The continued productivity of three leading research groups in Muscle Biology, Obesity and Cancer Biology require major improvements in imaging gradients, RF coils and physiologic gating and monitoring. The availability of a short bore 4.7 T Bruker magnet catalyzed the productivity of an integrated program of muscle studies using optical and MR spectroscopy to analyze metabolic and energy balances in human and animal muscles. New developments integrate optical NIR spectroscopy with MR in the investigation of mitochondrial dysfunction and integrate MR perfusion methods with spectroscopic measurements of metabolic fluxes to address important mechanisms in a range of maladies affecting muscle. Recent opportunities with collaborators elsewhere at this University enabled spectroscopic imaging of rat brain that measures molecules involved in cellular mechanisms regulating feeding and obesity. Further opportunities exist by combining MR and PET high resolution mouse imaging and in high resolution mouse imaging by leading cancer biology programs in our department and at the Fred Hutchinson Cancer Research Center. Research leadership by all of these NIH projects is jeopardized by inadequate gradients and RF coils and by the absence of tools for monitoring the physiological status of the animals in the magnet and for gating. This application requests funds to purchase a customized shim and gradient coils for this magnet, a very high gradient strength insert for rat and mouse studies, animal monitoring equipment and RF coils. The requested upgrades to our instrument will provide needed flexibility and capabilities for our twelve currently funded projects in the departments of Radiology, and Medicine at the University and at the Fred Hutchinson Cancer Research Center. All of these programs are internationally known for excellence in their fields. Human limb muscle bioenergetics, biomechanics and perfusion studies (Kushmerick, Conley, Marcinek and Marro) will continue their novel studies with this very high field instrument with clear-cut improvements in spatial resolution and signal to noise and in the ability to exploit novel multinuclear and multispectral (optics and NMR) methods. Quantification of metabolites in brain thought to be involved in regulation of feeding and obesity (Cummings) will for the first time be monitored dynamically during acute experiments and longitudinally in long term studies. High resolution 1H and 23Na imaging of liver, brain, prostate and implanted tumors will be facilitated for the studies of normal and transgenic mice (Sze and Miyaoka at UW and Grady, Kemp and Greenberg at FHCRC). The budget for this upgrade is modest for the large scope of projects being done. ? ?
| Amara, Catherine E; Marcinek, David J; Shankland, Eric G et al. (2008) Mitochondrial function in vivo: spectroscopy provides window on cellular energetics. Methods 46:312-8 |
