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Mapping the biodistribution and catabolism of 5-fluorouracil in tumor-bearing rats by chemical-shift selective 19F MR imaging.

A chemical-shift selective (CHESS) 19F MR imaging technique was used to map selectively the antineoplastic drug 5-fluorouracil (5-FU) and its major catabolite alpha-fluoro-beta-alanine (FBAL) in tumor-bearing rats. The pulse sequence employed a CHESS RF saturation pulse to suppress either the 5-FU or the FBAL resonance before the other component in the two-line 19F MR spectra was measured. Selective 5-FU and FBAL images with a spatial resolution of 10 x 10 x 15 mm3 (1.5 ml) were obtained in 40 min from six ACl rats with implanted Morris hepatoma. Because the transmitter frequency could always be set to the Larmor frequency of the 19F resonance employed for imaging, the images were free of chemical-shift artifacts in readout and slice-selection direction. Whereas FBAL appeared only in the liver, the kidneys, and the bladder, 5-FU could also be detected in all major organs and in the muscular system. In the Morris hepatomas, a small 5-FU uptake and no FBAL accumulation were measured. The CHESS 19F MRI technique provides useful physiological and biochemical data on the biodistribution of the antineoplastic drug 5-FU and on the different catabolic activities of the tissues.

Animals↗

Volume-selective water-suppressed proton spectra of human brain and muscle in vivo.

Volume-selective water-suppressed proton spectra were recorded from live human brain and muscle at 1.5T by combining a stimulated echo acquisition mode pulse sequence for localization and two saturation pulses for water suppression (Frahm et al., SMRM Abstracts, 1987). Metabolite signals were observed in voxels of size 4-64 cm3. Signals from -CH3 and beta-CH2 of N-acetylaspartate, =N-CH3 and =N-CH2 of phosphocreatine/creatine, -N(CH3)3 of choline and inositol protons were visible in the brain spectra from normal subjects. Differences in metabolite levels were observed between gray and white matters of brain from their water-suppressed spectra. Peaks from =N-CH3 of phosphocreatine/creatine and -N(CH3)3 of choline and carnitine were present in normal muscle spectra along with several resonances from fatty acyl chains.

Brain↗

1H NMR methods for the noninvasive study of metabolism and other processes involving small molecules in intact erythrocytes.

1H NMR methods are described with which resolved resonances can be obtained for many of the small molecules in intact erythrocytes. In one method, the more intense hemoglobin resonances are suppressed by transfer of saturation throughout the hemoglobin spin system by cross relaxation following a selective saturation pulse. In a second method, the hemoglobin resonances are eliminated with the spin-echo pulse sequence by using a between-pulse delay time long enough for complete elimination of the hemoglobin resonances by spin-spin relaxation. Selected examples of the study of erythrocyte biochemistry by 1H NMR are discussed.

Erythrocytes↗

HAT HMBC: a hybrid of H2BC and HMBC overcoming shortcomings of both.

A new 2D NMR experiment, HAT HMBC, that is a hybrid of H2BC and HMBC aims at establishing two-bond correlations absent in H2BC spectra because of vanishing (3)J(HH) coupling constants. The basic idea is to create an additional pi phase difference in the multiplet structure in HMBC peaks with respect to the (n+1)J(HH) coupling constant between the proton(s) attached to a (13)C and a (1)H separated by n bonds. Thus HMBC peaks associated with small J(HH) will be the most attenuated in a HAT HMBC spectrum in comparison to a regular HMBC spectrum, i.e. peaks associated with (n+1)J(HH) and (n)J(CH) will for n>2 usually be strongly attenuated. The HAT HMBC pulse sequences contain the same number of pulses as regular HMBC and are only a few milliseconds longer.

Algorithms↗

Pulsed cavitational ultrasound therapy for controlled tissue homogenization.

Methods were investigated to acoustically control the extent to which cavitation-mediated tissue homogenization is responsible for lesion formation in vitro. These results may guide potential therapeutic procedures that induce damage predominantly via mechanical disruption and, thereby, avoid limitations associated with thermal ablative modalities. Porcine myocardium was insonified at 750 kHz using pulse sequences consisting of high-amplitude pulses (22 MPa Pr) interleaved with variable-amplitude "sustaining" pulses (e.g., 6.9 MPa Pr), which were intended to provide sufficient acoustic input to maintain cavitation activity between primary pulses, but to increase the spatial peak temporal average intensity (I(SPTA)) only marginally. Using modest temporal-average intensities (e.g., I(SPTA) approximately 200 W/cm2), approximately 0.5 cm3 lesions were produced consisting of homogenate that could be irrigated away to reveal smooth cavities. The prevalence of homogenate in a given lesion was sensitive to both pulse-repetition frequency and sustaining pulse amplitude, suggesting the existence of optimum acoustic parameters for producing homogenized lesions largely via mechanical perturbation.

