While electron paramagnetic resonance imaging (EPRI) enables spatial mapping of free radicals in the whole body of small animals, it solely visualizes the free-radical distribution and does not typically provide anatomic visualization of the body. However, anatomic registration is often required for meaningful interpretation of the EPRI-derived free-radical images. An approach is reported for whole-body, EPRI-based, free-radical imaging along with proton MRI in mice. EPRI instrumentation with a 750-MHz narrow band microwave bridge and transverse oriented electric field reentrant resonator, with automatic coupling control and automatic tuning control capability, was used to map the spatial distribution of nitroxide free radicals in phantoms and in living mice, while low-field proton MRI at 16 MHz was used to define the anatomic structure to register the EPR images. Small capillary tubes containing an aqueous radical label were used as markers to enable image superimposition. With this coregistration technique, the EPRI free-radical images were precisely registered, enabling assignment of the location of the observed free-radical distribution within the organs of the mice.
Key words: in vivo EPR; in vivo NMR; proton MRI; co-imaging; automatic tuning; automatic couplingElectron paramagnetic resonance imaging (EPRI) has been widely used to map the distribution and metabolism of paramagnetic species in isolated organs and other ex vivo and in vivo biological systems (1-10). However, in contrast to proton NMR-based MRI, EPRI only detects the distribution and kinetics of free radicals, and consequently these images may not resemble the anatomic structure of the imaged object. Therefore, development of independent approaches for anatomic registration of EPR image data is of critical importance to facilitate accurate assignment of the distribution of free radicals within the body.Proton MRI has been well established over the last two decades as a precise method for the noninvasive delineation of internal anatomic structure, and has been widely applied in a wide range of research and clinical applications. As an MR technique, it is particularly powerful for anatomic mapping due to the high concentration and narrow linewidth of water protons in biological systems (11)(12)(13)(14)(15). By employing NMR images to define the anatomic structure with appropriate markers visualized by both EPRI and proton MRI, appropriate superimposition/registration can in principle be performed. This EPR/NMR coimaging (ENCI), while a seemingly simple concept, presents a number of unique technical challenges. These problems are primarily based on the need for high-resolution EPRI mapping of the registration markers and biological samples, appropriate NMR/EPR-detectable markers, and mechanical and computational approaches to appropriately fix the sample orientations and superimpose the images obtained. Largely because of these challenges, this type of co-imaging technique with 2D or 3D EPR image registration has not been previously achieved.App...