Detection of proton chemical exchange between metabolites and water in biological tissues

Metabolites in proton chemical exchange with water were detected via the water proton signal using saturation transfer techniques in model systems and biological tissues. The metabolites were selectively saturated and the resulting decrease in the much larger water proton pool was used to monitor the metabolite. This indirect detection scheme can result in a several orders of magnitude increase in sensitivity for metabolites over direct detection methods. A control irradiation scheme was devised to compensate for macromolecular/water magnetization transfer. Using this approach, significant chemical exchange regions at approximately 1 and 2.5 ppm were detected in kidney medulla. Using a difference imaging technique between a control irradiation above (-1.74 ppm) and below (+1.74 ppm) the water resonance, a chemical exchange image of the kidney was calculated. These data revealed a linear gradient of chemical exchange increasing from the cortex to the medulla. Studies on medullary acid extracts and urine revealed that the exchange observed in the kidney was predominantly with low molecular weight metabolites. Urea (1 ppm) was identified as contributing to the kidney/urine chemical exchange; however, other unidentified metabolites may also contribute to this effect. These studies demonstrate that tissue metabolites can be detected and imaged via the water protons using the signal amplification properties of saturation transfer in the presence of water/macromolecule magnetization transfer.