Animals↗

Low-frequency velocity correlation spectrum of fluid in a porous media by modulated gradient spin echo.

In addition to the fast correlation for local stochastic motion, the molecular velocity correlation function in a fluid enclosed within the pore boundaries features a slow long time-tail decay. Here we present its study by the NMR modulated gradient spin-echo method (MGSE) [1] on a system of water trapped in the space between the closely packed polystyrene beads. With MGSE pulse sequence, a repetitive train of RF pulses with interspersed gradient pulses periodically modulates the spin phase. It gives the spin echo attenuation proportional to a value of the molecular velocity correlation spectrum at the modulation frequency. Covering the frequency range between Hz and MHz, it is a complement to the quasi-elastic neutron scattering, and so a suitable technique for the investigation of low frequency molecular dynamics in fluids. In our experiment, it enables to extract the low frequency correlation spectrum of water molecules confined in porous media. The function exhibits a negative long time-tail characteristic (a low frequency decay of the spectrum), which can be interpreted as a molecular back scattering on boundaries. The results can be well fitted with the spectrum calculated from the solution of the Langevin equation for restricted diffusion (which exhibits an exponential decay) [2] as well as with the spectrum obtained when simulating the hydrodynamics of molecular motion constrained by capillary walls (which gives an algebraic decay) [3]. Despite much work on theories and simulation, which predict slow negative long time tail of molecular velocity correlation dynamics in confined fluids, the obtained velocity correlation spectrum is the first experimental evidence to confirm these effects. The obtained dependence of spin echo attenuation on time, gradient strength and modulation frequency is also the first experimental verification of the recently developed approach to the spin echo in porous media, that uses the spin phase average with the cumulant expansion to get the attenuation as a discord of spin spatial coherence [4].

Magnetic Resonance Spectroscopy↗

A simple scheme for the design of solvent-suppression pulses.

Excitation sculpting was first introduced as a way to efficiently suppress solvent signals. It requires a pulse sequence that acts as a null pulse at the solvent-resonance frequency and as an inversion pulse everywhere else. In this article, it is shown that such a goal can be achieved starting with "top-hat" inversion shaped pulses such as I-BURP-2 or gaussian cascade G3. The result is a Globally Antisymmetric Selective Pulse, or GASP. Numerical optimization was used to extend the performance of such pulses. Multifrequency signal suppression was shown to be possible through application of successive excitation sculpting modules.

Chromatography↗

Improved accuracy and consistency in T1 measurement of flowing blood by using inversion recovery GE-EPI.

Problems associated with techniques currently used to measure the T1 of flowing blood are evaluated and a method to improve the consistency and repeatability of measurements is presented. Similar to some currently used techniques, the pulse sequence employs a nonselective adiabatic inversion pulse followed by a series of ECG-gated gradient echo EPI (echo planar imaging) images to obtain images where the blood (fluid) signal exhibits a T1-dependent inversion recovery signal from which the spin lattice relaxation constant (T1) of the flowing fluid can be measured. The new method combines curve fitting with a measure of the curve null point to acquire more accurate and consistent T1 values. Simulation and experimental results show that this combined fitting-nulling method is more stable and consistent in measuring the T1 of flowing fluid. The feasibility of temperature measurement of a flowing fluid based on the temperature dependence of the T1 of water protons is shown in this paper. ECG gating is used to reduce the effects of cyclic intensity changes for measurement of T1 in pulsatile flowing blood.

Blood Flow Velocity↗

Conventional and cross-correlation brain-stem auditory evoked responses in the white leghorn chick: rate manipulations.

