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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS070839-03
Application #
8252167
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Babcock, Debra J
Project Start
2010-05-01
Project End
2015-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$394,498
Indirect Cost
$133,241
Name
University of Minnesota Twin Cities
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Zhu, Xiao-Hong; Chen, Wei (2018) In vivo X-Nuclear MRS Imaging Methods for Quantitative Assessment of Neuroenergetic Biomarkers in Studying Brain Function and Aging. Front Aging Neurosci 10:394
Zhu, Xiao-Hong; Lu, Ming; Chen, Wei (2018) Quantitative imaging of brain energy metabolisms and neuroenergetics using in vivo X-nuclear 2H, 17O and 31P MRS at ultra-high field. J Magn Reson 292:155-170
Lee, Byeong-Yeul; Zhu, Xiao-Hong; Woo, Myung Kyun et al. (2018) Interleaved 31 P MRS imaging of human frontal and occipital lobes using dual RF coils in combination with single-channel transmitter-receiver and dynamic B0 shimming. NMR Biomed 31:
Kim, Sang-Young; Chen, Wei; Ongur, Dost et al. (2018) Rapid and simultaneous measurement of phosphorus metabolite pool size ratio and reaction kinetics of enzymes in vivo. J Magn Reson Imaging 47:210-221
Cruttenden, Corey E; Taylor, Jennifer M; Hu, Shan et al. (2017) Carbon Nano-Structured Neural Probes Show Promise for Magnetic Resonance Imaging Applications. Biomed Phys Eng Express 4:
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
Zhu, Xiao-Hong; Chen, Wei (2017) In vivo17O MRS imaging - Quantitative assessment of regional oxygen consumption and perfusion rates in living brain. Anal Biochem 529:171-178
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
Wang, Ying; Wang, Xiao; Chen, Wei et al. (2017) Functional MRI BOLD response in sickle mice with hyperalgesia. Blood Cells Mol Dis 65:81-85
Lee, Byeong-Yeul; Zhu, Xiao-Hong; Rupprecht, Sebastian et al. (2017) Large improvement of RF transmission efficiency and reception sensitivity for human in vivo31P MRS imaging using ultrahigh dielectric constant materials at 7T. Magn Reson Imaging 42:158-163

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