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A Deuterated ¹³C-Urea Reference to Eliminate ¹H Imaging Artifacts in Hyperpolarized ¹³C MRI Studies

Collin J. Harlan¹, Zhan Xu ¹, Keith A. Michel^1,2, Christopher M. Walker¹, Sanjaya D. Lokugama³, Mark D. Pagel^2,3, and James A. Bankson^1,2
¹Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, ²The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, TX, United States, ³Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

Synopsis

Multiparametric and hyperpolarized (HP) ¹³C Magnetic Resonance Imaging (MRI) are attractive multi-modality methods for prostate cancer imaging studies because of their non-invasiveness and characterization of changes in tumor metabolism. A ¹³C-urea calibration reference is required when conducting HP ¹³C MRI studies, which must be heavily doped with Gd⁺ to facilitate rapid calibrations. Care must be taken to ensure that the highly relaxed ¹H signal does not compromise DCE-MRI via hyperintense imaging artifacts. Deuteration and lyophilization of ¹³C-urea can be useful in creating a calibration reference that does not lead to imaging artifacts in ¹H Images.

Introduction

The ability to manage and predict outcome for patients with prostate cancer is a critically important unmet clinical need. In regards to prostate cancer imaging, accurate disease characterization is at the forefront of importance. Multi-modality information gathered by noninvasive imaging techniques¹ is a promising method to achieve this goal. HP ¹³C MRI is an emerging metabolic imaging method that can result in a greater than 10,000-fold gain in signal intensity.² When paired with dynamic contrast-enhanced (DCE-) MRI, these modalities can inform on the quantitative analysis of ¹³C signal evolution.³Currently, ¹³C-enriched reference standards are required to enable fast and accurate calibration for HP ¹³C studies. However, care must be taken to ensure that the reference is compatible with both ¹H and ¹³C acquisitions. The goal of this study was to optimize the reagents used in a ¹³C-urea reference for a dual-tuned ¹³C/¹H endorectal coil (ERC) and minimize imaging artifacts in metabolic and multiparametric MRI studies involving hyperpolarized [1-¹³C]-pyruvate.

Methods

Due to a high amount of Gd⁺ doping for the purpose of reducing the spin-lattice relaxation time (T1) of urea, the ¹H signal produced by an undeuterated ¹³C-urea reference was rapidly relaxed, resulting in severe imaging artifacts in DCE-MRI. Hyperintense ringing artifacts in ¹H images were mitigated by reducing the ¹H concentration in a ¹³C-urea reference via deuteration and lyophilization.

Several references were fabricated and their SNR was compared using ¹H and ¹³C imaging sequences on a 3T MRI scanner (MR750, GE Healthcare, Waukesha, WI, USA). ¹H prostate phantom imaging using a T1-weighted 3D FSPGR sequence (3.068 ms repetition time, 1.344 ms echo time, 220 mm²field of view, 3.6 mm slice thickness, 1.8 mm slice spacing, and a 20-degree flip angle) was conducted to compare image quality and mean ¹H SNR of a non-deuterated urea reference and a deuterated urea reference.

Results

The deuterated ¹³C-urea reference provides strong ¹³C signal for calibration and an attenuated ¹H signal that does not interfere with heavily T1-weighted scans. ¹H 3D FSPGR MRI acquired of the ERC embedded with the non-deuterated ¹³C-urea reference inside a prostate phantom (Figure 1) showed hyperintense ringing artifacts in the phase and frequency encoding directions. The mean ¹H SNR of the undeuterated urea reference was 2.77 x 10³. ¹H 3D FSPGR MRI acquired of the ERC embedded with the deuterated reference (Figure 2) showed the removal of the hyperintense ringing artifacts. The mean ¹H SNR of the deuterated reference was 1.13 x 10². Therefore, the signal intensity of the non-deuterated urea reference compared to the deuterated reference showed a reduction by a factor of 25.

Discussion

The deuterated urea reference successfully avoided the ¹H imaging artifacts produced by the highly Gd⁺ doped, non-deuterated ¹³C-urea reference. The hyperintense ringing artifacts observed from the undeuterated reference would limit the diagnostic quality of the ¹H images and would negatively affect forthcoming DCE-MRI scans acquired in conjunction with HP ¹³C MRI. The deuterated reference was able to successfully reduce the mean ¹H SNR, which led to complete removal of hyperintense ringing artifacts. Furthermore, the ¹³C-urea signal from the deuterated reference was unaffected (Figure 3), allowing it to continue to serve as a calibration reference for future ¹³C studies. The deuterated reference is a fundamental ¹³C calibration tool which will not produce imaging artifacts during ¹H MRI and thus will support the acquisition of anatomical and functional data to compliment HP ¹³C imaging.

Conclusion

We designed a reference standard for calibration of ¹³C scans that does not compromise anatomic or functional ¹H MRI. The deuterated urea reference showed a reduction in signal intensity when compared to a non-deuterated reference embedded in the ERC, and eliminated ¹H ringing artifacts in heavily T1-weighted images. Two cycles of lyophilization of ¹³C-urea was sufficient to eliminate ¹H ringing artifacts and can be used to improve anatomical image quality in future clinical ¹H and HP [1-¹³C]-pyruvate MRI prostate cancer imaging studies.

Acknowledgements

This work was supported by funding from the National Cancer Institute of the National Institutes of Health (R01CA211150, P30CA016672). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

1. Kelloff GJ, Choyke P, Coffey DS, Prostate Cancer Imaging Working G. Challenges in clinical prostate cancer: role of imaging. AJR Am J Roentgenol. 2009;192(6):1455-1470.

2. Ardenkjaer-Larsen JH, Fridlund B, Gram A, et al. Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR. Proc Natl Acad Sci U S A. 2003;100(18):10158-10163.

3. Bankson JA, Walker CM, Ramirez MS, et al. Kinetic Modeling and Constrained Reconstruction of Hyperpolarized [1-13C]-Pyruvate Offers Improved Metabolic Imaging of Tumors. Cancer Res. 2015;75(22):4708-4717.

Figures

Figure 1. ¹H 3D FSPGR MRI acquired with ERC containing the non-deuterated ¹³C-urea reference inside a prostate phantom. There is a clear ¹H hyperintense ringing artifact produced by relaxed ¹³C-urea in H₂O.

Figure 2. ¹H 3D FSPGR MRI acquired with ERC containing the deuterated urea reference inside a prostate phantom. The hyperintense ringing artifact has been removed due to deuteration and lyophilization of ¹³C-urea.

Figure 3. NMR spectroscopy of ¹³C-urea samples containing different proton concentrations. (a) Non-lyophilized, once lyophilized, and twice lyophilized ¹³C-urea measured using the ¹H channel centered at 4.70 ppm show reduced ¹H signal after each cycle of deuteration. (b) Non-lyophilized, once lyophilized, and twice lyophilized urea measured using the ¹³C channel centered at 163.5 ppm demonstrate consistent ¹³C signal from each of these references.

Proc. Intl. Soc. Mag. Reson. Med. 28 (2020)

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