Publications

Purpose - Diffusion weighted imaging (DWI) is increasingly used in evaluating breast cancer, as complement to DCE measurements of superior spatial resolution. Extracting fine morphological features in DWI is complicated by limitations that sequences such as EPI face, when applied to heterogeneous organs. This study investigates the ability of spatiotemporal encoding (SPEN) MRI to screen breast cancers and define diffusivity features at mm and sub-mm resolutions on a 3T scanner. Methods - Twenty-one patients with biopsy-confirmed breast cancer lesions were examined by T2-weighted and DCE protocols, by EPI-based DWI, and by SPEN-based protocols optimized for SNR, robustness and spatial resolution, respectively. Results - Excellent agreement was found between the diffusivity parameters measured by all SPEN protocols and by EPI, with the lower ADCs characteristic of tumors being readily detected. SPEN provided systematically better SNR and improved qualitative results, particularly when dealing with small lesions surrounded by fatty tissue, or lesions close to tissue/air interfaces. SPEN-derived ADC maps collected at sub-mm in-plane resolutions recapitulated the high-resolution morphology shown by lesions using more sensitive DCE protocols. Conclusion - Measurements on a patient cohort validated SPEN's ability to quantify the diffusivity changes associated with the presence of breast cancers, while imaging the lesions with reduced distortions at sub-mm resolutions.

MRI leverages multiple modes of contrast to characterize stroke. High-magnetic-field systems enhance the performance of these MRI measurements. Previously, we have demonstrated that individually sodium and stem cell tracking metrics are enhanced at ultrahigh field in a rat model of stroke, and we have developed robust single-scan diffusion-weighted imaging approaches that utilize spatiotemporal encoding (SPEN) of the apparent diffusion coefficient (ADC) for these challenging field strengths. Here, we performed a multiparametric study of middle cerebral artery occlusion (MCAO) biomarker evolution focusing on comparison of these MRI biomarkers for stroke assessment during sub-acute recovery in rat MCAO models at 21.1 T. T-2-weighted MRI was used as the benchmark for identification of the ischemic lesion over the course of the study. The number of MPIO-induced voids measured by gradient-recalled echo, the SPEN measurement of ADC, and Na-23 MRI values were determined in the ischemic area and contralateral hemisphere, and relative performances for stroke classification were compared by receiver operator characteristic analysis. These measurements were associated with unique time-dependent trajectories during stroke recovery that changed the sensitivity and specificity for stroke monitoring during its evolution. Advantages and limitations of these contrasts, and the use of ultrahigh field for multiparametric stroke assessment, are discussed.

An efficient mixing scheme is introduced for establishing two-dimensional (2D) homonuclear correlations based on dipolar couplings. This mixing scheme achieves broadband dipolar recoupling using remarkably low powers even under ultrafast magic-angle spinning (MAS) rates. This Adiabatic Linearly FREquency Swept reCOupling (AL FRESCO) method applies a series of weak frequency-chirped pluses on the H-1 channel, for performing efficient C-13-C-13 magnetization transfers leading to cross peaks between sites separated over small or large chemical shift differences. The mixing scheme is nearly free from dipolar truncation effects, and thanks to the low RF powers it involves it can act over long mixing times (>= 1.5 sec). Key considerations required for optimizing this chirped pulse mixing scheme are discussed, and the new kind of correlations that can emerge from this method are demonstrated using uniformly C-13-labeled Barstar as test protein sample.

Dynamic Nuclear Polarization (DNP) can increase the sensitivity of Nuclear Magnetic Resonance (NMR), but it is challenging in the liquid state at high magnetic fields. In this study we demonstrate significant enhancements of NMR signals (up to 70 on C-13) in the liquid state by scalar Overhauser DNP at 14.1 T, with high resolution (similar to 0.1 ppm) and relatively large sample volume (similar to 100 mu L).

While C-13-based Incredible Natural Abundance DoublE QUAntum Transfer Experiment (INADEQUATE) experiments offer an attractive alternative for establishing molecular structures, they suffer from low sensitivities arising from the scarcity of spin pairs present at natural abundance. Herein we demonstrate that dissolution dynamic nuclear polarization (dDNP) provides sufficient sensitivity to acquire 1D C-13 INADEQUATE spectra in a single scan and at natural abundance. Moreover, if steps are adopted to endow sub-Hertz precision to these measurements, they allow one to measure carbon carbon J couplings over both one and multiple bonds for each chemical site. As these Jcc-couplings are usually sufficiently distinct to enable univocal pairing of the nuclei involved, essentially the same information as in 2D INADEQUATE can be obtained. The feasibility of the method is demonstrated for a range of compounds, including natural products such as a-pinene, menthol and limonene. Features and extensions of this approach are briefly discussed.

Purpose: To develop a rapid, non-CPMG high-resolution volumetric imaging approach, exhibiting a speed and in-plane resilience to field inhomogeneities comparable to RARE/turbo-spin-echo (TSE) while endowed with unique downsampling characteristics.Methods: A multi-scan extension of cross-term spatiotemporal encoding (xSPEN) is introduced and analyzed. The method simultaneously yields k(y)/k(z) data containing low and high frequency components, as well as transposed, low-resolution z/y images. This dual k-/spatial-domain information is captured by a multi-scan procedure that phase-encodes k(y) while simultaneously slice-selecting z. A reconstruction scheme converting this information into high resolution 3D images with fully multiplexed volumetric coverage is introduced and exemplified.Results: Phase-encoded xSPEN was tested by human brain imaging at sub-mm resolutions. The method exceeded 2D TSE's sensitivity by factors of approximate to 3-4, while providing similar resolution and SNR as 3D TSE in approximate to 50% acquisition times. The method's contrast is dominated by T-2 and is free from "bright-fat" effects associated to spin-echo trains. Further acceleration is enabled by the method's downsampling abilities. Tradeoffs between encoding time, number of measurements, spatial resolution, SNR, and artifact levels are also laid out.Conclusion: A new MRI strategy is introduced delivering high in-and through-plane resolutions while enjoying full Fourier multiplexing, leading to fast acquisitions with high SNR.

Many mutations that cause familial hypercholesterolemia localize to ligand-binding domain 5 (LA5) of the low-density lipoprotein receptor, motivating investigation of the folding and misfolding of this small, disulfide-rich, calcium-binding domain. LA5 folding is known to involve non-native disulfide isomers, yet these folding intermediates have not been structurally characterized. To provide insight into these intermediates, we used nuclear magnetic resonance (NMR) to follow LA5 folding in real time. We demonstrate that misfolded or partially folded disulfide intermediates are indistinguishable from the unfolded state when focusing on the backbone NMR signals, which provide information on the formation of only the final, native state. However,
13C labeling of cysteine side chains differentiated transient intermediates from the unfolded and native states and reported on disulfide bond formation in real time. The cysteine pairings in a dominant intermediate were identified using
13C-edited three-dimensional NMR, and coarse-grained molecular dynamics simulations were used to investigate the preference of this disulfide set over other non-native arrangements. The transient population of LA5 species with particular non-native cysteine connectitivies during folding supports the conclusion that cysteine pairing is not random and that there is a bias toward certain structural ensembles during the folding process, even prior to the binding of calcium.

Nuclear magnetic resonance (NMR) is an intrinsically insensitive technique, with Boltzmann distributions of nuclear spin states on the order of parts per million in conventional magnetic fields. To overcome this limitation, dynamic nuclear polarization (DNP) can be used to gain up to three orders of magnitude in signal enhancement, which can decrease experimental time by up to six orders of magnitude. In DNP experiments, nuclear spin polarization is enhanced by transferring the relatively larger electron polarization to NMR active nuclei via microwave irradiation. Here, we describe the design and performance of a quasi-optical system enabling the use of a single 395 GHz gyrotron microwave source to simultaneously perform DNP experiments on two different 14.1 T (1H 600 MHz) NMR spectrometers: one configured for magic angle spinning (MAS) solid state NMR; the other configured for solution state NMR experiments. In particular, we describe how the high power microwave beam is split, transmitted, and manipulated between the two spectrometers. A 13C enhancement of 128 is achieved via the cross effect for alanine, using the nitroxide biradical AMUPol, under MAS-DNP conditions at 110 K, while a 31P enhancement of 160 is achieved via the Overhauser effect for triphenylphosphine using the monoradical BDPA under solution NMR conditions at room temperature. The latter result is the first demonstration of Overhauser DNP in the solution state at a field of 14.1 T (1H 600 MHz). Moreover these results have been produced with large sample volumes (∼100 µL, i.e. 3 mm diameter NMR tubes).

Purpose: Spatio-temporal encoding (SPEN) experiments can deliver single-scan MR images without folding complications and with robustness to chemical shift and susceptibility artifacts. Further resolution improvements are shown to arise by relying on multiple receivers, to interpolate the sampled data along the low-bandwidth dimension. The ensuing multiple-sensor interpolation is akin to recently introduced SPEN interleaving procedures, albeit without requiring multiple shots. Methods: By casting SPEN's spatial rasterization in k-space, it becomes evident that local k-data interpolations enabled by multiple receivers are akin to real-space interleaving of SPEN images. The practical implementation of such a resolution-enhancing procedure becomes similar to those normally used in simultaneous acquisition of spatial harmonics or sensitivity encoding, yet relaxing these methods’ fold-over constraints. Results: Experiments validating the theoretical expectations were carried out on phantoms and human volunteers on a 3T scanner. The experiments showed the expected resolution enhancement, at no cost to the sequence's complexity. With the addition of multibanding and stimulated echo procedures, 48-slice full-brain coverage could be recorded free from distortions at submillimeter resolution, in 3 s. Conclusions: Super-resolved SPEN with SENSE (SUSPENSE) achieves the goals of multishot SPEN interleaving delivering single-shot submillimeter in-plane resolutions in scanners equipped with suitable multiple sensors. Magn Reson Med 79:796–805, 2018.

