Intermolecular Double-quantum Coherences Research Articles

Detection of iron-labeled single cells by MR imaging based on intermolecular double quantum coherences at 14 T

To evaluate the efficiency and feasibility of intermolecular multiple quantum coherence (iMQC) magnetic resonance (MR) imaging for single cell detection, we obtained intermolecular double quantum coherence (iDQC) and conventional gradient echo (GE) images of macrophage cells labeled by contrast agents in gel. The iDQC images obtained with echo-planar readout visualized the labeled cells effectively and with a higher contrast than seen in conventional GE images, especially at low planar resolutions and with thick slices. This implies that iDQC imaging with contrast agents could be a good alternative to conventional MR imaging for detecting labeled single cells or cell tracking under favorable conditions.

High‐resolution NMR spectroscopy in inhomogeneous fields via Hadamard‐encoded intermolecular double‐quantum coherences

A new pulse sequence based on intermolecular double-quantum coherences was proposed to obtain one-dimensional high-resolution liquid NMR spectra in inhomogeneous magnetic fields via Hadamard encoding. In contrast with the conventional intermolecular multiple-quantum coherences method with a two-dimensional acquisition to obtain one one-dimensional high-resolution spectrum, the new method can provide relatively high-resolution spectra directly through one-dimensional acquisition, and can greatly improve the signal-to-noise ratio of the spectrum within a relatively short acquisition time. Theoretical derivation was performed and analytical expressions of the resulting signals are given. Solution samples in purposely de-shimmed magnetic fields and pig brain tissue samples were tested. The experimental results demonstrate that this sequence can retain useful structural information, even when the field inhomogeneity is sufficiently severe to erase almost all spectral information with conventional one-dimensional single-quantum coherence techniques, and good solvent suppression can be achieved. This method may provide a promising technique for applications in in vivo and in vitro NMR.

High-resolution absorptive intermolecular multiple-quantum coherence NMR spectroscopy under inhomogeneous fields

Intermolecular multiple-quantum coherence (iMQC) is capable of improving NMR spectral resolution using a 2D shearing manipulation method. A pulse sequence termed CT-iDH, which combines intermolecular double-quantum filter (iDQF) with a modified constant-time (CT) scheme, is designed to achieve fast acquisition of high-resolution intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) spectra without strong coupling artifacts. Furthermore, double-absorption lineshapes are first realized in 2D intermolecular multi-quantum coherences (iMQCs) spectra under inhomogeneous fields through a combination of iZQC and iDQC signals to double the resolution without loss of sensitivity. Theoretically the spectral linewidth can be further reduced by half compared to original iMQC high-resolution spectra. Several experiments were performed to test the feasibility of the new method and the improvements are evaluated quantitatively. The study suggests potential applications for in vivo spectroscopy.

Observation of intermolecular double-quantum coherence signal dips in nuclear magnetic resonance

The correlated spectroscopy revamped by asymmetric Z-gradient echo detection (CRAZED) sequence is modified to investigate intermolecular double-quantum coherence nuclear magnetic resonance signal dips in highly polarized spin systems. It is found that the occurrence of intermolecular double-quantum coherence signal dips is related to sample geometry, field inhomogeneity and dipolar correlation distance. If the field inhomogeneity is refocused, the signal dip occurs at a fixed position whenever the dipolar correlation distance approaches the sample dimension. However, the position is shifted when the field inhomogeneity exists. Experiments and simulations are performed to validate our theoretic analysis. These signal features may offer a unique way to investigate porous structures and may find applications in biomedicine and material science.

