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Dynamic T₂^* Relaxometry of Hyperpolarized [1-¹³C]pyruvate MRI in the Human Brain and Kidneys

Xiaoxi Liu¹, Di Cui¹, Duan Xu¹, Robert Bok¹, Zhen J. Wang¹, Daniel B Vigneron^1,2, Peder E.Z. Larson^1,2, and Jeremy W. Gordon¹
¹Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Graduate Program in Bioengineering, University of California, Berkeley and San Francisco, San Francisco, CA, United States

Synopsis

Keywords: Quantitative Imaging, Hyperpolarized MR (Non-Gas)

We present dynamic T₂^* measurements for HP [1-¹³C]pyruvate and metabolites in a healthy human brain volunteer and two RCC patients at 3T. The T₂^* of pyruvate was shown to vary during the acquisition, whereas the T₂^* of lactate and bicarbonate was constant through time and across organs. The T₂^* of lactate was constant at gray matter (30.1±5.9ms), white matter (33.8±7.6ms), healthy kidney (38.94±6.9ms) and tumor (33.27±6.4ms), and the T₂^* of bicarbonate over whole-brain (109.5±12.8ms) and kidney (64.6±15.8ms). These relaxometry measurements will be useful for future sequence optimization and can be included in kinetic modeling to harmonize data across different TEs.

Introduction

Hyperpolarized (HP) ¹³C-labeled MRI is a noninvasive method to assess metabolic processes in vivo.^1,2 However, the signal-to-noise (SNR), spatial and temporal resolution of HP ¹³C imaging are limited by the unrenewable HP magnetization. A better understanding of the transverse relaxation (T₂^*) would be beneficial for sequence optimization and would improve quantification and data harmonization across sites³ since kinetic models^4,5 implicitly neglect T₂^* decay, but relaxometry studies in pre-clinical models and in humans have been limited⁶. To overcome this gap in our knowledge, in this work we quantified dynamic T₂^* of [1-¹³C]pyruvate and its products in a healthy brain volunteer and two renal carcinoma cell (RCC) patients using a metabolite-specific multi-echo GRE sequence.

Methods

Sequence: HP ¹³C data were acquired with a multi-slice metabolite-specific multi-echo spiral sequence (Fig.1(A)), which was implemented on a GE 3T scanner (MR750, GE Healthcare, Waukesha, WI) using commercial software (RTHawk, HeartVista, CA). In each repetition time (TR), one spectral-spatial RF pulse (25.17ms, passband 80Hz, and stopband 770Hz) was followed by ten single-shot gradient-refocused spiral readouts with 14ms echo-spacing.
Human Brain Study (N=1): The brain study used a birdcage coil for RF transmit with an integrated 24-channel receiver (Rapid Biomedical, Würzburg, Germany). The acquisition started 4s after the saline flush was completed, followed by frequency calibration and B₁⁺ mapping⁷. Acquisition parameters: FOV=24$$$\times$$$24cm², resolution=0.75$$$\times$$$0.75cm² (pyruvate) and 1.5$$$\times$$$1.5cm²(lactate/bicarbonate), slice thickness=2.1cm, flip angle=20° (pyruvate) and 30° (lactate/bicarbonate), TE1=12.6ms, ΔTE=14ms, TR=250ms, 4 slices, temporal resolution=3s.
Human Renal Cell Carcinoma Studies (RCC, N=2): Data were acquired with a semi-flexible quadrature transmit and 8-channel receive array (QTAR, Clinical MR Solutions, Brookfield, WI). The acquisitions were triggered by bolus tracking on the kidney. Acquisition parameters: FOV=57$$$\times$$$57cm², resolution=1.5$$$\times$$$1.5cm² (pyruvate) and 2$$$\times$$$2cm² (lactate), TR=200ms, 5 slices; all other parameters are the same as the brain study.
Data Reconstruction and Analysis: HP ¹³C data were reconstructed directly by inverse Fourier transform to the image domain after gridding⁸. The phase caused by B₀ inhomogeneity among different echoes were corrected by the dephasing maps measured from pyruvate signal at the timepoint with its highest signal. To quantify SNR improvement when summing echoes, echo images with SNR>2 were used. The regions-of-interest (ROIs) were manually drawn based on the proton images. The mean signal of an ROI was fitted to a mono-exponential function with noise offset correction9 to measure the T₂^* of each metabolite at each timepoint. All timepoints with echo SNR>3 were used to calculate T₂^*.

