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Determination of molecular self-diffusion coefficient using multiple spin-echo NMR spectroscopy with removal of convection and background gradient artifacts.

A new approach is presented for the measurement of the self-diffusion coefficients of molecules in solution. It has been applied to metabolites in biofluids such as seminal and blood plasma at physiological temperature. The method is based on the double-gradient-spin-echo pulse sequence in which CPMG and bipolar gradient pulses have been implemented. The double-gradient spin-echo is shown to be useful in reducing the thermal convection that can cause over-estimation of the diffusion coefficients. The multiple spin-echoes in association with the CPMG approach is also insensitive to background gradient artifacts. In addition, the CPMG sequence enables longer diffusion periods (up to seconds) to be used without phase distortion; therefore, the proposed method is suitable for determining the diffusion coefficients of small metabolites in biofluids, where the resonances of large molecules, such as proteins, are suppressed during the spin-echo period as a result of their fast relaxation.

Amino Acids↗

A modified CRISIS-HSQC for band-selective IMPRESS.

CRISIS (Compensation of Refocusing Inefficiency with Synchronized Inversion Sweep) is a powerful technique for obtaining multiplicity-edited HSQC spectra without compromising sensitivity. However, the stringent requirement for the duration of the CRISIS waveforms makes them unsuitable for other functions, such as band selection or IMPRESS (IMProved REsolution using Symmetrically Shifted pulses). We report here a modified CRISIS-gHSQC pulse sequence employing time-reversed 13C pi/2 EBURP-2 pulses. This IC-bs-gHSQC (IMPRESS-CRISIS-bs-gHSQC) sequence was found to be equally useful for acquiring multiplicity-edited, band-selective spectra individually or in tandem with IMPRESS. Remarkably, the latter provides multiple spectra in significantly less time and is the preferred approach when several crowded regions need to be assigned unambiguously. The use of adiabatic sweeps and the CRISIS pulses enable IC-bs-gHSQC to give better sensitivity than the original IMPRESS sequence for band-selective spectra.

Journal Article↗

Simultaneous outer volume and blood suppression by quadruple inversion-recovery.

A new method has been developed for reduced field-of-view (FOV) imaging with simultaneous blood suppression. This method combines suppression of signals from the outer volume and inflowing blood by using a small-FOV quadruple inversion-recovery (SFQIR) preparative pulse sequence consisting of two double-inversion pulse pairs separated by appropriate delays. Within each pair, inversion pulses are successively applied to the imaged slice and the slab orthogonal to the imaging plane with the thickness equal to the FOV size in the phase-encoding direction. Each double inversion results in the reinversion of the magnetization in the central part of the FOV, while the outer areas of the FOV and inflowing blood remain inverted. The SFQIR module was implemented for single- and multislice acquisition with a fast spin-echo readout sequence. Based on a theoretical model of the signal, the timing parameters of the sequence corresponding to the maximal suppression efficiency can be found by minimizing the variation of the normalized signal over the entire range of T1's that occur in tissues. The method was tested for black-blood imaging of the aorta and carotid arteries, and the results demonstrated its ability to eliminate motion and flow artifacts, reduce scan time, and improve spatial resolution.

Algorithms↗

Effects of hyperoxia on T2* and resonance frequency weighted magnetic resonance images of rodent tumours.

Experiments were performed to determine whether T2* and resonance frequency weighted MR images are sensitive to effects of hyperoxia on model tumors. Hyperoxia can increase tumor oxygen tension and thus affect T2* and/or the average resonance frequency within each image voxel due to the paramagnetism of oxygen itself or through modulation of the oxidation state of hemoglobin. Alternatively, changes in T2* during hyperoxia may reflect changes in tumor water content due to changes in systemic blood pressure. Mammary adenocarcinomas implanted in the flanks of rats were studied. Imaging sequences were preceded by two 90 degrees pulses separated by an evolution period of 50 or 75 ms and followed by a crusher gradient to eliminate transverse magnetization. This pulse sequence produced images which were sensitized to both T2* and the average resonance frequency of each voxel. Images were produced at 2 T using a gradient echo imaging method with a TR of 3 s. Images obtained during inhalation of air and 100% O2 were compared. Significant increases in image intensity were observed in most tumors during hyperoxia, particularly at the tumor center. The increase was accentuated when the evolution period was increased and greatly reduced when a 180 degrees refocusing pulse was placed at the center of the evolution period. These results suggest that hyperoxia reduces local magnetic susceptibility gradients leading to an increase in T2* or causes a shift in resonance frequency. The magnitude of this change may be a function of the rate at which oxygen is delivered to and metabolized by tumors and may also reflect tumor oxygen tension under normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Quantitative contrast-enhanced MR imaging of the optic nerve.

