Sources of functional apparent diffusion coefficient changes investigated by diffusion-weighted spin-echo fMRI.

The mechanism behind previously observed changes in the apparent diffusion coefficient (ADC) during brain activation is not well understood. Therefore, we investigated the signal source and spatial specificity of functional magnetic resonance imaging (fMRI) ADC changes systematically in the visual cortex of cats using diffusion-weighted (DW) spin-echo (SE) fMRI with b-values of 2, 200, and 800 s/mm(2), and echo times (TE) of 16, 28, and 60 ms at 9.4 T. For b > or = 200 s/mm(2), no ADC changes were detected in brain parenchyma, suggesting a minimal tissue contribution to the ADC change. For b < or = 200 s/mm(2), TE-dependent ADC increases were observed. When the venous blood contribution was minimized, the ADC change was higher at the middle cortical layer than at the cortical surface, which is mainly attributed to a functional elevation in arterial blood volume. At TE = 16 ms, the highest ADC changes occurred at the cortical surface with its large draining veins, which can mainly be explained by an additional contribution from the venous blood oxygenation changes. Our TE-dependent ADC results agree with computer simulations based on a three-compartment model. The contribution of arterial blood volume changes in ADC fMRI offers an improvement in spatial localization for SE-BOLD fMRI studies.