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Biomedical subjects

W Dreher

Publications and source records attributed to W Dreher.

At least 19 recordsLinked to original sources

Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.

Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Animals

Fast proton spectroscopic imaging employing k-space weighting achieved by variable repetition times.

A k-space weighted spectroscopic imaging (SI) method is presented that allows a reduction in the total data acquisition time by up to 55% compared with standard SI. The k-space weighting is achieved by varying the repetition time, thus realizing an inherent apodization that corresponds to a circularly symmetric generalized Hamming filter. The flip angle is varied with the repetition time to enhance the signal-to-noise ratio. These techniques were employed using a short echo time of 10 ms. In vivo measurements on healthy rat brain at 4.7 T were conducted, obtaining two-dimensional spectroscopic imaging data from a 25 x 25 circularly reduced k-space area in as little as 5 min. The signal-to-noise ratio is sufficiently high to detect J-coupled resonances such as myo-inositol or glutamate/glutamine, demonstrating the ability to combine short acquisition times with comprehensive metabolic information. The T1 dependency of the apodization and the corresponding point spread function was evaluated by computer simulations. The achievable signal-to-noise ratio per unit time was compared with standard SI giving a parameter-dependent advantage of approximately 20% of the standard SI method.

Animals

On the use of two-dimensional-J NMR measurements for in vivo proton MRS: measurement of homonuclear decoupled spectra without the need for short echo times.

The potential of two-dimensional (2D)-J NMR for in vivo proton MRS is examined. Single voxel measurements on the rat brain were performed at 4.7 T using point-resolved spectrocopy localization with a voxel size of 64 microliter and total measuring times of 10-15 min. It is shown that a series of measurements with only 16 or fewer different echo times (TE) enables good signal localization in the f1 axis corresponding to the coupling patterns. For data evaluation, the 2D-J NMR spectrum as well as cross-sections at given f1 values and projections onto the f2 axis are used. A comparison between cross-section spectra taken at different f1 values may help to solve problems of peak assignment. The projection of the 2D magnitude spectrum onto the f2 axis corresponds to a homonuclear decoupled 1D proton spectrum. Because the T2 relaxation times of several coupled resonances (e.g., myo-inositol and glutamate) are rather long, only minor losses in the quality of the projection spectra occur if the measurements with short TE (< or = 50 ms) are not used for data processing. Thus, homonuclear decoupled proton spectra detecting uncoupled and several coupled resonances can be measured with high quality in vivo, even on MR systems that are not equipped with actively shielded gradients, prohibiting data acquisition with TEs of 50 ms or less.

Animals

Parametric multiecho proton spectroscopic imaging: application to the rat brain in vivo.

A parametric multiecho variant of proton spectroscopic imaging (SI) is presented using a multiecho SI sequence with uniform phase-encoding of all echoes within each echo train. The acquisition of SI data sets at different echo times (TE) increases the amount of information obtained within the same total measuring time as in standard SI measurements. The gain in information can be used: (a) to choose the most appropriate TE for each metabolite signal with respect to T2, spin coupling, or problems caused by peak overlap; (b) to measure the relaxation time T2 of metabolite signals with high spatial resolution; or (c) to improve the signal-to-noise ratio for metabolite signals with long T2 values by adding spectra calculated from consecutive echoes. The method was tested in vivo on healthy rat brain and applied to study metabolic changes in rat brain lesions.

Animals

Application of the maximum entropy method for evaluating phosphorus-31-magnetic resonance spectra in patients with liver metastases.

RATIONALE AND OBJECTIVES: The clinical feasibility and application of the maximum entropy method for data analysis from in vivo phosphorus-31-magnetic resonance (P-31-MR) spectra of the liver were determined. METHODS: Image-guided localized P-31-MR spectroscopy was performed in 24 patients with liver metastases and in 20 healthy volunteers. The spectra were obtained with a whole body scanner operating at 1.5 T using a surface coil. Phosphomonoester/beta-adenosine triphosphate (ATP), phosphodiester/beta-ATP, and inorganic phosphate/beta-ATP were calculated from the maximum entropy method-spectra and from spectra evaluated with standard data processing (Fourier transformation spectra). RESULTS: Phosphomonoester/beta-ATP and phosphodiester/beta-ATP were increased significantly with both methods in patients' spectra. Maximum entropy method spectra showed a distinct pattern with low noise. It was easier to determine peak borders and to attach resonances to the different metabolites using this method. CONCLUSIONS: Maximum entropy method is an alternative method for evaluation and quantification of P-31-MR spectra data and is preferred to standard data processing with Fourier transformation in cases of reduced signal-to-noise ratio of spectra.

Aged

Magnetization transfer affects the proton creatine/phosphocreatine signal intensity: in vivo demonstration in the rat brain.

The effect of off-resonance preirradiation on proton spectra acquired from the healthy rat brain at 4.7 T is examined using a PRESS sequence. The creatine/phosphocreatine (Cr/PCr) signal at 3.0 ppm decreases in signal intensity for offset frequencies between +/- 10 kHz. This cannot be explained by RF bleedover, but is attributed to magnetization transfer between two pools of Cr/PCr, one with a long T2 relaxation time giving the observed NMR signal, the other corresponding to a broad resonance line being completely or partially saturated by off-resonance preirradiation. Possible interpretations of these results are discussed.

Animals

Double-echo multislice proton spectroscopic imaging using Hadamard slice encoding.

