Single shot three-dimensional pulse sequence for hyperpolarized 13 C MRI

Abstract

Purpose: Metabolic imaging with hyperpolarized ¹³ C-labeled cell substrates is a promising technique for imaging tissue metabolism in vivo. However, the transient nature of the hyperpolarization, and its depletion following excitation, limits the imaging time and the number of excitation pulses that can be used. We describe here a single-shot three-dimensional (3D) imaging sequence and demonstrate its capability to generate ¹³ C MR images in tumor-bearing mice injected with hyperpolarized [1-¹³ C]pyruvate.

Methods: The pulse sequence acquires a stack-of-spirals at two spin echoes after a single excitation pulse and encodes the kz-dimension in an interleaved manner to enhance robustness to B₀ inhomogeneity. Spectral-spatial pulses are used to acquire dynamic 3D images from selected hyperpolarized ¹³ C-labeled metabolites.

Results: A nominal spatial/temporal resolution of 1.25 × 1.25 × 2.5 mm³ × 2 s was achieved in tumor images of hyperpolarized [1-¹³ C]pyruvate and [1-¹³ C]lactate acquired in vivo. Higher resolution in the z-direction, with a different k-space trajectory, was demonstrated in measurements on a thermally polarized [1-¹³ C]lactate phantom.

Conclusion: The pulse sequence is capable of imaging hyperpolarized ¹³ C-labeled substrates at relatively high spatial and temporal resolutions and is robust to moderate system imperfections. Magn Reson Med 77:740-752, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords: imaging; lactate; metabolism; pyruvate; spiral trajectory; tumors.

Figure 1

Spectral‐spatial excitation pulse to excite alternately the [1‐¹³C]pyruvate and [1‐¹³C]lactate resonances. a: RF profile (in Gauss) and oscillating slice selection gradient (in Gauss/cm). b: Frequency response (15 ° at 0 Hz). c: Slice profiles for 15 ° and 90 ° flip angles. Note that although the design target of the pulse was 15 °, the quality of the excitation profile was maintained for the 90 ° flip angle pulse.

Figure 2

The pulse sequence (a) and its 3D k‐space trajectory (b). The pulse sequence includes a spectral‐spatial excitation pulse and two pairs of adiabatic inversion pulses. All phase encoding steps in the z‐direction were completed after a single excitation by using blipped gradients. Two spin echoes were acquired in two groups of spiral readouts, resulting in dual‐T₂ weighted contrast. The gradients within each acquisition interval were self‐refocused, and the sequence ends with spoiler gradients along all three axes. The whole of k‐space was acquired as a stack of interleaved spirals. The 1^st, 3^rd, 5^th, and 7^th spirals were acquired in the first group, while the 8^th, 6^th, 4^th, and 2^nd spirals were acquired in the second group. The kx‐ky matrix size is larger in the center of the kz‐direction and smaller in the peripheral planes, resulting in a spherical 3D k‐space.

Figure 3

¹H and ¹³C images (FOV of 40 × 40 × 20 mm³) acquired from a cylindrical phantom (inner diameter 7 mm) containing 8.5 M [1‐¹³C]lactate. Images were also acquired with a FOV in the z direction of 16 mm, 24 mm, 32 mm, and 40 mm (not shown). Proton T₂ weighted images (a). ¹³C images acquired using the 32 × 32 × 8 sequence (b), 16 × 16 × 8 sequence (c), and 16 × 16 × 12 sequence (d). The white bars at the periphery of the images relate the position of the sagittal and coronal slices to the displayed axial slice. The white curves in the sagittal and coronal views of the ¹³C images indicate the excitation profile and its location.

Figure 4

Slab profiles for a series of FOVs in the z‐direction for the three k‐space trajectory designs, compared with the simulated excitation pulse response. The slab profiles were obtained by summing over the x–y plane for images at each z position for each 3D dataset. For each subplot, the horizontal axis represents position in the z‐direction, in centimeters, and the y axis represents the signal intensity normalized to the maximum value.

Figure 5

The 3D point spread functions for sagittal, coronal and axial views for the 32 × 32 × 8 (a), 16 × 16 × 8 (b) and 16 × 16 × 12 (c) designs. The PSF of the 16 × 16 × 12 design shows a sharp improvement in the z‐direction when compared with the 32 × 32 × 8 design, at the expense of compromised x–y plane resolution.

Figure 6

Representative dynamic hyperpolarized [1‐¹³C]pyruvate (a) and [1‐¹³C]lactate images (b) acquired using the 32 × 32 × 8 design from a single slice (4^th), overlaid on the corresponding T₂ weighted ¹H image. The ¹³C images were interpolated to give a 256 × 256 in‐plane matrix, which was then overlaid on the ¹H image, which had the same matrix size. The tumor region is outlined in the pyruvate image acquired at the first time point (a). Images from all eight slices at 6 s and 7 s are shown for pyruvate (c) and lactate (d), respectively. The images at 14 s (pyruvate) and 15 s (lactate) were acquired with the encoding gradients on the z axis turned off and were used as a reference and are not displayed. The signal intensity at each pixel is indicated with a separate color scale for each panel, with the maxima indicated in arbitrary units.

Figure 7

Time course of the hyperpolarized ¹³C signals from pyruvate and lactate in the tumors of the three EL4 tumor‐bearing mice. The signals were summed across all the slices, for both pyruvate (solid line) and lactate (dashed line).

Figure 8

Analysis of B₀ homogeneity. a: Representative B₀ maps, expressed as ¹³C frequency variations, of the tumor region in a single mouse at all eight slice positions. The frequencies varied from ‐10 Hz to + 5 Hz, which is well below the limit of ±77.16 Hz (see the Discussion section). b: Histogram analysis of the B₀ maps in the tumor regions from all three mice and for all eight slice positions. c: Histogram analysis of the B₀ maps for regions of the whole animal covered by the 3D FOV. The B₀ maps were acquired using the water proton resonance and then converted to ¹³C frequency variations based on the ¹H and ¹³C gyromagnetic ratios.

Figure 9

Averaged $\Delta B_0$ variation in the z‐direction, for all three mice. The $\Delta B_0$ values were averaged within the tumor region for each slice. These curves show a smooth transition of $\Delta B_0$ between adjacent slices and thus minimal signal modulation in the z‐direction.