RESUMEN
Overhauser-enhanced MRI (OMRI) is an electron-proton double-resonance imaging technique of interest for its ability to non-invasively measure the concentration and distribution of free radicals. In vivo OMRI experiments are typically undertaken at ultra-low magnetic field (ULF), as both RF power absorption and penetration issues-a consequence of the high resonance frequencies of electron spins-are mitigated. However, working at ULF causes a drastic reduction in MRI sensitivity. Here, we report on the design, construction and performance of an OMRI platform optimized for high NMR sensitivity and low RF power absorbance, exploring challenges unique to probe design in the ULF regime. We use this platform to demonstrate dynamic imaging of TEMPOL in a rat model. The work presented here demonstrates improved speed and sensitivity of in vivo OMRI, extending the scope of OMRI to the study of dynamic processes such as metabolism.
Asunto(s)
Radicales Libres/metabolismo , Imagen por Resonancia Magnética , Animales , Espectroscopía de Resonancia por Spin del Electrón , Espectroscopía de Resonancia Magnética , Masculino , Ondas de Radio , Ratas Sprague-DawleyRESUMEN
SIGNIFICANCE: In vivo free radical imaging in preclinical models of disease has become a reality. Free radicals have traditionally been characterized by electron spin resonance (ESR) or electron paramagnetic resonance (EPR) spectroscopy coupled with spin trapping. The disadvantage of the ESR/EPR approach is that spin adducts are short-lived due to biological reductive and/or oxidative processes. Immuno-spin trapping (IST) involves the use of an antibody that recognizes macromolecular 5,5-dimethyl-pyrroline-N-oxide (DMPO) spin adducts (anti-DMPO antibody), regardless of the oxidative/reductive state of trapped radical adducts. Recent Advances: The IST approach has been extended to an in vivo application that combines IST with molecular magnetic resonance imaging (mMRI). This combined IST-mMRI approach involves the use of a spin-trapping agent, DMPO, to trap free radicals in disease models, and administration of an mMRI probe, an anti-DMPO probe, which combines an antibody against DMPO-radical adducts and an MRI contrast agent, resulting in targeted free radical adduct detection. CRITICAL ISSUES: The combined IST-mMRI approach has been used in several rodent disease models, including diabetes, amyotrophic lateral sclerosis (ALS), gliomas, and septic encephalopathy. The advantage of this approach is that heterogeneous levels of trapped free radicals can be detected directly in vivo and in situ to pin point where free radicals are formed in different tissues. FUTURE DIRECTIONS: The approach can also be used to assess therapeutic agents that are either free radical scavengers or generate free radicals. Smaller probe constructs and radical identification approaches are being considered. The focus of this review is on the different applications that have been studied, advantages and limitations, and future directions. Antioxid. Redox Signal. 28, 1404-1415.