Localized proton spectroscopy without water suppression: removal of gradient induced frequency modulations by modulus signal selection

Most Magnetic Resonance Spectroscopy (MRS) localization methods can generate gradient vibrations at acoustic frequencies and/or magnetic field oscillation, which can cause a time-varying magnetic field superimposed onto the static one. This effect can produce frequency modulations of the spectral resonances. When localized MRS data are acquired without water suppression, the associated frequency modulations are manifested as a manifold of spurious peaks, called sidebands, which occur symmetrically around the water resonance. These sidebands can be larger than the small metabolite resonances and can present a problem for the quantitation of the spectra, especially at short echo times. Furthermore, the resonance lineshapes may be distorted if any low frequency modulations are present. A simple solution is presented which consists of selecting the modulus of the acquired Free Induction Decay (FID) signal. Since the frequency modulations affect only the phase of the FID signal, the obtained real spectrum of the modulus is free from the spurious peaks where quantitative results may be directly obtained. Using this method, the distortions caused by the sidebands are removed. This is demonstrated by processing proton MRS spectra acquired without water suppression collected from a phantom containing metabolites at concentrations comparable to those in human brain and from a human subject using two different localization methods (PRESS and Chemical Shift Imaging PRESS-(CSI)). The results obtained illustrate the ability of this approach to remove the spurious peaks. The corrected spectra can then be fit accurately. This is confirmed by the results obtained from both the relative and the absolute metabolites concentrations in phantoms and in vivo.     

A phase rotation scheme for achieving very short echo times with localized stimulated echo spectroscopy

In a single-voxel stimulated echo localization sequence in magnetic resonance spectroscopy, magnetic field gradients are inserted within the echo time (TE) to filter signals generated through coherence pathways other than that leading to the stimulated echo. There is a significant penalty for these gradients as they increase the minimum TE, thereby leading to significant signal loss from spin-spin relaxation and phase distortions in coupled spin systems. Here, an RF phase rotation technique is described for a stimulated echo localization sequence that allows removal of the gradients in the TE intervals and, subsequently, reduction of the minimum TE to only 6 ms. Experiments carried out on six healthy volunteers on a 1.5-T whole-body MR system show a significant signal increase in the metabolite concentrations when measured with a 6-ms TE (N-acetyl-aspartate, 12%, P=.002; creatine, 15%, P=.04; and glutamate+glutamine, 92%, P=.02) compared to concentrations measured with data collected at TEs of 15 and 20 ms.     

Application of multiple inversion recovery for suppression of macromolecule resonances in short echo time (1)H NMR spectroscopy of human brain.

Macromolecules contribute broad "background" resonances to the (1)H NMR brain spectra at short echo times. The application of long echo times is the most widely used method for removing these resonances. Here, it is demonstrated that these background resonances may be suppressed at short echo times using multiple inversion recovery (MIR). In the technique presented, the MIR sequence consists of four adiabatic inversion pulses, applied preparatory to a 20-ms echo time stimulated echo localization sequence. The inversion times (359, 157, 69, and 20 ms) were selected to preferentially suppress macromolecules with longitudinal relaxation times between 38 and 300 ms. While the resulting spectra have lower overall signal-to-noise, baseline contributions from macromolecules are greatly reduced. Unlike the typical long TE acquisitions, the short TE MIR acquisition preserves the myo-inositol resonance.     

The application of phase rotation for localized in Vivo proton spectroscopy with short echo times

Single voxel localization techniques like STEAM or PRESS lead to the generation of unwanted signals, which must be destroyed by spoiling gradients. The duration of these gradients and the eddy currents they produce lead to comparatively long echo times on standard whole-body systems. This paper reports a way to observe the proper spectrum in the presence of large spurious signals. The method uses a phase-cycling scheme which separates all different signal contributions by two-dimensional Fourier transformation. Localized proton spectra from the human brain with echo times of 20 ms using the PRESS localization technique could be acquired on a 2 T whole-body system. Metabolites with short T₂ relaxation times like glutamate or inositol are observed.     

