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Biomedical subjects

C T Moonen

Publications and source records attributed to C T Moonen.

At least 55 records · Page 3Linked to original sources

Evaluation of restricted diffusion in cylinders. Phosphocreatine in rabbit leg muscle.

Interpretation of NMR diffusion data is complicated in the presence of diffusion barriers. In this study, restricted diffusion in cylinders is evaluated. A method is presented to determine the diameter of the cylinder and the unrestricted diffusion coefficient from the dependence of the trace of the diffusion tensor with diffusion time. This method is valid even if the orientation of the cylinders is unknown and varies within the sample. An example is given for the diffusion of phosphocreatine in the cylindrically shaped fibers of rabbit skeletal muscle.

Animals↗

Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method.

Dynamic physiological scanning, based on temporary changes in local field homogeneity during the passage of a contrast agent bolus, has been performed hitherto with echo-planar imaging (EPI) or conventional gradient-recalled techniques (FLASH). Here, it is shown that the T2* sensitivity of conventional FLASH techniques can be improved drastically on a conventional whole body instrument by delaying the gradient-echo until the subsequent TR-period without increasing total imaging time. Examples are given for a full k-space matrix (128 x 256) obtained within 2 s with a TE of 25 ms, resulting in images free of artifacts. The method is applied to bolus tracking through the brain of healthy volunteers during visual stimulation and in the dark. An average increase of regional cerebral blood volume (rCBV) in the visual cortex of 10.9% (n = 9, p = .001) was found.

Blood Volume↗

19F magnetic resonance imaging of cerebral blood flow with 0.4-cc resolution.

19F magnetic resonance imaging techniques were used to determine "wash-in" and "wash-out" curves of the inert, diffusible gas CHF3 from 0.4-cc voxels in the cat brain, and mass spectrometer gas detection was used to determine the CHF3 concentration in expired air. These two sets of data were used to calculate cerebral blood flow values in the 0.4-cc voxels, and the blood flow images were registered with high-resolution 1H magnetic resonance images. Data were collected both during the wash-in and wash-out phases of the experiment, but the two sets of data were analyzed separately to obtain independent estimates of the blood flow during the two phases, i.e., Qin and Qout. Repeated determinations of cerebral blood flow images were performed in individual animals, and the entire protocol was repeated on five different animals. The average values of Qin and Qout for a typical 0.4-cc voxel in the parietal cortex were 83 ml 100 g-1 min-1 and 72 ml 100 g-1 min-1, respectively. Monte Carlo calculations utilizing the noise in the 19F NMR signal from this voxel predict an average standard deviation for Qin and Qout of +/- 10%. The average standard deviation for repeated measurements (in the same animal) of Qin and Qout in this voxel was +/- 14%. We conclude that 19F magnetic resonance imaging approaches have the potential to image cerebral blood flow in humans.

Animals↗

Fast echo-shifted gradient-recalled MRI: combining a short repetition time with variable T2* weighting.

The principles of a fast T2*-sensitized MR imaging method (Moonen et al., Magn. Reson. Med. 26, 184 (1992)) are extended to further increase T2* sensitivity. It is shown that the period of T2*-weighting can be lengthened by n TR-periods by appropriate gradient schemes without RF refocusing resulting in progressively delayed gradient-recalled echoes. This extension of the echo-shifting concept thus introduces large flexibility in the choice of T2*-weighting without changing total imaging time. The coherence pathway formalism is used to evaluate and describe the selection of the desired echo and the attenuation of unwanted coherences. The new techniques are demonstrated for tracking a bolus of susceptibility contrast agent in cat brain. Relative blood-volume maps are derived with expected contrast between white and gray matter.

Animals↗

Fast proton spectroscopic imaging of human brain using multiple spin-echoes.

We introduce a multi-echo multi-slice MR proton spectroscopic imaging method, which allows for a dramatic reduction of the measurement time by acquiring multiple spin-echoes within a single repetition time. In the multi-echo multi-slice experiment discussed in this paper, a threefold reduction in measurement time is obtained by sacrificing some spectral resolution. Signal-to-noise ratio and spatial resolution are preserved. Metabolite images of N-acetyl aspartate, and total choline+total creatine from multiple slices through the human brain are presented and compared with images obtained with a conventional single-echo multi-slice method.

Brain↗

In vivo proton spectroscopy and spectroscopic imaging of [1-13C]-glucose and its metabolic products.

