Principles and Progress in Ultrafast Multidimensional Nuclear Magnetic Resonance

Mishkovsky, Mor; Frydman, Lucio

doi:10.1146/annurev.physchem.040808.090420

Cited by 78 publications

(95 citation statements)

References 72 publications

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“…It is interesting to compare these spontaneous polarization transfer processes with analogs based on J-transfers, discussed in the hyperpolarized literature [8,[10][11][12][13][25][26][27][28]. Although it is likely that coherent transfer sequences like INEPT could lead to larger single-shot 1 H signals, the mechanism here presented evidences a number of advantageous features.…”

Section: Discussionmentioning

confidence: 84%

Heteronuclear Cross‐Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

Donovan¹,

Lupulescu²,

Frydman³

2014

ChemPhysChem

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Dissolution DNP enables high-sensitivity solution phase NMR experiments on long-lived nuclear spin species such as 15 N and 13 C. This report explores certain features arising in solution-state 1 H NMR, upon polarizing low-γ nuclear species. Following solid state hyperpolarization of both 13 C and 1 H, solution-phase 1 H NMR experiments on dissolved samples revealed transient effects whereby peaks arising from protons bonded to the naturally-occurring 13 C nuclei, appeared larger than the typically dominant 12 C-bonded 1 H resonances. This enhancement of the satellite-peaks was examined in detail, with respect to a variety of mechanisms that could potentially originate it. Both two-and three-spin phenomena active in the solid state could lead to this kind of effect; still, experimental observations revealed that the enhancement originates from 13 C→ 1 H polarization transfer processes active in the liquid state. Kinetic equations based on modified heteronuclear cross-relaxation models were examined, and found to describe well the distinct patterns of growth and decay shown by the 13 C-bound 1 H NMR satellite resonances. The dynamics of these novel cross-relaxation phenomena were determined, and their potential usefulness as tools for investigating hyperpolarized ensembles and for obtaining enhanced-sensitivity 1 H NMR traces, is explored.

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Section: Discussionmentioning

confidence: 84%

Heteronuclear Cross‐Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

Donovan¹,

Lupulescu²,

Frydman³

2014

ChemPhysChem

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“…Central in the development of these new experiments is the spatiotemporal manipulation of the spin interactions, a concept that originated from a search for methods capable of delivering arbitrary multidimensional MR spectra in a single scan (10,11). The generality of the ensuing approach eventually led to several new routes for executing single-scan multidimensional MRI (12)(13)(14)(15)(16).…”

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confidence: 99%

Super‐resolved spatially encoded single‐scan 2D MRI

Ben‐Eliezer

Irani

Frydman

2010

Magnetic Resonance in Med

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129

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Single-scan MRI underlies a wide variety of clinical and research activities, including functional and diffusion studies. Most common among these ''ultrafast'' MRI approaches is echo-planar imaging. Notwithstanding its proven success, echo-planar imaging still faces a number of limitations, particularly as a result of susceptibility heterogeneities and of chemical shift effects that can become acute at high fields. The present study explores a new approach for acquiring multidimensional MR images in a single scan, which possesses a higher built-in immunity to this kind of heterogeneity while retaining echo-planar imaging's temporal and spatial performances. This new protocol combines a novel approach to multidimensional spectroscopy, based on the spatial encoding of the spin interactions, with image reconstruction algorithms based on super-resolution principles. Single-scan two-dimensional MRI examples of the performance improvements provided by the resulting imaging protocol are illustrated using phantom-based and in vivo experiments. Magn Reson Med 63:1594-1600, 2010. V C 2010 Wiley-Liss, Inc.Key words: single-scan imaging; super-resolution; ultrafast MRI; spatial encoded imaging; susceptibility compensation; EPI The last decades have witnessed a continuous growth in the use of single-scan MRI, both for clinical and research applications (1,2). These ''ultrafast'' protocols play an essential role in experiments demanding high temporal resolution like functional MRI (3-5); they also constitute integral components in high-dimensionality experiments such as diffusion tensor imaging (6). Foremost among the sequences enabling the acquisition of MR images in a single scan stands echo-planar imaging (EPI) (7), with its many different variants (8,9). EPI relies on a single excitation of all spins within the volume to be examined, followed by repetitive gradient oscillations that scan, in a single continuous acquisition, large regions of the image conjugate (k-space) domain. The rðrÞ spin density profile being sought is then retrieved by a numerical Fourier transform (FT) of the digitized information. Notwithstanding their real-time image-gathering capabilities, EPI-based protocols are still challenged by the relatively long data sampling times that they involve. These are ca. an order of magnitude longer than those typically involved in multiscan MRI and expose the protocol to progressive temporal artifacts arising from susceptibility variations, from unfavorable shimming conditions, or from chemical shift heterogeneities. These in turn put practical limitations to the organs and/or conditions that can be studied using ultrafast MRI protocols.By contrast to EPI's reliance on contributions arising simultaneously from the entire sample, we have recently begun exploring the consequences of relying on a progressive spatial encoding of MR images. Central in the development of these new experiments is the spatiotemporal manipulation of the spin interactions, a concept that originated from a search for methods capable of del...