Measuring cellular microstructures non-invasively and achieving specificity towards a celltype population within an interrogated in vivo tissue, remains an outstanding challenge in brain research. Magnetic Resonance Spectroscopy (MRS) provides an opportunity to achieve cellular specificity via the spectral resolution of metabolites such as N-Acetylaspartate (NAA) and myo-Inositol (mI), which are considered neuronal and astrocytic markers, respectively. Yet the information typically obtained with MRS describes metabolic concentrations, diffusion coefficients or relaxation rates rather than microstructures. Understanding how these metabolites are compartmentalized is a challenging but important goal, which so far has been mainly addressed using diffusion models. Here, we present direct in vivo evidence for the confinement of NAA and mI within sub-cellular components, namely, the randomly oriented process of neurons and astrocytes, respectively. Our approach applied Relaxation Enhanced MRS at ultrahigh (21.1 T) field, and used its high H-1 sensitivity to measure restricted diffusion correlations for NAA and mI using a Double Diffusion Encoding (DDE) filter. While very low macroscopic anisotropy was revealed by spatially localized Diffusion Tensor Spectroscopy, DDE displayed characteristic amplitude modulations reporting on confinements in otherwise randomly oriented anisotropic microstructures for both metabolites. This implies that for the chosen set of parameters, the DDE measurements had a biased sensitivity towards NAA and mI sited in the more confined environments of neurites and astrocytic branches, than in the cell somata. These measurements thus provide intrinsic diffusivities and compartment diameters, and revealed subcellular neuronal and astrocytic morphologies in normal in vivo rat brains. The relevance of these measurements towards human applications- which could in turn help understand CNS plasticity as well as diagnose brain diseases- is discussed.

Purpose: Cross-term spatiotemporal encoding (xSPEN) is a single-shot approach with exceptional immunity to field heterogeneities, the images of which faithfully deliver 2D spatial distributions without requiring a priori information or using postacquisition corrections. xSPEN, however, suffers from signal-to-noise ratio penalties due to its non-Fourier nature and due to diffusion losses—especially when seeking high resolution. This study explores partial Fourier transform approaches that, acting along either the readout or the spatiotemporally encoded dimensions, reduce these penalties. Methods: xSPEN uses an orthogonal (e.g., z) gradient to read, in direct space, the low-bandwidth (e.g., y) dimension. This substantially changes the nature of partial Fourier acquisitions vis-à-vis conventional imaging counterparts. A suitable theoretical analysis is derived to implement these procedures, along either the spatiotemporally or readout axes. Results: Partial Fourier single-shot xSPEN images were recorded on preclinical and human scanners. Owing to their reduction in the experiments’ acquisition times, this approach provided substantial sensitivity gains vis-à-vis previous implementations for a given targeted in-plane resolution. The physical origins of these gains are explained. Conclusion: Partial Fourier approaches, particularly when implemented along the low-bandwidth spatiotemporal dimension, provide several-fold sensitivity advantages at minimal costs to the execution and processing of the single-shot experiments. Magn Reson Med 79:1506–1514, 2018.

The use of frequency-swept radiofrequency (rf) pulses for enhancing signals in the magic-angle spinning (MAS) spectra of half-integer quadrupolar nuclides was explored. The broadband adiabatic inversion cross-polarization magic-angle spinning (BRAIN-CPMAS) method, involving an adiabatic inversion pulse on the S-channel and a simultaneous rectangular spin-lock pulse on the I-channel (H-1), was applied to I (1/2) -> S(3/2) systems. Optimal BRAIN-CPMAS matching conditions were found to involve low rf pulse strengths for both the I- and S-spin channels. At these low and easily attainable rf field strengths, level-crossing events among the energy levels |3/2 >, |1/2 >, | -1/2 >, | - 3/2 > that are known to complicate the CPMAS of quadrupolar nuclei, are mostly avoided. Zero- and double-quantum polarization transfer modes, akin to those we have observed for 1(1/2) -> S(1/2) polarization transfers, were evidenced by these analyses even in the presence of the quadrupolar interaction. H-1-Na-23 and H-1-B-11 BRAIN-CPMAS conditions were experimentally explored on model compounds by optimizing the width of the adiabatic sweep, as well as the rf pulse powers of the H-1 and Na-23/B-11 channels, for different MAS rates. The experimental data obtained on model compounds containing spin-3/2 nuclides, matched well predictions from numerical simulations and from an average Hamiltonian theory model. Extensions to half-integer spin nuclides with higher spins and potential applications of this BRAIN-CPMAS approach are discussed. (C) 2017 Elsevier Inc. All rights reserved.

Cross-polarization (CP) experiments employing frequency-swept radiofrequency (rf) pulses have been successfully used in static spin systems for obtaining broadband signal enhancements. These experiments have been recently extended to heteronuclear I, S = spin-1/2 nuclides under magic-angle spinning (MAS), by applying adiabatic inversion pulses along the S (low-gamma) channel while simultaneously applying a conventional spin-locking pulse on the I-channel (H-1). This study explores an extension of this adiabatic frequency sweep concept to quadrupolar nuclei, focusing on CP from H-1 (I = 1/2) to H-2 spins (S = 1) undergoing fast MAS (nu(r) = 60 kHz). A number of new features emerge, including zero- and double-quantum polarization transfer phenomena that depend on the frequency offsets of the swept pulses, the rf pulse powers, and the MAS spinning rate. An additional mechanism found operational in the H-1-H-2 CP case that was absent in the spin-1/2 counterpart, concerns the onset of a pseudo-static zero- quantum CP mode, driven by a quadrupole-modulated rf/dipolar recoupling term arising under the action of MAS. The best CP conditions found at these fast spinning rates correspond to double-quantum transfers, involving weak H-2 rf field strengths. At these easily attainable (ca. 10 kHz) rf field conditions, adiabatic level-crossings among the {vertical bar 1 ,vertical bar 0 ,broken vertical bar-1} m(S) energy levels, which are known to complicate the CP MAS of quadrupolar nuclei, are avoided. Moreover, the CP line shapes generated in this manner are very close to the ideal H-2 MAS spectral line shapes, facilitating the extraction of quadrupolar coupling parameters. All these features were corroborated with experiments on model compounds and justified using numerical simulations and average Hamiltonian theory models. Potential applications of these new phenomena, as well as extensions to higher spins S, are briefly discussed.

PurposeSingle-scan two-dimensional MRI has been generally constrained to acquisitions in high quality magnets. This study introduces a methodology, cross-term spatiotemporal encoding (xSPEN), that delivers such images under much poorer external field conditions.MethodsxSPEN departs from conventional k-space scanning, by relying on spatiotemporally encoding the image being sought. Unlike hitherto proposed SPEN methods, however, xSPEN's image readout does not take place using a field gradient along the direction being probed, but rather with the aid of an ancillary source of inhomogeneous frequency broadening. This ancillary dimension was here imposed by an orthogonal field gradient; for example, images along the y axis were read out by application of a z gradient. The principles and characteristics of this new approach, compatible with existing scanners and free from the need to collect auxiliary information such as field maps, are presented and discussed.ResultsSingle- and multi-slice in vitro, ex vivo, and in vivo MRI experiments, confirmed the unusual resilience of this new single-shot MRI method to multiple chemical sites on phantoms, animals and humans.ConclusionxSPEN can deliver single-scan MRI with good sensitivity and exceptional resilience to field inhomogeneities. This could enable investigations that have hitherto escaped from MRI's scope. Magn Reson Med 77:623-634, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine

Chemical exchange saturation transfer (CEST) experiments enhance the NMR signals of labile protons by continuously transferring these protons' saturation to an abundant solvent pool like water. The present study expands these principles by fusing into these experiments homonuclear isotropic mixing sequences, enabling the water-enhanced detection of non-exchangeable species. Further opportunities are opened by the addition of coupling-mediated heteronuclear polarization transfers, which then impose on the water resonance a saturation stemming from non-labile heteronuclear species like 13C. To multiplex the ensuing experiments, these relayed approaches are combined with time-domain schemes involving multiple Ramsey-labeling experiments imparting the frequencies of the non-labile sites on the water resonance, via chemical exchange. 13C and 1H NMR spectra were detected in this fashion with about two-fold SNR amplification vis-à-vis conventionally detected spectroscopies. When combined with non-uniform sampling principles, this methodology thus becomes a sensitive alternative to detect non-exchangeable species in biomolecules. Still, multiple parameters including the scalar couplings and solvent exchange rates, will affect the efficiency and consequently the practicality of the overall experiment.

PurposeThis study seeks to evaluate in vivo T-2 relaxation times of selectively excited stroke-relevant metabolites via H-1 relaxation-enhanced magnetic resonance spectroscopy (RE-MRS) at 21.1T (900 MHz).MethodsA quadrature surface coil was designed and optimized for investigations of rodents at 21.1T. With voxel localization, a RE-MRS pulse sequence incorporating the excitation of selected metabolites was modified to include a variable echo delay for T-2 measurements. A middle cerebral artery occlusion (MCAO) animal model for stroke was examined with spectra taken 24h post occlusion. Fourteen echo times were acquired, with each measurement completed in less than 2min.ResultsThe RE-MRS approach produced high-quality spectra of the selectively excited metabolites in the stroked and contralateral regions. T-2 measurements reveal differential results between these regions, with significance achieved for lactic acid.ConclusionUsing the RE-MRS technique at ultra-high magnetic field and an optimized quadrature surface coil design, full metabolic T-2 quantifications in a localized voxel is now possible in less than 27min. Magn Reson Med 77:520-528, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine

Multidimensional Nuclear Magnetic Resonance (NMR) provides a unique window into structure and dynamics at an atomic level. Traditionally, given the scan-by-scan time modulation involved in these experiments, the duration of nD NMR increases exponentially with spectral dimensionality. In addition, acquisition times increase as the number of spectral elements being sought in each indirect domain given by the ratio between the spectral bandwidth being targeted and the resolution desired. These long sampling times can be substantially reduced by exploiting information that is often available from lower dimensionality acquisitions. This work presents a novel approach that exploits previous 2D information to speed up the acquisition of 3D spectra, based on what we denote as a Time-Optimized FouriEr Encoding (TOFEE) of pre-targeted peaks. Such 3D TOFEE experiments, which present points in common with Hadamard-encoded 3D acquisitions, do not necessarily require more scans than their 2D counterparts. This is here demonstrated based on extensions of 2D Heteronuclear Single-quantum Coherence (HSQC) experiments, to 3D HSQC-TOCSY or 3D HSQC-NOESY acquisitions. The theoretical basis of this new approach is given, and experimental demonstrations are presented on small molecule and protein-based model systems. (C) 2016 Elsevier Inc. All rights reserved.

