Synopsis

Hyperpolarized ¹³C metabolic imaging is a powerful technique with proven safety and efficacy for human studies. The goal of this project was to investigate pyruvate metabolism in patients with prostate and breast cancer metastases with both echo-planar spectroscopic imaging (EPSI) and the echo-planar imaging (EPI) acquisitions in the same exam. The results revealed similarly valuable information of up-regulated LDH-catalyzed conversion of pyruvate to lactate with some advantages and differences between the two acquisition methods.

Purpose

Methods

Patients were imaged in a 3.0T MRI using a proton clinical protocol and two ¹³C sequences, acquired with custom-built ¹³C surface transceiver coil⁴. [1-¹³C]pyruvic acid was polarized in the SPINLab system to 35.4±4% polarization. The two ¹³C injections were separated by typically 30-45 minutes.

2D dynamic EPSI data were acquired from an axial slice with these features: multiband RF excitation with 10° on pyruvate and 20° on lactate, 3s temporal resolution with 20 timeframes, and a symmetric EPSI gradient¹. In-plane resolution and slice thickness varied depending on metastases size, ranging from 12x12x15mm³ to 20x20x20mm³. Dynamic spectra were summed in time, and the real component of the summed spectra was used for analysis.

Imaging data were acquired with a metabolite-specific imaging approach³. Metabolites were independently excited with a singleband spectral-spatial RF pulse (passband FWHM=130 Hz, stopband=868 Hz) and encoded with a single-shot echoplanar readout². Pyruvate, lactate, and alanine were independently excited with a TR of 100ms followed by a 2.7s delay to match the temporal resolution of EPSI. The flip angles for pyruvate (38°) and metabolites (68°) were chosen to have equal RF utilization per timeframe, and the spatial resolution and slice thickness was identical to the EPSI experiments. Data were reconstructed in Matlab using the Orchestra reconstruction toolbox (GE Healthcare)².

Results

5 patients were included in this study, and information regarding polarization, transfer time, and time to pyruvate peak is listed in Table 1. The quality control (QC) system calculated similar polarization levels, and no substantial difference was observed in the pyruvate peak time.

After spectral processing, the EPSI data could be displayed similar to EPI as metabolite dynamic images. Figure 1 demonstrated a representative dataset, including the T₁-weighted image, a coarse ΔB₀ map derived from EPSI pyruvate chemical shift variation, and dynamic images from both acquisitions. The outlined red timeframes demonstrated a spectral contamination artifact of elevated baseline due to high pyruvate signal, potentially resulting in AUC ratio inaccuracy. The quantitative analysis included AUC SNR and lactate-to-pyruvate ratio, as shown in Table 2. Overall, downstream metabolites presented similar SNR while the injected pyruvate SNR was about 2-fold different, resulting in a similar difference in L/P ratio.

Discussion and Conclusions

Both EPI and EPSI acquisitions detected up-regulated pyruvate to lactate conversion in the metastases; providing a valuable biomarker of cancer metabolism. As qualitatively demonstrated in Figure 1, both methods revealed similar contrast and signal evolution. A two-fold difference was observed in L/P ratio, possibly due to B₁ inhomogeneity. The apparent flip angle was chosen based on theoretical calculations assuming a homogeneous B₁, but this assumption is not valid for the figure-8 coil. Therefore, caution should be made when determining flip angle if a surface coil was used. Similarly, a coil setup with a homogeneous B₁+ field would likely alleviate the difference between the two methods. With the coarse ΔB₀ map provide by the EPSI approach, B₀ variation within the region of interest was tolerable by the EPI excitation bandwidth, thus excluded B₀ from the potential cause of difference.

Overall, the full-spectral encoding nature of the EPSI method provided valuable chemical shift information, enabling the generation of a ΔB₀ map to retrospectively assess and validate the RF excitation accuracy. However, it also required a substantially longer acquisition time as each timeframe took 2s. The single-shot EPI only took 0.3s for each timeframe, allowing volumetric acquisition without an impact on temporal resolution. This acquisition time difference also revealed that EPI is more robust against motion. Figure 1(d)-(e) demonstrated this motion artifact with EPSI data, the outlined blue timeframe showed an increased metabolite intensity corresponding to the end of a breath hold, while the EPI data did not present such artifact. The EPI method, however, required spectral-spatial pulses for chemical shift selection, which is more sensitive to operator error and off-resonance.

In conclusion, patients with liver and bone metastases were successfully evaluated by ¹³C HP MR and both spectral and imaging approaches provided valuable metabolic information. The metabolites ratio differences revealed the sensitivity of excitation parameters, suggesting the importance of accurate flip angle assessment.

Acknowledgements

References

[1] Nelson, Sarah J., et al. "Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C] pyruvate." Science translational medicine 5.198 (2013): 198ra108-198ra108.

[2] Gordon, Jeremy W., Daniel B. Vigneron, and Peder EZ Larson. "Development of a symmetric echo planar imaging framework for clinical translation of rapid dynamic hyperpolarized ¹³C imaging." Magnetic resonance in medicine 77.2 (2017): 826-832.

[3] Cunningham, Charles H., et al. "Pulse sequence for dynamic volumetric imaging of hyperpolarized metabolic products." Journal of magnetic resonance 193.1 (2008): 139-146.

[4] Zhu, Z., et al. "Hyperpolarized ¹³C Dynamic Breath-held Molecular Imaging to Detect Targeted Therapy Response in Patients with Liver Metastases. " Proc. Intl. Soc. Mag. Reson. Med. 1115 (2017).