Water suppression without signal loss in HR-MAS 1H NMR of cells and tissues

In cell and tissue samples, water is normally three orders of magnitude more abundant than other metabolites. Thus, water suppression is required in the acquisition of NMR spectra to overcome the dynamic range problem and to recover metabolites that overlap with the broad baseline of the strong water resonance. However, the heterogeneous cellular environment often complicates water suppression and the strong coupling of water to membrane lipids interferes with the NMR detection of membrane associated lipid components. The widely used water suppression techniques including presaturation and double pulsed field gradient selective echo result in more than a 70% reduction in membrane associated lipid components in proton spectra of cells and tissues compared to proton spectra acquired in the absence of water suppression. A water suppression technique based on the combination of selective excitation pulses and pulsed field gradients is proposed to use in the acquisition of high resolution MAS NMR spectra of tissue specimens and cell samples. This pulse sequence methodology enables efficient water suppression for intact cells and tissue samples and eliminates signal loss from cellular metabolites.     

Classification of brain tumours using short echo time 1H MR spectra

The purpose was to objectively compare the application of several techniques and the use of several input features for brain tumour classification using Magnetic Resonance Spectroscopy (MRS). Short echo time 1H MRS signals from patients with glioblastomas (n = 87), meningiomas (n = 57), metastases (n = 39), and astrocytomas grade II (n = 22) were provided by six centres in the European Union funded INTERPRET project. Linear discriminant analysis, least squares support vector machines (LS-SVM) with a linear kernel and LS-SVM with radial basis function kernel were applied and evaluated over 100 stratified random splittings of the dataset into training and test sets. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of binary classifiers, while the percentage of correct classifications was used to evaluate the multiclass classifiers. The influence of several factors on the classification performance has been tested: L2- vs. water normalization, magnitude vs. real spectra and baseline correction. The effect of input feature reduction was also investigated by using only the selected frequency regions containing the most discriminatory information, and peak integrated values. Using L2-normalized complete spectra the automated binary classifiers reached a mean test AUC of more than 0.95, except for glioblastomas vs. metastases. Similar results were obtained for all classification techniques and input features except for water normalized spectra, where classification performance was lower. This indicates that data acquisition and processing can be simplified for classification purposes, excluding the need for separate water signal acquisition, baseline correction or phasing.     

FID-acquired-echos (FAcE): a short echo time imaging method for flow artefact suppression.

The FID-Acquired-Echo sequence (FAcE) is a magnetic resonance imaging technique using fractional-echo acquisitions, with sequential separate sampling of the right and left k-space half planes. It reduces the minimal echo times by about a factor of two, compared to conventional full-(gradient)-echo sampling schemes. With this sequence, implemented on a commercial 1.5 Tesla whole body system, high resolution images are acquired with typical echo times between 3 and 4.5 msec. Using short echo times the signal dephasing caused by velocity and higher order spin motion is reduced. Further, due to the modified sampling scheme, the sequence exhibits, for triggered studies, partially a compensation of motion-induced phase shifts in the frequency-encoding direction. Thus, the sequence offers an alternative means for the reduction of motion-induced image artefacts to the use of flow compensating gradients, which usually makes a sequence more sensitive to higher order motion and introduces further eddy currents. Besides potential application for imaging of nuclei and tissues with short T2 relaxation times, and non-ECG-triggered in-flow angiography, the main application seems to be triggered-phase contrast imaging with focus on quantitation of blood flow. Its usefulness is largest in cases with irregular flow patterns, where considerable in-plane flow occurs.     

Electron spin echo at S-band: Nuclear modulations and decay in C60 powder

At S-band (≈ 3 GHz) the modulation amplitude of the Electron Spin Echo patterns is increased with respect to the amplitude at X-band: as a consequence, it is possible to reveal the presence of nuclei not detectable at X-band. In this paper the results obtained by running ESE experiments at S-band on a C₆₀ powder sample containing radicals are shown and discussed. The two- and three-pulse Electron Spin Echo patterns exhibit both¹³C modulation and proton modulation not detected at X-band. The experimental data are quantitatively analyzed by simulating the time-domain patterns and their Fourier transforms. It results that a noticeable amount of proton nuclei surrounds the intrinsic paramagnetic centers. On the basis of the analysis, a possible explanation of their existence is given.     

