Creating long-lived contrast agents for magnetic resonance imaging
Nuclear magnetic resonance (NMR) and its imaging analog magnetic resonance imaging (MRI) are powerful clinical imaging modalities. One of the limitations of NMR and MRI is low intrinsic signal strength. Some attempts to overcome this limitation have involved the use of hyperpolarized contrast agents, which have very large nuclear polarizations and, therefore, sensitivities that are orders of magnitude higher than ordinary molecules. Polarization can persist for as long as 100 seconds in some molecules before the polarized nuclei return to thermal equilibrium. While such a lifetime is sufficient for some imaging and/or spectroscopy studies, contrast agents with longer lifetimes are highly desirable to study additional processes of interest. These processes are related to diffusion, flow, slow molecular motion, chemical reactions, metabolism, and drug targeting and distribution, among others.
The present invention relates to methods of preparing magnetic resonance imaging and/or spectroscopy contrast agents having long-lived nuclear singlet states that can be accessed by pulse sequence transformation. The invention also permits the preparation of a wide range of contrast agent molecules themselves and methods for their use. Specifically, the invention encompasses the novel principle that a spin state which has absolutely zero magnetic resonance signal, but an extremely long lifetime, can be used to store magnetization. This stored magnetization can then be recovered into an observable transition, extending the capabilities of MRI. Furthermore, the invention’s contrast agents are chemically convertible to detection molecules under various physiological conditions.
- Extends the capabilities of MRI in both clinical and research settings
- Permits a wide range of new reagents
- Achieves longer effective relaxation times than the best systems currently in use