The BOLD-fMRI approach has revolutionized assessment of brain function. This complex effect represents MRI signal changes that are consequential to a hemodynamic response secondary to activation. As the BOLD response reflects the changing oxygen extraction fraction, OEF, it allows some insight into basic brain physiology. However, such interpretations are confounded by multiple contributions to the effect. BOLD is sensitive not only to intravascular oxygenation changes, but also to extravascular effects of such changes around parenchyma and around veins draining from activated cortex. In addition, BOLD is influenced by alterations in voxel composition due to changes in cerebral blood volume (CBV). Contributions of these effects to the BOLD signal intensity changes depend on magnetic field strength, voxel size, type of MRI experiment (spin echo/gradient echo). Thus, there are many variables and few observable parameters. In the previous period we have developed a new fMRI approach that can add several essential observables, namely tissue fractions, CBV and the tissue relaxation rates. We also re-interpreted the BOLD post-stimulus undershoot in terms of continued oxygen metabolism and showed that, surprisingly, BOLD spin-echo signals can occur in draining veins. The ultimate goal of this proposal is to gain a complete quantitative understanding of the physiological, physical, and spatial aspects of the BOLD effect.
In AIM 1 we propose experiments to confirm the proposed oxygen-metabolism based character of the BOLD post-stimulus undershoot and to develop strategies to use this undershoot for fMRI voxel selection.
In AIM 2 we propose experiments that can distinguish intravascular, extravascular, macrovascular, and microvascular BOLD components. These data will be used to evaluate existing extravascular BOLD theories.
In AIM 3 we measure the blood transverse relaxation rates for blood in which the transport properties of erythrocyte water channels are impaired by an aquaporin channel blocker. This will be combined with our previous data without blocker to evaluate the effect of exchange versus magnetic field gradients on the intravascular BOLD effect. Based on our blood data acquired in the previous grant period and our in vivo data proposed to be acquired here, we will derive a quantitative description for the BOLD effect that has only physiological and physical parameters. This formalism should allow description of the BOLD effect for all physiological perturbations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
3R01EB004130-08S1
Application #
7483863
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Mclaughlin, Alan Charles
Project Start
1999-04-01
Project End
2009-07-31
Budget Start
2007-08-01
Budget End
2009-07-31
Support Year
8
Fiscal Year
2007
Total Cost
$83,445
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hua, Jun; Stevens, Robert D; Huang, Alan J et al. (2011) Physiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism. J Cereb Blood Flow Metab 31:1599-611
Qin, Qin; Grgac, Ksenija; van Zijl, Peter C M (2011) Determination of whole-brain oxygen extraction fractions by fast measurement of blood T(2) in the jugular vein. Magn Reson Med 65:471-9
Hua, Jun; Qin, Qin; Pekar, James J et al. (2011) Measurement of absolute arterial cerebral blood volume in human brain without using a contrast agent. NMR Biomed 24:1313-25
Hua, Jun; Qin, Qin; Donahue, Manus J et al. (2011) Inflow-based vascular-space-occupancy (iVASO) MRI. Magn Reson Med 66:40-56
Donahue, Manus J; van Laar, Peter Jan; van Zijl, Peter C M et al. (2009) Vascular space occupancy (VASO) cerebral blood volume-weighted MRI identifies hemodynamic impairment in patients with carotid artery disease. J Magn Reson Imaging 29:718-24
Donahue, Manus J; Hua, Jun; Pekar, James J et al. (2009) Effect of inflow of fresh blood on vascular-space-occupancy (VASO) contrast. Magn Reson Med 61:473-80
Hua, Jun; Donahue, Manus J; Zhao, Jason M et al. (2009) Magnetization transfer enhanced vascular-space-occupancy (MT-VASO) functional MRI. Magn Reson Med 61:944-51
Ceritoglu, Can; Oishi, Kenichi; Li, Xin et al. (2009) Multi-contrast large deformation diffeomorphic metric mapping for diffusion tensor imaging. Neuroimage 47:618-27
Ng, Man-Cheuk; Hua, Jun; Hu, Yong et al. (2009) Magnetization transfer (MT) asymmetry around the water resonance in human cervical spinal cord. J Magn Reson Imaging 29:523-8
Donahue, Manus J; Stevens, Robert D; de Boorder, Michiel et al. (2009) Hemodynamic changes after visual stimulation and breath holding provide evidence for an uncoupling of cerebral blood flow and volume from oxygen metabolism. J Cereb Blood Flow Metab 29:176-85

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