High spatiotemporal resolution bSSFP imaging of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate with spectral suppression of alanine and pyruvate-hydrate

Abstract

Purpose: The bSSFP acquisition enables high spatiotemporal resolution for hyperpolarized ¹³C MRI at 3T, but is limited by spectral contamination from adjacent resonances. The purpose of this study was to develop a framework for in vivo dynamic high resolution imaging of hyperpolarized [1-¹³C]pyruvate and [1-¹³C]lactate generated in vivo at 3T by simplifying the spectrum through the use of selective suppression pulses.

Methods: Spectral suppression pulses were incorporated into the bSSFP sequence for suppression of [1-¹³C]alanine and [1-¹³C]pyruvate-hydrate signals, leaving only the pyruvate and lactate resonances. Subsequently, the bSSFP pulse width, time-bandwidth, and repetition time were optimized for imaging these dual resonances.

Results: The spectral suppression reduced both the alanine and pyruvate-hydrate signals by 85.5 ± 4.9% and had no significant effect on quantitation of pyruvate to lactate conversion (liver: P = 0.400, kidney: P = 0.499). High resolution (2 × 2 mm² and 3 × 3 mm²) sub-second 2D coronal projections and 3D 2.5 mm isotropic images were obtained in rats and tumor-bearing mice with 1.8-5 s temporal resolution, allowing for calculation of lactate-to-pyruvate ratios and k_PL.

Conclusion: The developed framework presented here shows the capability for dynamic high resolution volumetric hyperpolarized bSSFP imaging of pyruvate-to-lactate conversion on a clinical 3T MR scanner.

Keywords: 13C; SSFP; hyperpolarized; metabolism; pyruvate.

Figure 1

Depiction of pulse sequence and spectral suppression region. (A) Pulse sequence diagram for the 3D bSSFP sequence used in these studies, with the spectral suppression (Specsat) pulses and crusher gradients being played out 3 times and one time, respectively, prior to imaging. The sequence consists of m phase encodes and n time-points, with the 2D version sequence featuring one fewer set of phase encode gradients for projection imaging. (B) The suppression region for the spectral suppression pulse is shown here in the context of suppressing the two main peaks between [1-¹³C]pyruvate and [1-¹³C]lactate, [1-¹³C]alanine and [1-¹³C]pyruvate-hydrate. The relative frequency separation in Hz for 3T is shown below the spectrum.

Figure 2

Slab-selective MRS results of the spectral suppression pulse. (A) The effect of the spectral suppression pulse is shown as a function of the distance of the spectral suppression pulse center frequency to the lactate peak in a thermal phantom (blue line). At ≥100 Hz the pulse has no effect on the lactate peak, which is indicated by the green dashed line and is representative of the baseline lactate signal when no spectral suppression pulses are present. (B, C) Parts B and C show the spectrum from a liver slab before and after the spectral suppression pulses, respectively. The pyruvate and lactate peaks remain unaffected, while the alanine and pyruvate-hydrate peaks are sufficiently suppressed by 89.0 ± 5.1% and 90.7 ± 4.1%, respectively. (D, E) Parts D and E show similar results from a kidney slab as parts B and C, with the alanine and pyruvate-hydrate peaks sufficiently suppressed by 84.1 ± 4.2% and 83.4 ± 5.3%, respectively.

Figure 3

Simulated and experimental bSSFP signal responses. (A, B) Simulations of a α = 60° 6.8 ms sinc pulse (TBW = 2) with a 15.3 ms TR. Part A shows the frequency response on-resonance, i.e. when the transmit frequency is set to pyruvate, and part B shows the frequency response 390 Hz off-resonance, i.e. at the lactate resonance. Part B shows negligible excitation 390 ± 25 Hz off-resonance for this pulse width, TBW, and TR, indicating no contamination of the pyruvate image with lactate signal (and vice-versa when the transmit frequency is set to lactate due to the symmetric frequency response). (C, D) Parts C and D show the thermal phantom acquisition with the aforementioned pulse and TR, with the on-resonance and off-resonance responses matching the simulations in parts A and B.

Figure 4

Parts A (pyruvate) and B (lactate) show the first time-point (20 s after start of injection) of the 2 × 2 mm² in-plane resolution bSSFP acquisition, while parts D (pyruvate) and E (lactate) show the first time-point of the 3 × 3 mm² in-plane resolution bSSFP acquisition. Parts C and F show the carbon pyruvate image overlaid onto the ¹H anatomical image. The SNR (>40 for pyruvate and >15 for lactate) was high enough at both spatial resolutions to visualize pyruvate and lactate distribution in kidneys, heart, and vasculature. All images were zero-filled for display purposes.

Figure 5

Parts A and B show the resulting images of pyruvate and lactate, respectively, from all the time-points of the 2D dynamic coronal projection scan, which started at 5 s after the start of injection (represented by the 0 s in the first time-point). The SNR was high enough to visualize heart, vasculature, and kidneys for both metabolites, with the pyruvate signal lasting in the kidneys to the last time-point. Part C shows the resulting k_PL map with voxels in the vasculature and kidney featuring values that match up well with literature values (k_PL ≈ 0.013 s^-1 in kidneys and k_PL ≈ 0.004 s^-1 in vasculature (43)). Part D shows the AUC_lac/AUC_pyr map, with the AUC ratio values agreeing well with the k_PL values based on qualitative analysis, i.e. low heart and vasculature AUC ratio and k_PL, higher liver AUC ratio and k_PL, with kidneys being in between (44). The images in parts A and B were zero-filled for display purposes, while k_PL and AUC ratio maps are at native resolution.

Figure 6

In vivo 3D dynamic rat imaging results. (A, B) Results from a 3D dynamic 2.5 mm isotropic resolution acquisition in a healthy rat. Parts A and B are of pyruvate and lactate, respectively. Each part features a 3D view of a representative time-point (top two rows), all the time-points of the sum along the slice dimension (bottom row) showing how long the signal lasts for each metabolite, and a carbon overlay on a ¹H anatomical image of the slice outlined in orange. The SNR was also high enough in this acquisition to visualize each metabolite in heart, vasculature, and kidneys, although the signal doesn't last as long as the 2D coronal projections due to smaller voxel sizes, especially with lactate. All images were zero-filled for display purposes.

Figure 7

In vivo 3D dynamic tumor-bearing mouse results. (A, B) Results from a 3D dynamic 2.5 mm isotropic resolution acquisition in a tumor-bearing mouse. Parts A and B are of pyruvate and lactate, respectively, and the presented views are similar to Figure 6A and 6B. The SNR was high enough to visualize the metabolites and heart and tumor, with the signal lasting longer than in the rats, potentially due to a larger production of lactate in the tumor. All images were zero-filled for display purposes.