Biomedical subjects

W Dreher

Publications and source records attributed to W Dreher.

At least 19 recordsLinked to original sources

PubMed2001

Changes in apparent diffusion coefficients of metabolites in rat brain after middle cerebral artery occlusion measured by proton magnetic resonance spectroscopy.

Diffusion-weighted proton MR spectroscopy and imaging have been applied to a rat brain model of unilateral middle cerebral artery occlusion between 1 and 4 hr post occlusion. Similar apparent diffusion coefficients (ADC) of most metabolites were observed within each hemisphere. In the ischemic ipsilateral hemisphere, the ADCs were (0.083--0.116). 10(-3) mm(2)/sec for lactate (Lac), alanine (Ala), gamma-amino butyric acid (GABA), N-acetyl aspartate (NAA), glutamine (Gln), glutamate (Glu), total creatine (tCr), choline-containing compounds (Cho), and myo-inositol (Ins), in the contralateral hemisphere (0.138--0.158). 10(-3) mm(2)/sec for NAA, Glu, tCr, Cho, and Ins. Higher ADCs was determined for taurine (Tau) in the ipsilateral (0.144. 10(-3) mm(2)/sec) and contralateral (0.198. 10(-3) mm(2)/sec) hemisphere. In the ischemic hemisphere, a relative ADC decrease to 65--75% was observed for NAA, Glu, tCr, Cho, Ins and Tau, which was similar to the decrease of the water ADC (to 67%). The results suggest a common cause of the observed ADC changes and provide a broader experimental basis to evaluate theories of water and metabolite diffusion. Magn Reson Med 45:383-389, 2001.

Animals↗

PubMed2000

Isolation of n-decyl-alpha(1-->6) isomaltoside from a technical APG mixture and its identification by the parallel use of LC-MS and NMR spectroscopy

The identification of n-decyl alpha(1-->6)isomaltoside as a main component of technical alkyl polyglucoside (APG) mixtures by the parallel use of liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy is described. Following enrichment on a styrene-divinylbenzene-based solid-phase extraction material, unknown components were separated by reversed-phase liquid chromatography (LC). Chemical characterization was achieved by both mass spectrometry and NMR spectroscopy. It is demonstrated that the combination of LC-MS with various NMR techniques is very suitable for stereochemical assignment of unknown components in technical APG mixtures.

Journal Article↗

PubMed2000

Fast echo planar based correlation-peak imaging: demonstration on the rat brain in vivo.

Two-dimensional correlation spectroscopy (2D-COSY) was combined with a fast echo planar based spectroscopic imaging technique in a new sequence. It can be optimized according to the coupling patterns of particular metabolites by using a constant time (CT) variant of COSY with chemical shift selective excitation and refocusing. Experiments were performed with an evolution time of 110 ms which was determined by simulating the CT-COSY experiment at several evolution times for the spin systems of myo-inositol (Ins) and taurine (Tau). The sequence has a minimum total measurement time of 17 min and was tested on a spherical phantom filled with a solution of Ins. The in vivo application of this method on the healthy rat brain demonstrates its improved spectral resolution as cross-peak signals from both Ins and Tau can be separated clearly. Magn Reson Med 44:23-28, 2000.

Animals↗

PubMed2000

A new method for fast proton spectroscopic imaging: spectroscopic GRASE.

A new fast spectroscopic imaging method is presented which allows both a very short minimum total measurement time and effective homonuclear decoupling. After each excitation, all data points from N(GE) k(x)-k(y)-slices at different k(omega)-values are acquired by using a gradient and spin echo (GRASE) imaging sequence. The delay between consecutive gradient echoes, which are measured with uniform phase encoding between consecutive refocusing alpha-pulses, is the inverse of the spectral width (SW). A refocusing 180 degrees pulse, which is applied within a constant delay between excitation and the GRASE sequence, is shifted in a series of measurements by an increment N(GE)/(2 * SW) to cover the whole k(omega)-k(x)-k(y)-space. Spectroscopic GRASE was implemented on a 4.7 T imaging system and tested on phantoms and normal rat brain in vivo. Measurements were performed with a nominal voxel size of 1.5 x 1.5 x 3 mm(3) and a spatial 64 x 64 matrix. The total measurement time was 2 or 4 min using a repetition time of 1.9 sec, 96 chemical shift encoding steps, SW = 800 Hz, N(GE) = 3, and 2 or 4 accumulations.

Animals↗

PubMed2000

A fast variant of (1)H spectroscopic U-FLARE imaging using adjusted chemical shift phase encoding.

