Exciting developments in new experimental methods for multidimensional solid-state NMR spectroscopy have recently been achieved using optimal-control theory. These results, in turn, have triggered the development of new pulse sequences based on traditional analytical theories. This trend article summarises the key steps leading to these advancements. It also describes additional applications of optimal control beyond structural biology and envisions similar progress in the NMR of solid materials. Despite attractive features of optimal-control pulse sequences demonstrated in the proof-of-concept studies, their experimental utilization remains sparse, probably due to the lack of awareness among experimentalists. We hope this mini-review helps to spread optimal-control methods into routine experimental workflows. Furthermore, we offer a personal outlook on how numerical optimisations could in general enhance the experimental capabilities of solid-state NMR in the near future, with optimal control serving as a pioneer exploring new possibilities.
- Publication type
- Journal Article MeSH
- Review MeSH
Dipolar recoupling is a central concept in the nuclear magnetic resonance spectroscopy of powdered solids and is used to establish correlations between different nuclei by magnetization transfer. The efficiency of conventional cross-polarization methods is low because of the inherent radio frequency (rf) field inhomogeneity present in the magic angle spinning (MAS) experiments and the large chemical shift anisotropies at high magnetic fields. Very high transfer efficiencies can be obtained using optimal control–derived experiments. These sequences had to be optimized individually for a particular MAS frequency. We show that by adjusting the length and the rf field amplitude of the shaped pulse synchronously with sample rotation, optimal control sequences can be successfully applied over a range of MAS frequencies without the need of reoptimization. This feature greatly enhances their applicability on spectrometers operating at differing external fields where the MAS frequency needs to be adjusted to avoid detrimental resonance effects.
- Publication type
- Journal Article MeSH
Conducting large-scale solid-state NMR simulations requires fast computer software potentially in combination with efficient computational resources to complete within a reasonable time frame. Such simulations may involve large spin systems, multiple-parameter fitting of experimental spectra, or multiple-pulse experiment design using parameter scan, non-linear optimization, or optimal control procedures. To efficiently accommodate such simulations, we here present an improved version of the widely distributed open-source SIMPSON NMR simulation software package adapted to contemporary high performance hardware setups. The software is optimized for fast performance on standard stand-alone computers, multi-core processors, and large clusters of identical nodes. We describe the novel features for fast computation including internal matrix manipulations, propagator setups and acquisition strategies. For efficient calculation of powder averages, we implemented interpolation method of Alderman, Solum, and Grant, as well as recently introduced fast Wigner transform interpolation technique. The potential of the optimal control toolbox is greatly enhanced by higher precision gradients in combination with the efficient optimization algorithm known as limited memory Broyden-Fletcher-Goldfarb-Shanno. In addition, advanced parallelization can be used in all types of calculations, providing significant time reductions. SIMPSON is thus reflecting current knowledge in the field of numerical simulations of solid-state NMR experiments. The efficiency and novel features are demonstrated on the representative simulations.
Recently, proton-detected magic-angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy has become an attractive tool to study the structure and dynamics of insoluble proteins at atomic resolution. The sensitivity of the employed multidimensional experiments can be systematically improved when both transversal components of the magnetization are transferred simultaneously after an evolution period. The method of preservation of equivalent pathways has been explored in solution-state NMR; however, it does not find widespread application due to relaxation issues connected with increased molecular size. We present here for the first time heteronuclear transverse mixing sequences for correlation experiments at moderate and fast MAS frequencies. Optimal control allows to boost the signal-to-noise ratio (SNR) beyond the expected factor of 2 for each indirect dimension. In addition to the carbon-detected sensitivity-enhanced 2D NCA experiment, we present a novel proton-detected, doubly sensitivity-enhanced 3D hCANH pulse sequence for which we observe a 3-fold improvement in SNR compared to the conventional experimental implementation. The sensitivity gain turned out to be essential to unambiguously characterize a minor fibril polymorph of a human lambda-III immunoglobulin light chain protein that escaped detection so far.
- MeSH
- Immunoglobulin Light Chains MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Nuclear Magnetic Resonance, Biomolecular methods MeSH
- Proteins * chemistry MeSH
- Protons * MeSH
- Carbon MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Immunoglobulin Light Chains MeSH
- Proteins * MeSH
- Protons * MeSH
- Carbon MeSH
Dipolar recoupling in solid-state NMR is an essential method for establishing correlations between nuclei that are close in space. In applications on protein samples, the traditional experiments like ramped and adiabatic DCP suffer from the fact that dipolar recoupling occurs only within a limited volume of the sample. This selection is dictated by the radiofrequency (rf) field inhomogeneity profile of the excitation solenoidal coil. We employ optimal control strategies to design dipolar recoupling sequences with substantially larger responsive volume and increased sensitivity. We show that it is essential to compensate for additional temporal modulations induced by sample rotation in a spatially inhomogeneous rf field. Such modulations interfere with the pulse sequence and decrease its performance. Using large-scale optimizations we developed pulse schemes for magnetization transfer from amide nitrogen to carbonyl (NCO) as well as aliphatic carbons (NCA). Our experiments yield a signal intensity increased by a factor of 1.5 and 2.0 for NCA and NCO transfers, respectively, compared to conventional ramped DCP sequences. Consistent results were obtained using several biological samples and NMR instruments.