Apparent diffusion behaviors of spins in the presence of distant dipolar field in two-component solution NMR

The diffusion behaviors of spins in the presence of distant dipolar field in two-component spin systems during the second evolution period of a modified CRAZED sequence before acquisition were investigated. Theoretical formulas were deduced based on the distant dipolar field model. The simulation results and experimental observations are consistent with the theoretical predictions. This study shows that the relative intensities of signals from intermolecular zero-quantum coherences (iZQCs) and intermolecular double-quantum coherences (iDQCs) have the same diffusion attenuation characteristic under the combined effect of diffusion weighting gradients and distant dipolar field during the second evolution period. This diffusion attenuation may be different from that of conventional single-quantum coherence signal, depending on the relative orientation of the diffusion weighting gradients to the coherence selection gradients. The results presented herein are helpful for understanding the effect of distant dipolar field from a spin system on the diffusion behavior of other spin system and the signal properties in the iZQC or iDQC magnetic resonance imaging.

High-resolution MR spectroscopy via intermolecular double-quantum coherences in inhomogeneous B0 and B1 fields

Inhomogeneity in static field B 0 and/or RF field B 1 is inevitable under some circumstances. In this work, a method based on intermolecular double-quantum coherences is employed for high-resolution 1D MR spectroscopy via 2D acquisition under such a condition. High-resolution information on chemical shifts, multiplet patterns, J coupling constants and relative peak areas can be retained in the resulting 1D projected spectra, as shown with results from a narrow-bore NMR spectrometer and a whole-body clinical scanner.

Signal‐to‐noise ratio enhancement of intermolecular double‐quantum coherence MR spectroscopy in inhomogeneous fields with phased array coils on a 3 tesla whole‐body scanner

To improve signal-to-noise ratio (SNR) of intermolecular double-quantum coherence (iDQC) MRS on a 3 Tesla (T) whole-body scanner. A 32-channel phased array coil was used to acquire iDQC signal of a MRS phantom in the presence of large field inhomogeneity. The obtained individual spectra from the array elements were combined together in the time domain using a multichannel nonparametric singular value decomposition algorithm. The results were compared quantitatively with those acquired with a circularly polarized (CP) head coil. The achieved gain in SNR ranges from 1.63 to 2.10 relative to the CP coil, mainly depending on the relative position between the surface of the phased array coil and the voxel of acquisition. SNR enhancement of iDQC MRS in inhomogeneous fields on a 3T whole-body scanner is feasible with phased array coils. This can facilitate iDQC applications of high-resolution in vivo spectroscopy in the presence of field inhomogeneity for potential disease diagnosis in humans.

High‐resolution MRS in the presence of field inhomogeneity via intermolecular double‐quantum coherences on a 3‐T whole‐body scanner

Signals from intermolecular double-quantum coherences (iDQCs) have been shown to be insensitive to macroscopic field inhomogeneities and thus enable acquisition of high- resolution MR spectroscopy in the presence of large inhomogeneous fields. In this paper, localized iDQC (1)H spectroscopy on a whole-body 3-T MR scanner is reported. Experiments with a brain metabolite phantom were performed to quantify characteristics of the iDQC signal under different conditions. The feasibility of in vivo iDQC high-resolution MR spectroscopy in the presence of large intrinsic and external field inhomogeneity (in the order of hundreds of hertz) was demonstrated in the whole cerebellum of normal volunteers in a scan time of about 6.5 min. Major metabolite peaks were well resolved in the reconstructed one-dimensional spectra projected from two-dimensional iDQC acquisitions. Investigations on metabolite ratios, signal-to-noise ratio, and line width were performed and compared with results obtained with conventional point-resolved spectroscopy/MR spectroscopy in homogeneous fields. Metabolite ratios from iDQC results showed excellent consistency under different in vitro and in vivo conditions, and they were similar to those from point-resolved spectroscopy with small voxel sizes in homogeneous fields. MR spectroscopy with iDQCs can be applied potentially for quantification of gross metabolite changes due to diseases in large brain volumes with high field inhomogeneity.

