Hyperpolarized lithium-6 as a sensor of nanomolar contrast agents

Abstract

Lithium is widely used in psychotherapy. The (6)Li isotope has a long intrinsic longitudinal relaxation time T(1) on the order of minutes, making it an ideal candidate for hyperpolarization experiments. In the present study we demonstrated that lithium-6 can be readily hyperpolarized within 30 min, while retaining a long polarization decay time on the order of a minute. We used the intrinsically long relaxation time for the detection of 500 nM contrast agent in vitro. Hyperpolarized lithium-6 was administered to the rat and its signal retained a decay time on the order of 70 sec in vivo. Localization experiments imply that the lithium signal originated from within the brain and that it was detectable up to 5 min after administration. We conclude that the detection of submicromolar contrast agents using hyperpolarized NMR nuclei such as (6)Li may provide a novel avenue for molecular imaging.

Figure 1

Decay curves of a two-compartment phantom. Both curves were normalized to their first point. The compartment without contrast agent (upper curve) had a relaxation time of 181 ± 8 s, while the compartment with contrast agent decayed with T= 99 ± 2 s.

Figure 2

a) Series of spectra of hyperpolarized lithium in the rat brain. Individual spectra were processed with 5 Hz line broadening. Signal is visible up to 300 s after dissolution. b) Integrals of the same peaks in the rat head, corrected for the flip angle of the excitation pulse. The solid line is an exponential fit with a decay time of 72 ± 5 s.

Figure 3

a) Gradient echo axial scout image of the brain. The dorsal sagittal vein can be seen in the top of the brain as a bright spot. b) Lithium image with the skull from the proton image projected on top of it in white, and the dorsal sagittal vein as a black circle. The lithium signal is clearly located in the brain. Note that the distribution of the lithium signal was limited by the sensitive radius of the circular surface coil of 8 mm.

Figure 4

Lithium-6 spectrum localized in the brain, acquired 25 s after dissolution (top trace). The spectra below were acquired every 60 s after it. The time after dissolution is mentioned to the right of each trace. After 5.5 min, a signal is still visible (bottom trace). Processing consisted of zero-filling and apodization by 5Hz prior to FFT. The location of the voxel is indicated in the inset proton image.