Progression of visual-stimulus-evoked blood velocity response timing across the vascular network measured with individual-vessel phase-contrast fMRA

Most functional MRI (fMRI) studies of brain function aim to measure hemodynamic responses arising from the microvasculature within the tissue parenchyma, where spatial and temporal coupling with neuronal activity is thought to be tightest. However, the measured hemodynamic responses emerge from an interconnected vascular network that includes upstream feeding arteries, downstream draining veins, and the intervening microvascular compartments. Directly measuring and comparing vascular responses across multiple stages of this network may therefore provide more specific information about network-level hemodynamics--and how hemodynamics in one stage of the vascular hierarchy influence hemodynamics in others--that is not accessible from conventional fMRI signals alone. This can provide new insights into the relationship between the observed fMRI responses and the underlying neuronal activity of interest. This study extends our recently proposed dynamic phase-contrast functional MR angiography (PC-fMRA) method for tracking stimulus-evoked blood-velocity responses in large supplying arteries to enable concurrent hemodynamic measurements across multiple levels of the neurovascular complex. Here, we apply this method across several levels of the vascular hierarchy, from the basilar and posterior cerebral arteries to pial arteries, pial veins, and major draining venous sinuses such as the straight and superior sagittal sinuses. Stimulus-locked velocity increases were observed in individual vessels within each subject. Arterial responses occurred rapidly and nearly simultaneously across upstream and pial arterial segments, whereas venous responses exhibited temporal delays relative to the arterial responses. The average arterial-to-venous response time delay differed between the onset and offset phases, measuring approximately 4.1 s during response onset and 1.3 s during response offset, and also varied across different vessel segments. A simplified Windkessel model--used to interpret these findings--predicted similar inflow-outflow delays, suggesting that these temporal differences may reflect the transient filling and draining dynamics within compliant vascular compartments intervening between supplying arteries and draining veins. Our results demonstrate the feasibility of using dynamic PC-fMRA to measure vessel-specific hemodynamic responses across the human neurovascular complex. By providing quantitative measurements of macrovascular responses that serve as inputs to and outputs from intervening vascular compartments, this approach offers a framework for probing the hemodynamics within these compartments and studying vascular network behavior during neuronal activation, which may also help improve the physiological interpretation of fMRI signals in humans.