So far, fast spectroscopic imaging (SI) using the U-FLARE sequence has provided metabolic maps indirectly via Fourier transformation (FT) along the chemical shift (CS) dimension and subsequent peak integration. However, a large number of CS encoding steps N(omega) is needed to cover the spectral bandwidth and to achieve sufficient spectral resolution for peak integration even if the number of resonance lines is small compared to N(omega) and even if only metabolic images are of interest and not the spectra in each voxel. Other reconstruction algorithms require extensive prior knowledge, starting values, and/or model functions. An adjusted CS phase encoding scheme (APE) can be used to overcome these drawbacks. It incorporates prior knowledge only about the resonance frequencies present in the sample. Thus, N(omega) can be reduced by a factor of 4 for many (1)H in vivo studies while no spectra have to be reconstructed, and no additional user interaction, prior knowledge, starting values, or model function are required. Phantom measurements and in vivo experiments on rat brain have been performed at 4.7 T to test the feasibility of the method for proton SI.

Animals↗

PubMed1999

Combining CW and pulsed saturation allows in vivo quantitation of magnetization transfer observed for total creatine by (1)H-NMR-spectroscopy of rat brain.

Selective saturation of bound nuclei attenuates the MR visible CH(2) and the CH(3) signal of total creatine (tCr) in rat brain in vivo. The low contrast to noise ratio achieved during the limited experiment time makes it difficult to quantify the effect. It is shown that by combining data from continuous-wave and pulsed saturation experiments, quantitation is possible using the standard magnetization transfer model. The model parameters obtained are the transverse relaxation time of the bound spin fraction B, T2R = 31 +/- 8 micros, the exchange rate r(x) = 0.36 +/- 0.04 s(-1), and the concentration ratio of bound nuclei taking part in the exchange to free tCr magnetization, f = M0B/M0A = 0.04 +/- 0.01. The phenomenon can be explained by either an intermolecular exchange of free and bound creatine molecules or by through-space interaction with bound nuclei showing not necessarily the same chemical shift. Magn Reson Med 42:222-227, 1999.

Algorithms↗

PubMed1999

Detection of homonuclear decoupled in vivo proton NMR spectra using constant time chemical shift encoding: CT-PRESS.

A new pulse sequence, termed CT-PRESS, is presented, which allows the detection of in vivo 1H NMR spectra with effective homonuclear decoupling. A PRESS sequence with a short echo-time TE, used for spatial localization, is supplemented by an additional 180 degrees pulse. The temporal position of this 180 degree pulse is shifted within a series of experiments, while the time interval between signal excitation and detection is kept constant. CT-PRESS is a two-dimensional (2D) spectroscopic experiment as far as data acquisition and processing are concerned, although only diagonal signals are generated in the 2D spectrum. However, since the principle of constant time chemical shift encoding is used in the t1 domain, effective homonuclear decoupling is obtained by projecting the 2D spectrum onto the corresponding f1 axis. Thus, good spectral resolution and high signal-to-noise ratio are obtained. The main advantage, as compared to localized 2D J-resolved MRS, is that optimized experiments can be performed for coupled resonances of interest by choosing the sequence parameters dependent on the type of multiplets, the J-coupling constants and T2. Major fields of application will be parametric studies on coupled resonances, (e.g., T1, diffusion behavior or magnetization transfer) and/or the detection of spatial and temporal changes of metabolites with coupled spin systes.

Animals↗

PubMed1999

Improved proton spectroscopic U-FLARE imaging for the detection of coupled resonances in the rat brain in vivo.

Modifications of the pulse sequence for spectroscopic U-FLARE imaging are discussed to detect not only the predominant singlet signals of N-acetylaspartate, total creatine, and choline containing compounds or the doublet signal of lactate, but also the coupled resonances of glutamate, glutamine, taurine and myo-inositol. Effective homonuclear decoupling is achieved by use of constant time chemical shift encoding. A maximum signal-to-noise ratio (SNR) can be obtained for a certain coupled resonance of interest by optimizing the evolution period t(c) of the J modulated spin echo. Good reproducibility and a high SNR were achieved by combining several methods for water suppression and by using the displaced variant of U-FLARE. Measurements of a 3 mm slice of the rat brain were performed in vivo within 4 min, giving a nominal voxel size of 1.5 x 1.5 x 3.0 mm3 or 1.5 x 0.75 x 3.0 mm3. Thus, optimized spectroscopic U-FLARE is a powerful tool for proton spectroscopic imaging with high spectral, spatial and temporal resolution.

Animals↗

PubMed1999

Homonuclear uncoupled 1H-spectroscopy of the human brain using weighted accumulation schemes.