2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Dynamic nuclear polarization (DNP) is a versatile option to improve the sensitivity of NMR and MRI. This versatility has elicited interest for overcoming potential limitations of these techniques, including the achievement of solid-state polarization enhancement at ambient conditions, and the maximization of (13) C signal lifetimes for performing in?vivo MRI scans. This study explores whether diamond's (13) C behavior in nano- and micro-particles could be used to achieve these ends. The characteristics of diamond's DNP enhancement were analyzed for different magnetic fields, grain sizes, and sample environments ranging from cryogenic to ambient temperatures, in both solution and solid-state experiments. It was found that (13) C?NMR signals could be boosted by orders of magnitude in either low- or room-temperature solid-state DNP experiments by utilizing naturally occurring paramagnetic P1 substitutional nitrogen defects. We attribute this behavior to the unusually long electronic/nuclear spin-lattice relaxation times characteristic of diamond, coupled with a time-independent cross-effect-like polarization transfer mechanism facilitated by a matching of the nitrogen-related hyperfine coupling and the (13) C Zeeman splitting. The efficiency of this solid-state polarization process, however, is harder to exploit in dissolution DNP-enhanced MRI contexts. The prospects for utilizing polarized diamond approaching nanoscale dimensions for both solid and solution applications are briefly discussed.

PurposeEvaluate the usefulness of diffusion-weighted spatiotemporally encoded (SPEN) methods to obtain apparent diffusion coefficient (ADC) maps of fibroglandular human breast tissue, in the presence of silicone implants.MethodsSeven healthy volunteers with breast augmentation were scanned at 3 Tesla (T) using customized SPEN sequences yielding separate silicone and water H-1 images in one scan, together with their corresponding diffusion-weightings.ResultsSPEN's ability to deliver multiple spectrally resolved images in a single scan, coupled to the method's substantial robustness to magnetic field heterogeneities, served to acquire ADC maps that could be freed from contributions that did not belong to fibroglandular tissue.ConclusionSPEN-based sequences incorporating spectral discrimination and diffusion-weighting enable the acquisition of reliable ADC maps despite the presence of dominant signals from silicone implants, thereby opening new screening possibilities for the identification of malignancies in breast augmented patients. Magn Reson Med 75:2064-2071, 2016. (c) 2015 Wiley Periodicals, Inc.

Two-dimensional (2D) correlations between bonded heteroatoms, lie at the cornerstone of many uses given to contemporary nuclear magnetic resonance (NMR). Improving the efficiency with which these correlations are established is an important topic in modern NMR, with potential applications in rapid chemical analysis and dynamic biophysical studies. Alternatives have been developed over the last decade to speed up these experiments, based among others on reducing the number of data points that need to be sampled, and/or shortening the inter-scan delays. Approaches have also been proposed to forfeit multi-scan schemes altogether, and complete full 2D correlations in a single shot. Here we explore and discuss a new alternative enabling the collection of such very fast - in principle, single-scan - acquisitions of 2D heteronuclear correlations among bonded species, which operates on the basis of a partial reintroduction of J couplings. Similar approaches had been proposed in the past based on collecting coupled spectra for arrays of off-resonance decoupling values; the proposal that is here introduced operates on the basis of suitably incorporating frequency-swept pulses, into spin-echo sequences. Thanks to the offset-dependent amplitude modulations of the in- and anti-phase components that such sequences impart, chemical shifts of coupled but otherwise unobserved nuclear species, can be extracted from the relative intensities and phases of J-coupled multiplets observed in one-dimensional acquisitions. A description of the steps needed to implement this rapid acquisition approach in a quantitative fashion, as well as applications of the ensuing sequences, are presented.

A recent study explored the use of hyperpolarized water, to enhance the sensitivity of nuclei in biomolecules thanks to rapid proton exchanges with labile amide backbone and sidechain groups. Further optimizations of this approach have now allowed us to achieve proton polarizations approaching 25% in the water transferred into the NMR spectrometer, effective water T-1 times approaching 40 s, and a reduction in the dilution demanded for the cryogenic dissolution process. Further hardware developments have allowed us to perform these experiments, repeatedly and reliably, in 5 mm NMR tubes. All these ingredients - particularly the >= 3000x H-1 polarization enhancements over 11.7 T thermal counterparts, long T-1 times and a compatibility with high-resolution biomolecular NMR setups - augur well for hyperpolarized 2D NMR studies of peptides, unfolded proteins and intrinsically disordered systems undergoing fast exchanges of their protons with the solvent. This hypothesis is here explored by detailing the provisions that lead to these significant improvements over previous reports, and demonstrating 1D coherence transfer experiments and 2D biomolecular HMQC acquisitions delivering NMR spectral enhancements of 100-500x over their optimized, thermally-polarized, counterparts. (C) 2016 Elsevier Inc. All rights reserved.

Single-sided nuclear magnetic resonance (NMR) scanners find increased use in applications where non-destructive measurements are needed. These single-sided scanners are characterized by a weak magnetic field and a large stray magnetic field gradient. These characteristics make these scanners suitable for determining a sample's proton density profile, or for mapping NMR properties such as T (1), T (2) or diffusivity as a function of distance. The strong stray-field gradient generated by these magnets dictates a need for relatively high transmission/reception bandwidths, even when thin slices are involved. Consequently, scanning a large volume demands multiple separate measurements, associated with long scan times, potential inaccuracies associated with mechanical misplacements and limitations in tackling certain in vivo or dynamic systems. This work explores the consequences of replacing the hard pulses in the usual multi-echo sequence used in this kind of scanner, with frequency-swept (chirped) pulses. It was found that, under identical echo times and number of echoes, peak power-limited cases like the ones usually involved in these setups endow chirped-pulse sequences with a higher sensitivity than their square-pulse counterparts. Furthermore, data can be extracted in this manner faster; it can also be measured from larger slabs following a single excitation, thereby avoiding the need for multiple mechanical motions of the scanner/sample. Still, at least with the system hereby assayed, hardware limitations prevented us from utilizing equally short echo times for square- as well as chirped-pulse implementations. Given the shorter echo delays that could be used in the square-pulse versions, optimal acquisitions ended up endowing the latter with the best overall sensitivity defined as signal intensity per unit acquisition time. Potential bypasses of this limitation are briefly discussed.

PurposeEvaluating the usefulness of diffusion-weighted spatio-temporal encoding (SPEN) methods to provide quantitative apparent diffusion coefficient (ADC)-based characterizations of healthy and malignant human breast tissues, in comparison with results obtained using techniques based on spin-echo echo planar imaging (SE-EPI). MethodsTwelve healthy volunteers and six breast cancer patients were scanned at 3T using scanner-supplied diffusion-weighted imaging EPI sequences, as well as two fully refocused SPEN variants programmed in-house. Suitable codes were written to process the data, including calculations of the actual b-values and retrieval of the ADC maps. ResultsSystematically better images were afforded by the SPEN scans, with negligible geometrical distortions and markedly weaker ghosting artifacts arising from either fat tissues or from strongly emitting areas such as cysts. SPEN-derived images provided improved characterizations of the fibroglandular tissues and of the lesions' contours. When translated into the calculation of the ADC maps, there were no significant differences between the mean ADCs derived from SPEN and SE-EPI: if reliable images were available, both techniques showed that ADCs decreased by nearly two-fold in the malignant lesion areas. ConclusionSPEN-based sequences yielded diffusion-weighted breast images with minimal artifacts and distortions, enabling the calculation of improved ADC maps and the identification of decreased ADCs in malignant regions. Magn Reson Med 73:2163-2173, 2015. (c) 2014 Wiley Periodicals, Inc.

PurposeThis study quantifies in vivo ischemic stroke brain injuries in rats using ultrahigh-field single-scan MRI methods to assess variations in apparent diffusion coefficients (ADCs). MethodsMagnitude and diffusion-weighted spatiotemporally encoded imaging sequences were implemented on a 21.1 T imaging system, and compared with spin-echo and echo-planar imaging diffusion-weighted imaging strategies. ADC maps were calculated and used to evaluate the sequences according to the statistical comparisons of the ipsilateral and contralateral ADC measurements at 24, 48, and 72 h poststroke. ResultsSusceptibility artifacts resulting from normative anatomy and pathological stroke conditions were particularly intense at 21.1 T. These artifacts strongly distorted single-shot diffusion-weighted echo-planar imaging experiments, but were reduced in four-segment interleaved echo-planar imaging acquisitions. By contrast, nonsegmented diffusion-weighted spatiotemporally encoded images were largely immune to field-dependent artifacts. Effects of stroke were apparent in both magnitude images and ADC maps of all sequences. When stroke recovery was followed by ADC variations, spatiotemporally encoded, echo-planar imaging, and spin-echo acquisitions revealed statistically significant increase in ADCs. ConclusionsConsideration of experiment duration, image quality, and mapped ADC values provided by spatiotemporally encoded demonstrates that this single-shot acquisition is a method of choice for high-throughput, ultrahigh-field in vivo stroke quantification. Magn Reson Med 73:1483-1489, 2015. (c) 2014 Wiley Periodicals, Inc.

