dynamic Nuclear Polarization (CIDNP), Para-Hydrogen Induced Polarization (PHIP), and the related Signal Amplification By Reversible Exchange (SABRE). Here we review the recent literature on polarization transfer mechanisms, in particular focusing on the role of Level Anti-Crossings (LACs) therein.So-called “spontaneous” polarization transfer may occur both at low and high magnetic fields. In addition, transfer of spin polarization can be accomplished by using especially designed pulse sequences. It is now clear that at low field spontaneous polarization transfer is primarily due to coherent spin-state mixing under strong coupling conditions. However, thus far the important role of LACs in this process has not received much attention. At high magnetic field, polarization may be transferred by cross-relaxation effects. Another promising high-field technique is to generate the strong coupling condition by spin locking using strong radio-frequency fields. Here, an analysis of polarization transfer in terms of LACs in the rotating frame is very useful to predict which spin orders are transferred depending on the strength and frequency of the B1 field. Finally, we will examine the role of strong coupling and LACs in magnetic-field dependent nuclear spin relaxation and the related topic of long-lived spin-states.

Arterial Spin–Labeled Perfusion Imaging in Acute Ischemic Stroke

Arterial spin labeling (ASL) is an MRI method that enables the measurement of tissue perfusion without the use of exogenous contrast agents by magnetically tagging the water in inflowing blood.1 It was first proposed in the early 1990s and, since then, has been primarily a research technique. Recent advances in pulse sequence design and the more widespread availability of higher-field (ie, 3T) MRI scanners, both of which improve the signal-to-noise ratio (SNR) of the technique dramatically, have resulted in increased adoption in the clinical neuroimaging community. All 3 major MRI vendors now support some form of ASL imaging as a product. At first glance, it would seem that ASL is a particularly ill-suited technique to image acute ischemic stroke. The ASL signal is roughly proportional to cerebral blood flow (CBF), which is markedly decreased in the core of large vessel ischemic stroke. Furthermore, what CBF does remain is often supplied by circuitous collateral routes, leading to longer arterial arrival times. Because the magnetic label decays with the blood T1 (typically between 1.2 and 1.8 s at clinical magnetic field strengths), the ASL signal will not accurately represent CBF in these regions under normal operating conditions. Finally, there is extensive research and clinical experience with another MRI perfusion method, bolus dynamic susceptibility contrast (DSC), which can be acquired relatively rapidly in the acute setting. Remarkably, despite these limitations, an increasing number of studies are showing that there is a place for ASL in the workup of acute ischemic stroke with MRI. In this review, I highlight recommended imaging parameters for ASL stroke studies, discuss typical image quality and artifacts, review the recent clinical literature of ASL in stroke (particularly vis a vis the more routine and accepted method of DSC), mention limitations, and finally discuss the future of this promising …

Multiecho acquisition of O-space data.

Nonlinear gradient encoding methods, such as O-Space imaging, have been shown to provide good images from very few echoes. Acquiring data in a train of spin or gradient echoes is a very flexible way to further speed acquisition time. However, combining these strategies presents significant challenges, both in terms of the contrast and artifacts. We present strategies in both pulse sequence design and image processing to mitigate these effects. The three strategies include a new echo ordering that takes into account the unique way that O-Space samples the k-space of the image; a new postprocessing filter that allows tuning of T2-weighting by emphasizing the contribution of low frequency spatial information at selectable points in space and time; and an offset between linear and nonlinear gradients that makes the central point of each echo unique. Simulations indicate that these strategies mitigate artifacts introduced by T2 (or T2*) decay and produce contrast that reflects relaxation at a given echo time. Turbo spin echo O-Space is theoretically feasible, and the greater undersampling should make it possible to use shorter echo trains for a given scan time.