During the acute stages of optic neuritis damage to the blood-optic nerve barrier can be detected using i.v. paramagnetic contrast-enhanced MR imaging. Quantification of the enhancement pattern of the optic nerve, intraorbital fat and muscle was determined in 15 normal subjects using 3 fat-suppression MR imaging methods: T1-weighted spin-echo and spoiled gradient-echo sequences preceded by a fat-frequency selective pulse (FATSAT+SE and FATSAT+SPGR, respectively) and a pulse sequence combining CHOPPER fat suppression with a fat-frequency selective preparation pulse (HYBRID). Pre- and postcontrast-enhanced studies were acquired for FATSAT+SE and FATSAT+SPGR. There was no significant enhancement of the optic nerve by either method (mean increase of 0.96% and 5.3%, respectively), while there was significant enhancement in muscle (mean 118.2% and 108.2%, respectively; p < 0.005) and fat (mean increase of 13% and 37%, respectively; p < 0.05). Postcontrast optic nerve/muscle signal intensity ratios (mean, SD) were 0.51 (0.07), 0.58 (0.05) and 0.75 (0.05) for FATSAT+SE, FATSAT+SPGR and HYBRID, respectively. These results suggest a practical methodology and range of values for normal signal intensity increases and ratios of tissue signal that can be used as objective measures of optic neuritis for natural history studies and treatment trials.

Adipose Tissue↗

Boundary of quantum evolution under decoherence.

Relaxation effects impose fundamental limitations on our ability to coherently control quantum mechanical phenomena. In this article, we use principles of optimal control theory to establish physical limits on how closely a quantum mechanical system can be steered to a desired target state in the presence of relaxation. In particular, we explicitly compute the maximum amplitude of coherence or polarization that can be transferred between coupled heteronuclear spins in large molecules at high magnetic fields in the presence of relaxation. Very general decoherence mechanisms that include cross-correlated relaxation have been included in our analysis. We give analytical characterization for the pulse sequences (control laws) that achieve these physical limits and provide supporting experimental evidence. Exploitation of cross-correlation effects has recently led to the development of powerful methods in NMR spectroscopy to study very large biomolecules in solution. For two heteronuclear spins, we demonstrate with experiments that cross-correlated relaxation optimized pulse (CROP) sequences provide significant gains over the state-of-the-art methods. It is shown that despite large relaxation rates, coherence can be transferred between coupled spins without any loss in special cases where cross-correlated relaxation rates can be tuned to autocorrelated relaxation rates.

Magnetic Resonance Spectroscopy↗

31P MRS of myocardial inorganic phosphate using radiofrequency gradient echoes.

Determination of the chemical shift and integral of the myocardial intracellular inorganic phosphate (Pi) resonance by 31P magnetic resonance spectroscopy (MRS) is often precluded due to a large overlapping signal from 2,3-diphosphoglycerate (2,3-DPG) from chamber and myocardial blood. This report demonstrates the use of radiofrequency (RF) magnetic field gradient echoes (RFGE) to eliminate signals from 2,3-DPG in flowing blood, while retaining signals from intracellular myocardial Pi, ATP, and phosphocreatine (PCr). The ECG-triggered 31P spectra were acquired from the myocardium of open chest pigs using a Philips Gyroscan 2-T magnetic resonance spectrometer. A 2.5-cm-diameter surface coil attached to the myocardium was used to provide the RF gradient as well as for excitation and detection of signals. Optimal performance of the RFGE pulse sequence was obtained when the RF gradient pulses were centered at peak diastole or peak systole. Under these conditions, 2,3-DPG signals were completely suppressed, and sensitivity was usually sufficient to allow detection of a well-resolved Pi signal. Myocardial pH determined from RFGE experiments was 7.16 +/- 0.10, and the ratio of the integrals of the Pi and ATP resonances (Pi/ATP) was 0.24. The mean signal-to-noise ratio (S/N) for PCr in control spectra acquired in 4 min was 19/1, while the mean S/N for PCr in RFGE-edited spectra acquired in 15 min was 11/1, demonstrating that the present implementation of the RFGE method results in significant loss in sensitivity. These experiments demonstrate that RFGE-editing allows accurate determination of the chemical shift and integral of the Pi resonance in blood-perfused myocardium in situ.

2,3-Diphosphoglycerate↗

Dissecting and implementing STEAM spectroscopy.

A rapid, simple method for constructing a site-specific STEAM sequence from a basic Hahn three-pulse sequence is presented. The method assures maximum signal available from the hardware.

Image Enhancement↗

Localized 1H NMR spectroscopy of rat spinal cord in vivo.

