MRI CEST at 1T with large µeff Ln(3+) complexes T m(3+)-HPDO3A: An efficient MRI pH reporter.

PURPOSE: Chemical exchange saturation transfer (CEST) sensitivity relies on the prototropic exchange rate kex between the agent and the "bulk" water protons. To exploit large kex, a large frequency separation (Δω) between the pools of exchanging protons is necessary. For this reason, high magnetic fields are preferred. Herein it is shown that the use of paramagnetic CEST agents based on lanthanide (III) ions with large effective magnetic moments allows the carrying out of CEST experiments at the relatively low field strength of 1 tesla (T). METHODS: Measurements were performed on a 1T MR-scanner using continuous wave (cw)-presaturation with a spin echo sequence. ParaCEST complexes have been synthetized by mixing the ligand and Ln(III)Cl3 in a stoichiometric ratio at room temperature and pH 7. RESULTS: Different lanthanide chelates were investigated (Tm-, Dy-, Yb-, Eu-HPDO3A, and Eu-DOTAMGly). Ratiometric (Tm-HPDO3A) and selective detection (Eu-DOTAMGly and Tm-HPDO3A) experiments have been proven feasible in vivo. CONCLUSION: In vitro experiments demonstrated the feasibility of the CEST methodology at 1T for nearly every paraCEST candidate under investigation, except for Eu-HPDO3A. Among the studied compounds, Tm-HPDO3A proved suitable for the application of a ratiometric method for assessing pH both in vitro and in vivo.

Comparison of acquisition schemes for hyperpolarised ¹³C imaging.

The aim of this study was to characterise and compare widely used acquisition strategies for hyperpolarised (13)C imaging. Free induction decay chemical shift imaging (FIDCSI), echo-planar spectroscopic imaging (EPSI), IDEAL spiral chemical shift imaging (ISPCSI) and spiral chemical shift imaging (SPCSI) sequences were designed for two different regimes of spatial resolution. Their characteristics were studied in simulations and in tumour-bearing rats after injection of hyperpolarised [1-(13)C]pyruvate on a clinical 3-T scanner. Two or three different sequences were used on the same rat in random order for direct comparison. The experimentally obtained lactate signal-to-noise ratio (SNR) in the tumour matched the simulations. Differences between the sequences were mainly found in the encoding efficiency, gradient demand and artefact behaviour. Although ISPCSI and SPCSI offer high encoding efficiencies, these non-Cartesian trajectories are more prone than EPSI and FIDCSI to artefacts from various sources. If the encoding efficiency is sufficient for the desired application, EPSI has been proven to be a robust choice. Otherwise, faster spiral acquisition schemes are recommended. The conclusions found in this work can be applied directly to clinical applications.

Metabolic imaging of hyperpolarized [1-(13) C]acetate and [1-(13) C]acetylcarnitine - investigation of the influence of dobutamine induced stress.

PURPOSE: The metabolism of acetate in the heart resembles fatty acid metabolism, which is altered in several diseases like ischemia, diabetes mellitus, and heart failure. A signal-to-noise ratio (SNR) optimized imaging framework for in vivo measurements of hyperpolarized [1-(13) C]acetate and its metabolic product [1-(13) C]acetylcarnitine (ALCAR) in rats at 3 Tesla (T) is presented in this work. METHODS: A spectrospatial pulse was combined with IDEAL encoding to acquire well separated metabolic maps. The influence of dobutamine induced stress onto this metabolic system was investigated in spectra and in an imaging study. RESULTS: An increase of the ALCAR to acetate ratio with dobutamine induced stress was shown in slice selective spectra containing the rat hearts and skeletal muscles. Metabolic maps of acetate and ALCAR were acquired with an acceptable SNR. Quantification of the apparent conversion rate showed stable results in the heart in a time-window of 30 s. The effect of dobutamine on the signal intensities was shown to originate mainly from skeletal than cardiac muscles. CONCLUSION: The acetate activation was mapped with hyperpolarized [1-(13) C]acetate in a clinical 3T system. Quantitative measurement of the activity was possible in the heart, indicating that dobutamine induced stress does not improve the ALCAR SNR in the heart.

Bolus tracking for improved metabolic imaging of hyperpolarised compounds.

Dynamic nuclear polarisation has enabled real-time metabolic imaging of pyruvate and its metabolites. Conventional imaging sequences rely on predefined settings and do not account for intersubject variations in biological parameters such as perfusion. We present a fully automatic real-time bolus tracking sequence for hyperpolarised substrates which starts the imaging acquisition at a defined point on the bolus curve. This reduces artefacts due to signal change and allows for a more efficient use of hyperpolarised magnetisation. For single time point imaging methods, bolus tracking enables a more reliable and consistent quantification of metabolic activity. An RF excitation with a small flip angle is used to obtain slice-selective pyruvate tracking information in rats. Moreover, in combination with a copolarised urea and pyruvate injection, spectrally selective tracking on urea allows obtaining localised bolus tracking information without depleting the pyruvate signal. Particularly with regard to clinical application, the bolus tracking technique could provide an important step towards a routine assessment protocol which removes operator dependencies and ensures comparable results.