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“…Advances in fast data collection in NMR spectroscopy (16,17) suggested that it may be possible to monitor conformational changes of riboswitches, which occur with relatively slow time course of seconds (8,12), using real-time multidimensional NMR. Here we report the successful collection of 2D ultraSO-FAST NMR spectra (18), recorded at repetition rates of about 0.5 Hz, to follow the complete conformational change from ligand-free to ligand-bound form of the adenine riboswitch.…”

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confidence: 99%

Real-time multidimensional NMR follows RNA folding with second resolution

Lee

Gal

Frydman

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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100

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Conformational transitions and structural rearrangements are central to the function of many RNAs yet remain poorly understood. We have used ultrafast multidimensional NMR techniques to monitor the adenine-induced folding of an adenine-sensing riboswitch in real time, with nucleotide-resolved resolution. By following changes in 2D spectra at rates of approximately 0.5 Hz, we identify distinct steps associated with the ligand-induced folding of the riboswitch. Following recognition of the ligand, long range looploop interactions form and are then progressively stabilized before the formation of a fully stable complex over approximately 2-3 minutes. The application of these ultrafast multidimensional NMR methods provides the opportunity to determine the structure of RNA folding intermediates and conformational trajectories.dynamics | riboswitches | ultrafast NMR | conformational transition R iboswitches are genetic control elements found in untranslated regions of prokaryotic and, less often, eukaryotic mRNAs (1). Their function in gene regulation depends on their ability to change structure in response to ligand binding, a property shared with many other functional RNAs (2, 3). They are composed of a ligand-binding domain that is very well conserved to specifically recognize the target metabolite and an expression platform whose structure is altered when the ligand-binding domain is occupied. The change in structure in the expression platform modulates transcription termination or translation initiation in response to changes in metabolite concentration (4, 5). While the structural basis for ligand recognition is known for many riboswitches, how the associated conformational changes occur is much less well understood. Yet the function of the riboswitches depends on their ability to change structure in response to ligand binding, and indeed the kinetics of ligand binding can affect gene regulation (6-8).Purine-sensing riboswitches have been studied with particular intensity because they represent ideal model systems to understand ligand recognition and riboswitch function. The structure of the adenine-sensing riboswitch aptamer domain bound to adenine has been determined by X-ray crystallography (9, 10) and studied extensively by NMR as well (11-13). These studies have shown how a single nucleotide can switch the specificity from adenine to guanine and revealed the architecture of the riboswitch. The structure is composed of three helices emanating from the junction; two hairpin loops capping helices 2 and 3 form a tuning fork-like architecture in the presence of the ligand (Fig. 1), while the three-way junction is responsible for direct adenine recognition. The structure of free adenine-sensing riboswitch aptamer is much more flexible, preventing so far a detailed structural characterization.Single molecule techniques have been applied to studying the time-dependent folding of the purine riboswitch while actively transcribed on the RNA polymerase (14, 15). These force spectroscopy studies have revealed multiple f...

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Principles and Progress in Ultrafast Multidimensional Nuclear Magnetic Resonance

Cited by 78 publications

References 72 publications

Heteronuclear Cross‐Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

Heteronuclear Cross‐Relaxation Effects in the NMR Spectroscopy of Hyperpolarized Targets

Super‐resolved spatially encoded single‐scan 2D MRI

Real-time multidimensional NMR follows RNA folding with second resolution

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