Development of a hybrid EPR/NMR coimaging system

Abstract

Electron paramagnetic resonance imaging (EPRI) is a powerful technique that enables spatial mapping of free radicals or other paramagnetic compounds; however, it does not in itself provide anatomic visualization of the body. Proton magnetic resonance imaging (MRI) is well suited to provide anatomical visualization. A hybrid EPR/NMR coimaging instrument was constructed that utilizes the complementary capabilities of both techniques, superimposing EPR and proton-MR images to provide the distribution of paramagnetic species in the body. A common magnet and field gradient system is utilized along with a dual EPR and proton-NMR resonator assembly, enabling coimaging without the need to move the sample. EPRI is performed at ϳ1.2 GHz/ ϳ40 mT and proton MRI is performed at 16.18 MHz/ϳ380 mT; hence the method is suitable for whole-body coimaging of living mice. The gradient system used is calibrated and controlled in such a manner that the spatial geometry of the two acquired images is matched, enabling their superposition without additional postprocessing or marker registration. The performance of the system was tested in a series of phantoms and in vivo applications by mapping the location of a paramagnetic probe in the gastrointestinal ( Key words: proton MRI; EPR imaging; free radicals, oxygen; image coregistration; in vivo NMR; in vivo EPRThe techniques of electron paramagnetic resonance (EPR) spectroscopy and imaging (EPRI) have been widely used to measure and map the distribution of paramagnetic materials and free radicals in biological systems, including ex vivo tissues and in vivo living animals (1-8). These techniques provide unique information that enables measurement and imaging of the processes of free radical metabolism, tissue oxygenation, and nitric oxide generation in normal physiology and disease (9 -17). While EPRI provides specific mapping of the location of a given paramagnetic species, this is often not sufficient in itself to enable anatomic mapping of the precise organ-specific location of the paramagnetic probe in the body of a living animal. On the other hand, proton magnetic resonance imaging (MRI) has been established as a powerful diagnostic imaging technique capable of obtaining high-resolution images of the anatomical structure of humans and animals (18 -22). While proton MRI is a powerful technique for imaging biological systems based on their high content of water, it can not directly localize low, submillimolar levels of free radicals.Several noninvasive MRI-based methods for detection and mapping of paramagnetic substances in vivo are under development. Both contrast-enhanced MRI (15,16) and proton electron double resonance imaging (PEDRI) (23,24) utilize proton MRI-based detection and therefore automatically provide coregistration of free radical distribution with anatomical structure. The availability of anatomic information, as well as superior spatial and temporal resolution, make MRI-based techniques more efficient in these aspects compared to direct EPRI methods. However, since t...

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