Publications
2012
Recently, new ultrafast imaging sequences such as rapid acquisition by sequential excitation and refocusing (RASER) and hybrid spatiotemporal encoding (SPEN) magnetic resonance imaging (MRI) have been proposed, in which the phase encoding of conventional echo planar imaging (EPI) is replaced with a SPEN. In contrast to EPI, SPEN provides significantly higher immunity to frequency heterogeneities including those caused by B0 inhomogeneities and chemical shift offsets. Utilizing the inherent robustness of SPEN, it was previously shown that RASER can be used to successfully perform functional MRI (fMRI) experiments in the orbitofrontal cortex - a task which is challenging using EPI due to strong magnetic susceptibility variation near the air-filled sinuses. Despite this superior performance, systematic analyses have shown that, in its initial implementation, the use of SPEN was penalized by lower signal-to-noise ratio (SNR) and higher radiofrequency power deposition as compared to EPI-based methods. A recently developed reconstruction algorithm based on super-resolution principles is able to alleviate both of these shortcomings; the use of this algorithm is hereby explored within an fMRI context. Specifically, a series of fMRI measurements on the human visual cortex confirmed that the super-resolution algorithm retains the statistical significance of the blood oxygenation level dependent (BOLD) response, while significantly reducing the power deposition associated with SPEN and restoring the SNR to levels that are comparable with those of EPI.
Object An approach has been recently introduced for acquiring arbitrary 2D NMR spectra or images in a single scan, based on the use of frequency-swept RF pulses for the sequential excitation and acquisition of the spins response. This spatiotemporal-encoding (SPEN) approach enables a unique, voxel-by-voxel refocusing of all frequency shifts in the sample, for all instants throughout the data acquisition. The present study investigates the use of this full-refocusing aspect of SPEN-based imaging in the multi-shot MRI of objects, subject to sizable field inhomogeneities that complicate conventional imaging approaches. Materials and methods 2D MRI experiments were performed at 7 T on phantoms and on mice in vivo, focusing on imaging in proximity to metallic objects. Fully refocused SPEN-based spin echo imaging sequences were implemented, using both Cartesian and back-projection trajectories, and compared with k-space encoded spin echo imaging schemes collected on identical samples under equal bandwidths and acquisition timing conditions. Results In all cases assayed, the fully refocused spatiotemporally encoded experiments evidenced a ca. 50 % reduction in signal dephasing in the proximity of the metal, as compared to analogous results stemming from the k-space encoded spin echo counterparts. Conclusion The results in this study suggest that SPENbased acquisition schemes carry the potential to overcome strong field inhomogeneities, of the kind that currently preclude high-field, high-resolution tissue characterizations in the neighborhood of metallic implants.
Dissolution DNP experiments are limited to a single or at most a few scans, before the non-Boltzmann magnetization has been consumed. This makes it impractical to record 2D NMR data by conventional, t1-incremented schemes. Here a new approach termed HyperSPASM to establish 2D heteronuclear correlations in a single scan is reported, aimed at dealing with this kind of challenge. The HyperSPASM experiment relies on imposing an amplitude-modulation of the data by a single Δt1 indirect-domain evolution time, and subsequently monitoring the imparted encoding on separate echo and anti-echo pathway signals within a single continuous acquisition. This is implemented via the use of alternating, switching, coherence selection gradients. As a result of these manipulations the phase imparted by a heteronucleus over its indirect domain evolution can be accurately extracted, and 2D data unambiguously reconstructed with a single-shot excitation. The nature of this sequence makes the resulting experiment particularly well suited for collecting indirectly-detected HSQC data on hyperpolarized samples. The potential of the ensuing HyperSPASM method is exemplified with natural-abundance hyperpolarized correlations on model systems.
Efficient acquisition of ultra-wideline solid-state NMR powder patterns is a continuing challenge. In particular, when the breadth of the powder pattern is much larger than the cross-polarization (CP) excitation bandwidth, transfer efficiencies suffer and experimental times are greatly increased. Presented herein is a CP pulse sequence with an excitation bandwidth that is up to ten times greater than that available from a conventional spin-locked CP pulse sequence. The pulse sequence, broadband adiabatic inversion CP (BRAIN-CP), makes use of the broad, uniformly large frequency profiles of chirped inversion pulses, to provide these same characteristics to the polarization transfer process. A detailed theoretical analysis is given, providing insight into the polarization transfer process involved in BRAIN-CP. Experiments on spin-1/2 nuclei including 119Sn, 199Hg and 195Pt nuclei are presented, and the large bandwidth improvements possible with BRAIN-CP are demonstrated. Furthermore, it is shown that BRAIN-CP can be combined with broadband frequency-swept versions of the Carr-Purcell-Meiboom-Gill experiment (for instance with WURST-CPMG, or WCPMG for brevity); the combined BRAIN-CP/WCPMG experiment then provides multiplicative signal enhancements of both CP and multiple-echo acquisition over a broad frequency region.