Rate-dependent changes in the chick brain-stem auditory evoked response (BAER) using conventional averaging and a cross-correlation technique were investigated. Five 15- to 19-day-old white leghorn chicks were anesthetized with Chloropent. In each chick, the left ear was acoustically stimulated. Electrical pulses of 0.1-ms duration were shaped, attenuated, and passed through a current driver to an Etymotic ER-2 which was sealed in the ear canal. Electrical activity from stainless-steel electrodes was amplified, filtered (300-3000 Hz) and digitized at 20 kHz. Click levels included 70 and 90 dB peSPL. In each animal, conventional BAERs were obtained at rates ranging from 5 to 90 Hz. BAERs were also obtained using a cross-correlation technique involving pseudorandom pulse sequences called maximum length sequences (MLSs). The minimum time between pulses, called the minimum pulse interval (MPI), ranged from 0.5 to 6 ms. Two BAERs were obtained for each condition. Dependent variables included the latency and amplitude of the cochlear microphonic (CM), wave 2 and wave 3. BAERs were observed in all chicks, for all level by rate combinations for both conventional and MLS BAERs. There was no effect of click level or rate on the latency of the CM. The latency of waves 2 and 3 increased with decreasing click level and increasing rate. CM amplitude decreased with decreasing click level, but was not influenced by click rate for the 70 dB peSPL condition. For the 90 dB peSPL click, CM amplitude was uninfluenced by click rate for conventional averaging. For MLS BAERs, CM amplitude was similar to conventional averaging for longer MPIs.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Effects of stimulus rate on the feline brain-stem auditory evoked response during development. I. Peak latencies.

The effects of stimulation rate on the brain-stem auditory evoked response (BAER) of developing and adult cats were investigated. Age ranged from 10-post-natal days to young adults. Clicks were presented at levels of 90 dB pSPL and 20 dB above each animal's click threshold (20 dB SL). For all animals, a conventional BAER rate series was obtained at rates of 5, 10, 30, 60, and 90 Hz. BAERs were also obtained using pseudorandom pulse sequences called maximum length sequences (MLSs). The minimum time between pulses, the minimum pulse interval (MPI), included 0.5, 1, 2, 4, and 6 ms, which correspond to average rates of 1000, 500, 250, 125, and 83 Hz, respectively. Dependent variables included the latencies of the first four BAER peaks, labeled i through iv. MLS BAERs were indistinguishable from conventional BAERs at all ages studied. In general, for both conventional and MLS BAERs, peak latencies and the i-iv interval increased with increasing stimulus rate. Although absolute peak latencies and the i-iv interval decreased systematically with age, the relative shift in latency and i-iv interval induced by increasing stimulus rate decreased during development. The enhanced sensitivity to stimulus rate observed at younger ages was not the consequence of the threshold improvement that occurs during development since similar observations were made when stimuli were presented at a constant absolute level (90 dB pSPL) or at a constant level above threshold (20 dB SL). In addition, successive BAER peaks exhibited progressively larger latency shifts with increasing stimulus rate at all ages studied. These data suggest that higher stimulus rates produce greater neural adaptation resulting in prolonged BAER peak latencies. Furthermore, the effects of adaptation are cumulative across synapses, and the mechanisms responsible for the acquisition of adult-like adaptation properties develop during the early post-natal period in the cat.

Animals↗

Application of NMR screening techniques for observing ligand binding with a protein receptor.

Water ligand observed via gradient spectroscopy (WaterLOGSY), saturation transfer difference and NOE pumping NMR techniques were used to identify ligand binding with a receptor. Although these experiments were originally designed to observe ligands in complexes, their application is limited by the affinity of ligands towards target molecules. Here the improved WaterLOGSY pulse sequence was developed by incorporating the double pulsed field gradient spin-echo and gradient-tailored excitation WATERGATE sequences. The efficiency of these ligand-observed NMR screening techniques was investigated using the ribonuclease T1-inhibitor system.

Binding Sites↗

Characterization and prediction of gradient acoustic noise in MR imagers.

Gradient acoustic noise has been measured and characterized for an epoxy-potted, shielded gradient assembly in a 1.5 T MRI system. Noise levels vary by 10 dB or more as a function of longitudinal position in the scanner and reflect the pattern of forces applied to the gradient assembly. The noise level increases slightly (1-3 dB) with a patient in the scanner. The spectrum of the noise is similar (but not identical) to the spectrum of the input signal. A gradient-pulse-to-acoustic-noise transfer function was obtained by using a white noise voltage input to the gradient system. The transfer function enabled us to accurately predict acoustic noise output for a pulse sequence consisting of a series of trapezoidal pulses on a single axis and for a clinical fast spin echo sequence with gradients present on all three axes.

Humans↗

Calibration of the radio frequency field for magnetic resonance imaging.

We have developed and validated the performance of a novel slice selective pulse sequence that allows direct calibration of the RF field using a simple rectangular pulse. The new sequence offers a number of substantial advantages. It operates at steady state and has an accurate calibration response at short repetition times. The slice selection train is insensitive to RF field strength changes caused by patient loading. The issue of patient motion has been addressed in our data collection and analysis routines. The applicability of the method to human scanning has been demonstrated in the automated RF power calibration routine of a commercial imaging system.