Apparent diffusion behaviour of intermolecular double-quantum coherence modulated by a distant dipolar field in solution NMR

A modified correlated spectroscopy (COSY) revamped with asymmetric Z-gradient echo detection sequence was designed to investigate the influence of diffusion behaviour on intermolecular double-quantum coherence signal attenuation during the pre-acquisition period. Theoretical formulas were deduced and experimental measurements and simulations were performed. It is found that the diffusion behaviour of intermolecular double-quantum coherence in the pre-acquisition period may be different from that of conventional single-quantum coherence, depending on the relative orientation of diffusion weighting gradients to coherence selection gradients. When the orientation of the diffusion weighting gradients is parallel or anti-parallel to the orientation of the coherence selection gradients, the diffusion is modulated by the distant dipolar field. This study is helpful for understanding the signal properties in intermolecular double-quantum coherence magnetic resonance imaging.

Fast acquisition of high-resolution NMR spectra in inhomogeneous fields via intermolecular double-quantum coherences

A pulse sequence, IDEAL-II, is proposed based on the concept of intermolecular dipolar-interaction enhanced all lines [Z. Chen et al., J. Am. Chem. Soc. 126, 446 (2004)] for obtaining one-dimensional (1D) high-resolution liquid NMR spectra in inhomogeneous fields via two-dimensional acquisitions. With the new acquisition scheme, the range of magnetic field inhomogeneity rather than chemical shift is sampled in the indirect dimension. This enables a great reduction in acquisition time and amount of data, much improved over the original IDEAL implementation. It is applicable to both isolated and J-coupled spin systems in liquid. For the latter, apparent J coupling constants are magnified threefold in spectra obtained with this sequence. This allows a more accurate measurement of J coupling constants in the cases of small J coupling constants or large inhomogeneous fields. Analytical expression was derived based on intermolecular multiple-quantum coherence treatments. Solution samples that were purposely deshimmed and biological samples with intrinsic field inhomogeneities were tested. Experimental results demonstrate that this sequence retains useful structural information including chemical shifts, relative peak areas, and multiplet patterns of J coupling even when the field inhomogeneity is severe enough to almost erase all spectroscopic information with conventional 1D single-quantum coherence techniques. This sequence is more applicable to weakly coupled and uncoupled spin systems, potentially useful for studying metabolites in in vivo NMR spectroscopy and for characterizing technologically important new materials in combinatorial chemistry.

High-resolution NMR spectroscopy in inhomogeneous fields via heteronuclear intermolecular multiple-quantum coherences

A heteronuclear CRAZED pulse sequence was utilized to obtain high-resolution NMR spectra via heteronuclear intermolecular zero-quantum coherences (iZQCs) or intermolecular double-quantum coherences (iDQCs) in inhomogeneous fields. It overcomes the difficulty of selective excitation in homonuclear CRAZED experiments when the chemical shifts of solvent and solute are close to each other. In the 1D spectrum extracted from the 2D data, chemical shifts, coupling constants, multiplet patterns, and relative peak areas are almost independent of the magnetic field inhomogeneity. Theoretical predictions were verified by experimental observations.

IDQC anisotropy map imaging for tumor tissue characterization in vivo

Intermolecular double quantum coherences (iDQCs), signals that result from simultaneous transitions of two or more separated spins, are known to produce images that are highly sensitive to subvoxel structure, particularly local anisotropy. Here we demonstrate how iDQCs signal can be used to efficiently detect the anisotropy created in breast tumor tissues and prostate tumor tissues by targeted (LHRH-conjugated) superparamagnetic nanoparticles (SPIONs), thereby distinguishing the necrotic area from the surrounding tumor tissue.

Hypercapnia-induced effects on image contrast based on intermolecular double-quantum coherences

