This presentation covers macro- and micro-anatomy of cerebral vasculature and the basic mechanism and physiology of cerebral perfusion.
Objective
To understand the basic of vascular anatomy in the brain and physiology of cerebral perfusion.Blood Vessel: There are three types of blood vessels: The arteries carry the blood away from the heart. The capillaries allow for the exchange of water and chemicals between the blood and the tissues. The veins bring blood from the capillaries back to the heart. The arteries and veins have three layers, tunica intima, tunica media, and tunica adventia. The tunica media is composed of smooth muscle which adjusts the caliber of the vessels, and is thicker in the arteries than it is in the veins. A capillary is a smallest blood vessel (5-10 micron in diameter) with single layer of endothelial cell. The average density of capillaries is ~600/mm3, which implies a mean separation of ~40 microns between adjacent capillaries averaging ~1 mm in length (1). These micro-vessels are the site of exchange of many substances (exit: water, oxygen, glucose, enter: water, CO2, lactic acid etc.) with extracelluar fluid. In central nerve system, capillary endothelial cells form the blood brain barrier (BBB) which is a highly selective semipermeable membrane barrier that separates the blood from the brain and extracelluar fluid. This barrier results from the tight junctions between endothelial cells. Gd contrast agents cannot pass BBB in the normal condition. However, in pathological conditions where BBB is disrupted, Gd may be able to go across vascular walls to extravascular extracelluar spaces. Extravascular tissue has extracellular and intracellular compartments; relative fractions of extracellular and intracellular compartment are 20 and 80%, respectively.Brain
Vasculature: Arterial blood supply to the brain is usually divided into anterior and posterior circulations. The internal carotid arteries supply the anterior part of the cerebrum, and vertebral and basilar arteries supply the posterior part of the brain including the brainstem, and cerebellum. The venous drainage of the cerebrum can be separated into two subdivisions: superficial and deep.
Physiology:Cerebral blood flow (CBF) is the blood supply to the brain in a given period of time. In adults, CBF is the typically 750-900 mL/min or 15% of the cardiac output. The is equal to an average perfusion of 40-65 mL/min/100g with gray matter about 3~4 times higher than white matter (2-4). Excessive amount of blood (hyperemia) can raise intracranial pressure (ICP), which can compress and damage brain tissue. Reduced blood flow (ischemia) results if blood flow to the brain is below 18 to 20 mL/min/100g, and tissue death occurs if flow dips below 8 to 10 mL/min/100g. CBF is equal to the CPP divided by the cerebrovascular resistance (CVR): CBF = CPP/CVR. Thus, CBF is determined by the factors affecting CPP and CVR. CVR is controlled by four major mechanisms:1) pressure autoregulation; 2) CO2 and O2; 3) metabolism; 4) neural control. Cerebral blood vessels can adjust the blood flow by changing their calibers in a process called “autoregulation”. They constrict when blood pressure is raised and dilate when it is lowered. They also constrict and dilate in response to different chemical concentrations. For example, they dilate in response to increased CO2 level in the blood and constrict to lowered its level. Cerebral perfusion pressure (CPP) is the net pressure gradient causing cerebral blood flow to the brain. CPP is the difference in the pressures between the arterial and venous circulation, but in CPP is affected by another pressure within the skull (intracranial pressure: ICP). CPP = MAP – (CVP or ICP, whichever is highest) where MAP is the mean arterial pressure and CVP is the central venous pressure. Within the range of 50 to 150 mm Hg of CPP, CBF remains constant because of autoregulation. The reduction in CBF is compensated for by an increase in oxygen extraction fraction (OEF) from the blood. Cerebral infarction occurs when the decrease in perfusion exceeds the ability of increased OEF to meet metabolic demand. In major cerebral arterial occlusive disease, increased OEF can be a risk factor for ischemic stroke. Mean transit time (MTT) corresponds to the average time (sec), that red blood cells spend within a determinate volume of capillary circulation. MTT is expressed by the formula: MTT= CBV/CBF (central volume theory). MTT is the inverse of the CPP index, and is a valuable indicator of the cerebral circulation. The typical MTT is around 3-4 secs (5, 6). CBV is the amount of blood in brain tissue (mL blood/100mL tissue). In early stages of cerebrovascular alterations, CBV can serve as a sensitive indicator for evaluating tissue variability and function. The volume of arterial CBV is approximately 20–30% of the intravascular space occupied by all blood vessels, while the volume of venous blood vessels and capillaries is approximately 70–80% (7).
1. Robert A. Freitas Jr. Nanomedicine, Volume I: Basic Capabilities. 1999.
2. Zhang K, Herzog H, Mauler J, et al. Comparison of cerebral blood flow acquired by simultaneous [15O]water positron emission tomography and arterial spin labeling magnetic resonance imaging. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2014;34(8):1373-80.
3. Ito H, Kanno I, Kato C, et al. Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan. Eur J Nucl Med Mol Imaging. 2004;31(5):635-43.
4. Rostrup E, Knudsen GM, Law I, Holm S, Larsson HB, Paulson OB. The relationship between cerebral blood flow and volume in humans. Neuroimage. 2005;24(1):1-11.
5. Ito H, Kanno I, Takahashi K, Ibaraki M, Miura S. Regional distribution of human cerebral vascular mean transit time measured by positron emission tomography. Neuroimage. 2003;19(3):1163-9.
6. Ibaraki M, Ito H, Shimosegawa E, et al. Cerebral vascular mean transit time in healthy humans: a comparative study with PET and dynamic susceptibility contrast-enhanced MRI. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2007;27(2):404-13.
7. Hua J, Liu P, Kim T, et al. MRI techniques to measure arterial and venous cerebral blood volume. Neuroimage. 2018.