Functional magnetic resonance imaging (fMRI) using blood-oxygenation-level-dependent (BOLD) contrast is a common method for studying human brain function non-invasively. Gradient-echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the signal specificity can be degraded due to signal leakage from the activated lower layers to the superficial layers in depth-dependent (also called laminar or layer-specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using VAscular-Space-Occupancy (VASO) measurements have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms (e.g., blood volume and oxygenation change) and to interpret the measured depth-dependent responses we need models that reflect vascular properties at this scale. For this purpose, we adapted a cortical vascular model previously developed to predict the layer-specific BOLD signal change in human primary visual cortex to also predict layer-specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental findings provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus-evoked CBV changes mainly occur in intracortical arteries as well as small arterioles and capillaries and that the contribution from venules is small for a long stimulus (~30 sec). Our results confirm the notion that VASO contrast is less susceptible to large vessel effects compared to BOLD.

Functional magnetic resonance imaging (fMRI) using a blood‐oxygenation‐level‐dependent (BOLD) contrast is a common method for studying human brain function noninvasively. Gradient‐echo (GRE) BOLD is highly sensitive to the blood oxygenation change in blood vessels; however, the spatial signal specificity can be degraded due to signal leakage from activated lower layers to superficial layers in depth‐dependent (also called laminar or layer‐specific) fMRI. Alternatively, physiological variables such as cerebral blood volume using the VAscular‐Space‐Occupancy (VASO) contrast have shown higher spatial specificity compared to BOLD. To better understand the physiological mechanisms such as blood volume and oxygenation changes and to interpret the measured depth‐dependent responses, models are needed which reflect vascular properties at this scale. For this purpose, we extended and modified the “cortical vascular model” previously developed to predict layer‐specific BOLD signal changes in human primary visual cortex to also predict a layer‐specific VASO response. To evaluate the model, we compared the predictions with experimental results of simultaneous VASO and BOLD measurements in a group of healthy participants. Fitting the model to our experimental data provided an estimate of CBV change in different vascular compartments upon neural activity. We found that stimulus‐evoked CBV change mainly occurs in small arterioles, capillaries, and intracortical arteries and that the contribution from venules and ICVs is smaller. Our results confirm that VASO is less susceptible to large vessel effects compared to BOLD, as blood volume changes in intracortical arteries did not substantially affect the resulting depth‐dependent VASO profiles, whereas depth‐dependent BOLD profiles showed a bias towards signal contributions from intracortical veins.

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