Homonuclear uncoupled H-spectroscopy based on 2-dimensional (2D) J-resolved spectroscopy is a well suited technique for the assessment of J-coupled metabolite resonances. In comparison with 1-dimensional H-spectroscopy this technique largely reduces problems due to spectral overlap between low molecular weight metabolite resonances and superimposed broad macromolecule resonances, as well as overlap between adjacent multiplets. Usually, 2D J-resolved spectroscopic data were acquired using a constant number of accumulations for each of the various echo times. In contrast to this, a weighted accumulation scheme has been applied in this study, using an echo time dependent number of accumulations. The aims of this modification were to reduce the acquisition time and to improve the signal-to-noise ratio per unit acquisition time (SNRt). Four different sine-bell like accumulation schemes and a reference scheme using a constant number of accumulations have been applied on five normal volunteers. Localized spectra obtained from the parieto-occipital white matter were compared with regard to SNRt and linewidth. A reduction in acquisition time of 45%, related to the reference scheme, and an increase in SNRt of 25-30% were achieved using a sine-bell accumulation scheme in combination with a quarter sine-wave apodization of the short echo time data. Down to an acquisition time of 122 s no significant line broadening has been observed in comparison with the reference scheme.

Brain↗

PubMed1999

Fast spectroscopic imaging for non-invasive thermometry using the Pr[MOE-DO3A] complex.

The praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-tr iacetate) was evaluated as a temperature-sensitive contrast agent using the temperature dependence (approximately 0.12 ppm degrees C(-1)) of the chemical shift of its methoxy side group signal. Pr[MOE-DO3A] was employed in combination with spectroscopic imaging (SI) methods for the determination of spatially resolved 2D and 3D temperature distributions in phantoms. Conventional SI and fast echo planar SI sequences (EPSI) were implemented on a 4.7 T MR imaging system fulfilling the demands for non-invasive thermometry (NIT) with respect to thermal and temporal resolution, being <1 degree C and <20 s total measuring time, respectively. The sequences are based on a fast spin echo SI method taking into account the very short relaxation times of the Pr complex methoxy group (T1 = 28 ms, T2 = 13 ms) and its chemical shift difference (-24 ppm) from water. Calibration curves were measured in a uniformly heated water phantom and 2D SI methods were applied to dynamic heating experiments. The average differences between the temperatures measured via fibreoptic thermometer and those derived from the spectroscopic methods were < or =0.2 degrees C. Furthermore, 3D EPSI experiments with a 16 x 16 x 16 matrix size yielded temperature measurements within 17 s from voxels of size 3 x 3 x 3 mm3.

Calibration↗

PubMed1998

Restricted diffusion and exchange of intracellular water: theoretical modelling and diffusion time dependence of 1H NMR measurements on perfused glial cells.

Intracellular diffusion properties of water in F98 glioma cells immobilized in basement membrane gel threads, are investigated with a pulsed-field-gradient spin-echo NMR technique at diffusion times from 6 to 2000 ms and at different temperatures. In extended model calculations the concept of 'restricted intracellular diffusion at permeable boundaries' is described by a combined Tanner-Kärger formula. Signal components in a series of ct experiments (constant diffusion time) are separated due to different diffusion properties (Gaussian and restricted diffusion), and physiological as well as morphological cell parameters are extracted from the experimental data. The intracellular apparent diffusion coefficients strongly depend on the diffusion time and are up to two orders of magnitude smaller than the self diffusion constant of water. Propagation lengths are found to be in the range of 4-7 microns. Hereby intracellular signals of compartments with a characteristic diameter could be selected by an appropriate gradient strength. With cg experiments (constant gradient) a mean intracellular residence time for water is determined to be about 50 ms, and the intrinsic intracellular diffusion constant is estimated to 1 x 10(-3)mm2/s. Studying the water diffusion in glial cells provides basic understanding of the intracellular situation in brain tissue and may elucidate possible influences on the changes in the diffusion contrast during ischemic conditions.

Animals↗

PubMed1998

Magnetization transfer attenuates metabolite signals in tumorous and contralateral animal brain: in vivo observations by proton NMR spectroscopy.

Tumorous and contralateral rat brain was examined by in vivo single voxel proton NMR spectroscopy. Magnetization transfer (MT) experiments cause attenuation of various metabolite signals. Selective saturation of immobile metabolites was achieved by pulsed RF preirradiation. The method is compared with continuous wave MT generation. In contralateral tissue, MT attenuation is detected for both the CH3 and the CH2 protons of (phospho-)creatine (Cr + PCr) and for a signal at 3.44 ppm ascribed to taurine. Significant attenuation is also observed for a signal at 3.78 ppm that is commonly ascribed to the alphaCH proton of glutamate and glutamine (Glx); however, no effect is observed for the gammaCH2 protons of Glx. Within implanted F98 glioma tumors, only the CH3 signal of Cr + PCr shows significant MT attenuation. Although the MT effect detected for lactate in the tumors fails to reach significance, a significant effect is observed for the lactate signal acquired during 3 to 9 min postmortem.

Animals↗

PubMed1998

Temporal and regional changes during focal ischemia in rat brain studied by proton spectroscopic imaging and quantitative diffusion NMR imaging.

