Human brain is a highly aerobic organ. With only five percent of the total body mass, it utilizes one fifth of the oxygen consumed by the entire body. Aerobic respiration is essential for providing the substantial energy needs of the normal brain activities in our daily life. Questions regarding the cerebral metabolic rate of oxygen consumption (CMRO2) are encountered frequently in biomedical research for understanding normal brain function and metabolic abnormalities associated with brain dysfunction and diseases. Modern neuroimaging techniques such as functional magnetic resonance (MR) imaging (fMRI) have revolutionized our ability to study brain function and human behavior. However, despite numerous research attempts and significant technology advances of the past three decades, current capability of neuroimaging approaches for accurate and noninvasive measurement of CMRO2 in human brain remains ultimately limited or problematic. To fill this technique gap, we have dedicated substantial efforts in recent years to develop and advance the high-field 17O-based MR spectroscopic imaging (MRSI) method for directly imaging CMRO2. This method relies on an inhalation of 17O-isotope-enriched oxygen gas, which is non-radioactive and stable, into the human body while monitoring the dynamic change of oxidative production of the 17O-labeled metabolic water in the brain using the 3D 17O MRSI. We have found that the 17O MR detection sensitivity increases almost quadratically with the magnetic field strength;and the feasibility, reliability and applicability of the 17O MR- based approach for noninvasively, quantitatively imaging CMRO2 at high/ultrahigh fields have been rigorously evaluated and verified in the animal models. Nevertheless, there are tremendous technical and methodological challenges to contend with before we can translate this 17O-based CMRO2 neuroimaging technology for biomedical applications in healthy humans and patients. In this grant application, we will address the most critical challenges with a number of innovative solutions and MR technologies aiming to rigorously validate and ultimately establish a rapid, accurate, cost-effective and completely noninvasive CMRO2 neuroimaging modality suitable for three-dimensional CMRO2 imaging of the entire human brain. The success of the proposed research will provide an important step towards closing the technology gap and making the novel CMRO2 neuroimaging tool available to a broad biomedical research community for studying the central roles of oxygen metabolism in the human brains under physiologic and pathologic conditions.

Public Health Relevance

Abnormality in brain oxygen metabolism has been linked to many neurodegenerative diseases, brain dysfunctions and aging problems. However, in general, it is lack of robust and cost-effective in vivo tools for noninvasively imaging the cerebral metabolic rate of oxygen (CMRO2) in the human brain owing to numerous technical challenges. The success of the proposed research aiming to establish a quantitative 17O-MR based CMRO2 neuroimaging modality will fill this technology gap and advance the biomedical fields, in particular, in studying the central roles of cerebral oxidative metabolism in human brain function and dysfunction. It will also provide a great opportunity for moving forward the translational medical research, ultimately, leading to a clinical imaging tool for diagnosis of brain diseases.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Biomedical Imaging Technology Study Section (BMIT)
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Babcock, Debra J
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University of Minnesota Twin Cities
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Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi et al. (2017) A comparison study between the saturation-recovery-T1 and CASL MRI methods for quantitative CBF imaging. Magn Reson Imaging 37:179-186
Cui, Meng; Zhou, Yifeng; Wei, Bowen et al. (2017) A proof-of-concept study for developing integrated two-photon microscopic and magnetic resonance imaging modality at ultrahigh field of 16.4 tesla. Sci Rep 7:2733
Einstein, Samuel A; Weegman, Bradley P; Kitzmann, Jennifer P et al. (2017) Noninvasive assessment of tissue-engineered graft viability by oxygen-17 magnetic resonance spectroscopy. Biotechnol Bioeng 114:1118-1121
Lu, Ming; Zhu, Xiao-Hong; Chen, Wei (2016) In vivo (31) P MRS assessment of intracellular NAD metabolites and NAD(+) /NADH redox state in human brain at 4 T. NMR Biomed 29:1010-7
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
Deelchand, Dinesh Kumar; Nguyen, Tra-My; Zhu, Xiao-Hong et al. (2015) Quantification of in vivo ³¹P NMR brain spectra using LCModel. NMR Biomed 28:633-41
Wang, Xiao; Zhu, Xiao-Hong; Zhang, Yi et al. (2015) Simultaneous Imaging of CBF Change and BOLD with Saturation-Recovery-T1 Method. PLoS One 10:e0122563
Taylor, Jennifer M; Zhu, Xiao-Hong; Zhang, Yi et al. (2015) Dynamic correlations between hemodynamic, metabolic, and neuronal responses to acute whole-brain ischemia. NMR Biomed 28:1357-65
Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul et al. (2015) In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proc Natl Acad Sci U S A 112:2876-81
Lu, Ming; Zhu, Xiao-Hong; Zhang, Yi et al. (2014) Intracellular redox state revealed by in vivo (31) P MRS measurement of NAD(+) and NADH contents in brains. Magn Reson Med 71:1959-72

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