Achieving homonuclear 1H decoupling remains one of the key challenges in liquid-state NMR. Such spectra would endow a variety of organic and analytical applications with an increased resolution, and would ideally do so even in a one-dimensional format. A number of parallel efforts aimed at achieving this goal using two-dimensional acquisitions have been proposed; approaches demonstrated over recent years include, among others, new modes for achieving purely-absorptive J spectroscopy, the use of spatially-selective manipulations, and exploiting the natural spin dilution afforded by heteronuclei. The present study relies on the latter approach, and explores the use of BIRD pulses distinguishing between protons bonded to 13C from those bonded to 12C, to achieve homonuclear decoupling in a continuous 1D scan. Studies on several representative compounds demonstrate that this goal can be implemented in a robust format, provided that suitable care is also taken to suppress unwanted coherences, of making all manipulations sufficiently broad-banded, and to provide adequate heteronuclear decoupling of the targeted protons. Dependable homonuclear decoupling performance can then be achieved, with minimal line width, fine-tuning, and sensitivity penalties.
We show that coupled-spin network manipulations can be made highly effective by repeated projections of the evolving quantum states onto diagonal density-matrix states (populations). As opposed to the intricately crafted pulse trains that are often used to fine-tune a complex network's evolution, the strategy hereby presented derives from the "quantum Zeno effect" and provides a highly robust route to guide the evolution by destroying all unwanted correlations (coherences). We exploit these effects by showing that a relaxationlike behavior is endowed to polarization transfers occurring within a N-spin coupled network. Experimental implementations yield coupling constant determinations for complex spin-coupling topologies, as demonstrated within the field of liquid-state nuclear magnetic resonance.
Since the pioneering works of Carr-Purcell and Meiboom-Gill [Carr HY, Purcell EM (1954) Phys Rev 94:630; Meiboom S, Gill D (1985) Rev Sci Instrum 29:688], trains of π-pulses have featured amongst the main tools of quantum control. Echo trains find widespread use in nuclear magnetic resonance spectroscopy (NMR) and imaging (MRI), thanks to their ability to free the evolution of a spin-1/2 from several sources of decoherence. Spin echoes have also been researched in dynamic decoupling scenarios, for prolonging the lifetimes of quantum states or coherences. Inspired by this search we introduce a family of spin-echo sequences, which can still detect site-specific interactions like the chemical shift. This is achieved thanks to the presence of weak environmental fluctuations of common occurrence in high-field NMR - such as homonuclear spin-spin couplings or chemical/biochemical exchanges. Both intuitive and rigorous derivations of the resulting "selective dynamical recoupling" sequences are provided. Applications of these novel experiments are given for a variety of NMR scenarios including determinations of shift effects under inhomogeneities overwhelming individual chemical identities, and model-free characterizations of chemically exchanging partners.
The power of NMR spectroscopy lies in its ability to obtain information about the structure and dynamics of individual atoms in complex molecules. The narrow frequency ranges of the NMR-active nuclei (1H, 13C, 15N, 31P) in biological macromolecules such as proteins, nucleic acids, and their complexes result in severe resonance overlap in one-dimensional spectra, making it practically impossible to extract atom-resolved information even for relatively small biopolymers. In order to deal with this problem, multidimensional NMR techniques are commonly used to spread and correlate the signals of individual nuclear spins along different frequency dimensions. A major drawback of conventional multidimensional NMR is the long experimental time needed for recording its data-a reflection of the hundreds or even thousands of experimental repetitions that are inherent to this kind of spectroscopy. While acquisition times for one-and two-dimensional spectra are on the order of seconds and minutes, respectively, typical three-dimensional NMR experimental times could be as long as days. For obtaining the four-and higher-dimensional spectra that may be of particular interest to the study of large molecular systems or of disordered proteins, acquisition times become altogether unreasonable. Moreover, as a large number of different spectra must be recorded during the NMR investigation of a macromolecule, this demands a high stability of the ensuing samples. Long experimental times also represent a major limitation for high-throughput studies as performed in the context of structural proteomics. It follows from all these considerations that reduced acquisition times could make data acquisition more efficient, and greatly enhance the structural and dynamic capabilities of biomolecular NMR. They could also enable real-time investigations of kinetic molecular processes, such as biochemical reactions, protein/RNA folding, and molecular assemblies by multidimensional spectroscopy. In this chapter, we review some of the fast multidimensional NMR data acquisition techniques that have emerged in recent years and their underlying concepts, and we discuss fields of biomolecular NMR research that could benefit from such fast NMR methods.
Recent years have witnessed unprecedented advances in the development of fast multidimensional NMR acquisition techniques. This progress could open valuable new opportunities for the elucidation of chemical and biochemical processes. This study demonstrates one such capability, with the first real-time Two-dimensional (2D) dynamic analysis of a complex organic reaction relying on unlabeled substrates. Implementing such measurements required the development of new ultrafast 2D methods, capable of monitoring multiple spectral regions of interest as the reaction progressed. The alternate application of these acquisitions in an interleaved, excitation-optimized fashion, allowed us to extract new structural and dynamic insight concerning the reaction between aliphatic ketones and triflic anhydride in the presence of nitriles to yield alkylpyrimidines. Up to 2500 2D NMR data sets were thus collected over the course of this nearly 100 min long reaction, in an approach resembling that used in functional magnetic resonance imaging. With the aid of these new frequency-selective low-gradient strength experiments, supplemented by chemical shift calculations of the spectral coordinates observed in the 2D heteronuclear correlations, previously postulated intermediates involved in the alkylpyrimidine formation process could be confirmed, and hitherto undetected ones were revealed. The potential and limitations of the resulting methods are discussed.