Sidebands in CEST MR-How to recognize and avoid them.

PURPOSE: Clinical scanners require pulsed CEST sequences to maintain amplifier and specific absorption rate limits. During off-resonant RF irradiation and interpulse delay, the magnetization can accumulate specific relative phases within the pulse train. In this work, we show that these phases are important to consider, as they can lead to unexpected artifacts when no interpulse gradient spoiling is performed during the saturation train. METHODS: We investigated sideband artifacts using a CEST-3D snapshot gradient-echo sequence at 3 T. Initially, Bloch-McConnell simulations were carried out with Pulseq-CEST, while measurements were performed in vitro and in vivo. RESULTS: Sidebands can be hidden in Z-spectra, and their structure becomes clearly visible only at high sampling. Sidebands are further influenced by B0 inhomogeneities and the RF phase cycling within the pulse train. In vivo, sidebands are mostly visible in liquid compartments such as CSF. Multi-pulse sidebands can be suppressed by interpulse gradient spoiling. CONCLUSION: We provide new insights into sidebands occurring in pulsed CEST experiments and show that, similar as in imaging sequences, gradient and RF spoiling play an important role. Gradient spoiling avoids misinterpretations of sidebands as CEST effects especially in liquid environments including pathological tissue or for CEST resonances close to water. It is recommended to simulate pulsed CEST sequences in advance to avoid artifacts.

Helical Gearbox Defect Detection with Machine Learning Using Regular Mesh Components and Sidebands.

The current paper presents helical gearbox defect detection models built from raw vibration signals measured using a triaxial accelerometer. Gear faults, such as localized pitting, localized wear on helical pinion tooth flanks, and low lubricant level, are under observation for three rotating velocities of the actuator and three load levels at the speed reducer output. The emphasis is on the strong connection between the gear faults and the fundamental meshing frequency GMF, its harmonics, and the sidebands found in the vibration spectrum as an effect of the amplitude modulation (AM) and phase modulation (PM). Several sets of features representing powers on selected frequency bands or/and associated peak amplitudes from the vibration spectrum, and also, for comparison, time-domain and frequency-domain statistical feature sets, are proposed as predictors in the defect detection task. The best performing detection model, with a testing accuracy of 99.73%, is based on SVM (Support Vector Machine) with a cubic kernel, and the features used are the band powers associated with six GMF harmonics and two sideband pairs for all three accelerometer axes, regardless of the rotation velocities and the load levels.

Removal of 2H-decoupling sidebands in 13CHD2 13C-CEST profiles.

A unique aspect of NMR is its capacity to provide integrated insight into both the structure and intrinsic dynamics of biomolecules. Chemical exchange phenomena that often serve as probes of dynamic processes in biological macromolecules can be quantitatively investigated with chemical exchange saturation transfer (CEST) experiments. 2H-decoupling sidebands, however, always occur in the profiles of 13CHD2 13C-CEST experiments when using the simple CW (continuous wave) method, which may obscure the detection of minor dips of excited states. Traditionally, these sidebands are manually eliminated from the profiles before data analysis by removing experimental points in the range of 2H-decoupling field strength ±50 Hz away from the major dips of the ground state on either side of the dips. Unfortunately, this may also eliminate potential minor dips if they overlap with the decoupling sidebands. Here, we developed methods that use pseudo-continuous waves with variable RF amplitudes distributed onto ramps for 2H decoupling. The new methods were thoroughly validated on Bruker spectrometers at a range of fields (1H frequencies of 600, 700, and 850 MHz, and 1.1 GHz). By using these methods, we successfully removed the sidebands from the NMR profiles of 13CHD2 13C-CEST experiments.

Characterization of soft X-ray FEL pulse duration with two-color photoelectron spectroscopy.

The pulse duration of soft X-ray free-electron laser (FEL) pulses of SACLA BL1 (0.2-0.3 nC per bunch, 0.5-0.8 MeV) were characterized by photoelectron sideband measurements. The intensity of the He 1 s-1 photoelectron sidebands generated by a near-infrared femtosecond laser was measured as a function of the time delay between the two pulses using an arrival time monitor. From the width of the cross-correlation trace thus derived, the FEL pulse duration was evaluated to be 28 ± 5 fs full width at half-maximum in the photon energy range between 40 eV and 120 eV.

