Muhammad Mushhood Ur Rehman (1), Junaid Kalia (2)
1 - MBBS, Services Institute of Medical Sciences, Lahore
2 - Founder, AINeuroCare
IntroductionCerebral VasculatureHaemodynamicsAutoregulation of Cerebral Blood FlowMyogenic Control of Cerebral Blood FlowMetabolic Control of Cerebral Blood FlowNeurogenic Control of Cerebral Blood FlowNeurovascular CouplingTable 1: Different Physiological and Pathological conditions and their association with CBF auto-regulationEffect of Blood Gas Levels and TemperatureMeasurement of Cerebral Blood FlowTable 2: Common methods of cerebral blood flow measurement along with their features and limitationsFurther ReadingsBibliography
- Brain tissue has high metabolic demand and high neuronal activity requires functional hyperemia for supply of nutrients and Oxygen
- 20% of total body oxygen and 25% of glucose utilization is dedicated to brain
- Various autoregulatory mechanisms and local and neuronal factors work together to ensure adequate brain perfusion
- Cerebral blood flow is defined as the volume of arterial blood delivered to a unit mass of brain tissue per unit of time.
- It is described in ml of blood per 100 gram of brain tissue per minute.
- The normal value is 50 ml/100g/min
- White matter has relatively lower CBF i.e. 20 ml/100g/min
- Grey matter has relatively higher CBF i.e. 80 ml/100g/min
- Highly complex interconnected network of vessels
- Feeding vessels include:
- Right and left internal carotid arteries anteriorly (~70 %)
- Right and left vertebral arteries posteriorly
- Vertebral arteries join to form basilar artery
- Internal carotid and basilar artery are linked by circle of Willis
- Circle of Willis connects these vessels on inferior surface of brain and consists of:
- Right and left anterior cerebral arteries (Branches of Internal Carotid Arteries)
- Anterior and posterior communicating arteries
- Middle cerebral arteries are also connected to circle of Willis
- Flow of blood through brain can be described by Ohm’s law:
Q = △P/R
Q is cerebral blood flow
△P is pressure difference across the arterial and venous segment
R is resistance to flow
- This indicates:
- Direct relation between pressure difference and cerebral blood flow.
- Increase in pressure difference ➨ Increase in cerebral blood flow
- Decrease in resistance ➨ increase in cerebral blood flow
- Resistance of vessel is determined by radius of vessel, length of vessel, and hematocrit i.e viscosity (Poiseuille’s law)
- Cerebral blood flow is mainly determined by change in vessel radius specially in small vessels i.e arterioles
- To maintain adequate cerebral blood flow, decrease in blood pressure will require an increase in vessel radius (opposite to normal vessel response).
- Cerebral perfusion pressure (CPP) and cerebrovascular resistance (CVR) are main factors that control Cerebral blood flow.
CPP = Mean arterial pressure (MAP) - Intracranial Pressure (ICP)
MAP is average arterial pressure throughout one cardiac cycle
MAP = Diastolic Pressure + 1/3(Pulse Pressure)
ICP is pressure of CSF in subarachnoid space
- Changes in CPP can be due to physiological (exercise) or pathological (TBI) processes.
- During cerebral autoregulation, an optimal perfusion pressure is maintained by changes in CVR.
- Cerebral blood flow is kept relatively constant through change in vessel diameter at CPP range of 40-140 mmHg.
- CBF is regulated by change in vessel radius between 50-150 mmHg MAP
- Cerebral autoregulation acts as a negative feedback mechanism to control the effect of increased MAP on CPP and keep CPP constant by reducing the radius of vessels when MAP is raised and vice versa.
- Static cerebral autoregulation ➨ CBF and MAP changes under steady state conditions (minutes or hours)
- Dynamic cerebral autoregulation ➨ Transient changes in CBF and MAP and CBF (in seconds)
- The change in radius of vessels is the single most important factor in CBF autoregulation.
- Increased hematocrit ➨ increased viscosity ➨ low CBF
- Decreased hematocrit ➨ decreased viscosity ➨ increase CBF
- CBF is controlled by means of myogenic, metabolic, and neurogenic factors and partial pressure of arterial blood gases (CO2 and O2), cerebral metabolism, and the autonomic nervous system are primary determinants of CBF.
- Myogenic mechanism is response of small arteries to intravascular pressure changes
- Arterial membrane depolarization resulting in influx of Ca2+ in the arterial wall through voltage-dependent Ca2+ channels.
- It is a fast process mediated by EDRF and NO and occurs within 1-10 sec of change in pressure.
- Metabolic response alteration in blood flow secondary to blood pressure changes
- Changes in diameter of cerebral vasculature in response to alterations in the concentration of vasodilator metabolites like adenosine
- Neurogenic response consists of perivascular neurons that autoregulate the cerebral blood flow by gliovascular interactions and intramural vascular signaling.
- Astrocytes act as mediators for signaling from neurons to cerebral vasculature.
- Extrinsic nerves from peripheral nerve ganglia control surface vessels (Pial arteries) and large arteries (ICA, VA, MCA) whereas intrinsic nerves from intrinsic brain neurons control vessels within the brain parenchyma which has high basal tone and respond less to neurotransmitters.
