First in-human evaluation of [1-13C]pyruvate in D2O for hyperpolarized MRI of the brain: A safety and feasibility study

Abstract

Purpose: To investigate the safety and value of hyperpolarized (HP) MRI of [1-¹³C]pyruvate in healthy volunteers using deuterium oxide (D₂O) as a solvent.

Methods: Healthy volunteers (n = 5), were injected with HP [1-¹³C]pyruvate dissolved in D₂O and imaged with a metabolite-specific 3D dual-echo dynamic EPI sequence at 3T at one site (Site 1). Volunteers were monitored following the procedure to assess safety. Image characteristics, including SNR, were compared to data acquired in a separate cohort using water as a solvent (n = 5) at another site (Site 2). The apparent spin-lattice relaxation time (T₁) of [1-¹³C]pyruvate was determined both in vitro and in vivo from a mono-exponential fit to the image intensity at each time point of our dynamic data.

Results: All volunteers completed the study safely and reported no adverse effects. The use of D₂O increased the T₁ of [1-¹³C]pyruvate from 66.5 ± 1.6 s to 92.1 ± 5.1 s in vitro, which resulted in an increase in signal by a factor of 1.46 ± 0.03 at the time of injection (90 s after dissolution). The use of D₂O also increased the apparent relaxation time of [1-¹³C]pyruvate by a factor of 1.4 ± 0.2 in vivo. After adjusting for inter-site SNR differences, the use of D₂O was shown to increase image SNR by a factor of 2.6 ± 0.2 in humans.

Conclusions: HP [1-¹³C]pyruvate in D₂O is safe for human imaging and provides an increase in T₁ and SNR that may improve image quality.

Keywords: brain; deuterium oxide (D2O); hyperpolarized 13C‐pyruvate.