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Dynamic 13 C MR spectroscopy as an alternative to imaging for assessing cerebral metabolism using hyperpolarized pyruvate in humans - PubMed

. 2022 Mar;87(3):1136-1149.

doi: 10.1002/mrm.29049. Epub 2021 Oct 22.

Affiliations

Dynamic 13 C MR spectroscopy as an alternative to imaging for assessing cerebral metabolism using hyperpolarized pyruvate in humans

Junjie Ma et al. Magn Reson Med. 2022 Mar.

Abstract

Purpose: This study is to investigate time-resolved 13 C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1-13 C]pyruvate in the human brain.

Methods: Time-resolved 13 C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1-13 C]pyruvate. 13 C MRS with low flip-angle excitations and a multichannel 13 C/1 H dual-frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice-wise areas under the curve (AUCs) of 13 C-metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO3- . Linear regression analysis between brain volumes and HP signals was performed. Region-focused pyruvate metabolism was estimated using coil-wise 13 C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45-minutes interval.

Results: [1-13 C]Lactate relative to the total 13 C signal (tC) was 0.21-0.24 in all slices. [13 C] HCO3- /tC was 0.065-0.091. Apparent conversion rate constants from pyruvate to lactate and HCO3- were calculated as 0.014-0.018 s-1 and 0.0043-0.0056 s-1 , respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1-13 C]pyruvate.

Conclusions: Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1-13 C]pyruvate.

Keywords: dynamic nuclear polarization; human brain; hyperpolarized pyruvate; magnetic resonance spectroscopy; reproducibility.

© 2021 International Society for Magnetic Resonance in Medicine.

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Conflict of interest statement

Conflict of Interest

G.D.R. and A.P.C. are employees of GE Healthcare.

Figures

Figure 1.
Figure 1.. 13C/1H dual-frequency RF head coil.

The 13C/1H dual-frequency RF head coil that consists of 1H quadrature Tx and Rx, 13C quadrature Tx and 8-channel 13C receive Rx arrays was developed for this study.

Figure 2.
Figure 2.. SNR comparison between 13C MRS with small flip-angle excitation and 13C MRI with 90° excitation.

(A) 1H T2-weighted fast spin echo image of the gadolinium-doped spherical [13C]HCO3− phantom was acquired with the 13C/1H dual-frequency RF head coil. (B) 13C images of the phantom with three nominal in-plane spatial resolutions (3.0 cm × 3.0 cm, 1.5 cm × 1.5 cm and 1.0 cm × 1.0 cm) were acquired using a 2D slice-selective spiral imaging sequence with 90° excitation. (C) 13C spectrum acquired using MRS with 6.5° flip-angle from the same phantom.

Figure 3.
Figure 3.. Time-averaged 13C spectra of four axial brain slices.

(A) Time-averaged, coil-combined, and phase-corrected spectra, normalized by the maximum pyruvate peak, from a representative participant. Prescription of four axial slices for HP 13C MRS is shown in the sagittal 1H MRI. (B) HP [1-13C]lactate, [13C]HCO3–, [1-13C]alanine, and [1-13C]pyruvate-hydrate, normalized by total HP 13C (tC). Measurement from slice #1, #2, #3 and #4 are color-coded in black, red, blue, and green, respectively. (C) Metabolite ratios of lactate-to-pyruvate, HCO3–-to-pyruvate, pyruvate-hydrate-to-pyruvate, and HCO3–-to-lactate.

Figure 4.
Figure 4.. Correlation of HP signals to brain volumes.

(A) Area under the curves (AUCs) for HP [1-13C]pyruvate (black dots), [1-13C]lactate (red dots), and [13C]HCO3– (blue dots) from each brain slice in relation to the brain volumes of WM, GM, and CSF within the slice. (B) HP 13C signal intensities of each metabolite relative to the total HP 13C signal (tC) within the slice in relation to fractional brain volumes of WM, GM, and CSF of the slice. Lines indicate linear regressions (solid: p-value ≤ 0.05, dotted: p > 0.5). Lac: [1-13C]lactate, Bic: [13C]HCO3–, Ala: [1-13C]alanine, Pyr-Hyd: [1-13C]pyruvate hydrate, Pyr: [1-13C]pyruvate, WM: white matter, GM: grey matter, CSF: cerebrospinal fluid.

Figure 5.
Figure 5.. Coil-wise reconstruction of HP 13C spectra.

Time-averaged 13C spectra and metabolite ratios for individual 13C coil elements. [1-13C]Lactate and [13C]HCO3–, normalized by total HP 13C signals (tC), from each 13C channel are color-coded in red and blue, respectively, and overlaid on the corresponding brain slice (slice #1) to indicate the region-weighted measurements.

Figure 6.
Figure 6.. Kinetic analysis.

(A) Representative time-curves of HP [1-13C]pyruvate (black filled circle), [1-13C]lactate (red cross), [13C]HCO3– (blue empty circle), and [1-13C]pyruvate-hydrate (green triangle). Times-to-peak and initial slope for pyruvate, lactate, and HCO3– are shown. (B) Measured (markers) and fitted (solid lines) for [1-13C]lactate (red) and [13C]HCO3– (blue) in slices #1 – #4 from a representative participant. Measured [1-13C]pyruvate is shown in black. (C) Initial slopes of [1-13C]lactate (red) and [13C]HCO3– (blue) relative to the initial slope of [1-13C]pyruvate, (D) times-to-peak for [1-13C]pyruvate (black), [1-13C]lactate (red), and [13C]HCO3– (blue) from the start of HP [1-13C]pyruvate injection, and (E) apparent conversion rate constants from [1-13C]pyruvate to [1-13C]lactate (kPL, red) and to [13C]HCO3– (kPB, blue) for each brain slice.

Figure 7.
Figure 7.. Time-resolved metabolic ratios.

(A) HCO3–/tC, (B) lactate/tC and (C) HCO3–/lactate increased over time after each HP injection while (D) pyruvate-hydrate/pyruvate was maintained constant. The increasing behavior of these metabolite ratios was consistent over different brain slices.

Figure 8.
Figure 8.. Reproducibility of HP [1-13C]pyruvate.

(A) Area under the curves (AUCs) for pyruvate, lactate, and bicarbonate, normalized by total HP 13C signals (tC), (B) apparent pyruvate conversion rate constants to lactate (kPL) and bicarbonate (kPB), and (C) initial slopes of lactate and bicarbonate production relative to the pyruvate slope were comparable between two consecutive HP [1-13C]pyruvate studies. The two HP pyruvate MRS data were acquired with a 45-min interval between the injections.

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