Metabolism of [1-13C]-glucose was studied in situ in cat brain using gradient-enhanced proton-detected heteronuclear spectroscopy. Proton detection of [1-13C]-glucose, [3-13C]-lactate, 4-[13C]-glutamine, 4-[13C]-glutamate and the combined signals 2-[13C]-glutamate/glutamine and 3-[13C]-glutamate/glutamine was achieved, despite the fact that some of the associated proton resonances are close to the water signal. Two-dimensional [1H-13C]-spectra demonstrate the possibility of in situ spectral assignment with 1H sensitivity and 13C resolution. Spectroscopic images of glucose and its metabolic products were also acquired, showing the possibility to study spatial dependence of metabolism.

Animals↗

A functional MRI technique combining principles of echo-shifting with a train of observations (PRESTO).

We present a fast MRI technique sensitized to microscopic susceptibility effects. The method combines elements of echo-shifted gradient-recalled MR imaging (TE > TR) with the acquisition of multiple k-space lines within a single TR-period. The sequence results in a much reduced imaging time as compared with conventional gradient-echo MRI methods. The feasibility of the method is demonstrated for susceptibility bolus tracking in the cat brain using an imaging time of 153 ms. The relative cerebral blood volume maps created with this method are comparable with those obtained with conventional methods.

Animals↗

Measurement of brain activity with bolus administration of contrast agent and gradient-echo MR imaging.

This study was performed to measure changes in cerebral blood volume (CBV) associated with visual activation by use of bolus administration of contrast agent and conventional, clinically configured magnetic resonance (MR) hardware and software. Fast gradient-recalled acquisition in the steady state technique was used to study five healthy subjects during visual activation and a control dark state. MR images were obtained every 2.048 seconds for 2 minutes. A bolus of gadopentetate dimeglumine was injected during visual stimulation and darkness. Cine images produced from the series of rapid images clearly depicted arterial, capillary, and venous phases. Analysis of serial concentration maps derived from the rapid images revealed expected differences between the relative CBV of gray matter and that of white matter, as well as significantly increased relative CBV in calcarine cortex during visual activation versus the control state (mean increase, 15.24%; range, 6.41%-27.78%; P < .05). These results confirm those reported in echo-planar imaging studies and demonstrate that brain function can be assessed with the bolus method by means of MR imaging hardware and software with conventional clinical configurations.

Blood Volume↗

Multisection proton MR spectroscopic imaging of the brain.

The authors developed a hydrogen-1 proton magnetic resonance (MR) imaging method in which metabolic information is acquired by obtaining multiple sections through the brain. A spin-echo sequence is used for section selection, an octangular outer volume saturation pulse for lipid suppression, and a chemical-shift-selective saturation pulse for water suppression. High-quality maps of choline, creatine, and N-acetylaspartate were obtained in six studies performed in four volunteers. Water and lipid signal from the skull area was well suppressed by the pulse sequence used.

Adult↗

On the precision of diffusion/perfusion imaging by gradient sensitization.

Computer simulation is used to assess the precision and accuracy of diffusion and perfusion parameters derived from a set of gradient-sensitized images. Under ideal experimental conditions, a moderate signal-to-noise level (ca. 40) suffices to estimate diffusion coefficients to within 20% relative precision. However, estimation of a typical cerebral perfusion fraction of 5% to within 20% relative precision requires signal-to-noise levels of ca. 400. Simulations also show that systematic errors in perfusion fraction estimation, as well as underestimation of the uncertainties in perfusion parameters (by chi-squared analysis), will be found at moderate signal-to-noise levels.

Algorithms↗

In vivo 17O NMR study of rat brain during 17O2 inhalation.

In vivo 17O NMR has been used to monitor the H2(17)O concentration in rat brain during inhalation of 17O2. The results are discussed in terms of oxygen consumption in the brain and recirculation into the brain of H2(17)O produced in other organs.

Animals↗

A fast gradient-recalled MRI technique with increased sensitivity to dynamic susceptibility effects.

A fast imaging method that is based on gradient-recalled echoes of spins whose excitation and echo formation are separated by more than one TR period is presented. This method does not incorporate chemical-shift refocusing and thus results in drastically increased sensitivity to dynamic susceptibility effects, while maintaining a short total imaging time. The efficiency of the new technique is demonstrated in dynamic contrast-enhanced experiments (bolus tracking) in the cat brain using a duration of 600 ms for each image. Blood volume maps are derived with expected contrast between white and gray matter.

