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Fast acquisition of hyperpolarized MR with Multi-echo EPI
Kofi Deh1, Kristin L Granlund1, and Kayvan R Keshari1,2

1Radiology & Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY, United States, 2Weill Cornell Medical College, New York, NY, United States

Synopsis

An EPI acquisition can efficiently acquire data, allowing multiple images to be acquired before the transverse signal decays due to T2*. These images (acquired at different echo times) can be reconstructed into images of individual species, as with Dixon or IDEAL. This approach can be used to efficiently acquire hyperpolarized data by limiting the number of excitations to preserve longitudinal magnetization for subsequent time points or enabling the use of larger flip angles for higher SNR. In this abstract, we demonstrate the feasibility of this approach with thermal phantoms (acetate, alanine, and urea) and with hyperpolarized phantoms (pyruvate and urea).

Introduction

Hyperpolarized MRI (HP MRI) is useful for non-invasively probing in vivo metabolism due to the signal enhancement provided by dynamic nuclear polarization and the ability to observe the metabolism of an injected substrate to its downstream products. HP MRI can be used to study cancer metabolism by observing the conversion of [1-13C]pyruvate to [1-13C]lactate, as increased lactate production is a hallmark of cancer (the Warburg effect1). The longitudinal hyperpolarized magnetization is non-recoverable and decreases with T1 and RF excitation. Therefore, efficient sampling schemes are needed to acquire useful data. Early studies used spatially resolved spectroscopic acquisitions2, but the achievable resolution is limited by the number of excitations required and the corresponding loss in transverse magnetization. Recent studies are using imaging acquisitions with spatial-spectral excitations3,4 or multiple echo times4,5 to generate images of individual metabolites. In this abstract, we present a multi-echo technique that acquires a set of echoes following a single RF excitation pulse, reducing the number of excitations needed to reconstruct a set of metabolite images.

Methods

All experiments were performed on a 3T preclinical BrukerBiospec scanner using a dual-tuned transmit/receive 1H/13C birdcage coil. Images were acquired with a T2* EPI sequence: multiple EPI readouts with different echo times are acquired following a single RF excitation (Figure 1). A 16x16 matrix is acquired with a 32x32-cm FOV. A 2DEPSI sequence6 was used to determine the ratio of chemical species in each voxel for comparison.

Thermal Experiment Phantoms composed of various mixtures of 13C-enriched chemicals were prepared for testing the method. Phantom 1 consisted of [13C]urea and [1-13C]acetate; and Phantom 2 consisted of [13C]urea, [1-13C]alanine, and [1-13C]acetate. For thermally polarized phantoms, the following acquisition parameters were used: TR=1000ms, TE1=11.5ms, ∆TE=6.3ms, and 300 averages for a total scan time of 5min.

Hyperpolarized experiment To test the performance of the reconstruction in a hyperpolarized setting, two phantoms were imaged: Phantom 1 consisted of [1-13C]pyruvate. Phantom 2 consisted of [1-13C]pyruvate and [13C]urea. For hyperpolarized phantoms, the following acquisition parameters were used: TR=200 ms, TE1=11.5ms, ∆TE=4.7ms, and 150 time points for a total scan time of 30s.

Reconstruction Complex DICOM images were processed offline in MATLAB with an iterative reconstruction8. The chemical shifts of the phantoms were determined using a non-localized spectroscopy sequence.

Results

Thermal experiment 2DEPSI spectra are used to determine the ratio of metabolites in each phantom (Figure 2). Individual EPI images are shown as well as the reconstructed metabolite images. As expected, the relative amplitude of the phantoms changes with TE as the different species destructively interfere due to different resonance frequencies. In the metabolite images, we see that Phantom 1 only appears in the urea and acetate images, while Phantom 2 appears in all three metabolite images. This demonstrates that the reconstruction correctly decomposed into the corresponding metabolite images.

