Investigators have recently shown that the Systolic 1 based pulsatile apparent resistance (S1-PaR) is more sensitive to an increase in intracranial pressure than a simple pulsatility index (PI) based upon middle cerebral artery flow velocity (MCAFV) alone. S1-PaR is a so-called blood pressure (BP) corrected PI. It is designed to detect a difference between middle cerebral artery PI and arterial blood pressure PI.
The apparent resistance is defined by aR = BP / MCAFV similar to Ohm's law: R = I / V: resistance is current divided by voltage (difference).
Central to the work of Neuromon B.V. is the theory of arterial acceleration. This theory proposes that the pressure wave of the heart is amplified by a shortlasting contraction in the conducting vessels of the arterial tree: Sys1. The second phase of systole (Sys2) is the result of the stroke volume being ejected into the aorta. The propagation of the Sys1 is presumably faster than of Sys2, since the first is based upon a rapidly spreading depolarization within the smooth muscle cells of the arterial wall via the abundant presence of gap junctions. The propagation of the Sys2 wave is slower since it is dampened by the visco-elastic properties of the arterial tree.
Arterial acceleration increases the penetration force of the Sys1 component, whereas Sys2 and diastolic flow velocity will be more sensitive to intracranial pressure elevation. This is typically the case when systolic spikes are seen in the MCAFV signal: only allowing flow during Sys1 and none during Sys2 and the diastolic phase.
Therefore, the relation between arterial blood pressure and MCAFV will be different during Sys1 compared to diastole. This leads to the definition of the PaR:
S1-PaR = (ED_aR - Sys1_aR) / TAVM_aR (with TAVM as abbreviation for time averaged mean).
The working of this parameter can be demonstrated in Neuromon's cardiovascular simulation. Let's start with simple settings of the model: no reflex activity but with arterial acceleration active.
In the simulation (red curve is arterial blood pressure (ABP) and blue curve is right middle cerebral artery flow velocity (MCAFV)):
This gives us the following results:
And the following waveforms (red curve is arterial blood pressure (ABP) and blue curve is right middle cerebral artery flow velocity (MCAFV)):
After normalization (dividing both signals by their time averaged means) and swapping the x- and y-axis:
Under these circumstances the relation between ABP and MCAFV (aR: symbolized by the angle of the lines with the x-axis) is similar during systole and diastole. Deviations from the ideal curve are partly due to a time lag between MCAFV-Sys2 in relation to ABP-Sys2. (Note that the pulsatility index (PI) is the width of the graph projected along the x-axis.)
What happens during elevated ICP? In the model ICP is assumed constant and adds up to normal venous pressure lowering the arterio-venous pressure difference that drives the blood flow.. During diastole, the relative effect of elevated ICP is larger than during systole and it may even lead to the cessation of flow at the so called critical closing pressure (CCP). Settings of the model (note: intracranial pressure):
The simulation (red curve is arterial blood pressure (ABP) and blue curve is right middle cerebral artery flow velocity (MCAFV)):
Leading to the following results:
And the following waveforms (red curve is arterial blood pressure (ABP) and blue curve is right middle cerebral artery flow velocity (MCAFV)):
After normalization (dividing both signals by their time averaged means) and swapping the x- and y-axis:
The increase in ICP brings the MCAFV closer to zero and under these circumstances the relation between ABP and MCAFV (aR: symbolized by the angle of the lines with the x-axis) is quite different during systole and diastole resulting in an increased value of S1-PaR. (Note that the PI is the width of the graph projected to the x-axis.)
S1-PaR = (ED_ABP/TAVM_ABP) / (ED_MCAFV/TAVM_MCAFV) - (S1_ABP/TAVM_ABP) / (S1_MCAFV/TAVM_MCAFV)
Comparing different parameters for a range of ICP values:
S1-PaR and PI rapidly increase when the end diastolic flow velocity becomes zero (at ICP > 30 mmHg). The CrCP increases more steadily since it is calculated over the full beat to beat average and the effect of the diastolic flow velocity becoming zero is more gradual.
In a series of 6 presentations the background of the model for cardiovascular simulation will be explained.
Presentation 1 discusses the CNS ischemic response.
8:09
Presentation 2 discusses the expanding arterial tree.
7:19
Presentation 3 discusses the theory of arterial acceleration.
