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

Isoflurane is a frequently used anesthetic in small‐animal dissolution dynamic nuclear polarization‐magnetic resonance imaging (DNP‐MRI) studies. Although the literature suggests interactions with mitochondrial metabolism, the influence of the compound on cardiac metabolism has not been assessed systematically to date. In the present study, the impact of low versus high isoflurane concentration was examined in a crossover experiment in healthy rats. The results revealed that cardiac metabolism is modulated by isoflurane concentration, showing increased [1‐13C]lactate and reduced [13C]bicarbonate production during high isoflurane relative to low isoflurane dose [average differences: +16% [1‐13C]lactate/total myocardial carbon, –22% [13C]bicarbonate/total myocardial carbon; +51% [1‐13C]lactate/[13C]bicarbonate]. These findings emphasize that reproducible anesthesia is important when studying cardiac metabolism. As the depth of anesthesia is difficult to control in an experimental animal setting, careful study design is required to exclude confounding factors

High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE

The purpose of this work was to increase the resolution of hyperpolarized metabolic imaging of the rat heart with accelerated imaging using k–t principal component analysis (k–t PCA) and k–t compressed sensing (k–t SPARSE). Fully sampled in vivo datasets were acquired from six healthy rats after the injection of hyperpolarized [1‐13C]pyruvate. Data were retrospectively undersampled and reconstructed with either k–t PCA or k–t SPARSE. Errors of signal–time curves of pyruvate, lactate and bicarbonate were determined to compare the two reconstruction algorithms for different undersampling factors R. Prospectively undersampled imaging at 1 × 1 × 3.5‐mm3 resolution was performed with both methods in the same animals and compared with the fully sampled acquisition. k–t SPARSE was found to perform better at R < 3, but was outperformed by k–t PCA at R ≥ 4. Prospectively undersampled data were successfully reconstructed with both k–t PCA and k–t SPARSE in all subjects. No significant difference between the undersampled and fully sampled data was found in terms of signal‐to‐noise ratio (SNR) performance and metabolic quantification. Accelerated imaging with both k–t PCA and k–t SPARSE allows an increase in resolution, thereby reducing the intravoxel dephasing of hyperpolarized metabolic imaging of the rat heart

Overestimation of cardiac lactate production caused by liver metabolism of hyperpolarized [1-13C]pyruvate

PURPOSE: The purpose of this work was to study the contribution of liver [1-13 C]lactate to the lactate signal detected in the heart following injection of hyperpolarized [1-13 C]pyruvate. METHODS: A slice-selective saturation scheme was incorporated into a hybrid metabolic imaging and spectroscopy approach to selectively presaturate lactate in the liver. Imaging and slice-selective spectroscopy of [1-13 C]pyruvate and its downstream metabolites were sequentially interleaved in the same experiment with optional presaturation of liver [1-13 C]lactate. Six healthy rats were measured, and metabolic data in the heart acquired with and without presaturation of liver lactate were compared. RESULTS: When using liver lactate presaturation, a statistically significant reduction of the lactate/pyruvate ratio was observed in the spectroscopic data of the left ventricle (0.18 ± 0.03 versus 0.24 ± 0.04; p < .05) as well as in the imaging data of the blood pool (0.05 ± 0.01 versus 0.11 ± 0.01; p < .05). No significant difference in myocardial lactate was observed when using myocardium only as the region of interest in the imaging data (0.08 ± 0.01 versus 0.11 ± 0.02; p = .2). CONCLUSION: Liver metabolism leads to statistically significant overestimation of cardiac lactate production in slice-selective or nonselective spectroscopic experiments. Therefore, metabolic imaging is preferred over spectroscopy to separate left-ventricular compartments within the slice and hence avoid contamination of cardiac lactate signals. Alternatively, presaturation pulses should be used in combination with spectroscopy approach

Production of highly polarized [1- 13 C]acetate by rapid decarboxylation of [2- 13 C]pyruvate - application to hyperpolarized cardiac spectroscopy and imaging

