Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease

- BOLD and CBF fMRI upon acetazolamide (ACZ) in patients with cerebrovascular disease.
- Neuronally evoked BOLD response reduced or even negative after ACZ.
- Neuronally evoked CBF response remained positive and similar after ACZ.
- Relationship between BOLD and CBF responses may be compromised under baseline changes.
- Simulations suggest an altered flow-metabolism coupling in these patients.

Blood-oxygenation-level-dependent (BOLD) MRI is widely used for inferring neuronal activation and is becoming increasingly popular for assessing cerebrovascular reactivity (CVR) when combined with a vasoactive stimulus. The BOLD signal contains changes in cerebral blood flow (CBF) and thus information regarding neurovascular coupling and CVR. The BOLD signal, however, is also modulated by changes in cerebral blood volume (CBV) and cerebral metabolic rate of oxygen (CMRO2), as well as changes in the physiological baseline state. Here, we measured BOLD and CBF responses upon neuronal (visual) activation, before and after a vasodilatory challenge (acetazolamide, ACZ) in patients with vertebrobasilar steno-occlusive disease. After ACZ, the neuronal activation induced BOLD response was reduced or even negative (3 out of 8 subjects), whereas the CBF response remained similar. We show that BOLD alone cannot correctly assess the neuronal activation and underlying neurovascular coupling. The generally assumed positive relationship between BOLD and CBF responses may be severely compromised under changes in the physiological baseline state. Accompanying CBF measurements contain crucial information, and simulations suggest an altered flow-metabolism coupling in these patients.

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