title: A conceptual model for CO₂-induced redistribution of cerebral blood flow with experimental confirmation using BOLD MRI.
abstract: Cerebrovascular reactivity (CVR) is the change in cerebral blood flow (CBF) in response to a change in a vasoactive stimulus. Paradoxical reductions in CBF in response to vasodilatory stimulation ('steal') are associated with vascular pathology. However, a pathophysiological interpretation of 'steal' requires a comprehensive conceptual model linking pathology and changes in blood flow. Herein, we extend a simple model explaining steal published in the late 1960s by incorporating concepts of CBF regulation from more recent studies to generate a comprehensive dynamic model. The main elements of the model are: (a) the relationship between changes in CBF and the arterial partial pressure of carbon dioxide (PaCO₂) in healthy vascular regions is sigmoidal; (b) vascular regions vasodilate to compensate for decreased perfusion pressure, leading to (c) an encroachment on vasodilatory reserve and, reduced CVR; (d) a vasodilatory stimulus may increase CBF capacity above the flow capacity of major cerebral blood vessels; and (e) this limitation induces competitive intra-cerebral redistribution of flow from territories with low vasodilatory reserve to those with high reserve. We used CVR measurements generated by applying precise, computer-controlled changes in PaCO₂ as the vasoactive stimulus, and measured blood oxygen level dependent (BOLD) MRI signals as high resolution surrogates of CBF to test predictions derived from this model. Subjects were 16 healthy adults and 16 patients with known cerebral steno-occlusive diseases. We observed regional sigmoidal PaCO₂-BOLD response curves with a range of slopes; graded changes in PaCO₂ resulted in redistributions of BOLD signal consistent with the known underlying vascular pathology and predictions of the model. We conclude that this model can be applied to provide a hemodynamic interpretation to BOLD signal changes in response to hypercapnia, and thereby aid in relating CVR maps to pathophysiological conditions.
authors: Institute of Medical Sciences, University of Toronto, Toronto, Canada.
authors: O
authors: O
authors: Sobczyk
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Canada.
authors: A
authors: A
authors: Battisti-Charbonney
authors: Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
authors: J
authors: J
authors: Fierstra
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Canada.
authors: D M
authors: DM
authors: Mandell
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Canada.
authors: J
authors: J
authors: Poublanc
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Canada.
authors: A P
authors: AP
authors: Crawley
authors: Joint Department of Medical Imaging and the Functional Neuroimaging Laboratory, University Health Network, Toronto, Canada.
authors: D J
authors: DJ
authors: Mikulis
authors: Department of Anaesthesia and Pain Management University Health Network, University of Toronto, Canada; Department of Physiology, University of Toronto, Canada. Electronic address: j.duffin@utoronto.ca.
authors: J
authors: J
authors: Duffin
authors: Institute of Medical Sciences, University of Toronto, Toronto, Canada; Department of Anaesthesia and Pain Management University Health Network, University of Toronto, Canada; Department of Physiology, University of Toronto, Canada.
authors: J A
authors: JA
authors: Fisher
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000008:administration & dosage*; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D008959:Models, Neurological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D002245:Carbon Dioxide
keywords: Carbon dioxide; Cerebrovascular reactivity; Humans; Reverse steal; Steal