Hyperpolarized magnetic resonance (HP-MR) is emerging as a technology uniquely suited for rapidly assessing pathway-specific metabolic flux in living tissue. Complex transient and chronic adaptations in cellular biochemistry form the basis of sustained energetic balance in organisms, and therefore the ability to measure perturbations of these metabolic pathways has the potential to diagnose broadly underlying pathology and quantitatively assess the response to therapy. The potential and safety of HP-MR has been sufficiently well established through preclinical studies that the technology is featured in a human clinical trial. Unfortunately, the expense, bulk, and complexity of current instruments preclude access of this technology to the majority of clinicians and biomedical researchers. This proposal aims to bridge the critical gap between potential public health impact and access of the underlying technology to the clinicians and biomedical researchers. To accomplish this, an ultra-compact and inexpensive hyperpolarization instrument will be developed that would be compatible for use with all existing (wide bore) human and preclinical MR imaging consoles.
In Aim 1, we will develop a nonmagnetic, remotely controlled chemical reactor module for parahydrogen based hyperpolarization.
In Aim 2, we will develop compact electronic controllers for synchronizing chemical reaction, spin transformations, and post reaction filtering. Compatibility with existing instruments is paramount to a primary objective of this proposal to ensure wide access of the HP-MR technology to clinicians and biomedical researchers. Moreover, the efficiency of the parahydrogen based technology being pursued here is tailored to the symmetry properties of the metabolic contrast agent spin systems, with higher fields expected to differentially outperform as the spin system becomes more symmetric.
In Aim 3, we therefore utilize the diverse MR platforms available from the Vanderbilt Institute of Imaging Science to validate the compatibility of the instrument by interfacing the proposed polarizer instrument and imaging hyperpolarized contrast agent production, on a variety of clinical and preclinical research scanners at several field strengths and configurations.
HP-MR has proven sufficiently sensitive to discern abnormal metabolism that underlies pathology, and has also been shown capable of detecting response to therapy. The technology has progressed rapidly over the last few years to the point of human clinical trials, but current instrumentation is prohibitively expensive to all but a handful of sits. The proposed research will develop a powerful and precise polarizer module that is fully compatible with the large network of existing MR scanners, providing maximum leverage of prior public investments and ensuring the widest possible dissemination among clinicians and biomedical researchers.
|Kovtunov, Kirill V; Truong, Milton L; Barskiy, Danila A et al. (2014) Long-lived spin States for low-field hyperpolarized gas MRI. Chemistry 20:14629-32|
|Moore, Jay; Colón, Raul D; Tadanki, Sasidhar et al. (2014) Heteronuclear refocusing by nonlinear phase and amplitude modulation on a single transmitter channel. J Magn Reson 245:58-62|
|Shchepin, Roman V; Coffey, Aaron M; Waddell, Kevin W et al. (2014) Parahydrogen induced polarization of 1-(13)C-phospholactate-d(2) for biomedical imaging with >30,000,000-fold NMR signal enhancement in water. Anal Chem 86:5601-5|
|Barskiy, Danila A; Kovtunov, Kirill V; Koptyug, Igor V et al. (2014) The feasibility of formation and kinetics of NMR signal amplification by reversible exchange (SABRE) at high magnetic field (9.4 T). J Am Chem Soc 136:3322-5|
|Kovtunov, Kirill V; Barskiy, Danila A; Coffey, Aaron M et al. (2014) High-resolution 3D proton MRI of hyperpolarized gas enabled by parahydrogen and Rh/TiO2 heterogeneous catalyst. Chemistry 20:11636-9|