title: Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.
abstract: The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation- a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system's responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2.
authors.affiliation: Fluidics and Biocomplexity Group, Department of Engineering Science, University of Oxford, Oxford, Parks Road, Oxford, United Kingdom.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Hadjistassou
authors.affiliation: Faculty of Engineering, University of Auckland, Auckland, New Zealand.
authors.forename: Keri
authors.initials: K
authors.lastname: Moyle
authors.affiliation: Department of Mechanical Engineering, University College London (UCL), Torrington Place, London, United Kingdom.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ventikos
mesh_terms: D000465:Algorithms; D002560:Cerebrovascular Circulation; D003198:Computer Simulation; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D055806:Microvessels / Q000378:metabolism; D008954:Models, Biological; D010084:Oxidation-Reduction; D010100:Oxygen / Q000097:blood*; D011485:Protein Binding
chemical_list: D006454:Hemoglobins; D010100:Oxygen