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. Adenosine triphosphate (ATP), which mainly formed in mitochondria through oxidative phosphorylation and F1F0-ATPase, provides energy for driving most cellular activities in the brain. This oxidative ATP metabolism plays essential roles in brain bioenergetics, function and disease. The sole approach possible for directly assessing the metabolic rate of ATPase reaction in situ is the use of in vivo 31P MRS combined with magnetization transfer (MT). However, previous work of perfused heart suggested that the apparent ATP synthesis rate measured by in vivo 31P MT approach was not coupled with the net rate of oxidative phosphorylation and its change. In contrast, our recent work has shown that the measured cerebral metabolic rate of ATP (CMRATP) via ATPase reaction is closely matched with the net oxidative phosphorylation rate in anesthetized animals and awaked human, and it is also sensitive to the change of brain activity induced by varied baseline activity and/or brain stimulation. These compelling findings have led to our central hypothesis: In vivo 31P MT approach should be suitable for measuring and imaging CMRATP, which directly reflects the net rate of oxidative phosphorylation of ADP for producing the majority of brain ATP molecules;and establishment of this in vivo approach can provide an invaluable, completely noninvasive neuroimaging modality for studying the central roles of oxidative ATP metabolism in regulating neuroenergetics associated with brain function and dysfunction. This hypothesis will be tested by four specific aims: 1) to further optimize and improve in vivo 31P MT measurements and quantification methods for accurately determining CMRATP using an animal model at high field;2) to conduct concurrent noninvasive measurements of CMRATP and the cerebral metabolic rate of oxygen (CMRO2) using our newly developed high-field in vivo 17O MRS imaging approach in resting brains with varied baseline activity levels, and to examine if CMRATP is sensitive to brain activity change, and if CMRATP correlates to the rate of oxidative phosphorylation under a wide physiological range of brain activity;3) to conduct functional activation studies using visual stimulation to examine if CMRATP increases in the activated visual cortex for supporting higher energy demand and stimulus-evoked neuronal activity;4) to conduct extracellular neuron-recording studies under resting and activated conditions, and to correlate electrophysiology results with CMRATP results for providing new insights into the neuro-ATP-metabolic coupling relationships in the resting and activated brain. The significance of this research lies in two layers: to establish a unique neuroimaging modality for imaging CMRATP: a most fundamental and direct measure of brain energy;and to understand the possible roles of oxidative ATP metabolism in neuroenergetics and neurophysiology for supporting brain function and work.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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University of Minnesota Twin Cities
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Bolan, Patrick J; Kim, Eunhee; Herman, Benjamin A et al. (2017) MR spectroscopy of breast cancer for assessing early treatment response: Results from the ACRIN 6657 MRS trial. J Magn Reson Imaging 46:290-302
U?urbil, Kamil (2017) Imaging at ultrahigh magnetic fields: History, challenges, and solutions. Neuroimage :
Wilson, Sylia; Malone, Stephen M; Hunt, Ruskin H et al. (2017) Problematic alcohol use and hippocampal volume in a female sample: disentangling cause from consequence using a co-twin control study design. Psychol Med :1-12
Lyzinski, Vince; Fishkind, Donniell E; Fiori, Marcelo et al. (2016) Graph Matching: Relax at Your Own Risk. IEEE Trans Pattern Anal Mach Intell 38:60-73
Musgrove, Donald R; Hughes, John; Eberly, Lynn E (2016) Fast, fully Bayesian spatiotemporal inference for fMRI data. Biostatistics 17:291-303
Andronesi, Ovidiu C; Loebel, Franziska; Bogner, Wolfgang et al. (2016) Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate. Clin Cancer Res 22:1632-41
Thatcher, R W; Palmero-Soler, E; North, D M et al. (2016) Intelligence and eeg measures of information flow: efficiency and homeostatic neuroplasticity. Sci Rep 6:38890
Uroševi?, Snežana; Luciana, Monica; Jensen, Jonathan B et al. (2016) Age associations with neural processing of reward anticipation in adolescents with bipolar disorders. Neuroimage Clin 11:476-85
Kennedy, James T; Collins, Paul F; Luciana, Monica (2016) Higher Adolescent Body Mass Index Is Associated with Lower Regional Gray and White Matter Volumes and Lower Levels of Positive Emotionality. Front Neurosci 10:413
Wiesner, Hannes M; Balla, Dávid Z; Shajan, G et al. (2016) (17)O relaxation times in the rat brain at 16.4 tesla. Magn Reson Med 75:1886-93

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