The pharmacokinetics of hyperpolarized xenon: Implications for cerebral MRI

Abstract

In this work, a compartmental model to predict the concentration of hyperpolarized xenon (Xe) in the brain is developed based on the well established kinetics of Xe and estimated T1 values for the compartments. For the gaseous compartments, T1 was set to 12 seconds. For the tissue compartments, T1 was set to 6 seconds. Three gas delivery techniques were modeled: hyperventilation followed by breath-hold, continual breathing, and hyperventilation followed by continual breathing. Based on Xe CT, it is estimated that the maximum concentration of Xe that could be breathed is 80%. Based on this value and the estimated maximum polarization of 50%, the peak gray matter concentration of hyperpolarized Xe is calculated to be .036 mM. This leads to an estimated signal-to-noise ratio (SNR), at 2 T, for hyperpolarized Xe that is a factor of 50 lower than the SNR for proton MRI. The peak concentration of hyperpolarized Xe was also calculated over a wide range of gas and tissue T1 values. This model also predicts that the arterial blood will have a concentration of hyperpolarized Xe that is 10 times greater than the concentration in gray matter. An interactive version of the model can be found on the World Wide Web at http:(/)/ric.uthscsa.edu/staff /charlesmartinphd.html.

Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI

“…3 shows representative axial images of lean ( Whereas before stimulation no appreciable signal is observed in the interscapular BAT (iBAT) region of these animals, a strong localized signal enhancement is observed during adrenergic stimulation of thermogenesis only in the area corresponding to iBAT. The local signal enhancement is also more than 10-fold, and from a simple signal to noise ratio (SNR) comparison with our 129 Xe-enriched thermally polarized phantom we estimated the local xenon concentration to be on the order of few micromolars, or more than two orders of magnitude larger than the maximum xenon concentration expected in the brain upon inhalation (29). 129 Xe resonances as acquired in a lean (A) and in an obese (B) animal before and during NE stimulated thermogenesis.…”

Genetically encoded reporters for hyperpolarized xenon magnetic resonance imaging

“…To assess the feasibility of HyperCEST imaging in vivo, we implemented a previously published pharmacokinetic model of inhaled hyperpolarized xenon aimed at estimating cerebral tissue concentrations of polarized nuclei 7 . Model parameters were adjusted to represent rat experimental subjects 3 , and combined with a simulated saturation and imaging pulse sequence to determine its ability to detect the presence of 400 pM GVs in brain tissue.…”

“…The simulation assumed an initial reservoir concentration of 3.96 mM isotopically enriched hyperpolarized 129 Xe gas based on a Xe density of 5.15mg/ml (ref 7 ) with 10% polarization. Supplementary Fig.…”

“…6a). Using the assumptions of Martin et al 7 , this results in a signal-to-noise ratio (SNR) 64-fold lower than that expected for thermally polarized protons based on equation 9, where γ Xe and γ H are the gyromagnetic ratios of 129 Xe and 1 H (11.77 and 42.577, respectively), C H is the proton concentration (assumed to be 80 M) and the B o field and temperature are taken to be 1.5 T and 310 K.…”

Hyperpolarized Xenon Brain MRI

“…Hyperpolarized 129 Xe transport in the brain has been modeled using appropriate adaptations of the Kety-Schmidt theory (Martin et al, 1997;Peled et al, 1996). Martin and co-workers derived the equation of the cerebral xenon concentration during hyperpolarized 129 Xe delivery to the lungs as follow:…”