Natural abundance C-13 NMR spectra of biological extracts are recorded in a single scan provided that the samples are hyperpolarized by dissolution dynamic nuclear polarization combined with cross polarization. Heteronuclear 2D correlation spectra of hyperpolarized breast cancer cell extracts can also be obtained in a single scan. Hyperpolarized NMR of extracts opens many perspectives for metabolomics.

Samples prepared following dissolution dynamic nuclear polarization (DNP) enable the detection of NMR spectra from low- nuclei with outstanding sensitivity, yet have limited use for the enhancement of abundant species like (1)Hnuclei. Small- and intermediate-sized molecules, however, show strong heteronuclear cross-relaxation effects: spontaneous processes with an inherent isotopic selectivity, whereby only the C-13-bonded protons receive a polarization enhancement. These effects are here combined with a recently developed method that delivers homonuclear-decoupled (1)Hspectra in natural abundance samples based on heteronuclear couplings to these same, C-13-bonded nuclei. This results in the HyperBIRD methodology; a single-shot combination of these two effects that can simultaneously simplify and resolve complex, congested (HNMR)-H-1 spectra with many overlapping spin multiplets, while achieving 50-100 times sensitivity enhancements over conventional thermal counterparts.

Speeding up the acquisition of multidimensional nuclear magnetic resonance (NMR) spectra is an important topic in contemporary NMR, with central roles in high-throughput investigations and analyses of marginally stable samples. A variety of fast NMR techniques have been developed, including methods based on non-uniform sampling and Hadamard encoding, that overcome the long sampling times inherent to schemes based on fast-Fourier-transform (FFT) methods. Here, we explore the potential of an alternative fast acquisition method that leverages a priori knowledge, to tailor polychromatic pulses and customized time delays for an efficient Fourier encoding of the indirect domain of an NMR experiment. By porting the encoding of the indirect-domain to the excitation process, this strategy avoids potential artifacts associated with non-uniform sampling schemes and uses a minimum number of scans equal to the number of resonances present in the indirect dimension. An added convenience is afforded by the fact that a usual 2D FFT can be used to process the generated data. Acquisitions of 2D heteronuclear correlation NMR spectra on quinine and on the anti-inflammatory drug isobutyl propionic phenolic acid illustrate the new method's performance. This method can be readily automated to deal with complex samples such as those occurring in metabolomics, in incell as well as in in vivo NMR applications, where speed and temporal stability are often primary concerns. (c) 2014 AIP Publishing LLC.

H-1 magnetic resonance spectroscopy (MRS) yields site-specific signatures that directly report metabolic concentrations, biochemistry and kinetics-provided spectral sensitivity and quality are sufficient. Here, an enabling relaxation-enhanced (RE) MRS approach is demonstrated that by combining highly selective spectral excitations with operation at very high magnetic fields, delivers spectra exhibiting signal-to-noise ratios >50:1 in under 6s for similar to 5 x 5 x 5 (mm)(3) voxels, with flat baselines and no interference from water. With this spectral quality, MRS was used to interrogate a number of metabolic properties in stroked rat models. Metabolic confinements imposed by randomly oriented micro-architectures were detected and found to change upon ischaemia; intensities of downfield resonances were found to be selectively altered in stroked hemispheres; and longitudinal relaxation time of lactic acid was found to increase by over 50% its control value as early as 3-h post ischaemia, paralleling the onset of cytotoxic oedema. These results demonstrate potential of H-1 MRS at ultrahigh fields.

A main obstacle arising when using ex situ hyperpolarization to increase the sensitivity of biomolecular NMR is the fast relaxation that macromolecular spins undergo upon being transferred from the polarizer to the spectrometer, where their observation takes place. To cope with this limitation, the present study explores the use of hyperpolarized water as a means to enhance the sensitivity of nuclei in biomolecules. Methods to achieve proton polarizations in excess of 5% in water transferred into the NMR spectrometer were devised, as were methods enabling this polarization to last for up to 30 s. Upon dissolving amino acids and polypeptides sited at the spectrometer into such hyperpolarized water, a substantial enhancement of certain biomolecular amide and amine proton resonances was observed. This exchange-driven H-1 enhancement was further passed on to side-chain and to backbone nitrogens, owing to spontaneous one-bond Overhauser processes. N-15 signal enhancements >500 over 11.7 T thermal counterparts could thus be imparted in a kinetic process that enabled multiscan signal averaging. Besides potential bioanalytical uses, this approach opens interesting possibilities in the monitoring of dynamic biomolecular processes, including solvent accessibility and exchange process.

Line narrowing has been traditionally achieved in solid-state H-1 NMR spectroscopy by applying pulse sequences that combine multiple-pulse operations with magic-angle spinning (MAS), to effectively average out the dipoledipole homonuclear Hamiltonian. The present study explores a new alternative that departs from the usual concept of directly acting on the strongly coupled spins with radiofrequency pulses; instead, we seek to achieve a net homonuclear dipolar decoupling in solids by exploring the reintroduction of MAS-averaged heteronuclear dipolar couplings between the H-1 nuclei and directly bonded C-13 or N-15 nuclei. This recouplinganti-recoupling (RaR) scheme thus relies on the recoupling of the dipolar interaction with heteronuclear spins, which, under fast MAS, will exceed the strength and will not commute with the homonuclear (HH)-H-1-H-1 coupling one is intending to average out. Subsequent removal (antiRecoupling) of these heteronuclear interactions can lead to narrowed H-1 resonances, without ever pulsing on the aforementioned channel. The line-narrowing properties of RaR are illustrated with numerical simulations and with experiments on model organic solids.

Dynamical decoupling, a generalization of the original NMR spin-echo sequence, is becoming increasingly relevant as a tool for reducing decoherence in quantum systems. Such sequences apply non-equidistant refocusing pulses for optimizing the coupling between systems, and environmental fluctuations characterized by a given noise spectrum. One such sequence, dubbed Selective Dynamical Recoupling (SDR) [P. E. S. Smith, G. Bensky, G. A. Alvarez, G. Kurizki, and L. Frydman, Proc. Natl. Acad. Sci. 109, 5958 (2012)], allows one to coherently reintroduce diffusion decoherence effects driven by fluctuations arising from restricted molecular diffusion [G. A. Alvarez, N. Shemesh, and L. Frydman, Phys. Rev. Lett. 111, 080404 (2013)]. The fully-refocused, constant-time, and constant-number-of-pulses nature of SDR also allows one to filter out "intrinsic" T-1 and T-2 weightings, as well as pulse errors acting as additional sources of decoherence. This article explores such features when the fluctuations are now driven by unrestricted molecular diffusion. In particular, we show that diffusion-driven SDR can be exploited to investigate the decoherence arising from the frequency fluctuations imposed by internal gradients. As a result, SDR presents a unique way of probing and characterizing these internal magnetic fields, given an a priori known free diffusion coefficient. This has important implications in studies of structured systems, including porous media and live tissues, where the internal gradients may serve as fingerprints for the system's composition or structure. The principles of this method, along with full analytical solutions for the unrestricted diffusion-driven modulation of the SDR signal, are presented. The potential of this approach is demonstrated with the generation of a novel source of MRI contrast, based on the background gradients active in an ex vivo mouse brain. Additional features and limitations of this new method are discussed. (C) 2014 AIP Publishing

PurposeTo introduce a method that provides simultaneous spatial and spectral selectivity, whose implementation is less demanding thanand quality comparable toconventional 2D spectral-spatial counterparts. TheorySpatiotemporal encoding concepts lead to a spatially selective, chemical-shift-dependent echo, with simultaneous dephasing of all other off-resonant species. The approach only requires applying a pair of suitable radiofrequency-swept pulses, and allows arbitrary shaping of the spatial profiles. MethodsBased on arguments derived for chirp pulses operating in the sequential-sweep approximation, quadratic-phase SLR excitation and refocusing waveforms were designed and used to collect 2D slice- and shift-selective images on a 7 T microimaging system (phantoms). The same strategy was used to obtain multi-slice echo-planar and spin-echo images of breast on human volunteers in a 3 T scanner. ResultsThe method managed to deliver excellent shift-selective multi-slice images in phantoms and human volunteers. Simultaneous water and fat images were also collected in a single, interleaved acquisition mode on both platforms, using straightforward sequence and reconstruction modifications of the basic scheme. ConclusionA new way to achieve chemical shift selectivity with high quality spatial profiling is achieved, without the usual requirements for playing out fast oscillating gradients in conjunction with carefully timed radiofrequency pulses. Magn Reson Med 71:746-755, 2014. (c) 2013 Wiley Periodicals, Inc.

Two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy is widely used in chemical and biochemical analyses. Multidimensional NMR is also witnessing increased use in quantitative and metabolic screening applications. Conventional 2D NMR experiments, however, are affected by inherently long acquisition durations, arising from their need to sample the frequencies involved along their indirect domains in an incremented, scan-by-scan nature. A decade ago, a so-called ultrafast (UF) approach was proposed, capable of delivering arbitrary 2D NMR spectra involving any kind of homo-or heteronuclear correlation, in a single scan. During the intervening years, the performance of this subsecond 2D NMR methodology has been greatly improved, and UF 2D NMR is rapidly becoming a powerful analytical tool experiencing an expanded scope of applications. This review summarizes the principles and main developments that have contributed to the success of this approach and focuses on applications that have been recently demonstrated in various areas of analytical chemistry-from the real-time monitoring of chemical and biochemical processes, to extensions in hyphenated techniques and in quantitative applications.

