This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our long-term goal to translate much of our early 13C isotopomer methods to in vivo metabolic studies for clinical applications is now a realistic possibility. Thus, the focus of the renewed support will be to investigate fundamental metabolic questions using hyperpolarized 13 C MR measurements in isolated, perfused rat hearts and mouse livers with the intent to translate these findings into direct clinical practice. As in the past, we believe these fundamental studies are extremely important as we begin to apply these latest MR technologies to the study of human metabolic diseases. This project has four specific aims: 1) Develop hyperpolarized 13C methods to measure flux through individual enzyme catalyzed steps and through specific spans of the TCA cycle. 2) Develop a hyperpolarized 13C method to measure gluconeogenesis in isolated perfused mouse livers. 3) Develop a hyperpolarized 13C method to measure flux through the pentose phosphate pathway in perfused hearts and livers. 4) Develop the tools necessary to image tissue red-ox by 13C MRS using hyperpolarized redox indicators.
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