A movable, actively decoupled surface coil has been employed to obtain a localized 1H NMR spectrum from the lumbosacral spinal cord of a live Lewis rat. A volume selective 'VOSY' normally spelled out as 'volume selective spectroscopy' spectroscopy pulse sequence that incorporates 'phase ramped' selective RF pulses, has been used to minimize random phase jitter in the NMR signal as a result of the large frequency shifts required to locate the voxel in the center of the cord while using intense gradient pulses. Spectra from 13-microliters voxels in healthy rats and in rats inoculated with guinea pig spinal cord and complete Freund's adjuvant, resulting in experimental autoimmune encephalomyelitis, are shown.

Animals↗

Tissue characterisation of atherosclerotic carotid plaques by MRI.

Carotid artery plaques with intraplaque haemorrhage or atheromatous debris have been found to be associated with an increased risk of embolic stroke. Other methods have failed to detect plaque morphology, and it is not clear whether MRI allows differentiation between prognostically and therapeutically relevant plaque types. We examined 17 carotid bifurcation plaques which had been removed in toto by MRI. For quantifying MR signal intensities (I) the contrast-to-noise ratio (CNR) was used: (ITissue-IRef)/SDRef, with normal saline (0.9%) as reference (Ref) and the standard deviation (SD) of the noise. Measurements were correlated with the histopathological appearance of "simple plaques", consisting of fibrous intimal thickening, lipid deposits and/or atheromatous tissue with cholesterol crystals, largely calcified plaques, and "complicated plaques", containing recent intramural haemorrhage or friable atheromatous debris. Significantly different mean CNR could be measured in the three plaque types on T1- and T2-weighted sequences (p < 0.00001) and using the FLASH pulse sequence with a flip angle of 15 degrees (p < 0.001). With the T1-weighted sequence simple plaques showed a CNR of 4.4 +/- 2.3, calcified plaques -4.8 +/- 2.6 and complicated plaques 15.1 +/- 4.3. Using this technique, each single plaque could be correctly classified, an unalterable prerequisite for a clinical application. To date, motion artefacts due to patient movement or insufficiently triggerable vessel pulsation in combination with relative long acquisition times (6-7 min) have limited in vivo investigations. If these problems could be overcome, MRI might become a valuable technique for studying carotid plaque morphology.

Calcinosis↗

A new approach for simultaneous measurement of ADC and T2 from echoes generated via multiple coherence transfer pathways.

The study of rotational and translational diffusion requires the measurement of both T2 and apparent diffusion coefficient (ADC), quantities that are typically measured in separate experiments. The exploitation of echoes generated via multiple coherence transfer pathways offers an opportunity for measuring T2 and ADC values simultaneously in a single experiment. A series of RF pulses can generate multiple echoes via different coherence pathways with each one being uniquely encoded. Here, we demonstrate one pulse sequence that uses an initial theta; RF pulse to generate three coherence orders (C = 0, -1, +1). In the particular version of the method discussed here only two are used (C = 0, +1). Each order is encoded with a different b value from which the ADC is derived. The coherence order echo C = 0 is refocused to quantify T2. The performance of the method--dubbed simultaneous measurement of ADC and relaxation time (SMART)--is demonstrated on a set of samples differing in T2 and ADC achieved by varying the relative volume fractions in mixtures of gadolinium-doped H2O and D2O. The regional SMART derived T2 and ADC agree well with those obtained with conventional double-spin-echo and pulsed gradient spin-echo methods.

Contrast Media↗

Implementing quantum gates on oriented optical isomers.

Optical enantiomers are proposed to encode molecular two-qubit information processing. Using sequences of pairs of nonresonant optimally polarized pulses, different schemes to implement quantum gates, and to prepare entangled states, are described. We discuss the role of the entanglement phase and the robustness of the pulse sequences which depend on the area theorem. Finally, possible scenarios to generalize the schemes to n-qubit systems are suggested.

Journal Article↗

Control of cavitation activity by different shockwave pulsing regimes.

The aim of the study was to control the number of inertial cavitation bubbles in the focal area of an electromagnetic lithotripter in water independently of peak intensity, averaged intensity or pressure waveform. To achieve this, the shockwave pulses were applied in double pulse sequences, which were administered at a fixed pulse repetition frequency (PRF) of 0.33 Hz. The two pulses of a double pulse were separated by a variable short pulse separation time (PST) ranging from 200 micros to 1500 ms. The number and size of the cavitation bubbles were monitored by scattered laser light and stroboscopic photographs. We found that the number of inertial cavitation bubbles as a measure of cavitation dose was substantially influenced by variation of the PST, while the pressure pulse waveform, averaged acoustic intensity and bubble size were kept constant. The second pulse of each double pulse generated more cavitation bubbles than the first. At 14 kV capacitor voltage, the total number of cavitation bubbles generated by the double pulses increased with shorter PST down to approximately 400 micros, the cavitation lifespan. The results can be explained by cavitation nuclei generated by the violently imploding inertial cavitation bubbles. This method of pulse administration and cavitation monitoring could be useful to establish a cavitation dose-effect relationship independently of other acoustic parameters.

