Reinvestigating hyperpolarized (129)Xe longitudinal relaxation time in the rat brain with noise considerations.

The longitudinal relaxation time of hyperpolarized (HP) (129)Xe in the brain is a critical parameter for developing HP (129)Xe brain imaging and spectroscopy and optimizing the pulse sequences, especially in the case of cerebral blood flow measurements. Various studies have produced widely varying estimates of HP (129)Xe T(1) in the rat brain. To make improved measurements of HP (129)Xe T(1) in the rat brain and investigate how low signal-to-noise ratio (SNR) contributes to these discrepancies, we developed a multi-pulse protocol during the washout of (129)Xe from the brain. Afterwards, we applied an SNR threshold theory to both the multi-pulse protocol and an existing two-pulse protocol. The two protocols yielded mean +/- SD HP (129)Xe T(1) values in the rat brain of 15.3 +/- 1.2 and 16.2 +/- 0.9 s, suggesting that the low SNR might be a key reason for the wide range of T(1) values published in the literature, a problem that might be easily alleviated by taking SNR levels into account.

Signal-to-noise ratio comparison of encoding methods for hyperpolarized noble gas MRI.

Some non-Fourier encoding methods such as wavelet and direct encoding use spatially localized bases. The spatial localization feature of these methods enables optimized encoding for improved spatial and temporal resolution during dynamically adaptive MR imaging. These spatially localized bases, however, have inherently reduced image signal-to-noise ratio compared with Fourier or Hadamad encoding for proton imaging. Hyperpolarized noble gases, on the other hand, have quite different MR properties compared to proton, primarily the nonrenewability of the signal. It could be expected, therefore, that the characteristics of image SNR with respect to encoding method will also be very different from hyperpolarized noble gas MRI compared to proton MRI. In this article, hyperpolarized noble gas image SNRs of different encoding methods are compared theoretically using a matrix description of the encoding process. It is shown that image SNR for hyperpolarized noble gas imaging is maximized for any orthonormal encoding method. Methods are then proposed for designing RF pulses to achieve normalized encoding profiles using Fourier, Hadamard, wavelet, and direct encoding methods for hyperpolarized noble gases. Theoretical results are confirmed with hyperpolarized noble gas MRI experiments.

Hyperpolarized (129)Xe T (1) in oxygenated and deoxygenated blood.

The viability of the new technique of hyperpolarized (129)Xe MRI (HypX-MRI) for imaging organs other than the lungs depends on whether the spin-lattice relaxation time, T(1), of (129)Xe is sufficiently long in the blood. In previous experiments by the authors, the T(1) was found to be strongly dependent upon the oxygenation of the blood, with T(1) increasing from about 3 s in deoxygenated samples to about 10 s in oxygenated samples. Contrarily, Tseng et al. (J. Magn. Reson. 1997; 126: 79-86) reported extremely long T(1) values deduced from an indirect experiment in which hyperpolarized (129)Xe was used to create a 'blood-foam'. They found that oxygenation decreased T(1). Pivotal to their experiment is the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles); this necessitated a complicated analysis to extract the T(1) of (129)Xe in blood. In the present study, the experimental design minimizes gas exchange after the initial bolus of hyperpolarized (129)Xe has been bubbled through the sample. This study confirms that oxygenation increases the T(1) of (129)Xe in blood, from about 4 s in freshly drawn venous blood, to about 13 s in blood oxygenated to arterial levels, and also shifts the red blood cell resonance to higher frequency.

Evaluation of carrier agents for hyperpolarized xenon MRI.

Several biocompatible carrier agents, in which xenon is highly soluble and has a long T(1), were tested, and injected in living rats. These included saline, Intralipid suspension, perfluorocarbon emulsion and (129)Xe gas-filled liposomes. The T(1) of (129)Xe in these compounds ranged from 47 to 116 s. Vascular injection of these carrier agents was tolerated well, encouraging their use for further experiments in live animals. In vivo spectra, obtained from gas-filled liposomes and perfluorocarbon solutions, suggest that these carrier agents have potential for use in angiography and perfusion imaging.

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging.

The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments.

T(1) of (129)Xe in blood and the role of oxygenation.

In previous experiments by the authors, in which hyperpolarized (129)Xe was dissolved in fresh blood samples, the T(1) was found to be strongly dependent on the oxygenation level, the values increasing with oxygenation: T(1) was about 4 s in deoxygenated samples and about 13 s in oxygenated samples. C. H. Tseng et al. (1997, J. Magn. Reson. 126, 79-86), on the other hand, recently reported extremely long T(1) values using hyperpolarized (129)Xe to create a "blood foam" and found that oxygenation decreased T(1). In their experiments, the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles) necessitated a complicated analysis to extract the effective blood T(1). In the present study, the complications of hyperpolarized (129)Xe exchange dynamics have been avoided by using thermally polarized (129)Xe dissolved in whole blood and in suspensions of lysed red blood cells (RBC). During T(1) measurements in whole blood, the samples were gently and continuously agitated, for the entire course of the experiment, to avert sedimentation. Oxygenation was found to markedly increase the T(1) of (129)Xe in blood, as originally measured, and it shifts the RBC resonance to a higher frequency. Carbon monoxide has a similar but somewhat stronger effect.