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.

Design of a vertical Loss-in-Weight feeder prototype with experimental proof of concept validation.

Loss-in-Weights (LiW) feeders are commonly oriented in a horizontal way. In this work, an experimental proof of concept, including mechanical and electrical design, construction, and operation, of a vertical LiW feeder prototype is performed. In a systematic design process, based on functional design specifications, the semi-automated vertical LiW feeder for dosing a wide range of powders, especially cohesive ones, is developed. The new dosing machine is assessed with regard to a number of key features such as high dosing accuracy, first-in-first-out powder discharge, easily interchange of the powder container, and flexibility in controlling the speed of the auger and stirrer motors independently. An experimental sensitivity analysis to study the functionality of the dosing machine and to investigate the weight variability of the weighing platform, i.e. mass flow rate, and quantity of dosed mass, is carried out. The results of the sensitivity analysis and the powder dosing tests of five diverse powders using different auger and stirrer geometries verified the proof of concept prototype.HighlightsA systematic design approach for validating a proof of concept of a vertical loss in weight feeder is appliedA full mechanical CAD design and implementation along with electric installation and software programming are executedSensitivity analysis approach is performed to validate the functionality of the semi-automated machine and successfully dispense dissimilar powders tested with different process parametersThe machine is characterized with a number of key features: first-in-first-out powder discharge, high dosing accuracy, flexible and modular concept design, flexibility in controlling the speed of the auger and the stirrer independently, lightweight and user-friendly design.