Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) provides a critical tool to the medical and scientific communities. Despite the indispensable role of the BOLD fMRI technique in mapping human brain function, its biophysical and physiological sources are not well known because the BOLD effect has a complex dependence on many parameters including cerebral blood flow (CBF), and venous cerebral blood volume (CBV). For full utilization of the capabilities of this technique, it is imperative to investigate the origin of BOLD signals and to determine the spatial limits of fMRI. This requires an in-depth examination of the physiological basis of fMRI signals. In this application, we aim to further elucidate sources of BOLD fMRI signals, and vascular responses induced by neural activity using the well-established cortical layer model in animals at 9.4T. The hypotheses to be tested are 1) intrinsic spatial specificity of the fMRI signal is improved with spin-echo BOLD technique at high fields, 2) hemodynamic change induced by neural activity is not widespread, and 3) blood volume change induced by neural activity is dominant in arterial vascularure. Conventional gradient-echo BOLD signals are sensitive to susceptibility changes in all sizes of venous vessels, with a spatial resolution closely related to the spacing between intracortical veins. To improve spatial specificity, the spin-echo technique can be applied because it will refocus the static susceptibility effects around large vessels. The ultimate limit of spatial resolution in fMRI techniques is dictated by vascular responses induced by neural activity. Based on CBV-weighted intrinsic optical imaging studies, the CBV change is diffuse and extends far beyond the actual neuronal activation site. Poor specificity may be due to the contamination by large surface vessels and/or poor spatial specificity in regulation of CBV response. This will be examined by CBV-weighted fMRI following an injection of a long half-life contrast agent. However, it is unknown whether CBV change induced by neural activity is dominant in artery or venous vasculatures. Determination of the exact source of CBV changes is crucial because the BOLD signal is dependent on both baseline venous CBV and its changes. Further, it is imperative to determine the inter-relationship between spin-echo BOLD, CBF, arterial CBV, and total CBV in order to understand the mechanism of BOLD signals. The long-term goal of these investigations is to determine the detailed biophysical mechanisms and origins of BOLD signals, and the inherent spatial limits of BOLD and CBV-weighted fMRI. This investigation combining MR physics and physiology will provide important insight into how finely the hemodynamic response is tuned to neural activity and will help to pinpoint the characteristics of the vasculature involved in blood flow regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003375-09
Application #
7183486
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Mclaughlin, Alan Charles
Project Start
1999-05-15
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
9
Fiscal Year
2007
Total Cost
$303,644
Indirect Cost
Name
University of Pittsburgh
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Poplawsky, Alexander John; Kim, Seong-Gi (2014) Layer-dependent BOLD and CBV-weighted fMRI responses in the rat olfactory bulb. Neuroimage 91:237-51
Zong, Xiaopeng; Lee, Juyoung; John Poplawsky, Alexander et al. (2014) Compressed sensing fMRI using gradient-recalled echo and EPI sequences. Neuroimage 92:312-21
Kim, Tae; Shin, Wanyong; Kim, Seong-Gi (2014) Fast magnetization transfer and apparent T1 imaging using a short saturation pulse with and without inversion preparation. Magn Reson Med 71:1264-71
Zong, Xiaopeng; Wang, Ping; Kim, Seong-Gi et al. (2014) Sensitivity and source of amine-proton exchange and amide-proton transfer magnetic resonance imaging in cerebral ischemia. Magn Reson Med 71:118-32
Vazquez, Alberto L; Fukuda, Mitsuhiro; Crowley, Justin C et al. (2014) Neural and hemodynamic responses elicited by forelimb- and photo-stimulation in channelrhodopsin-2 mice: insights into the hemodynamic point spread function. Cereb Cortex 24:2908-19
Moon, Chan Hong; Fukuda, Mitsuhiro; Kim, Seong-Gi (2013) Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution. Neuroimage 64:91-103
Kim, Seong-Gi; Harel, Noam; Jin, Tao et al. (2013) Cerebral blood volume MRI with intravascular superparamagnetic iron oxide nanoparticles. NMR Biomed 26:949-62
Jin, Tao; Kim, Seong-Gi (2013) Characterization of non-hemodynamic functional signal measured by spin-lock fMRI. Neuroimage 78:385-95
Jin, Tao; Wang, Ping; Zong, Xiaopeng et al. (2013) MR imaging of the amide-proton transfer effect and the pH-insensitive nuclear overhauser effect at 9.4 T. Magn Reson Med 69:760-70
Fukuda, Mitsuhiro; Vazquez, Alberto L; Zong, Xiaopeng et al. (2013) Effects of the ??-adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex. Eur J Neurosci 37:80-95

Showing the most recent 10 out of 50 publications