Animals↗

NMR studies on p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens and salicylate hydroxylase from Pseudomonas putida.

p-Hydroxybenzoate hydroxylase from Pseudomonas fluorescens and salicylate hydroxylase from Pseudomonas putida have been reconstituted with 13C- and 15N-enriched FAD. The protein preparations were studied by 13C-NMR, 15N-NMR and 31P-NMR techniques in the oxidized and in the two-electron-reduced states. The chemical shift values are compared with those of free flavin in water or chloroform. It is shown that the pi electron distribution in oxidized free p-hydroxybenzoate hydroxylase is comparable to free flavin in water, and it is therefore suggested that the flavin ring is solvent accessible. Addition of substrate has a strong effect on several resonances, e.g. C2 and N5, which indicates that the flavin ring becomes shielded from solvent and also that a conformational change occurs involving the positive pole of an alpha-helix microdipole. In the reduced state, the flavin in p-hydroxybenzoate hydroxylase is bound in the anionic form, i.e. carrying a negative charge at N1. The flavin is bound in a more planar configuration than when free in solution. Upon binding of substrate the resonances of N1, C10a and N10 shift upfield. It is suggested that these upfield shifts are the result of a conformational change similar, but not identical, to the one observed in the oxidized state. The 13C chemical shifts of FAD bound to apo(salicylate hydroxylase) indicate that in the oxidized state the flavin ring is also fairly solvent accessible in the free enzyme. Addition of substrate has a strong effect on the hydrogen bond formed with O4 alpha. It is suggested that this is due to the exclusion of water from the active site by the binding of substrate. In the reduced state, the flavin is anionic. Addition of substrate forces the flavin ring to adopt a more planar configuration, i.e. a sp2-hybridized N5 atom and a slightly sp3-hybridized N10 atom. The NMR results are discussed in relation to the reaction catalyzed by the enzymes.

4-Hydroxybenzoate-3-Monooxygenase↗

Complete separation of intracellular and extracellular information in NMR spectra of perfused cells by diffusion-weighted spectroscopy.

A method is outlined that completely separates intracellular and extracellular information in NMR spectra of perfused cells. The technique uses diffusion weighting to exploit differences in motional properties between intra- and extracellular constituents. This allows monitoring of intracellular metabolism, and of transport of small drugs and nutrients through the cell membrane, under controlled physiological conditions. As a first example, proton spectra of drug-resistant MCF-7 human breast cancer cells are studied, and uptake of phenylalanine is monitored.

Cell Membrane Permeability↗

Double-quantum surface-coil NMR studies of sodium and potassium in the rat brain.

Double-quantum filtered and conventional single-pulse sodium and potassium NMR spectra were obtained from in situ rat brain at 7.0 T. using a surface coil. In contrast to the ca. 14% decrease observed in single-pulse sodium NMR spectra upon death, increases as large as ca. 800% were observed in double-quantum filtered sodium spectra. Conversely, a ca. 26% increase was observed in single-pulse potassium spectra upon death, while double-quantum filtered potassium spectra decreased below the noise level, for the shortest preparation time used. The decay rate of double-quantum sodium coherence in the in situ rat brain after death was dependent upon the double-quantum preparation time: this behavior results from the nonuniformity of the brain, and may be related to physiological compartmentalization. The potential application to sodium NMR imaging of cerebral functionality is briefly discussed.

Animals↗

Restricted and anisotropic displacement of water in healthy cat brain and in stroke studied by NMR diffusion imaging.

The occlusion of the middle cerebral artery in cat brain was used as an experimental stroke model to investigate the physical basis of the recently reported lowered diffusion constant of water in acute infarcted brain tissue (Moseley et al., Magn. Reson. Med. 14, 330, 1990). The original findings were confirmed in this study of 12 animals investigated with the diffusion-sensitized stimulated echo sequence. The following additional results were obtained: First, the onset of significant lowering of the diffusion constant in the stroke area varied significantly (up to 2.5 h depending on the animal). Second, the affected area is much more clearly outlined in diffusion-weighted images than in T2-weighted images, even in the period between 3 to 12 h following occlusion. Third, for diffusion times between 50 and 2000 ms. the diffusion constant of water is independent of diffusion time in healthy tissue, as well as in the stroke area. Fourth, the diffusion anisotropy is similar in healthy and in stroke area and remains similar regardless of the diffusion time used.

Animals↗