INTRODUCTION

Abdominal MRI plays an important role in clinical diagnostics, allowing evaluation of abdominal pathology for patients diagnosed with metastatic cancer in the abdomen. Yet, one of the challenges of MRI that limits its widespread applicability is the inherently low sensitivity of magnetic resonance at thermal equilibrium. Hyperpolarization by dissolution dynamic nuclear polarization is an emerging technique that significantly improves the signal to noise ratio by several orders of magnitude. This technique has been successfully developed in conjunction with MRI to image metabolism in humans by administering hyperpolarized metabolic molecules. Here, we show dynamics of hyperpolarized [1-¹³C] pyruvate images acquired by a custom-built ¹³C jacket coil, demonstrating its applicability to image patients diagnosed with metastatic cancer in the abdomen for future hyperpolarization studies.

METHODS

Hyperpolarization of [1-¹³C] pyruvate
The 80 μL pyruvate prep consisted of 14.2 M [1-¹³C] pyruvate and 15 mM free radical (GE healthcare). The prep was hyperpolarized in a 5.0 T SpinLab Hyperpolarizer (GE healthcare). After 3 hours, the prep was rapidly dissolved with preheated 40 mL Tris buffer (100 mM in H₂O supplement with 0.1 mM EDTA, pH 7.4). The resulting solution was immediately diluted in H₂O to a final concentration of 4.7 mM and transferred to a jacket coil preinstalled in a 3 T scanner (GE healthcare) for signal acquisition.
¹³C MRI
All MR data were acquired on a wide-bore 3 T scanner (MR750w, GE healthcare). T₁ – weighted images (axial and coronal view) were acquired for anatomical reference using a spin-echo sequence. The jacket coil (Clinical MR Solutions) was custom-designed for ¹³C hyperpolarization studies. It was used for excitation and detection on ¹³C. The ¹³C images were acquired using a spiral sequence,^1,2 axial, 32 × 32 cm² field of view, 1 × 1 cm² in-plane resolution. For the thermally polarized experiment, the images were acquired with 60 scans, 90^o flip angle, 6 s repetition time for each ¹³C resonance, 10 cm single slice. For the hyperpolarization experiment, the images were acquired with 60 scans, 15^o flip angle for hyperpolarized [1-¹³C] pyruvate and 90^o flip angle for thermally polarized ¹³C-urea (6 M, thermal reference), 10 s repetition time for each ¹³C resonance, 7 slices 1.5 cm/slice.

RESULTS

To test the image quality achievable by the jacket coil (Figure 1), T₁-weighted images were first acquired to localize the sphere phantoms containing ¹³C-labelled compounds (Figure 2a). Then single-slice images were acquired on the thermally polarized ¹³C-labelled phantoms using a spiral sequence. The images of each ¹³C resonance were generated by summing the signal for each time point (Figure 2b). The locations and signal intensity of the resulting images matched that of the T₁-weighted anatomical images and concentrations of the ¹³C-labelled phantoms, respectively. To further determine the appropriate parameter setup and image quality for future hyperpolarization experiments in patients, dynamics of hyperpolarized [1-¹³C] pyruvate in a phantom were acquired with the same sequence where multiple slices were excited (Figure 2c). Dynamic curves were generated by summing the signal for each time point within each slice and therefore allowing for obtaining T₁ relaxation time of [1-¹³C] pyruvate (Figure 2d). The derived T₁ relaxation time of hyperpolarized [1-¹³C] pyruvate in H₂O is ~ 60 s with a polarization level of 20 %, which will be further improved by using D₂O as dissolution solvent.³ The fitted T₁ values are consistent among slices which indicates the robustness of the method.

DISCUSSION

Hyperpolarized pyruvate imaging have been safely performed in humans for cardiac, brain, and prostate studies.⁴ These studies investigated cancer metabolism in a region of interest within the body by monitoring the change of the hyperpolarized metabolic flux. However, for patients diagnosed with metastatic cancer, it often requires to image for multiple regions of interest since metastases in cancer spans a wide range of the body and therefore results in lesions in multiple areas. Here we present the preliminary work on acquiring dynamics of hyperpolarized [1-¹³C] pyruvate by a custom-built ¹³C jacket coil, with the purpose of demonstrating the applicability of the method to detect the spread of metastatic cancer in the abdomen for future human studies. The jacket coil (Figure 1) provides coverage and ¹³C RF excitation over the whole abdominal area and therefore allowing to detect lesions in multiple areas. Due to the nonrenewability of hyperpolarized ¹³C signal, the spiral sequence was used for rapid data acquisition. The sequence allows to excite each ¹³C metabolite sequentially using spatial-spectral pulses followed by signal read-out by a singlet-shot spiral trajectory, with the prerequisite that the chemical shift frequencies are known beforehand and the magnetic field is homogeneous across the sample. The matched signal to noise ratio of the thermally polarized images with the concentrations of ¹³C-labelled phantoms as well as the consistency of the fitted T₁ values among slices in the hyperpolarization experiment demonstrate the applicability of the method to future human studies.

CONCLUSION

In summary, we presented the applicability of using a custom-built ¹³C jacket coil to image dynamics of hyperpolarized [1-¹³C] pyruvate. The images acquired by a spiral sequence using the jacket coil exhibit a good quality, demonstrating the feasibility of the method to detect the spread of metastatic cancer for future hyperpolarization studies in humans.

Acknowledgements

This work was supported by R01 CA195476, R01 CA237466, R01 CA252037, S10 OD016422, and NIH/NCI Cancer Center Support grant P30 CA008748.