This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cells actively maintain a gradient in sodium concentrations between the intracellular and extracellular compartments. This concentration gradient is critically important to a host of normal cellular functions, and the high energetic expense of its maintenance causes it to be sensitively affected by many pathologies. It has recently been discovered that axonal trauma can lead to sodium channel (NaCh) dysfunction and persistent axonal Na+ influx. Because it is capable of a sensitive determination of the spatial distribution, motional characteristics, and local environment of the sodium nucleus in vivo, we propose that sodium magnetic resonance imaging (MRI) is a uniquely suitable technique for noninvasive diagnosis and monitoring of diffuse axonal injury due to the changes in sodium handling that occur early in the pathology and persist throughout its course. We are currently investigating changes in brain sodium signal intensity in a well-characterized miniature pig model of diffuse axonal injury. Proton and sodium images of the minature pig are acquired before and after rotational injury. Sodium images are intensity normalized to external agarose standard phantoms or to homeostatic internal compartments with known sodium concentrations (e.g. vitreous humor, cerebrospinal fluid) and then coregistered to the proton images. Region-of-interest (ROI) analysis is used to compare sodium signal intensities in the pre- and post-injury states. We propose that there will be significant changes in the signal intensity between the pre- and post-injury states, particularly in brain white matter where the most substantial injury is thought to occur.
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