Results and Discussion

Figure 2 shows area-under-curve (AUC) echo images for each metabolite in the brain. Lactate exhibited the fastest decay, indicating the shortest T₂^* value (grey matter (GM): 30.1±5.9ms; white matter (WM): 33.8±7.6ms). Because of B₀ inhomogeneity, the signal decays faster in the prefrontal cortex. Bicarbonate images had lower SNR but the T₂^* over the whole brain was well-fit by the mono-exponential decay model and was much longer than lactate (109.5±12.8ms). Figure 3 shows the improvement in image quality when summing all echoes with signal above the noise floor, providing a 1.28±0.23 and 1.44±0.28-fold gain in SNR for lactate and bicarbonate, respectively. Figures 4 and 5 show the dynamic T₂^* curves of pyruvate and lactate in human studies. In Fig. 4, the lactate T₂^* in both GM and WM are constant in the first ten timepoints, which matches the T₂^* values fitted on the lactate AUC images. However, the pyruvate T₂^* values were variable in sinus vein, GM and WM. Due to the spiral PSF and partial volume effects, the T₂^* at the first timepoint in the sinus may be affected by the GM signal. However, after the bolus arrives, the pyruvate T₂^* for all three regions was substantially reduced after the peak signal.
Figure 5 shows the pyruvate and lactate T₂^* through the first 10 timepoints (30s) in the two RCC patients. Both metabolites displayed the same general trends as in the brain – the lactate T₂^* is constant through time in both the tumor and contralateral healthy kidney, whereas the pyruvate T₂^* decreases during the acquisition. Interestingly, the lactate T₂^* measured in the kidneys, tumor, and brain were all similar, whereas the pyruvate T₂^* was much longer in the kidneys and varied throughout the acquisition. The similar lactate T₂^* values may reflect the dominant influence of J-coupling, since [1-¹³C]lactate has higher J_CH-coupling constants and its lineshape is greatly affected by decoupling^10,11. Pyruvate is not dominated by J_CH-coupling, so the variation in pyruvate T₂^* during the acquisition and across organs may be indicative of extravasation from the vasculature to the extravascular/extracellular space or uptake into the cell.

Conclusion

This work describes dynamic T₂^* measurements for HP [1-¹³C]pyruvate and metabolites in a healthy human brain volunteer and two RCC patients. The T₂^* of pyruvate is shown to vary during the acquisition, whereas the T₂^* of lactate and bicarbonate is constant through time. Future studies will work to increase the sample size to confirm these results. These relaxometry measurements will be useful for future sequence optimization, can be used to further improve SNR by summing echoes, and can be included in kinetic modeling to harmonize data across sites and reduce errors in quantification at long echo times.

Acknowledgements

This work was supported by NIH grants U01EB026412, P41EB013598 and R01CA249099.

References

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Figures

Figure 1: (A) Sequence diagram of multi-echo sequence, which was used in the human study for dynamic T₂^* measurement.

Figure 2: HP ¹³C images at different echo times, but summed by area under the curve (AUC) across timepoints, with the fixed display range of each metabolite. See Figure 4 for T2W anatomical reference image.

Figure 3: Comparison of SNR differences when using summation of all echoes images versus only the first echo image of HP ¹³C lactate and bicarbonate from a single slice. Data are shown from a single slice and displayed in SNR units.

Figure 4: Dynamic T₂^* measurements of pyruvate and lactate in the human brain. (A) Pyruvate signal curves of sinus vein (blue), grey matter (red) and white matter (orange). (B) Pyruvate dynamic T₂^* measurements (dashed lines indicate ±95% confidence interval). (C) Lactate signal curves of grey matter and whiter matter. (D) Lactate dynamic T₂^* measurements from the first ten timepoints. (F) Representative decay curves and T₂^* fits from the 3rd (pyruvate) and 5th (lactate) timepoint.

Figure 5: Dynamic T₂^* measurements of pyruvate and lactate in the RCC patients. Contralateral, healthy appearing kidney dynamic T₂^* measurements (dashed lines indicate ±95% confidence interval) were shown in blue lines. Tumor dynamic T₂^* measurements were shown in red lines.

Proc. Intl. Soc. Mag. Reson. Med. 31 (2023)

0667

DOI: https://doi.org/10.58530/2023/0667