Fast and efficient free induction decay MR spectroscopic imaging of the human brain at 9.4 Tesla.

PURPOSE: The purpose of this work was to develop a fast and efficient MRSI-FID acquisition scheme and test its performance in vivo. The aim was to find a trade-off between the minimal total acquisition time and signal-to-noise ratio of the acquired spectra. METHODS: Measurements were performed on a 9.4 Tesla system. Sequence optimization included redesign of water suppression, optimization of the sequence gradients, and improvement of the sampling efficiency by minimizing the read-out time. This resulted in an acquisition time of 2:47 and 22:13 minutes for 2D (TR = 57 ms; 3-mm in-plane resolution) and 3D MRSI (TR = 57 ms; 16 slices; 3-mm isotropic resolution), respectively. RESULTS: Despite strong T1 weighting and first-order phase problems, it was possible to obtain spectra of an acceptable quality. The average line width calculated for the tCr peak across the entire field of view was 26.9 ± 9.6 Hz for 2D and 30.0 ± 11.3 Hz for 3D MRSI. In 3D measurements, the percent fraction of voxels fitted with Cramer-Rao lower bounds below 10% was 53.3 ± 4.1%, 63.4 ± 8.4%, and 81.0 ± 2.9% for Glu, tCr, and tNAA, respectively. CONCLUSION: Considering the typically long duration of high-resolution MRSI, the proposed technique may be of interest for clinical applications and/or studies that focus on following the biochemistry of dynamic processes. Magn Reson Med 78:1281-1295, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Measuring (13)C/(15)N chemical shift anisotropy in [(13)C,(15)N] uniformly enriched proteins using CSA amplification.

Extended chemical shift anisotropy amplification (xCSA) is applied for measuring (13)C/(15)N chemical shift anisotropy (CSA) of uniformly labeled proteins under magic-angle spinning (MAS). The amplification sequence consists of a sequence of π-pulses that repetitively interrupt MAS averaging of the CSA interaction. The timing of the pulses is designed to generate amplified spinning sideband manifolds which can be fitted to extract CSA parameters. The (13)C/(13)C homonuclear dipolar interactions are not affected by the π-pulses due to the bilinear nature of the spin operators and are averaged by MAS in the xCSA experiment. These features make the constant evolution-time experiment suitable for measuring CSA of uniformly labeled samples. The incorporation of xCSA with multi-dimensional (13)C/(15)N correlation is demonstrated with a GB1 protein sample as a model system for measuring (13)C/(15)N CSA of all backbone (15)NH, (13)CA and (13)CO sites.

Next-generation heteronuclear decoupling for high-field biomolecular NMR spectroscopy.

Ultra-high-field NMR spectroscopy requires an increased bandwidth for heteronuclear decoupling, especially in biomolecular NMR applications. Composite pulse decoupling cannot provide sufficient bandwidth at practical power levels, and adiabatic pulse decoupling with sufficient bandwidth is compromised by sideband artifacts. A novel low-power, broadband heteronuclear decoupling pulse is presented that generates minimal, ultra-low sidebands. The pulse was derived using optimal control theory and represents a new generation of decoupling pulses free from the constraints of periodic and cyclic sequences. In comparison to currently available state-of-the-art methods this novel pulse provides greatly improved decoupling performance that satisfies the demands of high-field biomolecular NMR spectroscopy.

Quantitative comparison of post-processing methods for reduction of frequency modulation sidebands in non-water suppression 1H MRS.