Recent advances in protein NMR spectroscopy and their implications in protein therapeutics research

Nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography are the two main methods for protein three-dimensional structure determination at atomic resolution. According to the protein structures deposited in the Protein Data Bank, X-ray crystallography has become the dominant method for structure determination, particularly for large proteins and complexes. However, with the developments of isotope labeling, increase of magnetic field strength, common use of a cryogenic probe, and ingenious pulse sequence design, the applications of NMR spectroscopy have expanded in biological research, especially in characterizing protein dynamics, sparsely populated transient structures, weak protein interactions, and proteins in living cells at atomic resolution, which is difficult if not impossible by other biophysical methods. Although great advances have been made in protein NMR spectroscopy, its applications in protein therapeutics, which represents the fastest growing segment of the pharmaceutical industry, are still limited. Here we review the recent advances in the use of NMR spectroscopy in studies of large proteins or complexes, posttranslation modifications, weak interactions, and aggregation, and in-cell NMR spectroscopy. The potential applications of NMR spectroscopy in protein therapeutic assays are discussed.

Evaluation of the Fast Inverse Laplace Transform for Three-Dimensional NMR Distribution Functions

A fast inverse Laplace transform (ILT) for the three-dimensional (3-D) nuclear magnetic resonance distribution was proposed by the authors with a designed pulse sequence and an efficient data-processing algorithm in Zhang et al. (Appl Magn Reson 44:849–857, 2013). In this paper, evaluation method to the 3-D ILT algorithm is introduced and the simulation results using simulated data with three different signal-to-noise ratios demonstrate that the precision and speed are excellent.

A comparison and evaluation of reduced-FOV methods for multi-slice 7 T human imaging

Eight different reduced field-of-view (FOV) MRI techniques suitable for high field human imaging were implemented, optimized, and evaluated at 7T. These included selective Inner-Volume Imaging (IVI) based methods, and Outer-Volume Suppression (OVS) techniques, some of which were previously unexplored at ultra-high fields. Design considerations included use of selective composite excitation and adiabatic refocusing radio-frequency (RF) pulses to address B1 inhomogeneities, twice-refocused spin echo techniques, frequency-modulated pulses to sharply define suppressed regions, and pulse sequence designs to improve SNR in multi-slice scans. The different methods were quantitatively compared in phantoms and in vivo human brain images to provide measurements of relative signal to noise ratio (SNR), power deposition (specific absorption rate, SAR), suppression of signal, artifact strength and prevalence, and general image quality. Multi-slice signal losses in out-of-slice locations were simulated for IVI methods, and then measured experimentally across a range of slice numbers. Corrections for B1 nonuniformities demonstrated an improved SNR and a reduction in artifact power in the reduced-FOV, but produced an elevated SAR. Multi-slice sequences with reordering of pulses in traditional and twice-refocused IVI techniques demonstrated an improved SNR compared to conventional methods. The combined results provide a basis for use of reduced-FOV techniques for human imaging localized to a small FOV at 7T.

Mitigate B1+ inhomogeneity using spatially selective radiofrequency excitation with generalized spatial encoding magnetic fields

High-field magnetic resonance imaging (MRI) has the challenge of inhomogeneous B(1)(+), and consequently inhomogeneous flip angle distribution, which causes spatially dependent contrast and makes clinical diagnosis difficult. We propose a two-step pulse design procedure in which (1) a combination of linear and nonlinear spatial encoding magnetic fields (SEMs) is used to remap the B(1)(+) map in order to reduce the dimensionality of the problem, (2) the locations, amplitudes, and phases of spoke pulses are estimated in one dimension. The advantage of this B(1)(+) remapping is that when the isointensity contours of a linear combination of SEMs are similar to the isointensity contours of B(1)(+), a simple pulse sequence design using time-varying SEMs can achieve a homogenous flip-angle distribution efficiently. We demonstrate that spatially selective radiofrequency (RF) excitation with generalized SEMs (SAGS) using both linear and quadratic SEMs in a multi-spoke k-space trajectory can mitigate the B(1)(+) inhomogeneity at 7T efficiently. Numerical simulations based on experimental data suggest that, compared with other methods, SAGS provide a formulation allowing multiple-pulse design, a similar average flip-angle distribution with less RF power, and/or a more homogeneous flip-angle distribution. Without using multiple RF coils for parallel transmission, SAGS can be used to mitigate the B(1)(+) inhomogeneity in high-field MRI experiments.