Algorithms↗

A comparative evaluation of "depth pulses" and related sequences for spatial discrimination in in-vivo NMR spectroscopy with surface coils.

The performance of a range of "depth pulses" and related pulse sequences for achieving enhanced spatial resolution in surface coil magnetic resonance spectroscopy (MRS) has been compared both experimentally and by computer simulation. A detailed analysis of the spatial selectivity of these sequences both on- and off-resonance suggests that the problem of combining good spatial resolution with adequate bandwidth has yet to be fully resolved. These and related problems, such as the shape of the sensitive volume and its dependence on resonance offset, are likely to limit the use of depth pulses, particularly where alternative methods of spatial selection are available.

Animals↗

LR-CAHSQC: an application of a Carr-Purcell-Meiboom-Gill-type sequence to heteronuclear multiple bond correlation spectroscopy.

A new pulse sequence, long-range CPMG-adjusted heteronuclear single quantum coherence (LR-CAHSQC), is proposed for the determination of long-range JCH coupling constants from a long-range 1H-13C correlation experiment. The long-range heteronuclear coupling constants can be directly extracted from COSY-type antiphase peak patterns. The current approach utilizes CPMG-sequences for polarization transfer, and thus avoids the evolution of homonuclear JHH couplings, which normally may introduce abnormalities into the cross peak pattern. The differences between LR-CAHSQC and normal LR-HSQC are discussed.

Algorithms↗

Actual flip-angle imaging in the pulsed steady state: a method for rapid three-dimensional mapping of the transmitted radiofrequency field.

A new method has been developed for fast image-based measurements of the transmitted radiofrequency (RF) field. The method employs an actual flip-angle imaging (AFI) pulse sequence that consists of two identical RF pulses followed by two delays of different duration (TR(1) < TR(2)). After each pulse, a gradient-echo (GRE) signal is acquired. It has been shown theoretically and experimentally that if delays TR(1) and TR(2) are sufficiently short and the transverse magnetization is completely spoiled, the ratio r = S(2)/S(1) of signal intensities S(1) and S(2), acquired at the beginning of the time intervals TR(1) and TR(2), depends on the flip angle (FA) of applied pulses as r = (1 + n * cos(FA))/(n + cos(FA)), where n = TR(2)/TR(1). The method allows fast 3D implementation and provides accurate B(1) measurements that are highly insensitive to T(1). The unique feature of the AFI method is that it uses a pulsed steady-state signal acquisition. This overcomes the limitation of previous methods that required long relaxation delays between sequence repetitions. The method has been shown to be useful for time-efficient whole-body B(1) mapping and correction of T(1) maps obtained using a variable FA technique in the presence of nonuniform RF excitation.

Adult↗

Two-dimensional excitation short echo time chemical shift imaging at 0.5 tesla.

Detection of short T2 metabolites such as glutamate and glutamine (glx) in the brain can be improved by minimizing the echo time (TE) of the pulse sequence. By combining two dimensions of localization during a single radiofrequency (RF) pulse, an elliptic excitation chemical shift imaging sequence (EECSI) that further reduces TE by a factor of 2 relative to a TE-optimized point resolved spectroscopy sequence chemical shift imaging sequence was developed. An additional set of outer volume saturation pulses is included to minimize the contamination from scalp and marrow space lipids. The sequence runs with conventional gradient hardware (1 G/cm, 17 T/m/s slew rate) at 0.5 T. The increase in the fitted areas of beta,gamma multiplet of glutamate and glx in a brain-mimicking phantom was by a factor of 1.66. In the thalamus of healthy volunteers, glx was increased by 1.44. Combined with the field strength-related improvements in glutamate and glx detection previously demonstrated at 0.5 T, EECSI offers further improvements for imaging glutamate and glx in vivo.

Brain↗

Rapid repetition of the "burst" sequence: the role of diffusion and consequences for imaging.

When the Burst pulse sequence (Hennig et al. MAGMA 1, 39-48 (1993)) is applied with elementary pulses of finite flip angle, a non-uniform longitudinal magnetization is created, in the form of a series of fine bands of saturated spins. Both during and after the pulse train, the molecules contained within these bands diffuse. In this paper a full description is given of the evolution of the non-uniform longitudinal magnetization subsequent to the pulse train and the theory is verified experimentally. The value of the diffusion coefficient influences strongly the signal obtained when the Burst sequence is repeated rapidly. The consequences of this for imaging are discussed and, in particular, for the so-called "frequency-shifted" Burst technique.

Humans↗