7:14
Presentation 4 discusses the use of Transcranial Doppler for monitoring.
9:01
Presentation 5 discusses the chemoceptor and baroceptor reflex.
12:17
Presentation 6 discusses the cardiovascular model.
13:09
Middle cerebral artery flow velocity decreases with age. When studying subjects with transcranial Doppler, these age-related changes should be taken into account. A recent paper by dr. A. Schaafsma promotes Z-scores as a way to correct for age. Z-scores express the distance in standard deviations to the middle cerebral artery flow velocity expected for age by linear regression.
A Z-score expresses how many standard deviations a given measurement is above (positive) or below (negative) the value expected for a given age. Z-scores for different parameters can be combined into a radar plot. An example is give to the right: data are provided for average Z-scores during hyperventilation (red), normoventilation (green) and CO2-retention (yellow).
A. Schaafsma, A new method for correcting middle cerebral artery flow velocity for age by calculating Z-scores. Journal of Neuroscience Methods. 307, 1–7 (2018).
In the theory of arterial stiffness the aorta and its major branches are seen as a reservoir that can absorb the stroke volume pumped in by the heart to release it in a gradual way during systole. The German term is Windkessel effect. When we become older the elastance of this Windkessel decreases and the aorta becomes stiffer. The blood ejected by the heart can no longer be buffered in the aorta and will penetrate the branches of the arterial tree causing an increase in pulsatility.
Where the aorta and its main branches have a high elasticity, this is assumed less in the distal arterial branches. Here the stiffness becomes larger and the elastance less. These differences, according to the theory of arterial stiffness, explains why pulsatility increases towards periphery. It assumes non-linearity: the vessels have less resistance to blood flow during systole as during diastole. In peripheral arteries this will cause an increase in pulse pressure (the difference between systolic and diastolic pressure).
Because this arterial stifness in the periphery, pressure waves traveling from the heart to the periphery are reflected in opposite direction. This effect increases the pressure at a given location in the arterial tree in a rather complex way, depending on the timing of forward versus backward traveling waves. This explains why, after a first rapid increase, there is a dip in the systolic pressure during the second phase of systole.
Issues unexplained
There are issues with the theory of arterial stiffness. In the first place it does not take into account the branching of the arterial tree: although individual arteries become stiffer there number increase exponentially making the total cross-sectional area manifold larger than at the origin of the aorta. The arterial tree should be seen as a funnel, the blood being pumped in at the narrow end and being distributed along a multitude of small arteries and arterioles.
Furthermore, the theory of arterial stiffness assumes energy loss during systole: the energy of heart contraction faces reflecting waves from a multitude of branching points: blood flow has to wait for diastole.
Finally, the theory of arterial stiffness does not explain how blood is distributed over the arterial tree. The general view is that arterioles open or close depending on local metabolic activity allowing blood to flow in at demand. Can blood reach remote capillary systems? Only when arterioles in proximal tissues are relatively closed. Can blood reach tissues under unfavorable conditions such as high tissue pressures? Only when tissues under more favorable conditions adopt a high arteriolar vascular tone.
Elaborate technical apparatus measure the forward and backward traveling waves and calculate a value for arterial stiffness (e.g. the augmentation index). Measurements of arterial stiffness have been shown to correlate with cardiovascular disease: the larger the arterial stiffness, the higher the risk for myocardial infarction and stroke. Is arterial stiffness indeed a passive process or may active contraction within the arteries' muscular layers be involved? This question leads us to the theory of arterial acceleration.
The theory of acceleration emerged from the understanding that the theory of arterial stiffness leaves a number of important observations unaccounted for. For instance, the theory of arterial acceleration displays the vascular system as a tube narrowing towards periphery. In fact, the total cross-sectional area of the arterial system increases towards periphery. This would cause the pressure wave originating form the heart to dilute on it's way across the arterial tree. It's pulsatility would decrease and it's propagation speed would become smaller.
In real life, the opposite is true: the pulsatility of the arterial blood pressure increases towards periphery and the propagation speed of the front of the pressure wave becomes larger. It is as if extra energy is added to the systolic phase of the blood pressure signal.
This has led to the theory of arterial acceleration that proposes that smooth muscle cells in the arterial wall briefly contract (or stiffen) at the onset of systole. This temporary stiffening would cause the sys1 component within the blood pressure (of blood flow velocity) signal.