Polarized experiment The intensity of the HP pyruvate is so large, that it is difficult to visualize the difference in signals due to the dynamic range. Instead, we present the average signal in ROIs in the metabolite images compared to the area under the curves of the spectra normalized to the pyruvate signal. The values of the spectroscopic data (second number) are lower due to T1 decay and RF excitations between the acquisitions, but show a similar trend.

Hydrate Urea

Phantom1: 12.7/2.6% 6.3/3.7%

Phantom2: 14.7/4.5% 10.4/5.3%

Discussion

A challenge for Dixon methods is identifying the species when only one is present in a voxel, a particular challenge for our phantom experiment where there is physical separation of the phantoms, an additional challenge for region-growing algorithms. The HP pyruvate signal resulted in an essentially single-species phantom. However, in an in vivo setting, the pyruvate and lactate signals will be on the same order and it will be easier to generate a contiguous field map, which will improve the robustness of the reconstruction.

The number of echoes that can be acquired, and thus the number of metabolites that can be reconstructed, is limited by T2* and resolution. Since all echoes are acquired after a single excitation, the echo spacing is restricted to values larger than the acquisition time. However, the overall scan time is shorter than a spatial-spectral or standard IDEAL acquisition because fewer repetitions are needed to acquire multiple images. With our resolution, we are still able to acquire 5 echoes in under 50ms. While we use an EPI readout, this method can be used by other single-shot trajectories, such as spiral.

Conclusion

This method reduces the number of excitations needed to acquire individual metabolite images, enabling the use of larger flip angles to improve SNR.

Acknowledgements

NIH R00 EB014328, R01 CA195476 and S10 OD016422; NIH/NCI Cancer Center Support Grant P30 CA008748; Geoffrey Beene Cancer Research Center, Center for Molecular Imaging and Nanotechnology at MSKCC, The Center for Experimental Therapeutics at MSKCC, Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and thePeter Michael Foundation.

References

1. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation. Science. 2009;324(5930):1029-1033. doi:10.1126/science.1160809

2. Nelson SJ, Kurhanewicz J, Vigneron DB, et al. Metabolic imaging of patients with prostate cancer using hyperpolarized [1-13C] pyruvate. Sci Transl Med. 2013;5(198):198ra108–198ra108.

3. Lau AZ, Chen AP, Ghugre NR, et al. Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart. Magn Reson Med. 2010;64(5):1323-1331. doi:10.1002/mrm.22525

4. Lau JYC, Geraghty BJ, Chen AP, Cunningham CH. Improved tolerance to off-resonance in spectral-spatial EPI of hyperpolarized [1-13C]pyruvate and metabolites. Magn Reson Med. 2018;80(3):925-934. doi:10.1002/mrm.27086

5. Wiesinger F, Weidl E, Menzel MI, et al. IDEAL spiral CSI for dynamic metabolic MR imaging of hyperpolarized [1-13 C]pyruvate. Magn Reson Med. 2012;68(1):8-16. doi:10.1002/mrm.23212 6. Chen AP, Cunningham CH, Ozturk‐Isik E, et al. High-speed 3T MR spectroscopic imaging of prostate with flyback echo-planar encoding. J Magn Reson Imaging. 2007;25(6):1288-1292. doi:10.1002/jmri.20916

7. Morze C von, Larson PEZ, Hu S, et al. Imaging of blood flow using hyperpolarized [13C]Urea in preclinical cancer models. J Magn Reson Imaging. 2011;33(3):692-697. doi:10.1002/jmri.22484

8. Reeder SB, Wen Z, Yu H, et al. Multicoil Dixon chemical species separation with an iterative least-squares estimation method. Magn Reson Med. 2004;51(1):35-45.

Figures

Pulse sequence.

Following a single slice-selective RF excitation, multiple images are acquired with different echo times using an EPI trajectory for efficient k space coverage.


Thermal phantoms.

A phantom with urea and acetate (left) and a phantom with urea, alanine, and acetate (right) are imaged with an agar phantom for loading the coil. Spectra acquired with a 2DEPSI sequence are shown for each phantom. EPI images are acquired at 5 different echo times and reconstructed into metabolite images.


Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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