Dose-Response Relationship, Radiation↗

Incremental flip angle snapshot FLASH MRI of hepatic lesions: improvement of signal-to-noise and contrast.

Incremental flip angle (IFA) snapshot fast low angle shot (FLASH) is a new modification of inversion recovery snapshot FLASH MR imaging. The method changes the flip angle incrementally from low to high during data acquisition and was applied in the evaluation of 16 focal hepatic lesions in 10 patients. Sequence comparisons were performed with a fixed flip angle inversion recovery snapshot FLASH sequence (standard), a T1- and T2-weighted spin-echo (SE) sequence, and a T1-weighted breath-hold FLASH sequence. Whereas snapshot FLASH images in both pulse sequences were free from physiological motion artifacts, SE and FLASH images showed respiratory artifacts in some patients. Quantitative analysis of IFA snapshot FLASH images at low hepatic and low lesion signal revealed both superior lesion-liver signal-difference-to-noise ratio (SD/N) and superior contrast compared with standard snapshot FLASH without additional artifacts. Unless motion artifacts were evident, SE and FLASH images showed a higher anatomic resolution but lower SD/N and lower contrast than IFA snapshot images. Because of its superior SD/N and contrast, IFA snapshot FLASH will likely widen the application of fast MR imaging techniques.

Humans↗

Approach to high-resolution ex situ NMR spectroscopy.

Nuclear magnetic resonance (NMR) experiments are typically performed with samples immersed in a magnet shimmed to high homogeneity. However, there are many circumstances in which it is impractical or undesirable to insert objects or subjects into the bore of a high-field magnet. Here we present a methodology based on an adaptation of nutation echoes that provides resolved spectra in the presence of matched inhomogeneous static and radiofrequency fields, thereby opening the way to high-resolution ex situ NMR. The observation of chemical shifts is regained through the use of multiple-pulse sequences of correlated, composite z-rotation pulses, producing resolved NMR spectra of liquid samples.

Magnetic Resonance Spectroscopy↗

Spectral Talbot phenomena of frequency combs induced by cross-phase modulation in optical fibers.

Cross-phase modulation (XPM) of a frequency comb (finite-duration optical pulse sequence) by an intense, long Gaussian pump pulse is theoretically investigated, and new effects, namely, frequency-domain self-imaging phenomena (integer and fractional Talbot effects), are reported. The conditions favorable for observing spectral self-imaging phenomena by XPM are derived and numerically confirmed. The effects of nonidealities in a practical experiment (e.g., group-delay walk-off and dispersion) are also evaluated. One can use spectral self-imaging to tune the free spectral range of a frequency comb (without affecting the shape and bandwidth of the individual passbands) simply by adjusting the pump power in a fiber XPM scheme.

Journal Article↗

Comparative gas phase and pulsed liquid phase sequencing on a modified Applied Biosystems 477A sequencer.

A simple and inexpensive modification of the Applied Biosystems 477A sequencer, to run in the pulsed liquid-phase and in the gas-phase mode of the Edman chemistry, is described. This modification is especially useful for sequencing samples on polyvinylidene difluoride (PVDF) membranes. Additional carriers are required if a sample on a PVDF membrane is sequenced with the pulsed liquid-phase degradation program of the 477A. In the gas-phase mode no such carriers are needed. This eliminates time-consuming preconditioning sequencer cycles and reduces the sequencer background. In addition, initial coupling yields in the gas-phase mode exceeded those in the pulsed liquid-phase mode, whereas the average repetitive yields were similar. Samples spotted onto glass fiber filters pretreated with polybrene and samples spotted or electroblotted onto PVDF membranes were examined. A number of advantages of the gas-phase mode are presented.

Amino Acid Sequence↗

In vivo tumor lactate relaxation measurements by selective multiple-quantum-coherence (Sel-MQC) transfer.

The frequency-selective multiple-quantum-coherence (Sel-MQC) lactate (Lac) filter offers complete lipid and water suppression in a single scan for robust in vivo detection of tumor Lac, even in the presence of abundant lipids. Conversion of the detected signal into accurate tissue concentrations of Lac requires knowledge of in vivo Lac T1 and T2 relaxation times. This work reports modifications to the Sel-MQC pulse sequence, T1- and T2-Sel-MQC, that facilitate relaxation measurements of Lac. The T1-Sel-MQC sequence combines an inversion prepulse with the Sel-MQC filter. The T2-Sel-MQC sequence incorporates a CH3-selective 180 degrees pulse during the MQ preparation period to overcome the J-modulation effects and allow the insertion of variable echo delays. The performance of these sequences was evaluated with the use of phantoms and subcutaneous murine tumor models in vivo. The present approach will allow investigators to correct for the relaxation-induced Lac signal loss in Sel-MQC experiments for the quantitative mapping of in vivo tumor Lac distribution.

Animals↗