The recent development of dissolution dynamic nuclear polarization (DNP) gives NMR the sensitivity to follow metabolic processes in living systems with high temporal resolution. In this article, we apply dissolution DNP to study the metabolism of hyperpolarized U-C-13,H-2(7)-glucose in living, perfused human breast cancer cells. Spectrally selective pulses were used to maximize the signal of the main product, lactate, whilst preserving the glucose polarization; in this way, both C-1-lactate and C-3-lactate could be observed with high temporal resolution. The production of lactate by T47D breast cancer cells can be characterized by Michaelis-Menten-like kinetics, with K-m=3.5 +/- 1.5mm and V-max=34 +/- 4 fmol/cell/min. The high sensitivity of this method also allowed us to observe and quantify the glycolytic intermediates dihydroxyacetone phosphate and 3-phosphoglycerate. Even with the enhanced DNP signal, many other glycolytic intermediates could not be detected directly. Nevertheless, by applying saturation transfer methods, the glycolytic intermediates glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, phosphoenolpyruvate and pyruvate could be observed indirectly. This method shows great promise for the elucidation of the distinctive metabolism and metabolic control of cancer cells, suggesting multiple ways whereby hyperpolarized U-C-13,H-2(7)-glucose NMR could aid in the diagnosis and characterization of cancer in vivo. Copyright (c) 2013 John Wiley & Sons, Ltd.

The metabolic status of muscle changes according to the energetic demands of the organism. Two key regulators of these changes include exercise and insulin, with exercise eliciting catabolic expenditure within seconds and insulin enabling anabolic energy investment over minutes to hours. This study explores the potential of time-resolved hyperpolarized dynamic C-13 spectroscopy to characterize the in vivo metabolic phenotype of muscle during functional and biochemical insulin-induced stimulation of muscle. Using [C-13(1)] pyruvic acid as a tracer, we find that despite the different time scales of these forms of stimulation, increases in pyruvate label transport and consumption and concomitant increases in initial rates of the tracer metabolism to lactate were observed for both stimuli. By contrast, rates of tracer metabolism to labeled alanine increased incrementally for insulin but remained unchanged following exercise-like muscle stimulation. Kinetic analysis revealed that branching of the hyperpolarized [C-13] pyruvate tracer between lactate and alanine provides significant tissue-specific biomarkers that distinguish between anabolic and catabolic fates in vivo according to the routing of metabolites between glycolytic and amino acid pathways.

Recent years have seen an increased interest in combining MRI thermometry with devices capable of destroying malignancies by heat ablation. Expected from the MR protocols are accurate and fast thermal characterizations, providing real time feedback on restricted tissue volumes and/or rapidly moving organs like liver. This article explores the potential advantages of relying on spatiotemporally encoded (SPEN) sequences for retrieving real-time thermometric images based on the water's proton resonance frequency (PRF) shifts. Hybrid spatiotemporal/k-space encoding single-scan MRI experiments were implemented on animal and human scanners, and their abilities to deliver single- and multi-slice real-time thermometric measurements based on PRF-derived phase maps in phantoms and in vivo, were compared against echo planar imaging (EPI) and gradient-echo counterparts. Under comparable acquisition conditions, SPEN exhibited advantages vis-A -vis EPI in terms of dealing with inhomogeneous magnetic field distortions, with shifts arising due to changes in the central frequency offsets, with PRF distributions, and for zooming into restricted fields-of-view without special pulse sequence provisions. This work confirms the ability of SPEN sequences, particularly when implemented under fully-refocused conditions, to exploit their built-in robustness to shift- and field-derived inhomogeneities for monitoring thermal changes in real-time under in vitro and in vivo conditions.

The longitudinal relaxation properties of NMR active nuclei carry useful information about the site-specific chemical environments and about the mobility of molecular fragments. Molecular mobility is in turn a key parameter reporting both on stable properties, such as size, as well as on dynamic ones, such as transient interactions and irreversible aggregation. In order to fully investigate the latter, a fast sampling of the relaxation parameters of transiently formed molecular species may be needed. Nevertheless, the acquisition of longitudinal relaxation data is typically slow, being limited by the requirement that the time for which the nucleus relaxes be varied incrementally until a complete build-up curve is generated. Recently, a number of single-shot-inversion-recovery methods have been developed capable of alleviating this need; still, these may be challenged by either spectral resolution restrictions or when coping with very fast relaxing nuclei. Here, we present a new experiment to measure the T(1)s of multiple nuclear spins that experience fast longitudinal relaxation, while retaining full high-resolution chemical shift information. Good agreement is observed between T(1)s measured with conventional means and T(1)s measured using the new technique. The method is applied to the real-time investigation of the reaction between D-xylose and sodium borate, which is in turn elucidated with the aid of ancillary ultrafast and conventional 2D TOCSY measurements.

During recent years, dynamical decoupling (DD) has gained relevance as a tool for manipulating and interrogating quantum systems. This is particularly relevant for spins involved in nuclear magnetic resonance (NMR), where DD sequences can be used to prolong quantum coherences, or to selectively couple or decouple the effects imposed by random environmental fluctuations. In this Letter, we show that these concepts can be exploited to selectively recouple diffusion processes in restricted spaces. The ensuing method provides a novel tool to measure restriction lengths in confined systems such as capillaries, pores or cells. The principles of this method for selectively recoupling diffusion-driven decoherence, its standing within the context of diffusion NMR, extensions to the characterization of other kinds of quantum fluctuations, and corroborating experiments, are presented.

Diffusion-weighted (DW) MRI is a powerful modality for studying microstructure in normal and pathological tissues. The accuracy derived from DW MRI depends on the acquisition of quality images, and on a precise assessment of the b-values involved. Conventional DW MRI tends to be of limited use in regions suffering from large magnetic field or chemical shift heterogeneities, which severely distort the MR images. In this study we propose novel sequences based on SPatio-temporal ENcoding (SPEN), which overcome such shortcomings owing to SPEN's inherent robustness to offsets. SPEN, however, relies on the simultaneous application of gradients and radiofrequency-swept pulses, which may impart different diffusion weightings along the spatial axes. These will be further complicated in DW measurements by the diffusion-sensitizing gradients, and will in general lead to complex, spatially-dependent b-values. This study presents a formalism for analyzing these diffusion-weighted SPEN (dSPEN) data, which takes into account the concomitant effects of adiabatic pulses, of the imaging as well as diffusion gradients, and of the cross-terms between them. These analytical b-values derivations are subject to experimental validations in phantom systems and ex vivo spinal cords. Excellent agreement is found between the theoretical predictions and these dSPEN experiments. The ensuing methodology is then demonstrated by in vivo mapping of diffusion in human breast - organs where conventional k-space DW acquisition methods are challenged by both field and chemical shift heterogeneities. These studies demonstrate the increased robustness of dSPEN vis-a-vis comparable DW echo planar imaging, and demonstrate the value of this new methodology for medium- or high-field diffusion measurements in heterogeneous systems. (C) 2013 Elsevier Inc. All rights reserved.

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. 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. 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. The results in this study suggest that SPEN-based 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.

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 Sn-119, Hg-199 and Pt-195 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 VVURST-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. (C) 2012 Elsevier Inc. All rights reserved.

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.

Recent years have witnessed efforts geared at increasing the sensitivity of NMR experiments, by relying on the suitable tailoring and exploitation of relaxation phenomena. These efforts have included the use of paramagnetic agents, enhanced (1)H-(1)H incoherent and coherent transfers processes in 2D liquid state spectroscopy, and homonuclear (13)C-(13)C spin diffusion effects in labeled solids. The present study examines some of the opportunities that could open when exploiting spontaneous (1)H-(1)H spin-diffusion processes, to enhance relaxation and to improve the sensitivity of dilute nuclei in solid state NMR measurements. It is shown that polarization transfer experiments executed under sufficiently fast magic-angle-spinning conditions, enable a selective polarization of the dilute low-gamma spins by their immediate neighboring protons. Repolarization of the latter can then occur during the time involved in monitoring the signal emitted by the low-gamma nuclei. The basic features involved in the resulting approach, and its potential to improve the effective sensitivity of solid state NMR measurements on dilute nuclei, are analyzed. Experimental tests witness the advantages that could reside from utilizing this kind of approach over conventional cross-polarization processes. These measurements also highlight a number of limitations that will have to be overcome for transforming selective polarization transfers of this kind into analytical methods of choice. (C) 2011 American Institute of Physics. [doi:10.1063/1.3643116]

The relatively long times that may be involved in high-resolution two-dimensional nuclear magnetic resonance (2D NMR) have stimulated the search for alternative schemes to collect these data. Particularly onerous situations arise when both high-resolution and large spectral widths are sought along the indirect domain. Strategies proposed for dealing with such cases include folding-over procedures, Hadamard encoding, and nonlinear data sampling. This communication discusses an alternative strategy, which exploits a partial prior knowledge regarding the position of the NMR resonances along the indirect domain together with customized excitations for every particular t(1) increment, to achieve an optimal sampling in terms of resolution and bandwidth. On the basis of such optimized encoding of the indirect-domain evolution, which can easily be coped with by modern spectrometers, it becomes possible to maximize the resolution of fine structures without compromising on the spectral bandwidths. The processing of the resulting data along the indirect domain is based on the use of two serially applied discrete Fourier transforms; one to distinguish the main bands in the spectrum and the other to resolve the latter's fine features. A number of simple heteronuclear correlation experiments illustrating the significant acquisition time savings and simultaneous improvements in resolution that can be achieved with the resulting double-Fourier encoding procedure are illustrated. Copyright (C) 2011 John Wiley & Sons, Ltd.

