Valerie A. Norton

PASADENA Hyperpolarization of Succinic Acid for MRI and NMR Spectroscopy

We use the PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) method to achieve 13C polarization of approximately 20% in seconds in 1-13C-succinic-d2 acid. The high-field 13C multiplets are observed as a function of pH, and the line broadening of C1 is pronounced in the region of the pK values. The 2JCH, 3JCH, and 3JHH couplings needed for spin order transfer vary with pH and are best resolved at low pH leading to our use of pH approximately 3 for both the molecular addition of parahydrogen to 1-13C-fumaric acid-d2 and the subsequent transfer of spin order from the nascent protons to C1 of the succinic acid product. The methods described here may generalize to hyperpolarization of other carboxylic acids. The C1 spin-lattice relaxation time at neutral pH and 4.7 T is measured as 27 s in H2O and 56 s in D2O. Together with known rates of succinate uptake in kidneys, this allows an estimate of the prospects for the molecular spectroscopy of metabolism.

Hyperpolarized 1H NMR Employing Low γ Nucleus for Spin Polarization Storage

Here, we demonstrate the utility of low gamma nuclei for spin storage of hyperpolarization followed by proton detection, which theoretically can provide up to approximately (gamma[1H]/gamma[X])(2) gain in sensitivity in hyperpolarized biomedical MR. This is exemplified by hyperpolarized 1-(13)C sites of 2,2,3,3-tetrafluoropropyl 1-(13)C-propionate-d(3) (TFPP), (13)C T(1) = 67 s in D(2)O, and 1-(13)C-succinate-d(2), (13)C T(1) = 105 s in D(2)O, pH 11, using PASADENA. In a representative example, the spin polarization was stored on (13)C for 24 and 70 s, respectively, while the samples were transferred from a low magnetic field polarizer operating at 1.76 mT to a 4.7 T animal MR scanner. Following sample delivery, the refocused INEPT pulse sequence was used to transfer spin polarization from (13)C to protons with an efficiency of 50% for TFPP and 41% for 1-(13)C-succinate-d(2) increasing the overall NMR sensitivity by a factor of 7.9 and 6.5, respectively. The low gamma nuclei exemplified here by (13)C with a T(1) of tens of seconds acts as an efficient spin polarization storage, while J-coupled protons are better for NMR detection.

Fast volumetric spatial-spectral MR imaging of hyperpolarized 13C-labeled compounds using multiple echo 3D bSSFP.

PURPOSE The goal of this work was to develop a fast 3D chemical shift imaging technique for the noninvasive measurement of hyperpolarized (13)C-labeled substrates and metabolic products at low concentration. MATERIALS AND METHODS Multiple echo 3D balanced steady state magnetic resonance imaging (ME-3DbSSFP) was performed in vitro on a syringe containing hyperpolarized [1,3,3-2H3; 1-(13)C]2-hydroxyethylpropionate (HEP) adjacent to a (13)C-enriched acetate phantom, and in vivo on a rat before and after intravenous injection of hyperpolarized HEP at 1.5 T. Chemical shift images of the hyperpolarized HEP were derived from the multiple echo data by Fourier transformation along the echoes on a voxel by voxel basis for each slice of the 3D data set. RESULTS ME-3DbSSFP imaging was able to provide chemical shift images of hyperpolarized HEP in vitro, and in a rat with isotropic 7-mm spatial resolution, 93 Hz spectral resolution and 16-s temporal resolution for a period greater than 45 s. CONCLUSION Multiple echo 3D bSSFP imaging can provide chemical shift images of hyperpolarized (13)C-labeled compounds in vivo with relatively high spatial resolution and moderate spectral resolution. The increased signal-to-noise ratio of this 3D technique will enable the detection of hyperpolarized (13)C-labeled metabolites at lower concentrations as compared to a 2D technique.

A selective 15N-to-1H polarization transfer sequence for more sensitive detection of 15N-choline

The sensitivity and information content of heteronuclear nuclear magnetic resonance is frequently optimized by transferring spin order of spectroscopic interest to the isotope of highest detection sensitivity prior to observation. This strategy is extended to 15N-choline using the scalar couplings to transfer polarization from 15N to cholines nine methyl 1H spins in high field. A theoretical analysis of a sequence using nonselective pulses shows that the optimal efficiency of this transfer is decreased by 62% as the result of competing 15N-(1)H couplings involving cholines four methylene protons. We have therefore incorporated a frequency-selective pulse to support evolution of only the 15N-methyl 1H coupling during the transfer period. This sequence provides a 52% sensitivity enhancement over the nonselective version in in vitro experiments on a sample of thermally polarized 15N-choline in D2O. Further, the 15N T1 of choline in D2O was measured to be 217+/-38 s, the 15N-methyl 1H coupling constant was found to be 0.817+/-0.001 Hz, and the larger of cholines two 15N-methylene 1H coupling constants was found to be 3.64+/-0.0 1Hz. Possible improvements and applications to in vivo experiments using long-lived hyperpolarized heteronuclear spin order are discussed.

Communication: partial polarization transfer for single-scan spectroscopy and imaging.

A method is presented to partially transfer nuclear spin polarization from one isotope S to another isotope I by the way of heteronuclear spin couplings, while minimizing the loss of spin order to other degrees of freedom. The desired I spin polarization to be detected is a design parameter, while the sequence of pulses at the two Larmor frequencies is optimized to store the greatest unused S spin longitudinal polarization for subsequent use. The unitary evolution for the case of I(N)S spin systems illustrates the potentially ideal efficiency of this strategy, which is of particular interest when the spin-lattice relaxation time of S greatly exceeds that of I. Explicit timing and pulses are tabulated for the cases for which M ≤ 10 partial transfers each result in equal final polarization of 1/M or more compared to the final I polarization expected in a single transfer for N = 1, 2, or 3 I spins. Advantages for the ratiometric study of reacting molecules and hyperpolarized initial conditions are outlined.