Anne Ziegler

In Vivo, Ex Vivo, and In Vitro One‐ and Two‐Dimensional Nuclear Magnetic Resonance Spectroscopy of an Intracerebral Glioma in Rat Brain: Assignment of Resonances

Abstract: An in vivo study of intracerebral rat glioma using proton‐localized NMR spectroscopy showed important modifications of the spectra in the tumor as compared with the contralateral brain. To carry out the assignment of the resonances of the glioma spectra, tumoral and normal rat brain tissues were studied in vivo, ex vivo, and in vitro by one‐dimensional and two‐dimensional proton spectroscopy. N‐Acetylaspartate was found at an extremely low level in the glioma. The change of peak ratio total creatine/3.2 ppm peak was found to be due to a simultaneous decrease of the total creatine content and an increase of the 3.2 ppm peak. The 3.2 ppm resonance in the glioma spectra has been shown to originate from choline, phosphocholine, glycerophosphocholine, taurine, inositol, and phosphoethanolamine. The increase of the 3.2 ppm peak in the glioma was found to result from the increase of taurine and phosphoethanolamine contents. The peak in the 1.3 ppm region of the glioma spectra was due to both lactate and mobile fatty acids. Moreover, two‐dimensional spectroscopy of excised tissues and extracts showed the presence of hypotaurine only in the tumor.

Xenon-129 MR imaging and spectroscopy of rat brain using arterial delivery of hyperpolarized xenon in a lipid emulsion.

Hyperpolarized 129Xe dissolved in a lipid emulsion constitutes an NMR tracer that can be injected into the blood stream, enabling blood‐flow measurement and perfusion imaging. A small volume (0.15 ml) of this tracer was injected in 1.5 s in rat carotid and 129Xe MR spectra and images were acquired at 2.35 T to evaluate the potential of this approach for cerebral studies. Xenon spectra consistently showed two resonances, at 194.5 ppm and 199.0 ppm relative to the gas peak. The signal‐to‐noise ratio (SNR) obtained for the two peaks was sufficient (ranging from 12 to 90) to follow their time courses. 2D transverse‐projection xenon images were obtained with an in‐plane resolution of 900 μm per pixel (SNR range 8–15). Histological analysis revealed no brain damage except in two rats that had received three injections. Magn Reson Med 46:208–212, 2001.

2D-spatial/2D-spectral spectroscopic imaging of intracerebral gliomas in rat brain.

1H‐MR spectroscopy in vivo is often hampered by poor spectral resolution. Spectral overlap can be avoided with two‐dimensional spectroscopic techniques. Correlation peak imaging has been implemented to measure unambiguously the distribution of several metabolites in a rat brain glioma model. Acquisition‐weighted spectroscopic imaging reduced the experimental time and provided excellent spatial localization. The choice of an appropriate spectral acquisition window granted good sensitivity. Spectroscopic images presenting a full two‐dimensional spectrum in every image pixel were acquired in seven rats at 7 Tesla in 195 min, with a nominal voxel volume of 75 μl. Among other metabolites, the distribution of hypotaurine, phosphoethanolamine, alanine, and even glucose could be visualized both in the C6‐glioma and in the unaffected brain. Magn Reson Med 43:211–219, 2000.

In vivo 129Xe NMR in rat brain during intra-arterial injection of hyperpolarized 129Xe dissolved in a lipid emulsion

Hyperpolarized 129Xe was dissolved in a lipid emulsion and administered to anaesthetized rats by manual injections into the carotid (approximately 1-1.5 mL in a maximum time of 30 s). During injection, 129Xe NMR brain spectra at 2.35 T were recorded over 51 s, with a repetition time of 253 ms. Two peaks assigned to dissolved 129Xe were observed (the larger at 194 +/- 1 ppm assigned to intravascular xenon and the smaller at 199 +/- 1 ppm to xenon dissolved in the brain tissue). Their kinetics revealed a rapid intensity increase, followed by a plateau (approximately 15 s duration) and then a decrease over 5 s. This behaviour was attributed to combined influences of the T1 relaxation of the tracer, of radiofrequency sampling, and of the tracer perfusion rate in rat brain. Similar kinetics were observed in experiments carried out on a simple micro-vessel phantom. An identical experimental set-up was used to acquire a series of 2D projection 129Xe images on the phantom and the rat brain.

