UNC-CH Physics and Astronomy Colloquium

Eduard Chekmenev, Vanderbilt University

“Hyperpolarized NMR Contrast Agents for Molecular Imaging”

The significant (usually orders-of-magnitude) increase in nuclear spin polarization above the thermal-equilibrium level is called hyperpolarization. Because the NMR signal is directly proportional to the nuclear spin polarization, the realized polarization enhancement manifests in the corresponding NMR signal and corresponding gains in detection sensitivity, which can be ~4-8 orders of magnitude depending on the detection field of the MRI scanner. Recent developments in NMR hyperpolarization have enabled a wide range of new in vivo molecular imaging modalities—ranging from functional imaging of the lungs to metabolic imaging of cancer. Our research explores selected advances in methods for the preparation and use of hyperpolarized contrast agents, many of which are already at or near the phase of their clinical validation. Biomedical applications of hyperpolarized contrast agents require (i) high polarization level of relatively long-lived hyperpolarized molecules, (ii) preparation of pure hyperpolarized substrates in (iii) biocompatible administration medium. Preparation of such agents in the context of conventional Parahydrogen Induced Polarization (PHIP) using molecular addition of parahydrogen and Signal Amplification By Reversible Exchange (SABRE) using reversible exchange of parahydrogen demands new advances in synthetic chemistry of contrast agents, i.e. sophisticated isotopic enrichment and synthetic schemes, and advances in chemistry and spin-physics of homogeneous and heterogeneous hydrogenation and exchange catalysis.

The significantly enhanced NMR hyperpolarization-endowed signal can enable high-quality clinical 3D images of hyperpolarized contrast agents to be obtained in as little as a few seconds. Moreover, because the hyperpolarized nuclear state is no longer endowed by the static magnetic field of the detecting NMR magnet, high-field MRI scanners are no longer mandatory, and lower-cost, less-confining, low-field 3D MRI can be used instead—with detection sensitivity potentially approaching or even surpassing that of high-field MRI.

This presentation will focus of our recent advances in (i) development of automated instrumentation for preparation of hyperpolarized contrast agents using parahydrogen and Xenon-129, (ii) developing new chemistries for preparation of hyperpolarized contrast agents to probe lung function using hyperpolarized proton MRI, elevated glycolysis in cancer, brain metabolism, and pH and hypoxia imaging, and (iii) improving hyperpolarized MRI detection sensitivity utilizing low-field MRI.