Enabling Metabolic Imaging Using Hyperpolarized 13C Magnetic Resonance

DESCRIPTION (provided by applicant): The signal from 13C enriched molecules is much too low to permit them to be observed in vivo using MRI. To overcome this problem, researchers have turned to the use of hyperpolarized (HP) 13C molecules; hyperpolarization dramatically increases the signal from the 13C nuclei in the molecules and an increase in signal to noise ratio (SNR) by as much as 10,000 can be obtained in this manner. The increased SNR makes it possible to build images of metabolic processes in the heart which can be used to construct models as to the metabolic signature of various forms of heart disease. Present methods of hyperpolarization suffer from drawbacks that will severely impact clinical deployment of HP 13C molecules. For example, the only currently commercially available hyperpolarizer requires that the 13C molecule be mixed with toxic substances to hyperpolarize the 13C nuclei. In addition, present hyperpolarizers are not readily scalable to production levels needed for commercial supply. MKT has developed a method of hyperpolarization and associated business model that directly addresses these issues. Hyperpolarization of samples is carried out by allowing nuclei to relax in a very low temperature, very high field environment. The use of the quantum liquids 3He and 4He allow the relaxation process to be very rapid and carried out without the use of toxic materials. The HP samples are extracted from the cryostat without undue loss of polarization; this enables them to be transported over large distances thus removing the need for the polarizer to be in close proximity to the MRI machine. The process is scalable and applicable to a wide variety of samples including those of metabolic interest such as 13C enriched acetic acid. Our long term goal is to manufacture and supply HP materials to the clinical MRI marketplace. Our short term goal is to demonstrate that 13C enriched acetic acid can be hyperpolarized using our proprietary technique, extracted from the cryostat, transported to a nearby hospital, reacted with a sodium hydroxide base solution to form HP sodium acetate solution and then used to carry out a variety of hyperpolarized Magnetic Resonance Spectroscopy (MRS) experiments. We will demonstrate that the QRS technique produces SNR gains in excess of 5000 in HP acetic acid samples as compared to acetic acid samples in thermal equilibrium at room temperature (Aim I). We will demonstrate that HP 13C acetic acid may be transported for 2 hours (or more) without significant loss of polarization (Aim II). This will demonstrate that acetic acid may be hyperpolarized at one site and transported to another for use in different MRS applications. Next, we will demonstrate conversion of HP 13C acetic acid to an HP 13C acetate solution with SNR in excess of 1000 as compared to acetic acid samples in thermal equilibrium at room temperature (Aim III). The HP sodium acetate solution will then be used to follow metabolism in MRS experiments conducted in a respiring suspension of yeast and in isolated perfused rat hearts (Aim IV). PUBLIC HEALTH RELEVANCE: Over 700,000 Americans will die from heart disease this year. The ability to image metabolic processes of the heart has the potential to greatly improve both diagnosis and treatment of heart disease. The production of metabolic images of the heart requires the development of hyperpolarized 13C enriched molecules such as sodium acetate; Millikelvin Technologies has developed a method of manufacturing hyperpolarized sodium acetate that does not require the addition of poisonous materials, can be scaled up to meet widespread demand and will keep costs down by delivering the hyperpolarized sodium acetate as a consumable.