Introduction

Hyperpolarized ¹³C magnetic resonace spectroscopic imaging (MRSI) is a powerful tool to study the metabolism of tumors¹, hearts² and other organs³. By hyperpolarization, the intrinsically low sensitivity of ¹³C-detection can be temporarily increased by a factor⁴ of 10⁴ up to 10⁵. Cryocoils minimize the intrinsic coil noise and promise an additional SNR gain of up to 10 compared to conventional room temperature coils⁵ which can be exploited to improve spectral quality and allows the usage of lower flipangles to preserve hyperpolarized magnetization.

Methods

The SNR of different coils was assessed using free induction decay (FID) chemical shift imaging (CSI) of a ¹³C-urea phantom.
Phantom: In vitro experiments were carried out with a 50ml Falcon Tube, containing 1.8M ¹³C-urea and 50mM DOTAREM^TM.
Animal: The in vivo experiment was carried out in a healthy mouse. Hyperpolarization was performed in a HyperSense DNP polarizer (Oxford Instruments). 300ml of 80mM hyperpolarized [1-¹³C]pyruvate were injected.
Imaging System
The experiment was carried out on a 7T small animal MRI Scanner (Agilent/GE/Bruker).
The RF coils used were:

• A ¹³C transmit-receive quadrature 20mm CryoProbe^TM (Bruker) with cryogenically cooled preamplifier, cooled with gaseous helium to approximately 30K/77K (coil/preamplifier) in combination with a ¹H 86mm volume resonator (Bruker).
• A ¹H/¹³C double-resonant transmit-receive 20mm surface coil (Bruker) at room temperature.
• A ¹H/¹³C dual-tuned dual-quadrature 31mm volume coil (Rapid Biomedical) at room temperature.

MR Measurement
Phantom: Imaging Parameters for the 2D CSI were FOV 32x32mm², imaging matrix 16x16, slice thickness 2mm, voxel size 2mm³, TR 200ms, TE 1.258ms, spectral bandwidth 6009.6Hz, 1024 acquisition points which yields a spectral resolution of 5.87Hz and repetitions 25.
For excitation, a Shinnar-Le Roux (SLR) pulse with 90° flipangle, 0.84ms duration and 5kHz bandwidth was used.
Animal: Time resolved 2D CSI was performed. A 3mm slice with 28x16mm² FOV (14x8 imaging matrix, 80 spectral points) was placed on the kidneys and a a spectroscopic image was acquired every 4.71s (TR 42.8ms). The excitation power was set to give a flipangle of 5˚ in the center of the right kidney.
B₁ Mapping
B₁ mapping was performed for each coil by repeatedly acquiring FLASH images with 30 different RF powers. In each voxel, the RF-dependent complex signal S was fit
$$S(RF_{power}) = A \cdot sin(\frac{\pi}{p} \cdot RF_{power}) $$
with A $$$\in \mathbb{C}$$$. A 90° flipangle is then reached with $$$RF_{power} = \frac{p^2}{4} $$$.

SNR Calculations
The SNR in each voxel was calculated by averaging the peak height in the magnitude spectrum over the 25 repetitions and dividing by the standard deviation (std) of a Rician distribution fit to 400 points in the noise region.
$$ SNR = \frac{mean(signal)}{std(noise)}$$
Cryocoil vs. standard surface coil: The SNR ratio map was calculated by dividing coil SNR maps. To fairly compare the SNR between coils, images with RF powers that gave similar excitation profiles were chosen.
Cryocoil vs. volume coil: The SNR ratio map was calculated by dividing the SNRs separately for each voxel. To compensate for the inhomogenous excitation B₁-profile of the cryocoil, in each voxel the acquisition with RF power that yielded the highest signal was chosen.

Results

Cryocoil vs. standard surface coil:The normalized signal profiles for both coils are similar (Fig. 2abc). The cryocoil provides an SNR gain (SNR ratio >1) in the whole phantom (Fig. 2i), around 5-8 up to 16mm away from the surface of the coils (Fig. 2i) and 6-7 around 2-4mm away from the coil (a suitable distance for mouse subcutaneous tumor studies, Fig. 2f).
Cryocoil vs. volume coil: The cryocoil provides an SNR gain (SNR ratio >1) up to 14.5mm (Fig. 3e), peaking at 10 close to the surface, and 6-8 around 2-4mm away from the coil (Fig. 3e). Within the RF power limits of the cryocoil, a 90° tipangle excitation can be reached up to 8mm into the phantom when using a SLR pulse of 0.84ms and 5kHz bandwith (Fig. 3e).
In vivo experiment: ¹³C-pyruvate and ¹³C-lactate signal are detected after injection, increased conversion of ¹³C-pyruvate to ¹³C-lactate can be observed in the kidneys. Signal can be observed above the noise for around 70s (pyruvate) and 100s (lactate).

Discussion

A fair comparison of sensitiy gain between volume and surface coils is difficult due to the difference in their excitation profile. The use of B₁-inhomogeneity insensitive adiabatic half passage RF pulses could help to overcome this problem. The hyperpolarized in vivo study shows high signal in the regions of interest close to the coil.

Conclusion

The use of a cryogenically cooled coil improves the SNR compared to both standard surface coils and volume coils up to a factor of 8 and 10, respectively. A proof-of-concept hyperpolarized in vivo MRSI study was performed that shows that localized determination of metabolism at relatively high signal is achieved with a cryocoil. The gain in SNR of a cryocoil could be used to increase spatial resolution, shorten acquisition time or acquire higher SNR spectra in SNR-limited and signal-constrained hyperpolarized ¹³C MRSI.

Acknowledgements

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 820374. The authors thank Sandra Sühnel for the help with the animal study.