First in‐human evaluation of [<scp>1‐<sup>13</sup>C</scp>]pyruvate in <scp>D<sub>2</sub>O</scp> for hyperpolarized <scp>MRI</scp> of the brain: A safety and feasibility study
Kofi Deh, Guannan Zhang, Angela Hijin Park, Charles H. Cunningham, Nadia Bragagnolo, Serge K. Lyashchenko, Shake Ahmmed, Avigdor Leftin, Elizabeth Coffee, Hedvig Hricak, Vesselin Z. Miloushev, Marius E. Mayerhoefer, Kayvan R. Keshari
Abstract
Abstract Purpose To investigate the safety and value of hyperpolarized (HP) MRI of [1‐ 13 C]pyruvate in healthy volunteers using deuterium oxide (D 2 O) as a solvent. Methods Healthy volunteers ( n = 5), were injected with HP [1‐ 13 C]pyruvate dissolved in D 2 O 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 (T 1 ) of [1‐ 13 C]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 D 2 O increased the T 1 of [1‐ 13 C]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 D 2 O also increased the apparent relaxation time of [1‐ 13 C]pyruvate by a factor of 1.4 ± 0.2 in vivo. After adjusting for inter‐site SNR differences, the use of D 2 O was shown to increase image SNR by a factor of 2.6 ± 0.2 in humans. Conclusions HP [1‐ 13 C]pyruvate in D 2 O is safe for human imaging and provides an increase in T 1 and SNR that may improve image quality.