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The Journal of Neuroscience, March 2, 2005, 25(9):2233-2244; doi:10.1523/JNEUROSCI.3032-04.2005

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Behavioral/Systems/Cognitive
Compartment-Resolved Imaging of Activity-Dependent Dynamics of Cortical Blood Volume and Oximetry

Ivo Vanzetta, Rina Hildesheim, and Amiram Grinvald

Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel

Optical imaging, positron emission tomography, and functional magnetic resonance imaging (fMRI) all rely on vascular responses to image neuronal activity. Although these imaging techniques are used successfully for functional brain mapping, the detailed spatiotemporal dynamics of hemodynamic events in the various microvascular compartments have remained unknown. Here we used high-resolution optical imaging in area 18 of anesthetized cats to selectively explore sensory-evoked cerebral blood-volume (CBV) changes in the various cortical microvascular compartments. To avoid the confounding effects of hematocrit and oximetry changes, we developed and used a new fluorescent blood plasma tracer and combined these measurements with optical imaging of intrinsic signals at a near-isosbestic wavelength for hemoglobin (565 nm). The vascular response began at the arteriolar level, rapidly spreading toward capillaries and venules. Larger veins lagged behind. Capillaries exhibited clear blood-volume changes. Arterioles and arteries had the largest response, whereas the venous response was smallest. Information about compartment-specific oxygen tension dynamics was obtained in imaging sessions using 605 nm illumination, a wavelength known to reflect primarily oximetric changes, thus being more directly related to electrical activity than CBV changes. Those images were radically different: the response began at the parenchyma level, followed only later by the other microvascular compartments. These results have implications for the modeling of fMRI responses (e.g., the balloon model). Furthermore, functional maps obtained by imaging the capillary CBV response were similar but not identical to those obtained using the early oximetric signal, suggesting the presence of different regulatory mechanisms underlying these two hemodynamic processes.

Key words: optical imaging; neurovascular coupling; arterioles; CBV; microvasculature; fMRI

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Received July 24, 2004; revised January 7, 2005; accepted January 8, 2005.

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