Simultaneous multislice proton spectroscopic imaging (SI) is presented using a pulse sequence with multifrequency selective RF excitation and Hadamard encoding in the slice direction, and conventional Fourier phase encoding in the in-plane directions. Double-echo data acquisition is used to increase the spectral information of the experiment. Tests on a phantom demonstrate the quality of the slice selection. Results of in vivo measurements of the healthy rat brain show that spectra with a high signal-to-noise ratio can be acquired from four slices within 32 min. The measurements were performed at 4.7 T using a field of view of 32 x 32 mm2, a slice thickness of 3 mm, and a voxel size of 12 microliters. The proposed method is a useful alternative to sequential multislice SI and 3D SI. Furthermore, it is possible to combine sequential and simultaneous multislice SI.

Animals

Fast perfluorocarbon imaging using 19F U-FLARE.

The application of an ultra-fast low angle RARE technique for the 19F imaging of perfluorocarbons (PFCs) used as temporary blood substitutes is described. This sequence is attractive for fast 19F imaging studies that measure the biodistribution of PFCs in vivo, due to its high signal-to-noise ratio. Extensions of this technique for the chemical shift selective measurement of fluorine T1 values are presented. Using the linear dependence between the oxygen partial pressure (pO2) and the T1 relaxation rate of PFC resonances this technique makes possible the fast in vivo measurement of oxygen tension. Using the sequence in a diffusion sensitized form 19F measurements of the diffusion constants of PFCs are also presented. Phantom experiments to test the methods, and in vivo images obtained in rat studies are given and discussed.

Animals

Fast proton spectroscopic imaging using the sliced k-space method.

The use of one-shot imaging methods for proton spectroscopic imaging (1H-SI) is examined. In particular the acquisition of Kx x Ky x Nt data points by means of Nt excitations, each acquiring a Kx x Ky k-space slice, is advocated. A number of strategies for realising this experiment, and combining it with water suppression and volume-selection are proposed. The practical implementation at 4.7 T for 1H-SI of the rat brain is described. Experimental results from a 32 x 32 spatial matrix with Nt = 64 are presented. Spectra obtained from volumes as low as 3.5 microliters and within measuring times of as little as 3.8 min are shown. In these choline, creatine/phosphocreatine and N-acetylaspartate are all clearly visible.

Animals

19F chemical shift imaging in perfluorocarbons.

The use of 19F chemical shift sensitive imaging techniques to monitor the biodistribution of perfluorocarbons (PFC) is discussed. For these experiments one has to study the spectroscopic properties of the PFC to be mapped for choosing high performance NMR imaging sequences. Three techniques used in our laboratory, a chemical shift selective approach, a method using spectrum simplification and a chemical shift sensitive NMR imaging method using adjusted phase encoding are discussed and illustrated by experiments.

Animals

Pulse sequence and parameter choice in NMR imaging as a problem of constrained multidimensional nonlinear optimization.

The advantage of the multiparametric nature of NMR imaging is connected with the problem of finding optimum pulse sequences and sequence parameters, which ensure a high contrast-to-noise ratio. For a given imaging task with m (m greater than or equal to 2) regions characterized by sets of NMR parameters (e.g., rho, T1, T2) two functions are proposed, which can be used to transform the search for an optimum pulse sequence into a problem of constrained multidimensional nonlinear optimization. The numerical algorithm is described and the results of two examples are presented and discussed. A short description of useful extensions of the proposed optimization approach, which are currently implemented, is given.

Magnetic Resonance Spectroscopy

Specifity and sensitivity of the inhibition of drug metabolism following inhalation of carbon disulphide-air mixtures.

A single 8-h exposure of adult female Wistar rats to 20 ppm carbon disulphide (CS2), the threshold limit value (TLV) in several countries, was sufficient to cause inhibition of the following drug-metabolizing reactions: formation of trichloroethanol and trichloroacetic acid from trichloroethylene (aliphatic C-hydroxylation), formation of 4-hydroxyantipyrine from antipyrine (quasi-aromatic C-hydroxylation), formation of acetaminophenol from acetanilid (aromatic C-hydroxylation) and phenacetin (oxidative odealkylation), respectively, and formation of 4-aminoantipyrine from aminopyrine (oxidative N-demethylation). The behaviour of these effects was dependent on the dose of CS2 administered in that the inhibitory process was enhanced when increasing the concentration to (50), 100, 200, and 400 ppm. The respective changes could be demonstrated by a short-duration (6-h) reduction in the urinary excretion of the metabolites. In the case of trichloroethylene the limitation in metabolite formation persisted for as long as 36 h due to the varying rate of formation of trichloroethanol and trichloroacetic acid. This deficiency in excretion was compensated in part during the subsequent elimination phase (up to 24 and 36 h, respectively), an observation which suggests the rapid reversibility of the alteration. As shown by the respective prolongation of the hexobarbital sleeping time in the rat, the side-chain oxidation of hexobarbital to ketohexobarbital was increasingly inhibited by rising concentrations of CS2 in the range of 20 to 400 ppm/8 h. On the basis of the present results it is concluded that CS2 also inhibits various oxygenases of the microsomal enzyme system. In adult female NMRI mice a significant inhibition of the microsomal procaine-hydrolyzing esterase of the liver was observed only after 400 ppm/8 h; however, this limitation did not affect the LD50 of procaine-HCl, particularly as the corresponding serum esterase activity also remained uninfluenced. The aromatic N-acetylation of sulphisomidine and the quasi-aromatic N-acetylation of 4-aminoantipyrine in rats failed to be significantly reduced by CS2 even after 400 ppm/8 h, nor did the same dose of CS2 affect the glucuronidation of 4-hydroxyantipyrine in the same animal species. It is concluded from the above results that the specificity and sensitivity of the inhibition of drug metabolism observed in small laboratory animals is probably similar to that prevailing in man. This assumption has already been substantiated for the oxidative N-demethylation of aminopyrine.

Acetanilides