Biomedical Applications of the Dynamic Nuclear Polarization and Parahydrogen Induced Polarization Techniques for Hyperpolarized ¹³C MR Imaging

Abstract

Since the first pioneering report of hyperpolarized [1-13 C]pyruvate magnetic resonance imaging (MRI) of the Warburg effect in prostate cancer patients, clinical dissemination of the technique has been rapid; close to 10 sites worldwide now possess a polarizer fit for the clinic, and more than 30 clinical trials, predominantly for oncological applications, are already registered on the US and European clinical trials databases. Hyperpolarized 13 C probes to study pathophysiological processes beyond the Warburg effect, including tricarboxylic acid cycle metabolism, intra-cellular pH and cellular necrosis have also been demonstrated in the preclinical arena and are pending clinical translation, and the simultaneous injection of multiple co-polarized agents is opening the door to high-sensitivity, multi-functional molecular MRI with a single dose. Here, we review the biomedical applications to date of the two polarization methods that have been used for in vivo hyperpolarized 13 C molecular MRI; namely, dissolution dynamic nuclear polarization and parahydrogeninduced polarization. The basic concept of hyperpolarization and the fundamental theory underpinning these two key 13 C hyperpolarization methods, along with recent technological advances that have facilitated biomedical realization, are also covered.

Heterogeneous Parahydrogen‐Induced Polarization of Diethyl Ether for Magnetic Resonance Imaging Applications

“…Moreover,w ee xpect that the additional several-fold gain of polarization would be possible in case of faster condensation process. 1 HT 1 measurements forn eat liquid DE at 7.05 Ty ielded9 .90 AE 0.04 sf or the CH 2 group and 9.12 AE 0.03 sf or the CH 3 group, meaning that liquefaction indeed can be av aluable approach for prolongation of HP DE lifetime. The use of an appropriate magnetic fieldm ay further increasethe relaxation time.…”

“…In spite of its vast functionality,M RI suffers from an inherently low detection sensitivity due to low polarization of nuclear spins. For example, at 3T (magnetic field of am odernh igh-field clinical MRI scanner) 1 Hn uclears pin polarization (P 1H )i so nly ca. 10 À5 meaningt hat only one nucleuso ut of ca.…”

“…100 000 contributes to the detected signal. [1][2][3] The sensitivity issue is especially critical for pulmonary MRI due to al ow spin density of lung tissues. Therefore, non-NMR imaging techniques such as computed tomographya nd chest radiography are usually employed for pulmonary imaging of COPD and other lung diseasesi ncluding COVID-19.…”

“…10 −5 meaning that only one nucleus out of ca. 100 000 contributes to the detected signal [1–3] . The sensitivity issue is especially critical for pulmonary MRI due to a low spin density of lung tissues.…”

Singulett‐Kontrast‐Magnetresonanztomographie: Freisetzung der Hyperpolarisation durch den Metabolismus**

“…Dieser Umstand, in Kombination mit der inhärent geringen Empfindlichkeit der MRT, macht Beobachtungen dieser biochemischen Reaktionen mittels MRT unmöglich. Jüngste Fortschritte auf dem Gebiet der hyperpolarisationsverstärkten Kernspinresonanz (NMR) haben es möglich gemacht, Metabolite Signale mit NMR‐Signalverstärkungen von 10 4 –10 5 zu erzeugen [1–16] . Ein Beispiel für eine solche Hyperpolarisationsmethode ist die parawasserstoffinduzierte Kernspin‐Polarisation (PHIP), bei der Wasserstoffgas das mit dem para‐Spin‐Isomer angereichert ist, mittels Hydrierung in ein ungesättigtes Molekül eingebracht wird, um ein Produkt mit hyperpolarisierten 1 H‐Kernspins zu erzeugen [17–26] .…”