A topic of active investigation in 2D NMR relates to the minimum number of scans required for acquiring this kind of spectra, particularly when these are dictated by sampling rather than by sensitivity considerations. Reductions in this minimum number of scans have been achieved by departing from the regular sampling used to monitor the indirect domain, and relying instead on non-uniform sampling and iterative reconstruction algorithms. Alternatively, so-called "ultrafast" methods can compress the minimum number of scans involved in 2D NMR all the way to a minimum number of one, by spatially encoding the indirect domain information and subsequently recovering it via oscillating field gradients. Given ultrafast NMR's simultaneous recording of the indirect- and direct-domain data, this experiment couples the spectral constraints of these orthogonal domains - often calling for the use of strong acquisition gradients and large filter widths to fulfill the desired bandwidth and resolution demands along all spectral dimensions. This study discusses a way to alleviate these demands, and thereby enhance the method's performance and applicability, by combining spatial encoding with iterative reconstruction approaches. Examples of these new principles are given based on the compressed-sensed reconstruction of biomolecular 2D HSQC ultrafast NMR data, an approach that we show enables a decrease of the gradient strengths demanded in this type of experiments by up to 80%. (C) 2011 Elsevier Inc. All rights reserved.

We experimentally and theoretically demonstrate the purity (polarization) control of qubits entangled with multiple spins, using induced dephasing in nuclear magnetic resonance setups to simulate repeated quantum measurements. We show that one may steer the qubit ensemble towards a quasiequilibrium state of a certain purity by choosing suitable time intervals between dephasing operations. These results demonstrate that repeated dephasing at intervals associated with the anti-Zeno regime leads to ensemble purification, whereas those associated with the Zeno regime lead to ensemble mixing.

We present a method that implements directional, perfect state transfers within a branched spin network by exploiting quantum interferences in the time domain. This method provides a tool for isolating subsystems from a large and complex one. Directionality is achieved by interrupting the spin-spin coupled evolution with periods of free Zeeman evolutions, whose timing is tuned to be commensurate with the relative phases accrued by specific spin pairs. This leads to a resonant transfer between the chosen qubits and to a detuning of all remaining pathways in the network, using only global manipulations. Since the transfer is perfect when the selected pathway is mediated by two or three spins, distant state transfers over complex networks can be achieved by successive recouplings among specific pairs or triads of spins. These effects are illustrated with a quantum simulator involving (13)C NMR on leucine's backbone; a six-spin network.

A new scheme for the acquisition of heteronuclear 2D correlations in NMR spectroscopy within a single scan, is proposed and demonstrated. The principles of this new scheme resemble those of Mansfield's "k-space walk" proposal, in the sense that they rely on repetitively transferring spin coherences back-and-forth between the two spin systems to be correlated. It is shown that if properly executed, these transfers enable the equivalent of a continuous sampling of the time-domain space supporting a 2D heteronuclear single-quantum correlation NMR spectrum. Details on how to execute the resulting "time-domain walk" experiments are given, and examples comparing it against conventional and other single-scan 20 acquisition alternatives are shown. Advantages, opportunities, and main drawbacks of this new ultrafast approach to 2D NMR, are briefly discussed. (C) 2009 Elsevier Inc. All rights reserved.

beta 2-microglobulin (beta 2m), the light chain of class I major histocompatibility complex, is responsible for the dialysis-related amyloidosis and, in patients undergoing long term dialysis, the full-length and chemically unmodified beta 2m converts into amyloid fibrils. The protein, belonging to the immunoglobulin superfamily, in common to other members of this family, experiences during its folding a long-lived intermediate associated to the trans-to-cis isomerization of Pro-32 that has been addressed as the precursor of the amyloid fibril formation. In this respect, previous studies on the W60G beta 2m mutant, showing that the lack of Trp-60 prevents fibril formation in mild aggregating condition, prompted us to reinvestigate the refolding kinetics of wild type and W60G beta 2m at atomic resolution by real-time NMR. The analysis, conducted at ambient temperature by the band selective flip angle short transient real-time two-dimensional NMR techniques and probing the beta 2m states every 15 s, revealed a more complex folding energy landscape than previously reported for wild type beta 2m, involving more than a single intermediate species, and shedding new light into the fibrillogenic pathway. Moreover, a significant difference in the kinetic scheme previously characterized by optical spectroscopic methods was discovered for the W60G beta 2m mutant.

The combination of ex situ dynamic nuclear polarization (DNP) with nuclear magnetic resonance (NMR) leads to signal-to-noise enhancements of 10(3)-10(4) compared to conventional NMR. Ex situ DNP, however, is ill-suited for collecting the array of transients needed in 2D NMR spectroscopy. Spatially encoded single-scan 2D NMR methods can circumvent this drawback, yet these "ultrafast" experiments can cover spectral, ranges of only approximate to 20 ppm using conventional hardware. To deal with this limitation, we discuss here new spatial/spectral encoding strategies capable of folding (13)C resonances into the desired spectral windows. This new approach allows one to obtain -following a single hyperpolarization process- multiple 2D heteronuclear correlations arising from different (13)C regions. In combination with ex situ DNP, these principles enable the acquisition of HMBC and HSQC 2D NMR spectra on approximate to 1 mM mixtures of natural products, characterizing with a high resolution sites spread over nearly 100 ppm bandwidths.

NMR experiments devised to aid in analyses Of tissues include magnetization transfer (MT), which can highlight the signals of biological macromolecules through cross-relaxation and/or chemical exchange processes with the bulk (1)H water resonance, and high-resolution magic-angle-spinning (HRMAS) methods, akin to those used in solid-state NMR to introduce additional spectral resolution via the averaging of spin anisotropies. This paper explores the result of combining these methodologies, and reports on MT "z-spectroscopy" between water and cell components in excised tissues under a variety of HRMAS conditions. Main features arising from the resulting (1)H "MTMAS" experiments include strong spinning sideband manifolds centered at the liquid water shift, high-resolution isotropic features coinciding with aliphatic and amide proton resonances, and a second sideband manifold arising as spinning speeds are increased. Interpretations are given for the origin of these various features, including simulations shedding further light onto the nature of MT NMR signals observed for tissue samples. Concurrently, histological examinations are reported validating the limits of HRMAS NMR procedures to the analysis of tissue samples preserved in a number of different ways. (C) 2009 Elsevier Inc. All rights reserved.

Single-scan 2D NMR relies on a spatial axis for encoding the indirect-domain internal spin interactions. Various strategies have been demonstrated for fulfilling the needs underlying this procedure. All such schemes use gradient-echoed sequences that leave at their conclusion solely the effects of the internal interactions along the indirect domain; they also include a real-time scheme that though simple, yields in general mixed-phase line shapes. The present paper introduces two new proposals geared up for easing the spatial encoding underlying single-scan 2D NMR methodologies. One of these is capable of delivering dispersive-free peaks along the indirect domain, and thereby purely-absorptive 2D line shapes, in amplitude-encoded experiments. The other demonstrates for the first time, the possibility to obtain single-scan 213 spectra without echoing the effects of the encoding gradient-simply by applying a single-pulse frequency sweep to encode the interactions. Both of these modes are compatible with homo- and heteronuclear correlations, and exhibit a number of complementary features vis-a-vis encoding alternatives that have so far been presented. The overall principles underlying these new spatially encoding protocols are derived, and their performance demonstrated with single-scan 2D NMR TOCSY and HSQC experiments on model compounds. Copyright (C) 2009 John Wiley & Sons, Ltd.

Multidimensional acquisitions play a central role in the progress and applications of nuclear magnetic resonance (NMR) spectroscopy. Such experiments have been collected traditionally as an array of one-dimensional scans, with suitably incremented delay parameters that encode along independent temporal domains the nD spectral distribution being sought. During the past few years, an ultrafast approach to nD NMR has been introduced that is capable of delivering any type of multidimensional spectrum in a single transient. This method operates by departing from the canonical nD NMR scheme and by replacing its temporal encoding with a series of spatial manipulations derived from magnetic resonance imaging. The present survey introduces the main principles of this subsecond approach to spectroscopy, focusing on the applications that have hitherto been demonstrated for single-scan two-dimensional NMR in different areas of chemistry.

Few analytical techniques rival the capabilities of two-dimensional nuclear magnetic resonance. A scheme enabling 2D NMR acquisitions within a single-scan has been recently demonstrated, based on combined field gradient and radiofrequency manipulations. Distortions were observed upon implementing such 'ultrafast' experiments on solids undergoing magic-angle-spinning, presumably due to interferences arising between the periodic time-dependencies involved in the mechanical and in the spin manipulations. Experimental and numerical setups were designed to investigate these effects, and to find conditions that minimize them. When devoid of these non-idealities, quality 2D NMR spectra could be retrieved from spinning polymers within a single-scan. (c) 2008 Elsevier B.V. All rights reserved.

Multidimensional spectroscopy plays a central role in contemporary magnetic resonance. A general feature of multidimensional NMR is its inherent multiscan nature, stemming from the methodology's reliance on a series of independent acquisitions to sample the spins' evolutions throughout the indirect time domains. Contrasting this traditional feature, an acquisition scheme has recently been reported that enables the collection of complete of multidimensional NMR data sets within one single scan. Provided that the signals to be observed are sufficiently strong, this new "ultrafast" protocol can thus shorten the acquisition times of multidimensional NMR experiments by several orders of magnitude. This new methodology operates by departing from temporal encoding principles used since the advent of Fourier-transform NMR, replacing them with a spatial encoding of the spin interactions. Spatial encoding operates in turn on the basis of novel radiofrequency irradiation and magnetic field gradient waveform manipulations, designed so as to impart on the sample a coherent spin magnetization pattern that reflects the internal interactions to be measured. Given the central role played by this new kind of spectroscopic-oriented manipulations in ultrafast NMR, we devote this review to surveying different variants that have hitherto been proposed for their implementation. These include both discrete and continuous versions, real- and constant-time implementations, as well as amplitude- and phase-modulated alternatives. The principles underlying these various spatial encoding approaches are treated, their operation is graphically illustrated as well as formally derived within suitable theoretical frameworks, and an in-depth comparison of their line shape characteristics is discussed. (c) 2008 American Institute of Physics.

