Simultaneous fMRI and metabolic MRS of hyperpolarized [1‐13C]pyruvate during nicotine stimulus in rat

Abstract

AbstractFunctional MRI (fMRI) and MRS (fMRS) can be used to noninvasively map cerebral activation and metabolism. Recently, hyperpolarized 13C spectroscopy and metabolic imaging have provided an alternative approach to assess metabolism. In this study, we combined 1H fMRI and hyperpolarized [1‐13C]pyruvate MRS to compare cerebral blood oxygenation level‐dependent (BOLD) response and real‐time cerebral metabolism, as assessed with lactate and bicarbonate labelling, during nicotine stimulation. Simultaneous 1H fMRI (multislice gradient echo echo‐planar imaging) and 13C spectroscopic (single slice pulse‐acquire) data were collected in urethane‐anaesthetized female Sprague–Dawley rats (n = 12) at 9.4 T. Animals received an intravenous (i.v.) injection of either nicotine (stimulus; 88 μg/kg, n = 7, or 300 μg/kg, n = 5) or 0.9% saline (matching volume), followed by hyperpolarized [1‐13C]pyruvate injection 60 s later. Three hours later, a second injection was administered: the animals that had previously received saline were injected with nicotine and vice versa, both followed by another hyperpolarized [1‐13C]pyruvate i.v. injection 60 s later. The low‐dose (88 μg/kg) nicotine injection led to a 12% ± 4% (n = 7, t‐test, p ~ 0.0006 (t‐value −5.8, degrees of freedom 6), Wilcoxon p ~ 0.0078 (test statistic 0)) increase in BOLD signal. At the same time, an increase in 13C‐bicarbonate signal was seen in four out of six animals. Bicarbonate‐to‐total carbon ratios were 0.010 ± 0.004 and 0.018 ± 0.010 (n = 6, t‐test, p ~ 0.03 (t‐value −2.3, degrees of freedom 5), Wilcoxon p ~ 0.08 (test statistic 3)) for saline and nicotine experiments, respectively. No increase in the lactate signal was seen; lactate‐to‐total carbon was 0.16 ± 0.02 after both injections. The high (300 μg/kg) nicotine dose (n = 5) caused highly variable BOLD and metabolic responses, possibly due to the apparent respiratory distress. Simultaneous detection of 1H fMRI and hyperpolarized 13C‐MRS is feasible. A comparison of metabolic response between control and stimulated states showed differences in bicarbonate signal, implying that the hyperpolarization technique could offer complimentary information on brain activation.