Longitudinally modulated ENDOR spectroscopy. Lineshape and signal dependence on relaxation times

A novel technique, named longitudinally modulated electron nuclear double resonance (LOMENDOR), is reported. The lineshape of the signal is studied as a function of the relaxation times of the spin system under study and as a function of the microwave and radiofrequency field strengths. Analytical expressions of the line intensity and width are obtained at low saturation factors. The experimental setup is described and the results are compared with theory. The application of LOMENDOR for the direct measurement of relaxation times is discussed in detail.     

Accurate 1H tumor spectra quantification from acquisitions without water suppression

Monovoxel magnetic resonance spectroscopy (MRS) is a technique extensively used for the study of brain tumors in many imaging centers. However, given the fact that monovoxel spectrum quality depends upon voxel size, region of acquisition and the presence of metal and/or blood residue after surgery can make the comparison of MRS brain tumor spectra more difficult than that of other pathologies. This study was conducted in order to evaluate whether it is possible to predict in which cases a tumor spectrum will be quantifiable from acquisitions obtained without water suppression, allowing comparison to other spectra. Three different methods were employed: a qualitative, clinical method and two quantitative ones (Amares and Quest). It was found that by using Quest, it is possible to estimate the number of acquisitions needed to obtain a quantifiable spectrum before its acquisition, something which was not feasible with Amares (given the base used). On examining the spectra as physicians would, it was found that after a certain number of acquisitions, they did not change. The study shows that it is possible to optimize MRS acquisition time in brain tumors and guarantee spectrum quantification for comparison of different MRS studies, obtained both from a single patient or different patients.     

Complete NMR fingerprints of proteins in H2O solution without solvent presaturation. An application of two-dimensional longitudinal two-spin-order spectroscopy

A method for obtaining complete two-dimensional ¹H NMR amide proton-C_α proton J-connectivity maps for proteins (the “fingerprint”) is describe. The method relies on the conversion of antiphase single-quantum coherence into longitudinal two-spin order which is made observable by utilizing a selective solvent-suppression readout pulse. Since irradiation of the solvent resonance is unnecessary in this experiment, J connectivities are observable even for protons resonating exactly at the solvent frequency. Thus, a complete protein fingerprint is obtained at a single set of experimental conditions. The method is demonstrated for a 75-amino-acid protein.     

Formation of correlations and energy-conservation at short times

The formation of correlations due to collisions in an interacting nucleonic system is investigated. Results from one-time kinetic equations are compared with the Kadanoff and Baym two-time equation with collisions included in Born approximation. A reasonable agreement is found for a proposed approximation of the memory effects by a finite duration of collisions. This form of collision integral is in agreement with intuitive estimates from Fermi's golden rule. The formation of correlations and the build up time is calculated analytically for the high temperature and the low temperature limit. Different approximate expressions are compared with the numerical results. We present analytically the time dependent interaction energy and the formation time for Gau?- and Yukawa type of potentials. Received: 25 November 1998 / Revised version: 11 January 1999     

Accurate quantification of (1)H spectra: from finite impulse response filter design for solvent suppression to parameter estimation.

A scheme for accurate quantification of (1)H spectra is presented. The method uses maximum-phase finite impulse response (FIR) filters for solvent suppression and an iterative nonlinear least-squares (NLLS) algorithm for parameter estimation. The estimation algorithm takes the filter influence on the metabolites of interest into account and can thereby correctly incorporate a large variety of prior knowledge into the estimation phase. The FIR filter is designed in such a way that no distortion of the important initial samples is introduced. The FIR filter method is compared numerically with the HSVD method for water signal removal in a number of examples. The results show that the FIR method, using an automatic filter design scheme, slightly outperforms the HSVD method in most cases. The good performance and ease of use of the FIR filter method combined with its low computational complexity motivate the use of the proposed method.     

