This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of the research is to investigate the extent to which the brain apparent diffusion coefficient (ADC) changes due to neuronal activation in an animal model. This work will contribute to understanding of the neuronal microenvironment during neuronal activity and potentially provide a new tool for non-invasive localization and possible quantitation of brain activity. Evidence from invasive, optical (infra-red) imaging of the surface of the brain during task activation indicates that there is the expected vascular response located primarily in the pial arterioles and the draining veins in the region of neuronal activation. This is the source of the blood-oxygenation-level dependent (BOLD) changes that underlie the bulk of functional magnetic resonance imaging (fMRI). There also appears to be a direct, cellular response shown to be related to glial and/or neuronal swelling due to changes in the intra/extra-cellular solute balance as a consequence of increased metabolic and membrane activity. The cellular response appears to be much more directly related to the actual region of neuronal activity than the vascular response. Preliminary data in human subjects supports the idea that the cellular swelling should also result in a change of the local tissue ADC that could be observed with MR imaging. There are major challenges to utilizing this ADC contrast such as the low contrast-to-noise ratio of the effect and motion artifacts from diffusion gradients. Early results in humans have shown a mixture of diffusion effects, some at the area of BOLD activation and others that seem unrelated. Due to the difficulties of controlling human motions and/or performing human drug interventions to modulate the effect it is proposed here to proceed to establish the effect in an animal model where motion can be controlled and interventions performed.
The aims of this research are: (1) establish the spatial extent of the ADC change compared to BOLD fMRI in a rat forepaw electrical stimulation model using a 7T small animal MR imaging system with very strong (400mT/m) gradients; (2) determine whether there are residual BOLD effects in the ADC signal by blocking vascular response in the pial arterioles using an infusion of a drug such as theophylline or caffeine to block vascular adenosine receptors and nitric oxide synthetase inhibitors to block nitric oxide signaling.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR005959-17
Application #
7358267
Study Section
Special Emphasis Panel (ZRG1-SSS-X (40))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
17
Fiscal Year
2006
Total Cost
$5,126
Indirect Cost
Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Tang, Xinyan; Jing, Liufang; Richardson, William J et al. (2016) Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration. J Orthop Res 34:1316-26
Hodgkinson, Conrad P; Bareja, Akshay; Gomez, José A et al. (2016) Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology. Circ Res 118:95-107
Schmeckpeper, Jeffrey; Verma, Amanda; Yin, Lucy et al. (2015) Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol 85:215-25
Roos, Justus E; McAdams, Holman P; Kaushik, S Sivaram et al. (2015) Hyperpolarized Gas MR Imaging: Technique and Applications. Magn Reson Imaging Clin N Am 23:217-29
He, Mu; Robertson, Scott H; Kaushik, S Sivaram et al. (2015) Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI. Magn Reson Imaging 33:877-85
Huang, Lingling; Walter, Vonn; Hayes, D Neil et al. (2014) Hedgehog-GLI signaling inhibition suppresses tumor growth in squamous lung cancer. Clin Cancer Res 20:1566-75
Huang, Jing; Guo, Jian; Beigi, Farideh et al. (2014) HASF is a stem cell paracrine factor that activates PKC epsilon mediated cytoprotection. J Mol Cell Cardiol 66:157-64
Yuan, Ying; Gilmore, John H; Geng, Xiujuan et al. (2014) FMEM: functional mixed effects modeling for the analysis of longitudinal white matter Tract data. Neuroimage 84:753-64
He, Mu; Kaushik, S Sivaram; Robertson, Scott H et al. (2014) Extending semiautomatic ventilation defect analysis for hyperpolarized (129)Xe ventilation MRI. Acad Radiol 21:1530-41
van Rhoon, Gerard C; Samaras, Theodoros; Yarmolenko, Pavel S et al. (2013) CEM43°C thermal dose thresholds: a potential guide for magnetic resonance radiofrequency exposure levels? Eur Radiol 23:2215-27

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