Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.

Constantinos Hadjistassou,Keri Moyle,Yiannis Ventikos,Jodie L Rummer

doi:10.1371/journal.pone.0149935

Constantinos Hadjistassou, Keri Moyle + Show 2 more

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https://doi.org/10.1371/journal.pone.0149935

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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.

Highlights

Advancing the prevailing understanding between functional neuroimaging and neuronal activity promises to bridge the knowledge gap between cellular neuroscience and brain imaging.PLOS ONE | DOI:10.1371/journal.pone.0149935 March 3, 2016Reproducing Hemoglobin Saturation and Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI)
Based on a systematic investigation, which explored a wide range of blood velocities and oxygen metabolic rates, we were able to narrow down the basal cerebral blood velocity (CBv) and CMRO2 to the representative values of 0.6 mm/s and 200 μmol/100g/ min, respectively
Once the stimulus has been removed and blood velocity has subsided to its basal value, the system resorts to its resting state CBv of 0.6 mm/s

Summary

Introduction

Advancing the prevailing understanding between functional neuroimaging and neuronal activity promises to bridge the knowledge gap between cellular neuroscience and brain imaging. Under certain conditions, spanning different spatial and temporal scales, responses between CBF and coupled CBF & CMRO2, and the interactions between these factors (and their causal effects) could foster unfavorable conditions for the manifestation of the BOLD response These parameters emphasize the BOLD phenomenon’s sensitivity to subtle physiological changes while rendering the interpretation of the MRI signal more challenging. The physics of the BOLD contrast, tied to the mechanisms of convection, diffusion and hemoglobin reaction kinetics, for our purposes, will be examined at the microscopic (capillary) scale, almost three orders of magnitude smaller than the volume of a typical functional voxel. At this scale, most of the oxygen is reversibly bound to hemoglobin. No initial dip should be anticipated in the absence of a time lag between activation and hemodynamic response (increased inlet CBv)

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