Introduction

Hyperpolarized carbon-13 MRI is a powerful, clinical technique to probe in vivo metabolism, and recent studies have demonstrated the technique in the brain, heart, and in cancer (1–4) The calibration of the system centre frequency and radiofrequency power is commonly achieved using external phantoms but errors in this calibration will significantly affect data quality. Previous work has assessed the use of dual tuned 23Na/13C coils to calibrate ¹³C experiments as part of the prescan (5,6) and here we develop this idea by using dedicated commercially available ¹³C coils to provide this data. Here we show that the sodium-23 resonance can be reliably used to calibrate clinical systems prior to data acquisition using dedicated, clinically available, ¹³C tuned coils providing all the necessary system parameters for successful data acquisition.

Methods

System centre frequency and transmit gain (TG) estimation
Four cylindrical phantoms filled with saline (150-17 mMoL^-1 NaCl) with a urea phantom (8 MoL^-1) on top were placed in the scanner (3T, HDx, GE Healthcare, WI) with either two ¹³C tuned 8-channel paddle coils or a single loop receive coil placed either side of the phantom or on top of the phantom, respectively. A Helmholtz loop transmitter (clamshell) was used for B₁ transmission. The ¹³C urea and ²³Na centre frequency and TG were acquired using a pulse-acquire Bloch-Siegert acquisition (hard pulse, pulse width = 0.5 ms, repetition time (TR) = 2 s, echo time (TE) = 0.5 ms, flip angle (FA) = 90 degrees)(7). The ratiometric difference in centre frequency between ²³Na/¹H and 13C-urea were averaged over all experiments. The difference in TG (dB) between ²³Na and ¹³C was calculated for all experiments. A linear fit between the TG at different loading states per nuclei was calculated.
In vivo experiments
Six female Danish land pigs were placed supine in the scanner. The single loop coil was placed on the biceps femoris muscle of the right lower limb, and used for acquisition with a ¹³C-lactate (4MolL^-1) phantom placed in the FOV of the coil. The 23Na and 13C centre frequency were recorded, as well as the TG required for ²³Na and ¹³C as described above before data acquisition (partially self-refocusing since pulse, spectral bandwidth = 5 kHz, number of samples = 2048, TR = 1 s, 128 time points, FA = 12 degrees, slice thickness = 40 mm). Spectral data were post-processed using matching pursuit fitting and kinetic modelling as well as calculating ratiometric results (lactate:pyruvate, bicarbonate:pyruvate) (8). Kinetic and ratiometric results were averaged over all experiments, and a linear correlation between k_PL and lactate:pyruvate was performed. All processing and statistical analysis was performed in Matlab (2018a, The Mathworks, MA).

Coil profile estimation
The RF amplifier was disabled and a noise only acquisition performed with the 8-channel paddle coils to calculate the noise covariance matrix at both ¹³C and ²³Na frequencies.
Transmit B₁ Simulations
Simulations of the clamshell B₁₊ performance at both ¹³C and ²³Na frequencies was performed (CST, Darmstad, Germany) and the ratio between ¹³C and ²³Na B₁₊ fields (T) computed.

Results

System f₀ and TG calibration can be performed with the ²³Na resonance for ¹³C experiments
The ratiometric difference in ²³Na and ¹³C Urea f₀ at 3T was 1.05180 ± 0.00001, with the mean difference in TG for ²³Na and ¹³C was 10.4 +/- 0.6 dB. Simulated B^₁₊ profiles agreed with this (Figure 2), with a predicted difference in 10.4 +/- 0.2 dB between 23Na and 13C. There was no significant correlation between saline loading and TG (R² < 0.1, p > 0.05). Simulations showing the transmit B₁ field at the ¹³C and ²³Na frequencies can be found in Figure 2A and B, respectively; Figure 2C shows the ratiometic difference between the two.

¹³C coil element noise coupling increases at ²³Na frequency
Noise correlation between the 8 channels in the paddle coil revealed good linearity at 13C frequency, however increased off-diagonal correlation was observed at ²³Na f₀, shown in Figure 3A and B, respectively.

In vivo hyperpoalrized ¹³C experiments are successful using a ²³Na prescan
Using the ²³Na prescan, hyperpolarized ¹³C MRS was successfully performed from the musculature of six pigs. The frequency scaling constant between ²³Na and [1-13C] pyruvate was 1.05179 ± 0.00001. Kinetic analysis revealed a mean k_PL of 0.007 +/- 0.002 s^-1 and correlated with lactate:pyruvate ratio (R² = 0.9, p = 0.01). Example summed spectra are seen in Figure 4.

Discussion

This study has provided the translational step required to provide a clinical pipeline for successful, accurate, prescan measures for hyperpolarized ¹³C experiments using the ²³Na resonance. Due to the high natural abundance of ²³Na in vivo, combined with the low frequency difference at 3T, it is possible to utilise this technique with dedicated, commercially available, coils – providing the translation step required for clinical application and uptake of this technique.

Acknowledgements

This study was funded by the Lundbeck Foundation, Medical Research Council, Cancer Research UK, and the Little Princess Trust.