Image: Hyperpolarization of fumarate for use as a biosensor (Photo courtesy of John Blanchard, James Eills)
Researchers have developed a new technique that could significantly simplify hyperpolarized magnetic resonance imaging (MRI), which developed around 20 years ago for observing metabolic processes in the body, and pave the way for major advances in MRI.
An interdisciplinary team of researchers led by Johannes Gutenberg University Mainz (JGU; Mainz, Germany) discovered the promising new concept that involves the hyperpolarization of the metabolic product fumarate using parahydrogen and the subsequent purification of the metabolite.
The potential applications of MRI are hindered by its low sensitivity and the technique is essentially limited to observing water molecules in the body. Researchers are therefore constantly working on different ways of improving MRI. A major breakthrough was achieved around 20 years ago when hyperpolarized magnetic resonance imaging was first developed: Because hyperpolarized molecules emit significantly stronger MRI signals, substances that are only present in low concentrations in the body can also be visualized. By hyperpolarizing biomolecules and introducing them in patients, it is possible to track metabolism in real time, thus providing doctors with much more information.
Hyperpolarized fumarate is a promising biosensor for the imaging of metabolic processes. Fumarate is a metabolite of the citric acid cycle that plays an important role in the energy production of living beings. For imaging purposes, the fumarate is tagged with carbon-13 as the atomic nuclei of this isotope can be hyperpolarized. Dynamic nuclear polarization is the current state-of-the-art method for hyperpolarizing fumarate, but this is expensive and relatively slow. The equipment required costs one to two million Euros.
Dynamic nuclear polarization is very difficult to use in everyday clinical practice due to the related high costs and technical complexity. Using parahydrogen, the research team was able to hyperpolarize this important biomolecule in a cost-effective and convenient way. However, parahydrogen-induced polarization, or PHIP for short, also has its disadvantages. The low level of polarization and the large number of unwanted accompanying substances are particularly problematic in the case of this chemistry-based technique. Among other things, transferring the polarization from parahydrogen into fumarate requires a catalyst, which remains in the reaction fluid just like other reaction side-products.
The solution to this problem is to purify the hyperpolarized fumarate through precipitation. The fumarate then takes the form of a purified solid and can be redissolved at the desired concentration later. This creates a product from which all toxic substances have been removed, making it ready to be used in the body. In addition, compared to previous experiments with PHIP, the polarization is increased to remarkable 30 to 45%. Preclinical studies have already shown that hyperpolarized fumarate imaging is a suitable method of monitoring how tumors respond to therapy as well as for imaging acute kidney injuries or the effects of myocardial infarction. This new way of producing hyperpolarized fumarate should greatly accelerate preclinical studies and bring this technology to more laboratories.
"This technique would not only be simpler, but also much cheaper than the previous procedure," said leader of the project Dr. James Eills, a member of the research team of Professor Dmitry Budker at Johannes Gutenberg University Mainz (JGU) and the Helmholtz Institute Mainz (HIM).
Johannes Gutenberg University Mainz