CBF–Metabolism Coupling

Introduction

The brain requires oxygen and glucose to meet its metabolic demands, and cerebral blood flow (CBF) is its supply channel. The brain has high energy requirements but limited storage capacity, which means persistent CBF is critical for its proper functioning and prevention of damage and death. Therefore, in spite of constituting only about 2% of total body weight, the brain is easily the most perfused organ with almost 15–20% of the total cardiac output directed as CBF. Moreover, a process called cerebral autoregulation thrives to maintain adequate CBF at a constant rate. The arteries supplying the brain namely the internal carotid arteries and vertebral arteries that merge to form the basilar artery arrange themselves into the “circle of Willis” creating collaterals in the cerebral circulation. This is a defense mechanism against CBF drop such that if an artery supplying the circle is blocked, blood flow from the other blood vessels is able to sustain cerebral circulation.

The demand–supply relationship between CBF and cerebral metabolism is tightly coupled and brain regions are either hypoperfused or hyperperfused depending on metabolic needs. A sudden decrease in CBF (either temporary or permanent) due to the occlusion of a cerebral artery is called cerebral ischemia and leads to ischemic stroke, neurological deficits, tissue damage, and even death. An excess of blood flow results in hyperemia in which the intracranial pressure may increase and evoke tissue compression and damage. Therefore, to maintain brain homeostasis, local neuronal activity and subsequent changes in CBF are tightly coupled and termed neurovascular coupling. The neurovascular unit is a conceptual model encompassing the anatomical and metabolic interactions among the neurons, vascular components (endothelial cells, pericytes, vascular smooth muscle cells), and glial cells (astrocytes and microglia) in the brain.

CBF Measurements

CBF–metabolism coupling is typically studied in two levels: at the whole-brain level and regionally depending on brain activation/stimulation. Advances in imaging techniques such as PET (positron emission tomography), MRI (magnetic resonance imaging), fMRI (functional MRI), NIRSI (near-infrared spectroscopic imaging), and optogenetics have fostered the understanding of CBF–metabolism coupling. There is clearly a close relationship between neural activity in the brain and local CBF which is captured by imaging techniques such as PET, fMRI, and NIRSI. Since hemoglobin, the oxygen-carrying component of blood releases more oxygen to activated neurons compared to inactive neurons, several imaging techniques rely on the differences in magnetic susceptibility (fMRI) and absorption coefficients (NIRSI, optical intrinsic signal imaging) between oxyhemoglobin and deoxyhemoglobin to image CBF variations in response to neural activity. Changes in CBF can be additionally imaged by laser Doppler technique, laser speckle contrast imaging, two-photon microscopy and optical coherence tomography among others. High spatial (differentiating local and global effects) and temporal (rapid sampling to reconstruct time course of dynamic processes) resolution two-dimensional and three-dimensional in vivo optical imaging is now available and is being used to study neurovascular coupling.