title: Neuronal activation induced BOLD and CBF responses upon acetazolamide administration in patients with steno-occlusive artery disease.
abstract: 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.
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: j.c.w.siero@umcutrecht.nl.
authors.forename: Jeroen C W
authors.initials: JC
authors.lastname: Siero
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Nolan S
authors.initials: NS
authors.lastname: Hartkamp
authors.affiliation: Radiology and Radiological Sciences, Vanderbilt University School of Medicine, Nashville, TN, USA; Physics and Astronomy, Vanderbilt University School of Medicine, Nashville, TN, USA; Neurology, Vanderbilt University School of Medicine, Nashville, TN, USA; Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Manus J
authors.initials: MJ
authors.lastname: Donahue
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Harteveld
authors.affiliation: Department of Neurology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Annette
authors.initials: A
authors.lastname: Compter
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Esben T
authors.initials: ET
authors.lastname: Petersen
authors.affiliation: Department of Radiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hendrikse
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000368:Aged; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000503:physiopathology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide
keywords: Arterial spin labeling; BOLD contrast; Cerebral blood flow; Cerebral hemodynamics; Cerebrovascular disease; Functional MRI (fMRI); Neurovascular coupling; Physiology