Global and regional cerebral blood flow measurements using NMR of injected hyperpolarized xenon-129

RATIONALE AND OBJECTIVES Xenon is an inert gas characterized by a nuclear halfspin and a high solubility in lipids. It appears to diffuse freely in biological tissues and, in particular, through the blood-brain barrier. Spin-exchange with optically pumped rubidiu mvapo rincrease sth enuclea rpolarizatio no f 129 Xe gas by several orders of magnitude above the polarization at thermal equilibrium, resulting in “hyperpolarized” (HP) xenon. HP xenon can be used as a magnetic resonance (MR) tracer because of its NMR-enhanced sensitivity combined with its high solubility. This HP tracer is a potential exogenous NMR probe for cerebral imaging studies. The purpose of this paper is to describe the preparation of this HP tracer and to demonstrate that it can be used in NMR for absolute cerebral perfusion measurements.

Localized 2D correlation spectroscopy in human brain at 3 T

The purpose of this study was to acquire a localized 2D (two-dimensional)1H correlation spectrum, in a volume of interest reasonably small, and within an experiment time compatible with clinical applications. A modified PRESS technique has been used. The last 180° pulse of the PRESS sequence has been converted into a 90° pulse for both refocusing and coherence transfer. 2D correlation spectroscopy was performed on healthy volunteers in a clinical magnet, at 3 T. within 34 min, for a voxel size of 27 cm3 This result makes it possible to consider clinical applications.

2D J-resolved spiral spectroscopic imaging at 7 T: Application to mobile lipid mapping in a rat glioma

Lactate (Lac) and mobile lipids (Lip), which are present in rat gliomas, are difficult to map because their 1H resonances overlap in the 1.3 ppm region. 2D J‐resolved spectroscopy enables proper separation of the two resonance lines. To obtain high‐spatial‐resolution mapping of Lac and Lip resonances within a reasonable experiment time, we coupled 2D J‐resolved spectroscopy with a fast spectroscopic imaging (SI) method, based on an out‐and‐in spiral k‐space description. The method was applied to a rat glioma at 7 T, and Lac and Lip maps were reconstructed. The duration of SI (2D spatial, 2D spectral) was 64 min for a theoretical in‐plane resolution of 1 × 1 mm, and a slice thickness of 2 mm (voxel size 8.2 μl, taking into account the point‐spread function (PSF)). Magn Reson Med 52:658–662, 2004.

Method to determine in vivo the relaxation time T1 of hyperpolarized xenon in rat brain.

The magnetic polarization of the stable 129Xe isotope may be enhanced dramatically by means of optical techniques and, in principle, hyperpolarized 129Xe MRI should allow quantitative mapping of cerebral blood flow with better spatial resolution than scintigraphic techniques. A parameter necessary for this quantitation, and not previously known, is the longitudinal relaxation time (T  1tissue ) of 129Xe in brain tissue in vivo: a method for determining this is reported. The time course of the MR signal in the brain during arterial injection of hyperpolarized 129Xe in a lipid emulsion was analyzed using an extended two‐compartment model. The model uses experimentally determined values of the RF flip angle and the T1 of 129Xe in the lipid emulsion. Measurements on rats, in vivo, at 2.35 T gave T  1tissue = 3.6 ± 2.1 sec (±SD, n = 6). This method enables quantitative mapping of cerebral blood flow. Magn Reson Med 49:1014–1018, 2003.

Out-and-in spiral spectroscopic imaging in rat brain at 7 T

With standard spectroscopic imaging, high spatial resolution is achieved at the price of a large number of phase‐encoding steps, leading to long acquisition times. Fast spatial encoding methods reduce the minimum total acquisition time. In this article, a k‐space scanning scheme using a continuous series of growing and shrinking, or “out‐and‐in,” spiral trajectories is implemented and the feasibility of spiral spectroscopic imaging for animal models at high B0 field is demonstrated. This method was applied to rat brain at 7 T. With a voxel size of about 8.7 μl (as calculated from the point‐spread function), a 30 × 30 matrix, and a spectral bandwidth of 11 kHz, the minimum scan time was 9 min 20 sec for a signal‐to‐noise ratio of 7.1 measured on the N‐acetylaspartate peak. Magn Reson Med 50:1127–1133, 2003.

Absolute metabolite quantification by in vivo NMR spectroscopy: IV. multicentre trial on MRSI localisation tests

The difference between the experimental and theoretical spatial response function (SRF) of a narrow tube with water is used for a localization test for magnetic resonance spectroscopic imaging (MRSI). From this difference a quantitative performance parameter is derived for the relative amount of signal within a limited region in the field of view. The total signal loss by the MRSI experiment and eddy currents is described by a parameter SL derived from the signal intensities of two echoes. Results of a European multi-centre trial show that this approach is suited for assessment of MRSI localization performance.