- The vessel tone of large arteries is maintained by:
- Sympathetic neurons ➨ Superior cervical ganglion ➨ Norepinephrine , Neuropeptide Y
- Parasympathetic neurons ➨ Otic and Pterygopalatine ganglion ➨ Acetylcholine, VIP, NO
- Capillary dilation is faster than arteriolar dilation and is assumed to be caused by active relaxation of pericytes.
- Veins contain 3/4th of cerebral blood volume but contribute less to autoregulation due to their less baseline tone.
- CBF is increased to accommodate greater metabolic demands of the brain via the process of neurovascular coupling.
- Neurovascular coupling is temporal and regional linkage between neuronal activity and blood supply to the brain and is mediated by a number of metabolic by-products (lactate, adenosine), neurotransmitters (dopamine, acetylcholine), and vasoactive mediators (Ca2+, H+).
- Uncoupling due to any pathologic process results in loss of normal functioning of brain processes
Table 1: Different Physiological and Pathological conditions and their association with CBF auto-regulation
Different Physiological and Pathological conditions and their association with CBF autoregulation
Effect on CBF and Autoregulation
↓Baroreceptor sensitivity , ↓CBFV , CA unaffected
Progressive physical exercise → No effect on CA (↑HR, ↑ABP) Hypoxic exercise → Impaired CA ( CBFV Maintained, ↓CO₂, ↑BBB Permeability)
Women with preeclampsia → Impaired CA
Acute Ischemic stroke (96 h) → dynamic CA impaired; static CA normal CA worse in the first 5 days post-stroke and recovered over the following 5 months
Type 1 Diabetes: If autonomic neuropathy or diabetic ketoacidosis + → CA Impaired Type 2 Diabetes: Distinct impairment in CA
Focal loss of static autoregulation: Impaired CA at CPP >95 mmHg and <55 mmHg Neurovascular uncoupling with initial decrease in CBF, then intermediate period with normal or ↑CBF and again ↓CBF till recovery
Without Aura → CA maintained With Aura → CA Impaired
Degree of stenosis and collateral circulation determines the level of CA impairment Recanalization/Endarterectomy restore CA
CA impaired → Decreased CBF → Vasospasm → Delayed Cerebral Ischemia [Disturbed CA in 5 days post-SAH → ↑ risk of DCI (21 days)]
Ictal Period → ↑ Cerebral Metabolism, ↑ CBF Postictal Period → ↓Cerebral Metabolism, ↓CBF
Severe the OSAS → Greater the CA disturbance ↓ CBFV , ↓ SaO2
CA preserved ; CBF might decrease if ABP is reduced to normal in chronic hypertensive patient
Note: CA: Cerebral autoregulation, ABP: Arterial Blood Pressure, OSAS: Obstructive Sleep Apnea Syndrome
- Increased arterial CO₂ dilates the cerebral vessels by changing extracellular pH and thus increasing blood flow.
- 1 mmHg increase in arterial PaCO₂ leads to 3-6 % elevation in CBF whereas 1 mmHg decrease in PaCO₂ reduce the CBF by 1-3%
- Hypoxia below 50 mmHg is potent vasodilator and thus increases cerebral blood flow.
- Cerebral metabolic rate decreases with hypothermia. 1 degree Celsius decrease in temperature reduces cerebral metabolic rate by 6-7 % and CBF decreases proportionately.
Figure 1: Relationship between PaCO₂ and PaO₂ and Cerebral Blood Flow
- The direct methods measure the delivery of arterial blood to the capillary bed and measure the amount of tracer delivered to brain tissue by blood flow.
- Most of the methods use exogenous or endogenous compounds whose passage is taken as an indicator of cerebral blood flow. These methods rely on Fick Principle.
- Indirect methods measure cerebral perfusion indirectly and do not quantify the direct measure of blood delivered to brain tissue.
Table 2: Common methods of cerebral blood flow measurement along with their features and limitations
Common methods of cerebral blood flow measurement along with their features and limitations
Nitrous oxide Method (Kety & Schmidt Method)
Intravascular measurement so can’t be repeated multiple times
Uncomfortable for patients High radiation dose limited spatial resolution
SPECT (Single photon emission computed tomography)
Expensive Not quantitative High radiation dose Inaccurate for low CBF
PET (Positron emission tomography) (Gold Standard)
Very-expensive High radiation dose
ASL - MRI (Arterial spin labeling - MRI)
Inaccurate for low and high CBF Less accurate than PET Low SNR
MRI - DSC (Dynamic susceptibility contrast-MRI)
Limited number of measurements Avoided in sensitive patients
TCD (Transcranial Doppler Ultrasound)
No volume estimation Prone to personal error Measure CBFV
Phase Contrast MRI
Intravoxel phase dispersion Displacement artifacts
NIRS (Near-Infrared Spectroscopy)
Complexity of signal recorded
Not suitable for all patients Accuracy is contrast dependent
Derived from: Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Cerebral Autoregulation: Control of Blood Flow in the Brain
Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics, 3(3), 031411.
Cerebral Blood Flow Measurements in Adults: A Review on the Effects of Dietary Factors and Exercise. Nutrients, 10(5), 530.
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