Effects of isoflurane anesthesia on hyperpolarized ¹³C metabolic measurements in rat brain

Abstract

Purpose Commonly used anesthetic agents such as isoflurane are known to be potent cerebral vasodilators, with reported dose-dependent increase in cerebral blood flow and cerebral blood volume. Despite the widespread use of isoflurane in hyperpolarized 13C pre-clinical research studies, a quantitative assessment of its effect on metabolic measurements is limited. This work investigates the effect of isoflurane anesthesia dose on hyperpolarized 13C MR metabolic measurements in rat brain for [1-13C]pyruvate and 2-keto[1-13C]isocaproate. Methods Dynamic 2D and 3D spiral chemical shift imaging was used to acquire metabolic images of rat brain as well as kidney and liver following bolus injections of hyperpolarized [1-13C]pyruvate or 2-keto[1-13C]isocaproate. The impact of a ‘low dose’ vs. a ‘high dose’ of isoflurane on cerebral metabolite levels and apparent conversion rates was examined. Results The cerebral substrate signal levels, and hence the metabolite-to-substrate ratios and apparent conversion rates, were found to depend markedly on isoflurane dose, while signal levels of metabolic products and their ratios, e.g. bicarbonate/lactate, were largely insensitive to isoflurane levels. No obvious dependence on isoflurane was observed in kidney or liver for pyruvate. Conclusion This study highlights the importance of careful attention to the effects of anesthesia on the metabolic measures for hyperpolarized 13C metabolic imaging in brain.

Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

“…A multitude of different anesthetics and anesthesia procedures are used throughout the literature, potentially affecting the acquired bio‐chemical information and thus imposing constraints on the comparability of studies performed under different circumstances. This is particularly true with the advancement of the metabolic imaging methods, such as hyperpolarized MRI and spectroscopy, which enable in vivo metabolic examinations in real time, and as such, are inherently sensitive to metabolic disturbances imposed by the anesthesia . Furthermore, some anesthetics have been shown to even protect animals against various conditions, such as renal ischemia‐reperfusion injury, during the investigations.…”

Assessing the influence of isoflurane anesthesia on cardiac metabolism using hyperpolarized [1‐13C]pyruvate

“…The effects of isoflurane in hyperpolarized Pyr measurements have been assessed in the rat brain, kidney and liver, demonstrating that dose variations of isoflurane do not confound metabolic measurements. However, a detailed examination of the potential influence of isoflurane modulation on cardiac metabolism has not been conducted to date.…”

Hyperpolarized 13C‐lactate to 13C‐bicarbonate ratio as a biomarker for monitoring the acute response of anti‐vascular endothelial growth factor (anti‐VEGF) treatment

“…The lactate to bicarbonate ratios (Fig. I) were relatively low in the cortex of the brain . Brain SNRs were calculated as 148.8 ± 20.9 for pyruvate, 200.6 ± 31.8 for lactate, 14.2 ± 1.2 for pyruvate hydrate and 70.2 ± 5.0 for bicarbonate maps.…”