Non-water suppression MRS (NWS MRS) has several advantages. First, the unsuppressed water signal can be used as internal calibration for metabolite quantification and as a reliable frequency/phase reference for retrospective motion correction. Second, it avoids the potential artifacts caused by incomplete water suppression (WS) and extra radiofrequency deposition from WS pulses. However, the frequency modulation (FM) sidebands originating from a large water signal will distort the spectrum. Among the methods proposed to solve the problems caused by FM sidebands, post-acquisition processing methods are superior in flexibility for general use compared with experimental methods. In this study, we propose two algorithms based on advanced matrix decomposition to remove the FM sidebands. These methods, the simultaneous diagonalization (QZ) algorithm and its subsequent variant, the simultaneously generalized Schur decomposition (SGSD) algorithm, were numerically evaluated using computer simulations. In addition, we quantitatively compared the performance of these methods and the modulus method in an in vitro experiment and in vivo NWS MRS against conventional WS data. Our results show that the proposed SGSD algorithm can reduce the FM sidebands to achieve superior estimation of concentration on three major metabolites. This method can be applied directly to spectra pre-acquired under various experimental conditions without modifying the acquisition sequences.

Exploring various modulation-sideband recoupling conditions of SHA+ sequence at fast MAS.

We explore modulation-sideband recoupling conditions of the (13)C-(13)C Second-order Hamiltonian among Analogous nuclei plus pulse sequence (SHA+), and found that this sequence can be used in two different recoupling regimes. The first regime, νR>Δνiso(max), is recommended for broad-band recoupling to avoid any rotational resonance broadening. In this regime, the spinning speed should be only slightly larger than Δνiso(max), to obtain the best transfer efficiency. The second regime, νR<Δνiso(max), can be used to observe long-range constraints with lower spinning speed, which increases the transfer efficiency, and may allow using bigger rotors to increase the S/N ratio.

Satellite-transition double cross-polarization HETCOR under fast MAS.

Double-cross polarization to the satellite-transitions (STs) of half-integer quadrupolar nuclei is demonstrated using proton-detected heteronuclear correlation (HETCOR) under fast magic-angle spinning (MAS). By placing the rf frequency away from the central-transition (CT) and selective to the STs, average Hamiltonian theory shows a scaled effective rf field with a phase equal to the complex ST spinning sideband being irradiated. Such an effective rf field can excite and spinlock STs but the phase spread usually leads to signal cancellation in one-step excitation or cross polarization experiments. The cancellation does not occur for two-step double cross-polarization (DCP) HETCOR experiments, therefore high efficiencies can be obtained. With careful magic-angle calibration, ST and double-quantum ST (DQST) HETCOR experiments are demonstrated with the 35Cl nuclei in histidine·HCl·H2O. These experiments provide additional information over the commonly observed CT spectra and near isotropic resolution in the case of DQST of spin S = 3/2 quadrupolar nuclei.

Pushing the limit of MQMAS for low-γ quadrupolar nuclei in pharmaceutical hydrochlorides.

Solid-state NMR of quadrupolar nuclei such as 35Cl has become a useful tool to characterize polymorphism in pharmaceutical hydrochlorides. The two-dimensional multiple-quantum magic-angle spinning (MQMAS) experiment can achieve isotropic resolution, and separate quadrupolar line shapes for samples with multiple sites but the pulse sequence efficiency is often low, limiting applications due to the intrinsically low NMR signals and rf field from the low gyromagnetic ratios γ. The use of cosine low-power MQMAS pulse sequences and high magnetic fields is presented to push the limit of MQMAS for insensitive low-γ quadrupolar nuclei. The improved efficiency and fields up to 35.2 T enable the acquisition of MQMAS spectra for pharmaceutical samples with multiple 35Cl sites, large quadrupolar couplings and/or in diluted dosage forms.

A novel method to generate and transmit 40-tupling frequency millimeter wave over fiber based on remodulation of MZMs.

An novel method to generate 40-tupling frequency millimeter (MMW) based on the remodulation of MZMs and a novel radio over fiber (ROF) system to transmit the generated MMW are proposed. At the central station (CS), the ±4th order sidebands generated by two Mach-Zehnder modulators (MZMs) in parallel are used as the optical carriers for the remodulation. The radio frequency (RF) signal for the remodulation can be generated by injecting the ±4th order sidebands in the photodetector (PD). The main components in the signal after remodulation are ±4th, ±12th and ±20th order sidebands, among them, the +20th sideband is filtered out by a fiber Bragg grating (FBG). After the +20th order sideband is modulated with the downlink data, the ±20th order sidebands are combined again and transmitted to the base station (BS) by optical fiber. At the BS, a part of -20th order sideband is filtered out with a FBG, and with which the uplink data is modulated on it and sent back to the CS for carrier wave reuse. The 40-tupling frequency MMW signal with downlink data is generated by beating the output signal from FBG in the PD. In the case of data rate is 2.5G/bps and the bit error rate is less than 10-9, the transmission distance can exceed 90 km, the power penalty of the uplink and downlink is less than 1 dB and 0.29 dB, respectively. Our scheme has simple structure, high frequency multiplier factor, it has important application prospects in MMW technology.