The acquisition of ideal powder line shapes remains a recurring challenge in solid-state wideline nuclear magnetic resonance (NMR). Certain species, particularly quadrupolar spins in sites associated with large electric field gradients, are difficult to excite uniformly and with good efficiencies. This paper discusses some of the opportunities that arise upon departing from standard spin-echo excitation approaches and switching to echo sequences that use low-power, frequency-swept radio frequency (rf) pulses instead. The reduced powers demanded by such swept rf fields allow one to excite spins in different crystallites efficiently and with orientation-independent pulse angles, while the large bandwidths of interest that are needed by the measurement can be covered, thanks to the use of broadband frequency sweeps. The fact that the spins' evolution and ensuing dephasing starts at the beginning of such rf manipulation calls for the use of spin-echo sequences; a number of alternatives capable of providing the desired line shapes both in the frequency and in the time domains are introduced and experimentally demonstrated. Sensitivity- and lineshape-wise these experiments are competitive vis-a-vis current implementations of wideline quadrupolar NMR based on hard rf pulses; additional opportunities that may derive from these ideas are also briefly discussed. (c) 2007 American Institute of Physics.

2D NMR relies on monitoring systematic changes in the phases incurred by spin coherences as a function of an encoding time t(1), whose value changes over the course of independent experiments. The intrinsic multi-scan nature of such protocols implies that resistive and/or hybrid magnets, capable of delivering the highest magnetic field strengths but possessing poor temporal stabilities, become unsuitable for 2D NMR acquisitions. It is here shown with a series of homo- and hetero-nuclear examples that such limitations can be bypassed using recently proposed 2D 'ultrafast' acquisition schemes, which correlate interactions along all spectral dimensions within a single-scan. (c) 2007 Published by Elsevier B.V.

Following unidirectional biophysical events such as the folding of proteins or the equilibration of binding interactions, requires experimental methods that yield information at both atomic-level resolution and at high repetition rates. Toward this end a number of different approaches enabling the rapid acquisition of 2D NMR spectra have been recently introduced, including spatially encoded "ultrafast" 2D NMR spectroscopy and SOFAST HMQC NMR. Whereas the former accelerates acquisitions by reducing the number of scans that are necessary for completing arbitrary 2D NMR experiments, the latter operates by reducing the delay between consecutive scans while preserving sensitivity. Given the complementarities between these two approaches it seems natural to combine them into a single tool, enabling the acquisition of full 2D protein NMR spectra at high repetition rates. We demonstrate here this capability with the introduction of "ultraSOFAST" HMQC NMR, a spatially encoded and relaxation-optimized approach that can provide 2D protein correlation spectra at similar to 1 s repetition rates for samples in the similar to 2 mM concentration range. The principles, relative advantages, and current limitations of this new approach are discussed, and its application is exemplified with a study of the fast hydrogen-deuterium exchange characterizing amide sites in Ubiquitin.

Multidimensional NMR spectroscopy plays an important role in the characterization of molecular structure and dynamics. A new methodology for acquiring this kind of spectra has been recently demonstrated, endowed with the potential to compress arbitrary multidimensional NMR acquisitions into a single scan. This "ultrafast" nD acquisition protocol is based on a spatiotemporal encoding of the indirect-domain spin evolution, followed by a repetitive decoding and reencoding of the information thus stored employing a train of alternating-sign gradients. Such train of switching gradients extending throughout the course of the data acquisition may pose extreme demands on a magnetic resonance system, particularly when dealing with nonshielded gradients, strong eddy currents, or rapidly relaxing spin systems. Limits to the in vivo applicability of such fast-switching scheme may also arise due to gradient-induced perineural stimulation. The present study describes a new approach to ultrafast nD NMR that reduces the number of gradient switchings during the acquisition period to zero, leading in essence to a constant-gradient acquisition scheme. This approach operates on the basis of a novel spatiotemporal encoding including discrete, temporally overlapping, frequency-shifted pulses. Principles and examples of this new approach are given; sensitivity limitations and signal-enhancing prospects of such constant-gradient acquisitions are also discussed and exemplified. (c) 2006 American Institute of Physics.

We have recently proposed a protocol for retrieving nuclear magnetic resonance (NMR) spectra based on a spatially-dependent encoding of the MR interactions. It has also been shown that the spatial selectivity with which spins are manipulated during such encoding opens up new avenues towards the removal of magnetic field inhomogeneities; not by demanding extreme B-o field uniformities, but rather by compensating for the dephasing effects introduced by the field distribution at a radiofrequency excitation and/or refocusing level. The present study discusses in further detail a number of strategies deriving from this principle, geared at acquiring both uni- as well as multi-dimensional spectroscopic data at high resolution conditions. Different variants are presented, tailored according to the relative sensitivity and chemical nature of the spin system being explored. In particular a simple multi-scan experiment is discussed capable of affording substantial improvements in the spectral resolution, at nearly no sensitivity or scaling penalties. This new compensation scheme is therefore well-suited for the collection of high-resolution data in low-field systems possessing limited signal-to-noise ratios, where magnetic field heterogeneities might present a serious obstacle. Potential areas of applications of these techniques include high-field in vivo NMR studies in regions near tissue/air interfaces, clinical low field MR spectroscopy on relatively large off-center volumes difficult to shim, and ex situ NMR. The principles of the different compensation methods are reviewed and experimentally demonstrated for one-dimensional inhomogeneities; further improvements and extensions are briefly discussed. (c) 2006 Elsevier Inc. All rights reserved.

Multidimensional spectroscopy plays a number of essential roles in contemporary magnetic resonance. It brings a resolution enhancement without which numerous NMR applications in organic and inorganic chemistry would be unattainable, it serves as a basic tool in the assignment and structural elucidation of complex biological structures, and it is an integral part of the image formation protocol in MRI. The present review describes a recent scheme which we have developed, enabling the acquisition of complete 2D NMR data sets within a single continuous acquisition. Provided that an analyte's signal is sufficiently strong, the acquisition time of multidimensional NMR experiments can thus be shortened by several orders of magnitude. The new methodology is compatible with existing multidimensional pulse sequences (COSY, TOCSY, HSQC, MRI) and can be implemented using conventional hardware. The spatial encoding of the NMR interactions - which is the new principle underlying this ultrafast NMR protocol - is discussed, and the protocol's performance is exemplified with a variety of homonuclear and heteronuclear 2D NMR and MRI acquisitions.

Single-scan multidimensional spectroscopy utilizes spatial dimensions for encoding the indirect-domain internal spin interactions. Various strategies have been hitherto demonstrated for fulfilling the encoding needs underlying this methodology; in analogy with their time-domain counterparts all of them have in common the fact that they proceed monotonically-starting at one end of the sample and concluding at the other. The present manuscript discusses another possibility that arises for the case of amplitude-modulated ultrafast nD NMR, whereby the spatial encoding progresses from both ends of the sample simultaneously towards the center. Such symmetric encoding is compatible with continuous or discrete excitations as well as with homonuclear or heteronuclear correlations, and exhibits a number of advantages vis-a-vis the unidirectional encodings that have been used so far: it originates echoes that are free from large first-order phase distortions, and yields nD peaks possessing a purely-absorptive character. It has the added advantage that for a given indirect-domain spectral resolution it can complete its task in half the time required by a conventional monotonic spatial encoding, leading to potentially important gains in sensitivity. The main features underlying this new spatially symmetric encoding protocol are derived, and its advantages are demonstrated with a series of amplitude-modulated homo- and hetero-nuclear 2D ultrafast NMR examples. (c) 2005 Elsevier Inc. All rights reserved.

Ultrafast 2D NMR replaces the time-domain parametrization usually employed to monitor the indirect-domain spin evolution, with an equivalent encoding along a spatial geometry. When coupled to a gradient-assisted decoding during the acquisition, this enables the collection of complete 2D spectra within a single transient. We have presented elsewhere two strategies for carrying out the spatial encoding underlying ultrafast NMR: a discrete excitation protocol capable of imparting a phase-modulated encoding of the interactions, and a continuous protocol yielding amplitude-modulated signals. The former is general but has associated with it a number of practical complications; the latter is easier to implement but unsuitable for certain 2D NMR acquisitions. The present communication discusses a new protocol that incorporates attractive attributes from both alternatives, imparting a continuous spatial encoding of the interactions yet yielding a phase modulation of the signal. This in turn enables a number of basic experiments that have shown particularly useful in the context of in vivo 2D NMR, including 2D J-resolved and 2D H,H-COSY spectroscopies. It also provides a route to achieving sensitivity-enhanced acquisitions for other homonuclear correlation experiments, such as ultra-fast 2D TOCSY. The main features underlying this new spatial encoding protocol are derived, and its potential demonstrated with a series of phase-modulated homonuclear single-scan 2D NMR examples. (c) 2005 Elsevier Inc. All rights reserved.

A new methodology capable of delivering complete 2D NMR spectra within a single scan was recently introduced. The resulting potential gain in time resolution could open new opportunities for in vivo spectroscopy, provided that the technical demands of the methodology are satisfied by the corresponding hardware. Foremost among these demands are the relatively short switching times expected from the applied gradient-echo trains. These rapid transitions may be particularly difficult to accomplish on imaging systems. As a step toward solving this problem, we assessed the possibility of replacing the square-wave gradient train currently used during the course of the acquisition by a shaped sinusoidal gradient. Examples of the implementation of this protocol are given, and successful ultrafast acquisitions of 2D NMR spectra with suitable spectral widths on a microimaging probe (for both phantom solutions and ex vivo mouse brains) are demonstrated. (C) 2004 Wiley-Liss, Inc.