The early development of focal ischemia after permanent occlusion of the right middle cerebral artery (MCA) was studied in six rats using interleaved measurements by diffusion-weighted NMR imaging (DWI) of water and two variants of proton spectroscopic imaging (SI), multiecho SI (TE: 136, 272, 408 ms) and short TE SI (TE: 20 ms). Measurements on a 4.7-T NMR imaging system were performed between the control phase and approximately 6 h postocclusion. In the center of the ischemic lesion of all rats, the apparent diffusion coefficient (ADC) decreased rapidly to 84.4 +/- 4.2% (mean +/- SD) of the control values approximately 2 min postocclusion. Approximately 6 h postocclusion, the ADC was reduced to 67.1 +/- 5.9%. In contrast, large differences between the animals were observed for the temporal increase of lactate (Lac) in the ipsilateral hemisphere. The maximum Lac signal was reached in four rats after 0.5-1.5 h, and in two rats was not reached even after 6 h postocclusion. Six h postocclusion, SI spectra measured at a TE of 136 ms revealed a decrease in the CH3 signal of N-acetylaspartate (NAA) to 67 +/- 13% of the control values. Differences were observed between the spatial regions of decreased NAA and increased Lac. In the lesions, a T2 relaxation time of Lac of 292 +/- 40 ms, considering a J-coupling constant of 6.9 Hz, was measured. Furthermore, a prolongation of the T2 of the CH3 signal of creatine/phosphocreatine (Cr/PCr) was observed in the lesion, from 163 +/- 22 ms during control to 211 +/- 41 ms approximately 6 h postocclusion. The experiments proved that DWI and proton SI are valuable tools to provide complementary information on processes associated with brain infarcts.

Animals↗

PubMed1998

Water signal attenuation in diffusion-weighted 1H NMR experiments during cerebral ischemia: influence of intracellular restrictions, extracellular tortuosity, and exchange.

The "concept of restricted intracellular water diffusion at permeable boundaries", which was recently used to model diffusion-weighted 1H NMR experiments on glioma cells, was applied to measurements on the rat brain in vivo. Combined with the "concept of extracellular tortuosity", various physiological states of the brain were simulated. Hereby, a variable intracellular volume fraction, intracellular exchange time, and extracellular tortuosity factor were considered for young, adult, and ischemic rat brains. The model simulated the cytotoxic shift of extracellular water, changes in membrane permeability and tissue morphology, and was able to explain the diffusion time dependence as well as the non-monoexponentiality of the diffusion attenuation curves. Preliminary diffusion time dependent experiments on the healthy rat brain (1H NMR imaging) agreed well with the theoretical concept. Hereby, the intracellular water signal was separated from extracellular signal contributions by large diffusion weighting. It showed the characteristic of restricted diffusion as well as a signal decay due to the exchange of intracellular water across the plasma membrane. A map of the mean intracellular exchange time for water in living animal brain was determined, and the upper limit in rat brain was evaluated to 15 ms. The presented methods can be applied to correlate local differences in a map of exchange times with tissue morphology and to detect pathological deviations of the exchange time, e.g., during ischemia.

Animals↗

PubMed1998

Characterization of middle cerebral artery occlusion infarct development in the rat using fast nuclear magnetic resonance proton spectroscopic imaging and diffusion-weighted imaging.

A nuclear magnetic resonance study of the middle cerebral artery occlusion in the rat is presented. Experiments were performed on seven animals before and after occlusion, which occurred in situ. The emphasis in this study was on evaluating rapid proton spectroscopic imaging. Data were acquired with experimental durations of between 4 and 15 minutes for a 32 by 32 spatial matrix, with 64 spectroscopic data points per spatial element. The spectroscopic data were interleaved with diffusion-weighted nuclear magnetic resonance water images of the same slice. The study was terminated at about 6 hours after occlusion. The brains were then frozen in liquid nitrogen for biochemical imaging. The results showed that the signal from N-acetyl aspartate decreased and that of lactate increased within the infarcted region. The temporal course of these intensity changes varied between animals. Nineteen cortical spreading depressions (CSD) were observed by electrophysiologic monitoring during the experiments. Of these, 11 could be unambiguously detected in the lactate images, and a further 3 were on the threshold of detectability. As only a single slice could be examined, it is possible that the centers of depression for the remaining 6 CSD were outside the slice. To the authors' knowledge, this is the first report of the measurement of CSD using proton spectroscopic imaging. Thus, it is shown that this method is valuable not only in following the continuous evolution of proton metabolites with a good spatial and temporal resolution, but also in observing transient phenomena which are believed to play an important role in the expansion of the infarcted territory.

Animals↗

PubMed1996

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↗

PubMed1996

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↗

PubMed1995

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↗