Intermolecular double-quantum coherences (iDQCs) are well known to be sensitive to magnetic-field perturbations inside tissues. However, the exact relation between iDQC contrast in magnetic resonance imaging (MRI) and the underlying physiology is less well understood. To investigate parameters that influence iDQC signal changes observed during neuronal activation, carbogen-inhalation experiments were performed to produce a pure hemodynamic response without affecting oxidative metabolism. Eight human volunteers were studied at 2.9 T using gradient-recalled echo (GRE) and spin-echo (SE) variants of a single-shot sequence selecting iDQCs. Results were compared with conventional recordings of the blood oxygen level-dependent (BOLD) effect. Maps of voxels responding to the carbogen challenge showed similar distributions for iDQC and conventional MRI after adjustment for different sensitivities. Strong diffusion weighting of iDQC sequences and transverse relaxation effects suggested quantitative suppression of intravascular signal contributions. A particular susceptibility to local gradients during the evolution period (in which iDQCs evolve at twice the Larmor frequency) plus a strong relaxation weighting during the detection period due to the use of a long echo time (for refocusing of the dipolar signal) produced iDQC signal changes up to 21.7% +/- 2.5%. These results agreed quantitatively with computations based on the balloon model of BOLD-weighted MRI without requiring further assumptions.

BOLD imaging in the mouse brain using a turboCRAZED sequence at high magnetic fields

Functional MRI (fMRI) based on the detection of intermolecular double-quantum coherences (iDQC) has previously been shown to provide pronounced activation signal. For fMRI in small animals at very high magnetic fields, the essential fast gradient echo-based readout methods become problematic. Here, rapid intermolecular double-quantum coherence (iDQC) imaging was implemented, combining the iDQC preparation sequence with a Turbo spin echo-like readout. Four-step phase cycling and a novel intensity-ordered k-space encoding scheme with separate acquisition of odd and even echoes were essential to optimize signal to noise ratio efficiency. Compared with a single echo readout of iDQC signal, acceleration of factor 16 was achieved in phantoms using the novel method at 17.6 Tesla. In vivo, echo trains consisting of 32 echoes were possible and images of the mouse brain were obtained in 30 s. The blood oxygen level dependent (BOLD) effect in the mouse brain upon change of breathing gas was observed as average signal change of (6.3 +/- 1.1)% in iDQC images. Signal changes in conventional multi spin echo images were (4.4 +/- 2.3)% and (8.3 +/- 3.8)% with gradient echo methods. Combination of T(2)*-weighting with the fast iDQC sequence may yield higher signal changes than with either method alone, and establish fast iDQC imaging a robust tool for high field fMRI in small animals.

Improvement in the contrast of CEST MRI via intermolecular double quantum coherences

The tremendous potential of chemical exchange saturation transfer (CEST) agents as an emerging class of magnetic resonance imaging contrast media has been demonstrated in recent years. In a CEST experiment, a high CEST contrast is always welcome. However, when the exchange rate is low, which may happen in exchangeable solute protons of low concentration, it is usually hard to obtain an excellent CEST efficiency. Recently, we noted that the intermolecular multiple quantum coherence signal is more sensitive to the changes of the magnetization magnitude than a conventional single quantum coherence signal. Consequently, it may be easier when used in obtaining a CEST contrast. In this note, a modified COSY (two-dimensional correlated spectroscopy) revamped with an asymmetric Z-gradient echo detection (CRAZED) sequence combined with an off-resonance saturation pulse followed by a standard spin-echo imaging sequence was designed to obtain a better CEST contrast image based on the intermolecular double quantum coherence method. An analytical expression was derived from a dipolar field theory. Experiments were performed on an agar–glucose phantom, and the results demonstrate the feasibility of our method.

Chemical exchange saturation transfer by intermolecular double-quantum coherence

A number of contrast enhancement effects based on the use of intermolecular multiple-quantum coherences, or distant dipolar field effects are known. This phenomenon is characterized by the dependence on the mth power of the initial magnetization (where m is the coherence order used). In this paper, we describe the contrast enhancement based on chemical exchange saturation transfer and NOE, which is achieved by the use of intermolecular double-quantum coherences (iDQC). The method was validated using clinically relevant systems based on glycosaminoglycans and a sample of cartilage tissue, showing that the CEST contrast, as well as, NOE are enhanced by iDQC.

