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.

Magnetic resonance microscopy for submillimeter samples in a horizontal MR scanner.

The spatial resolution in magnetic resonance imaging is mainly limited by low SNR, which is commonly addressed by long measurement times or dedicated hardware. In single digit micron resolutions, diffusion becomes a further limiting factor since depending on the gradient strength, the diffusion length of particles may approach the target resolutions. Spatial resolution improvement has been addressed by microscopy inserts comprising dedicated gradient systems and RF-coils, usually designed for NMR spectrometers that are often equipped with a deuterium lock for field drift compensations. The presented microscopy insert has been designed to provide single-digit micron resolutions on horizontal preclinical imaging systems utilizing their full imaging and user interface capabilities. The incorporated gradient provides an efficiency of 0.135 T/(m∙A) which in combination with the system's gradient amplifiers yields a maximum of 27 T/m. With the additional low noise amplifier added to the RF-path a three-fold SNR improvement could be achieved for small samples. Furthermore, a modified constant time imaging sequence was introduced to improve the capability of the setup for ultra-high-resolution imaging demonstrated on zebrafish embryos at different development stages with (9 µm)³ resolution.