Understanding the relationship between neural activity and functional magnetic resonance imaging (fMRI) signals is critical for pinpointing sites of neural activity and for determining strength of neural activity. The most extensively-used fMRI technique is based on blood oxygenation level dependent (BOLD) images whose contrast depends on alterations in the cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral blood volume (CBV) in response to increased neuronal activity. BOLD contrast also depends on the choice of many experimental variables, such as imaging technique (e.g., gradient-echo, spin-echo), static magnetic field strength, and echo time. Consequently, the relationship between neural activity and the BOLD effect found for one experimental condition cannot be easily generalized to other conditions. Therefore, fMRI based on a single physiological parameter, such as CBF or CBV, is preferable due to the independence of magnetic field and other experimental variables. The long-term goal of our investigations is to determine the spatial, temporal and magnitude relationships between neural activity and perfusion changes. In the last grant period (7/1/2002-present), we demonstrated that CBF and CBV responses induced by increased neural activity are relatively specific to sites of neural activity. The highest CBF and CBV responses occur within layer 4 in the somatosensory cortex and visual cortex, and within orientation-selective columns in the visual cortex. However, both the source of non-specific perfusion signals from neurally-inactive cortical columns and the quantitative relationship between neural activity and perfusion response at submillimeter resolution are unclear. In this competitive renewal application, we aim to pursue our examination of the neural correlates of perfusion-based signal changes at ultra-high field (9.4 Tesla) using the well-established animal model, which has been extensively investigated with electrophysiology, 2-deoxyglucose autoradiography, and optical imaging. Since CBV responses are closely correlated with CBF responses, functional CBV changes can be converted into CBF changes and vice versa. The CBV-weighted fMRI technique with exogenous contrast agent is more sensitive than CBF-weighted fMRI; so our proposed studies will focus on CBV-weighted fMRI. We also aim to evaluate CBV-weighted techniques that can be applied to human studies. Our proposed studies will provide insight into the size of a vascular functional unit, and consequently could provide a limit to ultimately achievable spatial localization by all hemodynamic-based mapping techniques, including fMRI, H215O-based positron emission tomography, and intrinsic optical imaging. ? ? ?
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