An open-source hyperpolarizer producing 13C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2–3 mL) of hyperpolarized 13C-succinate with %P13C ∼ 28% and 30 mM concentration and 13C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized 13C-phospholactate to 13C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice 13C MRI after tail vein injection of hyperpolarized 13C-phospholactate in mice.

With continuing hardware and pulse sequence advancements, modern MRI is gaining sensitivity to signals from short‐T2 1H species under practical experimental conditions. However, conventional MRI coils are typically not designed for this type of application, as they often contain proton‐rich construction materials that may contribute confounding 1H background signal during short‐T2 measurements. An example of this is shown herein. Separately, a loop‐gap style coil was used to compare different coil construction materials and configurations with respect to observed 1H background signal sizes in a small animal imaging system. Background signal sources were spatially identified and quantified in a number of different coil configurations. It was found that the type and placement of structural coil materials around the loop‐gap resonator, as well as the coil's shielding configuration, are critical determinants of the coil's background signal size. Although this study employed a loop‐gap resonator design, these findings are directly relevant to standard volume coils commonly used for MRI. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.

In this work we describe a large volume 340 mL 1H-X magnetic resonance (MR) probe for studies of hyperpolarized compounds at 0.0475 T. 1H/13C and 1H/15N probe configurations are demonstrated with the potential for extension to 1H/129Xe. The primary applications of this probe are preparation and quality assurance of 13C and 15N hyperpolarized contrast agents using PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) and other parahydrogen-based methods of hyperpolarization. The probe is efficient and permits 62 μs 13C excitation pulses at 5.3 Watts, making it suitable for portable operation. The sensitivity and detection limits of this probe, tuned to 13C, are compared with a commercial radio frequency (RF) coil operating at 4.7 T. We demonstrate that low field MR of hyperpolarized contrast agents could be as sensitive as conventional high field detection and outline potential improvements and optimization of the probe design for preclinical in vivo MRI. PASADENA application of this low-power probe is exemplified with 13C hyperpolarized 2-hydroxyethyl propionate-1-13C,2,3,3-d3.

Because of the extensive chemical, physical, and biomedical applications of parahydrogen, the need exists for the development of highly enriched parahydrogen in a robust and efficient manner. Herein, we present a parahydrogen enrichment equipment which substantially improves upon the previous generators with its ability to enrich parahydrogen to >98.5% and a production rate of up to 4 standard liters per minute with the added advantage of real-time quantification. Our generator employs a pulsed injection system with a 3/16 in. outside diameter copper spiral tubing filled with iron-oxide catalyst. This tubing is mated to a custom-made copper attachment to provide efficient thermal coupling to the cold head. This device allows for robust operation at high pressures up to 34 atm. Real-time quantification by benchtop NMR spectroscopy is made possible by direct coupling of the p-H2 outlet from the generator to a 1.4 T NMR spectrometer using a regular 5 mm NMR tube that is continuously refilled with the exiting parahydrogen gas at ∼8 atm pressure. The use of high hydrogen gas pressure offers two critical NMR signal detection benefits: increased concentration and line narrowing. Our work presents a comprehensive description of the apparatus for a convenient and robust parahydrogen production, distribution, and quantification system, especially for parahydrogen-based hyperpolarization NMR research.

Applications of parahydrogen induced polarization (PHIP) often warrant conversion of the chemically-synthesized singlet-state spin order into net heteronuclear magnetization. In order to obtain optimal yields from the overall hyperpolarization process, catalytic hydrogenation must be tightly synchronized to subsequent radiofrequency (RF) transformations of spin order. Commercial NMR consoles are designed to synchronize applied waves on multiple channels and consequently are well-suited as controllers for these types of hyperpolarization experiments that require tight coordination of RF and non-RF events. Described here is a PHIP instrument interfaced to a portable NMR console operating with a static field electromagnet in the milliTesla regime. In addition to providing comprehensive control over chemistry and RF events, this setup condenses the PHIP protocol into a pulse-program that in turn can be readily shared in the manner of traditional pulse sequences. In this device, a TTL multiplexer was constructed to convert spectrometer TTL outputs into 24 VDC signals. These signals then activated solenoid valves to control chemical shuttling and reactivity in PHIP experiments. Consolidating these steps in a pulse-programming environment speeded calibration and improved quality assurance by enabling the B0/B1 fields to be tuned based on the direct acquisition of thermally polarized and hyperpolarized NMR signals. Performance was tested on the parahydrogen addition product of 2-hydroxyethyl propionate-1-13C-d3, where the 13C polarization was estimated to be P13C = 20 ± 2.5 % corresponding to 13C signal enhancement approximately 25 million-fold at 9.1 mT or approximately 77,000-fold 13C enhancement at 3 T with respect to thermally induced polarization at room temperature.