On the use of single-frequency versus double-frequency satellite-transition pulses for MQMAS.

It has been shown recently that a rotor-period long pulse applied at a frequency selective to the satellite-transitions of half-integer quadrupole nuclei can efficiently interconvert central-transition (CT) and triple-quantum (TQ) coherences for the acquisition of MQMAS spectra [I. Hung, Z. Gan, J. Magn. Reson. 324 (2021) 106913; doi: https://doi.org/10.1016/j.jmr.2021.106913]. By using a pair of such pulses and selecting opposite changes in coherence order, the anisotropic phase of the effective rf field can be refocused. Efficient multiple-quantum interconversion has led to low-power MQMAS pulse sequences capable of obtaining isotropic NMR spectra for the largest quadrupolar couplings to date. In this work, we extend the satellite-transition selective pulses from single- to double-frequency (or cosine) irradiation. By applying average Hamiltonian theory in the quadrupolar jolting frame, it is shown that the phase for TQ/CT conversion converges when the double-frequency irradiation matches the mirror-image symmetry of the satellite-transitions. The coherent conversion explains the mechanism behind the double-frequency sweep (DFS) and fast amplitude modulation (FAM) methods used for MQMAS. However, the strict matching condition limits the bandwidth of such double-frequency pulses to less than one spinning frequency. The use of a pair of identical cosine satellite-transition pulses is proposed to refocus the residual anisotropic phase spread. The refocusing leads to a more efficient MQMAS pulse sequence with a broader bandwidth suitable for large quadrupolar couplings and chemical shift ranges. Comparisons with the recently presented single-frequency lpMQMAS and other MQMAS pulse schemes show that cos-lpMQMAS is more efficient, less susceptible to fluctuations in spinning frequency, and suffers from less distortion in quadrupolar line shapes, as demonstrated with model compounds of moderate and large quadrupolar couplings, 87RbNO3 and ß-71Ga2O3. In particular, the results for ß-71Ga2O3 show an order of magnitude increase in MQMAS efficiency.

Modulation sidebands spectra within inhomogeneous CW-EPR line detected by double modulation EPR spectroscopy.

Conventional modulation spectrum, MS, in continuous wave electron paramagnetic resonance, CW-EPR, is produced by applying longitudinal radiofrequency (RF) fields with the frequencies, ωrf, which exceeds the linewidth, 2πδ, of a single spectral line given in frequency units. The second longitudinal RF field with frequency, ωrf2, is employed to produce double modulation spectrum, DMS. In this work DMS are presented as a specific type of MS which can be produced from an ordinary homogenous line. The numerical simulations of DMS in the limit of low power saturation relied on the recently introduced multi-photon transitions formalism which includes one microwave photon in combination with an arbitrary number of radiofrequency photons. It is shown that DMS of an inhomogeneous line exhibits similar basic structure as MS and exhibits sideband peaks at multiples of basic radiofrequencies. Linewidths of these peaks are significantly narrower (cca. two - three orders of magnitude) than the inhomogeneous linewidth and can be correlated with the underlying homogeneous linewidth components on the basis of characteristic spin-lattice, T1, and spin-spin, T2, relaxation times. The capability to extract T1 and T2 from DMS was tested on the well-known E' defect in irradiated vitreous SiO2. The obtained results revealed the impact of "rapid passage" effect on DMS in improving the detection sensitivity of DMS in the study of paramagnetic centers with long relaxation times. Therefore, double modulation method can be considered as a complementary method for studying inhomegeneous broadening in the EPR spectra.

Interleaved spatial/spectral encoding in ultrafast 2D NMR spectroscopy.

