Metabolic imaging in the anesthetized rat brain using hyperpolarized [1-13C] pyruvate and [1-13C] ethyl pyruvate

Abstract

Formulation, polarization, and dissolution conditions were developed to obtain a stable hyperpolarized solution of [1-(13)C]-ethyl pyruvate. A maximum tolerated concentration and injection rate were determined, and (13)C spectroscopic imaging was used to compare the uptake of hyperpolarized [1-(13)C]-ethyl pyruvate relative to hyperpolarized [1-(13)C]-pyruvate into anesthetized rat brain. Hyperpolarized [1-(13)C]-ethyl pyruvate and [1-(13)C]-pyruvate metabolic imaging in normal brain is demonstrated and quantified in this feasibility and range-finding study.

FIG. 1

3-T Axial T2W proton reference images are shown in (a,c), and the corresponding color [1-¹³C] pyruvate images overlaid on grayscale proton anatomic images are shown on the right in (b,d). 8-M ¹³C-urea insert signal is projected across the chemical shift for quantitative reference. Top: 1.06 μmol g⁻¹ dose; image collected starting 20 sec after start of injection (rat H76). Bottom: 1.01 μmol g⁻¹ dose; image collected starting 36 sec after injection (rat H88).

FIG. 2

Spectral grid display and image of rat data collected at 36 sec after the start of [1-¹³C] pyruvate injection (rat H88). Grid is displayed at a sampled resolution of 2.5mm × 2.5mm in plane. Color-overlaid metabolite maps have been Fourier interpolated once in both in-plane dimensions, from 16 × 16 to 32 × 32.

FIG. 3

a: Metabolic images of [1-¹³C]-EP and [1-¹³C]-pyruvate are compared at an image delay of 20 sec (rat H76). Metabolite maps for the EP injection are shown across the top, and maps for the pyruvate injection, across the bottom. Phased and baseline- corrected spectral array for a 3 × 3 grid of brain voxels is illustrated in the center, along with the voxel positions on a reference image. Left center shows an annotated spectral grid for the EP injection and right center shows an annotated spectral grid for the pyruvate injection. b: Expanded and annotated brain ROI spectra from the EP run (bottom) and pyruvate run (top). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

FIG. 4

Metabolic images of [1-¹³C]-pyruvate with a 45-sec image delay and [1-¹³C]-EP with an image delay of 25 sec are compared (rat H91). Metabolite maps from the EP injection are shown at the top, and maps for the pyruvate injection, along the bottom. A phased and baseline-corrected spectral array for a 4 × 2 grid of brain voxels is illustrated in the center, along with the voxel positions on a reference proton image. The top right center panel shows the EP spectral grid and the bottom right center panel shows the [1-¹³C]-pyruvate results.

FIG. 5

Comparison of EP metabolic maps (rat H91) for lactate (a) and EP-hydrate (b), with pyruvate metabolic maps (rat H111) for lactate (c) and pyruvate (d) under optimum imaging conditions. High dose and image delay of 20 sec for pyruvate, slow injection rate and 25-sec image delay for EP. Excellent brain EP-hydrate and lactate distribution observed in (b) and (a). Characteristic large out-of-brain pyruvate signal level is observed following a pyruvate injection (d).