Measuring the nuclear magnetic resonance spectra of low-gamma heteronuclei such as N-15 constitutes an important analytical tool for the characterization of molecular structure and dynamics. The reduced resonance frequencies and magnetic moments of these heteronuclei, however, make the sensitivity of this kind of spectroscopy inherently lower than that of comparable H-1 NMR observations. A well-known solution to this sensitivity problem is indirect detection: a 2D NMR technique capable of enhancing the sensitivity of heteronuclear NMR by porting the actual data acquisition from the low-gamma nucleus to neighboring protons. This has become the standard method of observation in biomolecular NMR, where the resolution introduced by 2D spectroscopy is always a sought-after commodity. Indirect detection, however, has not gained a wide appeal in organic chemistry or in in vivo investigations, where one-dimensional heteronuclear NMR information usually suffices. The present study explores the possibility of retaining certain advantages derived from indirect detection while not giving up on the simple one-dimensional nature of heteronuclear NMR, by relying on the spatial-encoding scheme we have recently demonstrated for implementing single-scan multi-dimensional NMR spectroscopy. Preliminary results based on a 1D N-15 NMR can be enhanced significantly in this manner; the relevance of this experiment given the advent of dedicated H-1-observing cryogenic probeheads with very high sensitivities is briefly discussed.

We have recently demonstrated that the spatial encoding of internal nuclear magnetic resonance (NMR) spin interactions can be exploited to collect multidimensional NMR spectra within a single scan. Such experiments rely on an inhomogeneous spatial excitation of the spins throughout the sample, and lead to indirect-domain peaks via a constructive interference among the spatially resolved spin-packets that are thus created. The shape of the resulting indirect-domain echo peaks approaches a Sinc function when the chemical's distribution is uniform, but will depart from this function otherwise. It is hereby shown that a Fourier analysis of either the diagonal- or the cross-peaks resolved in these single-scan two-dimensional (2D) NMR experiments can in fact provide a weighted spatial distribution of the analyte originating such peak, thus opening up the possibility of completing spatially resolved multidimensional NMR measurements within a fraction of a second. Principles of this new mode of analysis are discussed, and examples where the potential of spatially resolved ultrafast 2D NMR spectroscopy is brought to bear are presented. Potential extensions of this approach to higher dimensions are also briefly addressed (C) 2003 Elsevier Inc. All rights reserved.

We have recently demonstrated that magnetic field gradients in combination with frequency selective pulses, can be employed to collect a complete multi-dimensional NMR spectrum within a single scan. Following similar guidelines, field gradients could also be exploited to parallelize other types of NMR experiments where the final results arise from the collection and analysis of a series of time-incremented spectra. The present Communication exemplifies this concept by showing how a combination of gradients can be employed to monitor within a single continuous acquisition, a slow dynamic process which is in turn followed by systematic increments in the duration of a magnetization transfer time. Further, since 2D exchange NMR spectra can nowadays be themselves collected within one scan, the acquisition of a complete set of mixing-incremented 2D exchange patterns could be achieved within a single experiment entailing a total time of approximate to 1 s. (C) 2003 Elsevier Inc. All rights reserved.

Multidimensional nuclear magnetic resonance (NMR) provides one of the foremost analytical tools available to elucidate the structure and dynamics of complex molecules in their native states. Executing this kind of experiment generally requires collecting an n-dimensional time-domain signal S, from which the spectrum arises via an appropriate Fourier analysis of its various time variables. This time-domain signal is actually measured directly only along one of the time axes, while the effects introduced by the remaining time variables are monitored via a parametric incrementation of their values throughout independent experiments. Two-dimensional (2D) NMR experiments thus usually require longer acquisition times than unidimensional experiments, 3D NMR is orders-of-magnitude more time consuming than 2D spectroscopy, etc. Very recently, we proposed and demonstrated an approach whereby data acquisition in 2D NMR can be parallelized, enabling the collection of complete 2D spectral sets within a single transient. The present paper discusses the extension of this 2D NMR methodology to an arbitrary number of dimensions. The principles of the ensuing ultrafast n-dimensional NMR approach are described, and a variety of homo- and heteronuclear 3D and 4D NMR spectra collected within a fraction of a second are presented.

New multidimensional NMR methods correlating the quadrupolar and heteronuclear dipolar interactions affecting a half-integer quadrupolar spin in the solid state are introduced and exemplified. The methods extend separated-local-field magic-angle spinning (SLF MAS) NMR techniques that have been used successfully in spin-(1)/(2) spectroscopy to the study of S greater than or equal to (3)/(2) nuclei. In our implementation, these techniques avoid homonuclear proton decoupling requirements by relying on moderately fast MAS rates (6-15 kHz) and use rotor-synchronized constant-time pulse sequences to achieve nearly arbitrary amplifications of the apparent dipolar coupling strengths. The result is a suite of simple 2D NMR experiments, whose line shapes carry valuable information about the structure and dynamics of solids containing quadrupolar and proton nuclei. The potential of these sequences was exploited to gather new insight into the structure and dynamics of a variety of boron-containing samples. These experimental SLF schemes were also extended to 3D NMR experiments that incorporate multiple-quantum MAS, thus enabling the resolution needed to study multiple chemical sites in a solid and providing a useful tool for the assignment of inequivalent sites.

The local ordering, morphology, and dynamics of aromatic cores and flexible alkyl spacers were analyzed for a homologous series of main-chain polymeric liquid crystals. C-13 NMR experiments showed that the nematic ordering achieved by these synthetic polymers was retained into the solid state if their quenchings occur while remaining within the strong NMR magnetic field. The degree of orientation in the resulting glasses was investigated by variable-angle NMR experiments and found to differ between polymers with an even number of methylene units in the flexible spacer vs those with an odd number. To further discern at a molecular level the nature of these differences, the structures of these polyesters were examined by high-resolution solid-state 13C NMR. It was found that while the odd-chained series displayed a conformational annealing upon aligning, even-chained polymers were generally in all-trans conformations both for as-synthesized and for aligned samples, Variable-temperature 1D and 2D NMR experiments also illustrated substantial differences in the degree of motional dynamics between the odd and even polymer series: whereas considerable rigidity was exhibited by the even-numbered series all the way up to 150 degreesC, a relatively high flexibility displayed by the odd-methylene polymers. In unison, these measurements provide insight into the significant changes that can be imparted into the structure and dynamics of main-chain thermiotropic polymers by subtle manipulations of their monomeric structures.

Multinuclear solid-state nuclear magnetic resonance studies (Re-185/187, Mn-55, As-75, and H-1 NMR) were undertaken on a series of polycrystalline inorganic salts incorporating diamagnetic XO4- groups, X being a half-integer quadrupolar nucleus. Exploiting data acquisition protocols that were recently developed for observing undistorted half-integer quadrupole central transitions, some of the largest quadrupole coupling constants reported to date by high field NMR were characterized (e(2)qQ/h approximate to 300 MHz). On repeating such measurements as a function of temperature, certain samples displayed reversible changes that could not be rationalized in terms of the usual temperature dependencies of the nuclear quadrupolar couplings. Instead, dynamic exchange processes between chemically or magnetically inequivalent sites had to be invoked. To quantitatively analyze these processes, the semiclassical Bloch-McConnell formalism for chemical exchange was extended to account for second-order quadrupole effects. Insight into the potential nature of the chemical dynamics was also obtained from quantum chemical calculations of the coupling parameters on model systems.

Second-order dipolar effects arise when a nucleus S is in close proximity to a quadrupolar spin I. These couplings originate from cross correlations between quadrupolar and dipolar interactions, and have the notable characteristic of not being susceptible to averaging by magic-angle-spinning. Therefore they can originate noticeable splittings in high resolution solid state nuclear magnetic resonance (NMR) spectra, as has been observed repeatedly for S = 1/2. With the advent of high resolution half-integer quadrupole spectroscopy, such effects have now also been noticed in higher (S = 3/2,5/2,...) spin systems. Within the last year these couplings have been reported for a number of complexes and analyzed in the high-field limit, when I's Larmor frequency largely exceeds its quadrupolar coupling. The present study discusses the generalization of these analyses to arbitrary quadrupolar/Zeeman ratios. The predictions of the essentially numerical treatment that results compare well with previously derived high-field analytical models, as well as with experimental solid state NMR spectra observed in a borane compound possessing a B-11-As-75 spin pair. An alternative analytical variant that can account for these effects in the low-field limit is also derived on the basis of average Hamiltonian theory; its results agree well with the predictions obtained from general numerical calculations of one-dimensional S spectra, but present peculiarities in the bi-dimensional NMR line shapes whose origins are briefly discussed. (C) 2001 American Institute of Physics.

The order and dynamics of two aromatic polyamides in their lyotropic phases were investigated with the aid of variable-director nuclear magnetic resonance (NMR). In these experiments polymers were dissolved in concentrated sulfuric acid and allowed to equilibrate inside the main NMR magnetic field B-0 to yield macroscopically-aligned liquid crystalline solutions. These ordered fluids were then rotated away from equilibrium for brief periods of time, and their natural abundance C-13 NMR spectra collected as a function of different angles between the liquid crystalline director and B-0. The resulting spectra showed peaks shifting as well as broadening as a function of the director's orientation, variations that were also found to be concentration- and temperature-dependent. All such changes could be successfully accounted for on the basis of an exchange model involving molecular reorientations of the polymer chains that are occurring in the intermediate NMR time scale. Based on this assumption, the experimental line shapes could be used to extract a detailed description of the macromolecular order and dynamics in these fluids. The former appeared substantially high, and not very different from the one characterizing order in commercial extruded aramide fibers. The latter enabled an estimation of the hydrodynamic radii adopted by the macromolecules in their mesophases, which ended up in close agreement with dimensions recently reported on the basis of small-angle neutron scattering analyses. (C) 2001 American Institute of Physics.