The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.
What is the organization of cerebral microvascular oxygenation and morphology
that allows adequate tissue oxygenation at different activity levels? We address this
question in the mouse cerebral cortex using microscopic imaging of intravascular O2
partial pressure and blood flow combined with numerical modeling. Here we show that
parenchymal arterioles are responsible for 50% of the extracted O2 at baseline
activity and the majority of the remaining O2 exchange takes place within the
first few capillary branches. Most capillaries release little O2 at baseline
acting as an O2 reserve that is recruited during increased neuronal activity or
decreased blood flow. Our results challenge the common perception that capillaries are the
major site of O2 delivery to cerebral tissue. The understanding of oxygenation
distribution along arterio-capillary paths may have profound implications for the
interpretation of BOLD fMRI signal and for evaluating microvascular O2 delivery
capacity to support cerebral tissue in disease.
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