Multiband spectral-spatial RF excitation for hyperpolarized [2-13 C]dihydroxyacetone 13 C-MR metabolism studies

Abstract

Purpose: To develop a specialized multislice, single-acquisition approach to detect the metabolites of hyperpolarized (HP) [2-¹³ C]dihydroxyacetone (DHAc) to probe gluconeogenesis in vivo, which have a broad 144 ppm spectral range (∼4.6 kHz at 3T). A novel multiband radio-frequency (RF) excitation pulse was designed for independent flip angle control over five to six spectral-spatial (SPSP) excitation bands, each corrected for chemical shift misregistration effects.

Methods: Specialized multiband SPSP RF pulses were designed, tested, and applied to investigate HP [2-¹³ C]DHAc metabolism in kidney and liver of fasted rats with dynamic ¹³ C-MR spectroscopy and an optimal flip angle scheme. For comparison, experiments were also performed with narrow-band slice-selective RF pulses and a sequential change of the frequency offset to cover the five frequency bands of interest.

Results: The SPSP pulses provided a controllable spectral profile free of baseline distortion with improved signal to noise of the metabolite peaks, allowing for quantification of the metabolic products. We observed organ-specific differences in DHAc metabolism. There was two to five times more [2-¹³ C]phosphoenolpyruvate and about 19 times more [2-¹³ C]glycerol 3-phosphate in the liver than in the kidney.

Conclusion: A multiband SPSP RF pulse covering a spectral range over 144 ppm enabled in vivo characterization of HP [2-¹³ C]DHAc metabolism in rat liver and kidney. Magn Reson Med 77:1419-1428, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Keywords: dihydroxyacetone; dynamic nuclear polarization; hyperpolarization; kidney; liver; metabolic imaging; multiband RF pulses; spectral-spatial RF pulses.

Figure 1

Spectral-spatial RF excitation pulse with independent flip angle control over five excitation bands. (a) RF and gradient waveforms. This 15.2 ms pulse was designed for a 1-cm slab, with the following resonances and their corresponding bandwidths and flip angles: 213.0ppm ± 2ppm (DHAc), 0°; 151.0ppm ± 1ppm (PEP), 67.5°; 96.1ppm ± 1ppm (DHAc hydrate), 0°; 88.0ppm ± 1ppm (additional resonance), 45°; and 73.0ppm ± 3ppm (G3P), 45°. (b) Spectral profile at the center of the slab (at 0 cm) and (b) spatial profile. The black curve displays the profiles of the RF designed with chemical shift misregistration correction (RF pulse shown in (a)), while the red curve characterizes the profiles. Urea was chosen as the center offset (0 Hz) envisioning the use of a urea phantom as a reference during in vivo experiments. Urea was not, however, one of the frequency bands controlled during the design of the experiment, which lead to a broader slice profile.

Figure 2

Schema of the two methods used for the acquisition of the [2-¹³C]DHAc spectra. For the “Multi-frequency shifts” method, the RF offset was changed to center a 21.6ppm effective excitation band for the spatially-selective pulses used on the metabolite region of interest, although slice misregistration resulted in excitation out of this band. The TR between excitations on the same band was 5 s. Conversely, the SPSP RF pulse allowed for acquisition of all the resonances of interest in a single excitation with no slice misregistration, and a TR of 3 s was chosen for dynamic spectra acquisition. Liver and kidney acquisitions were interleaved in both methods.

Figure 3

Signal intensity measurements of the SPSP RF pulse performance on slabs above, below, and through a ¹³C-urea phantom. (a) Sketch of the 2-cm-slab positions on the three syringes filled with a ¹³C-urea solution used as a phantom. (b) Six-band SPSP RF pulse performance. RF flip = 29° was calibrated at the transmitter frequency −2928 Hz (tdel=−4 us). (c) Five-band SPSP RF pulse performance. RF flip = 20° calibrated at the transmitter frequency −2895 Hz (tdel=−4 us). These calibration frequencies correspond to the G3P resonance as targeted in each pulse design. Shaded area is the simulated signal in the slab through the phantom.

Figure 4

¹³C-MRS acquired using the multi-frequency shifts method on a 2-cm slab on the liver and a 2-cm slab on the kidney. The RF pulse excitation bandwidth was 694.4 Hz (21.6ppm), whilst the acquisition bandwidth was 5 KHz (155.8ppm), centered on the frequency offset specified on the right of the image. The shaded areas highlight the excitation band on the center of the prescribed slab. Misregistered resonances can be seen outside the shaded area. The following flip angles were applied on each band: (a) 5°, (b,d,e) 20°, and (c) 30°. Signal was normalized to the DHAc peak in (a). Data shown is the sum of the first five dynamic spectra.

Figure 5

(a) ¹³C-MRS upon injection of hyperpolarized [2-¹³C]DHAc into a fasted rat using a five-band SPSP RF pulse to excite a 1-cm slab placed on the liver (black) and a 1-cm slab placed on the kidney (red). The following flip angles were applied: 0.3° at 213 ppm, 26° at 151 ppm, 2.3° at 96 ppm, 20° at 88 ppm and 20° at 73 ppm. The spectrum shown is the sum of the first five acquisitions. (b) Dynamic curves of the SNR of the metabolic products from (a). (c) Ratio of the integrals of the first five time points of PEP and G3P from the liver over the kidney (mean ± std, n=9). (d) Anatomic reference of the liver and kidney slabs.

Figure 6

Axial 2D MRSI of the liver. (a) A 3D balanced-SSFP ¹H image is shown for anatomic reference, and on the bottom is the same image with the G3P metabolite map overlayed on it. The liver contour is delineated in yellow, highlighting that metabolism of DHAc occurs mainly inside this organ. (b) Axial 2D ¹³C-MRSI acquired 12 s after the start of the injection of hyperpolarized [2-¹³C]DHAc into a fasted rat using the same SPSP RF pulse as in Figure 5. Acquisition parameters: slab thickness = 2 cm, matrix = 8 × 8, FOV = 8 × 8 cm², 10° flip angle calibrated at the transmitter frequency offset −2895 Hz. (c) Dynamic curves of the SNR of G3P and DHAc hydrate from the four voxels highlighted in orange.