Parahydrogen-Polarized [1-13 C]Pyruvate for Reliable and Fast Preclinical Metabolic Magnetic Resonance Imaging.

Hyperpolarization techniques increase nuclear spin polarization by more than four orders of magnitude, enabling metabolic MRI. Even though hyperpolarization has shown clear value in clinical studies, the complexity, cost and slowness of current equipment limits its widespread use. Here, a polarization procedure of [1-13 C]pyruvate based on parahydrogen-induced polarization by side-arm hydrogenation (PHIP-SAH) in an automated polarizer is demonstrated. It is benchmarked in a study with 48 animals against a commercial dissolution dynamic nuclear polarization (d-DNP) device. Purified, concentrated (≈70-160 mM) and highly hyperpolarized (≈18%) solutions of pyruvate are obtained at physiological pH for volumes up to 2 mL within 85 s in an automated process. The safety profile, image quality, as well as the quantitative perfusion and lactate-to-pyruvate ratios, are equivalent for PHIP and d-DNP, rendering PHIP a viable alternative to established hyperpolarization techniques.

Parahydrogen-Polarized Fumarate for Preclinical in Vivo Metabolic Magnetic Resonance Imaging.

We present a versatile method for the preparation of hyperpolarized [1-13C]fumarate as a contrast agent for preclinical in vivo MRI, using parahydrogen-induced polarization (PHIP). To benchmark this process, we compared a prototype PHIP polarizer to a state-of-the-art dissolution dynamic nuclear polarization (d-DNP) system. We found comparable polarization, volume, and concentration levels of the prepared solutions, while the preparation effort is significantly lower for the PHIP process, which can provide a preclinical dose every 10 min, opposed to around 90 min for d-DNP systems. With our approach, a 100 mM [1-13C]-fumarate solution of volumes up to 3 mL with 13-20% 13C-hyperpolarization after purification can be produced. The purified solution has a physiological pH, while the catalyst, the reaction side products, and the precursor material concentrations are reduced to nontoxic levels, as confirmed in a panel of cytotoxicity studies. The in vivo usage of the hyperpolarized fumarate as a perfusion agent in healthy mice and the metabolic conversion of fumarate to malate in tumor-bearing mice developing regions with necrotic cell death is demonstrated. Furthermore, we present a one-step synthesis to produce the 13C-labeled precursor for the hydrogenation reaction with high yield, starting from 13CO2 as a cost-effective source for 13C-labeled compounds.

Hyperpolarized Solution-State NMR Spectroscopy with Optically Polarized Crystals.

Nuclear spin hyperpolarization provides a promising route to overcome the challenges imposed by the limited sensitivity of nuclear magnetic resonance. Here we demonstrate that dissolution of spin-polarized pentacene-doped naphthalene crystals enables transfer of polarization to target molecules via intermolecular cross-relaxation at room temperature and moderate magnetic fields (1.45 T). This makes it possible to exploit the high spin polarization of optically polarized crystals, while mitigating the challenges of its transfer to external nuclei. With this method, we inject the highly polarized mixture into a benchtop NMR spectrometer and observe the polarization dynamics for target 1H nuclei. Although the spectra are radiation damped due to the high naphthalene magnetization, we describe a procedure to process the data to obtain more conventional NMR spectra and extract the target nuclei polarization. With the entire process occurring on a time scale of 1 min, we observe NMR signals enhanced by factors between -200 and -1730 at 1.45 T for a range of small molecules.

A CMOS NMR needle for probing brain physiology with high spatial and temporal resolution.

Magnetic resonance imaging and spectroscopy are versatile methods for probing brain physiology, but their intrinsically low sensitivity limits the achievable spatial and temporal resolution. Here, we introduce a monolithically integrated NMR-on-a-chip needle that combines an ultra-sensitive 300 µm NMR coil with a complete NMR transceiver, enabling in vivo measurements of blood oxygenation and flow in nanoliter volumes at a sampling rate of 200 Hz.

Comparison of prospective head motion correction with NMR field probes and an optical tracking system.

PURPOSE: The aim of this study was to compare prospective head motion correction and motion tracking abilities of two tracking systems: Active NMR field probes and a Moiré phase tracking camera system using an optical marker. METHODS: Both tracking systems were used simultaneously on human subjects. The prospective head motion correction was compared in an MP2RAGE and a gradient echo sequence. In addition, the motion tracking trajectories for three subjects were compared against each other and their correlation and deviations were analyzed. RESULTS: With both tracking systems motion artifacts were visibly reduced. The precision of the field probe system was on the order of 50 µm for translations and 0.03° for rotations while the camera's was approximately 5 µm and 0.007°. The comparison of the measured trajectories showed close correlation and an average absolute deviation below 500 µm and 0.5°. CONCLUSION: This study presents the first in vivo comparison between NMR field probes and Moiré phase tracking. For the gradient echo images, the field probes had a similar motion correction performance as the optical tracking system. For the MP2RAGE measurement, however, the camera yielded better results. Still, both tracking systems substantially decreased image artifacts in the presence of subject motion. Thus, the motion tracking modality should be chosen according to the specific requirements of the experiment while considering the desired image resolution, refresh rate, and head coil constraints.

A low-power high-sensitivity single-chip receiver for NMR microscopy.

In this paper, we present a fully-integrated receiver for NMR microscopy applications manufactured in a 0.13µm CMOS technology. The design co-integrates a 10-turn planar detection coil together with a complete quadrature, low-IF downconversion receiver on a single chip, which operates from a single 1.5V supply with a total power dissipation of 18mW. The detector's measured time-domain spin sensitivity is 3×10(13)(1)Hspins/Hz at 7T. Additionally, the paper discusses two important aspects of NMR microscopy using planar detection coils: the link between the detection coil's spin sensitivity and the achievable image SNR and the correction of image artifacts induced by the inhomogeneous sensitivity profile of planar detection coils. More specifically, we derive analytical expressions for both the theoretical image SNR as a function of the coil's spin sensitivity and the sensitivity correction for a known coil sensitivity profile in CTI MR imaging experiments. Both expressions are validated using measured data in the imaging section of the paper. Thanks to the improved spin sensitivity of the utilized integrated receiver chip compared to a previously presented design, we were able to obtain sensitivity corrected images in a 7T spectroscopy magnet with isotropic resolutions of 9.6µm and 5µm with single-shot SNRs of 37 and 15 in relatively short imaging times of 4.4h and 24h, respectively.