Hydrodynamic correlation functions of hard-sphere fluids at short times

The short-time behavior of the coherent intermediate scattering function for a fluid of hard-sphere particles is calculated exactly through ordert ⁴, and the other hydrodynamic correlation functions are calculated exactly through ordert ². It is shown that for all of the correlation functions considered the Enskog theory gives a fair approximation. Also, the initial time behavior of various Green-Kubo integrands is studied. For the shear-viscosity integrand it is found that at densityn³=0.837 the prediction of the Enskog theory is 32% too low. The initial value of the bulk viscosity integrand is nonzero, in contrast to the Enskog result. The initial value of the thermal conductivity integrand at high densities is predicted well by Enskog theory.     

Structure elucidation of fluorescent H1 antihistamines by ultraviolet resonance Raman spectroscopy: solvent structures of tripelennamine and mepyramine

Ultraviolet Resonance Raman (UVRR) spectroscopy—a Raman technique that combines high sensitivity with high selectivity and does not suffer from background fluorescence—is applied to the fluorescent H₁ antihistamines tripelennamine (TRP) and mepyramine (MEP) in aqueous solution to elucidate their molecular structure as a function of pH. In a previous investigation of these compounds (C. Tardioli, G. Gooijer G. van der Zwan, J. Phys. Chem. B, 113 , (2009), 6949), the presence of gauche conformers caused by intramolecular interaction of the protonated alkylamine tail with the pyridine nitrogen was assumed to explain the pH dependence of the fluorescence properties. In order to validate this assumption, use is made of the resonant excitation of the aminopyridine chromophore in TRP and MEP. In that way, structural information associated with the vibrations of that moiety can be obtained, and the changes it undergoes upon protonation can be monitored. Assignment of the vibrations was achieved with the help of a number of other compounds, and quantum chemical calculations. N,N‐Dimethylaminopyridine (2DMP) and its mono‐protonated form (2DMPH⁺) were investigated, since this molecule was shown to have optical properties closely resembling those of the aminopyridine moiety in TRP and MEP. Assignment of the vibrations of 2DMP was accomplished by comparison with the resonance Raman spectra of two other reference structures, 2‐aminopyridine and dimethylaniline—for which ordinary Raman data are available—and by Gaussian calculations. UVRR spectra of TRP and MEP could be readily interpreted on the basis of vibrational assignments of the parent chromophores, i.e. 2DMP and 2DMPH⁺. Vibrations of the aminopyridine chromophore in TRP and MEP at neutral pH, where the aminoalkyl chain is protonated, are modified when compared to the vibrational pattern recorded for a fully neutral molecule in alkaline solution. This implies an electronic redistribution in the ring originating from internal hydrogen bonding between the aminoalkyl tail and the aminopyridine chromophore. Copyright © 2010 John Wiley & Sons, Ltd.     

On the application of magic echo cycles for quadrupolar echo spectroscopy of spin-1 nuclei

Magic echo cycles are introduced for performing quadrupolar echo spectroscopy of spin-1 nuclei. An analysis is performed via average Hamiltonian theory showing that the evolution under chemical shift or static field inhomogeneity can be refocused simultaneously with the quadrupolar interaction using these cycles. Due to the higher convergence in the Magnus expansion, with sufficient RF power, magic echo based quadrupolar echo spectroscopy outperforms the conventional two pulse quadrupolar echo in signal to noise. Experiments highlighting a signal to noise enhancement over the entire bandwidth of the quadrupolar pattern of a powdered sample of deuterated polyethelene are shown.     

A high spatial resolution 1H magnetic resonance spectroscopic imaging technique for breast cancer with a short echo time

The high sensitivity but low specificity of breast MRI has prompted exploration of breast (1)H MRS for breast cancer detection. However, several obstacles still prevent the routine application of in vivo breast (1)H MRS, including poor spatial resolution, long acquisition time associated with conventional multi-voxel MRS imaging (MRSI) techniques, and the difficulty of "extra" lipid suppression in a magnetic field with relatively poor achievable homogeneity compared to the brain. Using a combination of a recently developed echo-filter (EF) suppression technique and an elliptical sampling scheme, we demonstrate the feasibility of overcoming these difficulties. It is robust (the suppression technique is insensitive to magnetic field inhomogeneity), fast (acquisition time of about 12 min) and offers high spatial resolution (up to 0.6 cm(3) per voxel at 1.5 T with a TE of only 60 ms). This approach should be even better at 3 T with higher resolution and/or shorter TE.