The possibility to record a full 2D spectrum in less than a second using ultrafast 2D NMR (UF2DNMR) is beneficial in many applications. However, the spatial encoding process on which UF2DNMR is based sets specific constraints on the spectral width and resolution of the resulting spectra. To overcome these limitations, a tailored encoding method using spatial/spectral pulses (SPSP) can be employed as an alternative to the traditional linear spatial encoding of interactions. Here we analyze and further develop this alternative spatial encoding strategy. We first carry out numerical simulations to describe the features of bidimensional SPSP pulses. Sidebands are identified along the spectral dimension of the excitation profile. An interleaved excitation scheme is then developed and implemented experimentally to suppress the unwanted signals that arise from these harmonic sidebands. Two examples are shown to illustrate the potential of the proposed approach. An ultrafast selective TOCSY spectrum is recorded to access sub-spectra and fully assign 1H NMR resonances of individual residues of cyclosporin A. An ultrafast HSQC spectrum of a mixture of metabolites is recorded with an optimized spectral width in the spatially encoded dimension.

Measurement of amide proton chemical shift anisotropy in perdeuterated proteins using CSA amplification.

Measuring 1H chemical shift anisotropy (CSA) is useful for probing proton environments and dynamics but remains a challenge due to strong homonuclear interaction and relatively small shift anisotropy, especially in proteins with multiple proton sites. Here the extended chemical shift anisotropy amplification (xCSA) method is applied for amide proton CSA measurement in uniformly 2H enriched proteins under fast magic angle spinning. The xCSA method is capable of distinguishing the sign of the CSA asymmetry parameter, complimenting other multiple-pulse recoupling methods. A three-dimensional xCSA experiment is demonstrated for measuring the proton CSA of amide sites in aGB1 protein sample and the possible correlation of amide proton CSA with protein secondary structure is discussed.

Kelvin probe force microscopy for local characterisation of active nanoelectronic devices.

Frequency modulated Kelvin probe force microscopy (FM-KFM) is the method of choice for high resolution measurements of local surface potentials, yet on coarse topographic structures most researchers revert to amplitude modulated lift-mode techniques for better stability. This approach inevitably translates into lower lateral resolution and pronounced capacitive averaging of the locally measured contact potential difference. Furthermore, local changes in the strength of the electrostatic interaction between tip and surface easily lead to topography crosstalk seen in the surface potential. To take full advantage of the superior resolution of FM-KFM while maintaining robust topography feedback and minimal crosstalk, we introduce a novel FM-KFM controller based on a Kalman filter and direct demodulation of sidebands. We discuss the origin of sidebands in FM-KFM irrespective of the cantilever quality factor and how direct sideband demodulation enables robust amplitude modulated topography feedback. Finally, we demonstrate our single-scan FM-KFM technique on an active nanoelectronic device consisting of a 70 nm diameter InAs nanowire contacted by a pair of 120 nm thick electrodes.

Multi-photon transitions and Rabi resonance in continuous wave EPR.

The study of microwave-radiofrequency multi-photon transitions in continuous wave (CW) EPR spectroscopy is extended to a Rabi resonance condition, when the radio frequency of the magnetic-field modulation matches the Rabi frequency of a spin system in the microwave field. Using the non-secular perturbation theory based on the Bogoliubov averaging method, the analytical description of the response of the spin system is derived for all modulation frequency harmonics. When the modulation frequency exceeds the EPR linewidth, multi-photon transitions result in sidebands in absorption EPR spectra measured with phase-sensitive detection at any harmonic. The saturation of different-order multi-photon transitions is shown to be significantly different and to be sensitive to the Rabi resonance. The noticeable frequency shifts of sidebands are found to be the signatures of this resonance. The inversion of two-photon lines in some spectral intervals of the out-of-phase first-harmonic signal is predicted under passage through the Rabi resonance. The inversion indicates the transition from absorption to stimulated emission or vice versa, depending on the sideband. The manifestation of the primary and secondary Rabi resonance is also demonstrated in the time evolution of steady-state EPR signals formed by all harmonics of the modulation frequency. Our results provide a theoretical framework for future developments in multi-photon CW EPR spectroscopy, which can be useful for samples with long spin relaxation times and extremely narrow EPR lines.