The human anterior cingulate cortex (ACC) is part of the default-mode network that shows predominant negative blood oxygen level-dependent (BOLD) responses in functional magnetic resonance imaging (fMRI). We combined fMRI during emotional processing and resting-state magnetic resonance spectroscopy measurements and observed that the concentration of GABA in the ACC specifically correlated with the amount of negative BOLD responses in the very same region. Our findings show that default-mode network negative BOLD responses during emotions are mediated by GABA.
Metabolic imaging with hyperpolarized [1-13 C]pyruvate offers the unique opportunity for a minimally invasive detection of cellular metabolism. Efficient and robust acquisition and reconstruction techniques are required for capturing the wealth of information present for the limited duration of the hyperpolarized state (~1 min). In this study, the Dixon/IDEAL type of water-fat separation is expanded toward spectroscopic imaging of [1- 13C]pyruvate and its down-stream metabolites. For this purpose, the spectral-spatial encoding is based on single-shot spiral image encoding and echo-time shifting in between excitations for the chemical-shift encoding. In addition, also a free-induction decay spectrum is acquired and the obtained chemical-shift prior knowledge is efficiently used in the reconstruction. The spectral-spatial reconstruction problem is found to efficiently separate into a chemical-shift inversion followed by a spatial reconstruction. The method is successfully demonstrated for dynamic, multislice [1- Within the past decade, hyperpolarization for in vivo MR imaging and spectroscopy has expanded from gaseous imaging agents toward liquid ones. Among others, dynamic nuclear polarization (DNP) in the amorphous state followed by rapid dissolution has demonstrated as a versatile method to increase the polarization of liquidstate MR imaging agents by more than four orders of magnitude as compared with thermal polarization levels (1,2). The lifetime of the obtained hyperpolarized liquid MR imaging agent is determined by the spin-lattice T 1 relaxation time, which is dependent on the nuclei and its relative position within the molecule considered.Among possible choices, in particular, labeled [1-13 C]pyruvate (noted subsequently as Pyr) has emerged as a promising marker for metabolic MR imaging due to its endogenous character and favorable properties in terms of hyperpolarization, i.e., high polarization levels of up to $50% and long T 1 relaxation times on the order of $30 s in vivo and $65 s ex vivo (2,3). In vivo, hyperpolarized Pyr gets converted into other MR detectable down-stream metabolites, namely lactate (Lac), alanine (Ala), pyruvate-hydrate (PyrH), and bicarbonate (BiC). The metabolites can be distinguished based on their spectral fingerprint, which consists of approximately singlet peaks at well-separated chemical-shift (CS) frequencies. Information about metabolic pathways and the corresponding turn-over ratios can be derived from the time evolution of the individual metabolite concentrations (4,5).Accordingly, hyperpolarized Pyr provides a wealth of detailed metabolic information during limited time duration, which is on the order of the T 1 relaxation time. Various sequences with different trade-offs between temporal and spatial resolution have been suggested for capturing the available information (6,7): small flip-angle (FA), short repetition time (TR), and slice-selective freeinduction decay (FID) acquisition of full spectra provide high temporal resolution with volume selection only along the...
A two-dimensional fitting procedure is introduced, capable of extracting the full amount of information from 2D J-resolved magnetic resonance spectroscopic data. The fitting procedure uses a linear combination of 2D model spectra. For reducing the degrees of freedom and increasing robustness, it is divided into a non-linear outer loop and an inner linear least-squares fit for the concentrations. In vitro and in vivo experiments on a whole-body 3 T MR scanner show the detectability of a wide range of metabolites in the human brain, namely total creatine, N-acetylaspartate, N-acetylaspartylglutamate, choline-containing compounds, glutamate, myo-inositol, glutathione, scyllo-inositol, gamma-aminobutyric acid, alanine and ascorbic acid.
Hyperpolarized 13C Magnetic Resonance Imaging (13C-MRI) provides a highly sensitive tool to probe tissue metabolism in vivo and has recently been translated into clinical studies. We report the cerebral metabolism of intravenously injected hyperpolarized [1–13C]pyruvate in the brain of healthy human volunteers for the first time. Dynamic acquisition of 13C images demonstrated 13C-labeling of both lactate and bicarbonate, catalyzed by cytosolic lactate dehydrogenase and mitochondrial pyruvate dehydrogenase respectively. This demonstrates that both enzymes can be probed in vivo in the presence of an intact blood-brain barrier: the measured apparent exchange rate constant (kPL) for exchange of the hyperpolarized 13C label between [1–13C]pyruvate and the endogenous lactate pool was 0.012 ± 0.006 s−1 and the apparent rate constant (kPB) for the irreversible flux of [1–13C]pyruvate to [13C]bicarbonate was 0.002 ± 0.002 s−1. Imaging also revealed that [1–13C]pyruvate, [1–13C]lactate and [13C]bicarbonate were significantly higher in gray matter compared to white matter. Imaging normal brain metabolism with hyperpolarized [1–13C]pyruvate and subsequent quantification, have important implications for interpreting pathological cerebral metabolism in future studies.
Aberrant neuronal activation patterns of the pgACC in anhedonic depression are related to deficits of glutamatergic metabolism.
This study aimed to investigate the role of regional f 0 inhomogeneity in spiral hyperpolarized 13 C image quality and to develop measures to alleviate these effects. Methods: Field map correction of hyperpolarized 13 C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off-resonance performance and image quality. An f 0 map-based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [ 13 C]bicarbonate was used to estimate blur. Results: Mean myocardial wall FWHM measurements were unchanged with the short readout pre-correction (14.1 ± 2.9 mm) and post-MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected, P = .007). Bicarbonate signal-to-noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared 158 | REED Et al. How to cite this article: Reed GD, Ma J, Park JM, et al. Characterization and compensation of f 0 inhomogeneity artifact in spiral hyperpolarized 13 C imaging of the human heart.
Dissolution dynamic nuclear polarization (DNP) enables the metabolism of hyperpolarized 13C‐labelled molecules, such as the conversion of [1‐13C]pyruvate to [1‐13C]lactate, to be dynamically and non‐invasively imaged in tissue. Imaging of this exchange reaction in animal models has been shown to detect early treatment response and correlate with tumour grade. The first human DNP study has recently been completed, and, for widespread clinical translation, simple and reliable methods are necessary to accurately probe the reaction in patients. However, there is currently no consensus on the most appropriate method to quantify this exchange reaction. In this study, an in vitro system was used to compare several kinetic models, as well as simple model‐free methods. Experiments were performed using a clinical hyperpolarizer, a human 3 T MR system, and spectroscopic imaging sequences. The quantitative methods were compared in vivo by using subcutaneous breast tumours in rats to examine the effect of pyruvate inflow. The two‐way kinetic model was the most accurate method for characterizing the exchange reaction in vitro, and the incorporation of a Heaviside step inflow profile was best able to describe the in vivo data. The lactate time‐to‐peak and the lactate‐to‐pyruvate area under the curve ratio were simple model‐free approaches that accurately represented the full reaction, with the time‐to‐peak method performing indistinguishably from the best kinetic model. Finally, extracting data from a single pixel was a robust and reliable surrogate of the whole region of interest. This work has identified appropriate quantitative methods for future work in the analysis of human hyperpolarized 13C data. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.
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