Purpose: The objective of the present work was to develop and implement an efficient approach to hyperpolarize [1-13 C]acetate and apply it to in vivo cardiac spectroscopy and imaging. Methods: Rapid hydrogen peroxide induced decarboxylation was used to convert hyperpolarized [2-13 C]pyruvate into highly polarized [1-13 C]acetate employing an additional step following rapid dissolution of [2-13 C]pyruvate in a home-built multi-sample dissolution dynamic nuclear polarization system. Phantom dissolution experiments were conducted to determine optimal parameters of the decarboxylation reaction, retaining polarization and T1 of [1-13 C]acetate. In vivo feasibility of detecting [1-13 C]acetate metabolism is demonstrated using slice-selective spectroscopy and multi-echo imaging of [1-13 C]acetate and [1-13 C]acetylcarnitine in the healthy rat heart. Results: The first in vivo signal was observed ~23 s after dissolution. At the corresponding time point in the phantom experiments, 97.9 ± 0.4% of [2-13 C]pyruvate were converted into [1-13 C]acetate by the decarboxylation reaction. T1 and polarization of [1-13 C]acetate was determined to be 29.7 ± 1.9% and a 47.7 ± 0.5 s. Polarization levels of [2-13 C]pyruvate and [1-13 C]acetate were not significantly different after transfer to the scanner. In vivo, [1-13 C]acetate and [1-13 C]acetylcarnitine could be detected using spectroscopy and imaging. Conclusion: Decarboxylation of hyperpolarized [2-13 C]pyruvate enables the efficient production of highly polarized [1-13 C]acetate that is applicable to study short-chain fatty acid metabolism in the in vivo heart

Nanometer size silicon particles for hyperpolarized MRI

Hyperpolarized silicon particles have been shown to exhibit long spin-lattice relaxation times at room temperature, making them interesting as novel MRI probes. Demonstrations of hyperpolarized silicon particle imaging have focused on large micron size particles (average particle size (APS) = 2.2 μm) as they have, to date, demonstrated much larger polarizations than nanoparticles. We show that also much smaller silicon-29 particles (APS = 55 ± 12 nm) can be hyperpolarized with superior properties. A maximum polarization of 12.6% in the solid state is reported with a spin-lattice relaxation time of 42 min at room temperature thereby opening a new window for MRI applications.ISSN:2045-232

Direct hyperpolarization of micro- and nanodiamonds for bioimaging applications – Considerations on particle size, functionalization and polarization loss

Due to the inherently long relaxation time of 13C spins in diamond, the nuclear polarization enhancement obtained with dynamic nuclear polarization can be preserved for a time on the order of about one hour, opening up an opportunity to use diamonds as a new class of long-lived contrast agents. The present communication explores the feasibility of using 13C spins in directly hyperpolarized diamonds for MR imaging including considerations for potential in vivo applications

Hyperpolarized metabolic imaging of myocardial ischemia-reperfusion in a small-animal model at 9.4T

ISSN:1097-6647ISSN:1532-429

Hyperpolarized metabolic MR imaging of acute myocardial changes and recovery after ischemia-reperfusion in a small-animal model

Purpose To implement hyperpolarized magnetic resonance (MR) imaging in an animal model of ischemia-reperfusion and to assess in vivo the regional changes in pyruvate metabolism within the 1st hour and at 1 week after a brief episode of coronary occlusion and reperfusion. Materials and Methods All animal experiments were performed with adherence to the Swiss Animal Protection law and were approved by the regional veterinary office. A closed-chest rat model was implemented by using an inflatable balloon secured around the left coronary artery. Animals were placed in an MR system 5-7 days after surgery. [1-13C]pyruvate was polarized by using a home-built multisample hyperpolarizer. Hyperpolarized pyruvate was injected at five stages: at baseline; at reperfusion after 15 minutes of coronary occlusion; and at 30 minutes, 60 minutes, and 1 week after ischemia reperfusion. The conversion of pyruvate into lactate and bicarbonate was imaged by using dedicated MR sequences alongside wall motion and delayed enhancement imaging. After imaging, the heart was removed and stained to delineate the area at risk (AAR). Differences between AAR and remote myocardium were assessed by using a repeated measures analysis of variance and a post hoc Bonferroni multiple comparison test. Results Data were collected in 12 animals. Occlusion led to hypokinesia of the anterior or anterolateral segments of the myocardium. At reperfusion, the average lactate-to-bicarbonate ratio increased in the AAR relative to that at baseline (from 1.93 ± 0.48 to 3.01 ± 0.74, P < .001) and was significantly higher when compared with that in the remote area (1.91 ± 0.38, P < .001). In the 60 minutes after occlusion, the lactate-to-bicarbonate ratio in the AAR recovered but was still elevated relative to that in the remote area. One week after ischemia-reperfusion, no difference between AAR and remote area could be detected. Conclusion Hyperpolarized metabolic MR imaging can be used to successfully detect acute changes in [1-13C]pyruvate metabolism after ischemia-reperfusion, thereby enabling in vivo monitoring of the metabolic effects of reperfusion strategies. © RSNA, 2015 Online supplemental material is available for this article