Heteronuclear intermolecular single-quantum coherences in liquid nuclear magnetic resonance

This paper analyses the heteronuclear Cosy Revamped by Asymmetric Z-gradient Echo Detection pulse sequence. General theoretical expressions of the pulse sequence with arbitrary flip angles were derived by using dipolar field treatment and signals originating from heteronuclear intermolecular single-quantum coherences (iSQCs) in highly-polarized two spin-1/2 systems were mainly discussed in order to find the optimal flip angles. The results show that signals from heteronuclear iSQCs decay slower than those from intermolecular double-quantum coherences or intermolecular zero-quantum coherences. Magical angle experiments validate that the signals are from heteronuclear iSQCs and insensitive to the imperfection of radio-frequency flip angles. All experimental observations are in excellent agreement with theoretical predictions. The quantum-mechanical treatment leads to similar predictions to the dipolar field treatment.

Functional MRI at 3T using intermolecular double-quantum coherence (iDQC) with spin-echo (SE) acquisitions

To reinvestigate the dependence of the signal and contrast on sequence parameters and tissue relaxation times for intermolecular double-quantum coherence (iDQC) signals, and to explore the possibility to use a spin-echo (SE)-iDQC sequence for detecting activation signals at 3T. Brain activations were detected in five human volunteers in a visual simulation study using a SE-iDQC sequence, in addition to a GE-iDQC and a conventional single-quantum coherence (SQC) blood-oxygenation-level-dependent (BOLD) sequence. A brain phantom was also used for some quantitative measurements. By choosing an optimal echo time TE (approximately T2) and iDQC evolution time tau(approximately 20 ms), robust brain activations were detected using the SE-iDQC sequence, in addition to the GE-iDQC and a conventional single-quantum coherence (SQC) BOLD sequence. A higher percentage signal change due to activation was observed for both the iDQC-based measurements in comparison to the conventional SQC acquisition. Even though a phenomenological analysis consistent with the experimental results was provided, a detailed model is still needed for the contrast mechanism at microscopic level to guide potential applications of brain functional imaging based on the SE-iDQC.

High-resolution NMR spectra under inhomogeneous fields via intermolecular double-quantum coherences

High-resolution NMR spectroscopy is a powerful tool for analyzing molecular structures and compositions. Line-widths of conventional liquid NMR signals are directly proportional to the overall magnetic field inhomogeneity the sample experiences. In many circumstances, spatial and temporal homogeneity of the magnetic field is degraded. In this paper, a modified pulse sequence based on intermolecular double-quantum coherences (iDQCs) was proposed to obtain 1D high-resolution NMR spectra under inhomogeneous fields using 2D acquisition. Analytical expressions were derived from the intermolecular multiple-quantum coherence (iMQC) treatments. Both experimental and simulated spectra provide high-resolution 1D projection spectra similar to conventional 1D high-resolution spectra. Moreover, the apparent J coupling constants are threefold magnified, which allows a more accurate measurement of small J coupling constants.

Functional contrast based on intermolecular double‐quantum coherences: Influence of the correlation distance

A functional MRI (fMRI) study with visual stimulation of healthy subjects was performed at 3T exploiting intermolecular double-quantum coherences. The correlation distance, d(c), was varied between 60 and 300 microm for different evolution times, tau. Robust activation was obtained in all experiments with average signal changes (DeltaS(2)) = 8.4 +/- 0.7% and 9.4 +/- 0.8% for tau = 15 and 20 ms, respectively) exceeding those normally associated with conventional blood oxygen level-dependent (BOLD) fMRI. Relaxation-rate changes (DeltaR(2) = 0.33 +/- 0.36 s(-1) and DeltaR(2)* = 0.77 +/- 0.54 s(-1)) were similar to those commonly obtained for the extravascular BOLD effect. The number of activated voxels increased with increasing d(c) until a plateau was reached at approximately equal 120 microm. Similar trends were observed for the activation-induced percent signal change and for the maximal Z-scores. These effects were quantitatively explained by a reduced sensitivity at short d(c) due to increasing signal attenuation related to diffusion and an increasing amount of signal fluctuations in the fMRI time series due to imperfect suppression of unwanted coherence pathways. Consistent indications of a preferential selection of susceptibility changes in blood vessels of a particular size were not obtained.