Triple resonance HCN and HCNCH experiments are reliable methods of establishing sugar-to-base connectivity in the NMR spectra of isotopicaly labeled oligonucleotides. However, with larger molecules the sensitivity of the experiments is drastically reduced due to relaxation processes. Since the polarization transfer between 13C and 15N nuclei relies on rather small heteronuclear coupling constants (11-12 Hz), the long evolution periods (up to 30-40 ms) in the pulse sequences cannot be avoided. Therefore any effort to enhance sensitivity has to concentrate on manipulating the spin system in such a way that the spin-spin relaxation rates would be minimized. In the present paper we analyze the efficiency of the two known approaches of relaxation rate control, namely the use of multiple-quantum coherence (MQ) and of the relaxation interference between chemical shift anisotropy and dipolar relaxation - TROSY. Both theoretical calculations and experimental results suggest that for the sugar moiety (H1'-C1'-N1/9) the MQ approach is clearly preferable. For the base moiety (H6/8-C6/8-N1/9), however, the TROSY shows results superior to the MQ suppression of the dipole-dipole relaxation at moderate magnetic fields (500 MHz) and the sensitivity improvement becomes dramatically more pronounced at very high fields (800 MHz). The pulse schemes of the triple-resonance HCN experiments with sensitivity optimized performance for unambiguous assignments of intra-residual sugar-to-base connectivities combining both approaches are presented.
- MeSH
- Quantum Theory MeSH
- Magnetics MeSH
- Nuclear Magnetic Resonance, Biomolecular methods MeSH
- Nucleosides chemistry MeSH
- RNA chemical synthesis chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Nucleosides MeSH
- RNA MeSH
A class of chemical-shift-selective (CHESS) water suppression (WS) schemes is presented in which the characteristic frequency-domain excitation profiles of "adiabatic" full-passage (AFP) RF pulses are utilized for frequency-selective excitation of the water resonance. In the proposed WS schemes, dubbed WASHCODE, hyperbolic secant (HS) pulses were used as the AFP pulses. Besides the high immunity of WS efficiency toward B(1) inhomogeneity, these sequences also exhibit extraordinary insensitivity to the dispersion of the water T(1) relaxation times. The actual performance of the proposed WS schemes was achieved in particular by optimizing the frequency offsets of WS HS pulses and the time intervals between them. To reduce the RF power requirements of these WS sequences for in vivo applications, HS pulses with the minimum possible frequency bandwidths were employed, which also substantially reduced the adverse effects on the observed proton MR spectra. The proposed WS schemes were evaluated by simulations based on the Bloch equations. Several WS sequences which looked particularly promising were verified experimentally on the human brain on a 3 T MR scanner using very short echo-time STEAM for volume selection and a standard single-loop surface coil for both signal transmission and reception. Routinely, water-suppression factors ranging from 2000 to 4000 were achieved in vivo without additional adjustment of parameters for individual subjects and without violating legal safety limits.
- MeSH
- Time Factors MeSH
- Humans MeSH
- Magnetic Resonance Spectroscopy * MeSH
- Brain metabolism MeSH
- Water chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Water MeSH
INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.
- Keywords
- cardiac resynchronization therapy, heart failure, hemodynamics, multipoint pacing, multisite pacing, repolarization,
- MeSH
- Action Potentials * MeSH
- Bundle-Branch Block * physiopathology therapy diagnosis MeSH
- Time Factors MeSH
- Cardiomyopathy, Dilated * physiopathology therapy diagnosis MeSH
- Electrocardiography * MeSH
- Ventricular Function, Left * MeSH
- Hemodynamics * MeSH
- Middle Aged MeSH
- Humans MeSH
- Predictive Value of Tests MeSH
- Aged MeSH
- Heart Rate MeSH
- Cardiac Resynchronization Therapy * MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The present study introduces a new ultra-high-frequency 14-lead electrocardiogram technique (UHF-ECG) for mapping ventricular depolarization patterns and calculation of novel dyssynchrony parameters that may improve the selection of patients and application of cardiac resynchronization therapy (CRT). METHODS: Components of the ECG in sixteen frequency bands within the 150 to 1000 Hz range were used to create ventricular depolarization maps. The maximum time difference between the UHF QRS complex centers of mass of leads V1 to V8 was defined as ventricular electrical dyssynchrony (e-DYS), and the duration at 50% of peak voltage amplitude in each lead was defined as the duration of local depolarization (Vd). Proof of principle measurements was performed in seven patients with left (left bundle branch block) and four patients with right bundle branch block (right bundle branch block) before and during CRT using biventricular and His-bundle pacing. RESULTS: The acquired activation maps reflect the activation sequence under the tested conditions. e-DYS decreased considerably more than QRS duration, during both biventricular pacing (-50% vs -8%) and His-bundle pacing (-77% vs -13%). While biventricular pacing slightly increased Vd, His-bundle pacing reduced Vd significantly (+11% vs -36%), indicating the contribution of the fast conduction system. Optimization of biventricular pacing by adjusting VV-interval showed a decrease of e-DYS from 102 to 36 ms with only a small Vd increase and QRS duration decrease. CONCLUSIONS: The UHF-ECG technique provides novel information about electrical activation of the ventricles from a standard ECG electrode setup, potentially improving the selection of patients for CRT and application of CRT.
- Keywords
- His-bundle pacing, biventricular pacing, cardiac resynchronization therapy, ultra-high-frequency ECG, ventricular electrical dyssynchrony,
- MeSH
- Action Potentials MeSH
- Bundle-Branch Block diagnosis physiopathology therapy MeSH
- Time Factors MeSH
- Electrocardiography * MeSH
- Ventricular Function, Left MeSH
- Ventricular Function, Right MeSH
- Bundle of His physiopathology MeSH
- Humans MeSH
- Proof of Concept Study MeSH
- Predictive Value of Tests MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Heart Rate * MeSH
- Cardiac Resynchronization Therapy * MeSH
- Heart Failure diagnosis physiopathology therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
