Hemodynamics and Functional Tests

Intracranial Hemodynamics and Functional Tests

Analysis of Cerebral Blood Flow

Autoregulation

Testing of Autoregulation

Neurovascular Coupling

Testing of Neurovascular Coupling

Metabolic Coupling

Testing of Metabolic Coupling

Other Tests to Assess Differences Between the Right and Left Sides as Markers of Impaired Collateral Function

Parameters of Cerebral Hemodynamics

Cerebral Blood Flow Velocity

Resistance Indices

Cerebral Blood Flow Volume

Cerebral Circulation Time

Cerebral Blood Volume

Analysis of Cerebral Blood Flow

In contrast to many other organ systems, the human brain has several characteristics that are important in analyzing and interpreting cerebral perfusion. At rest, the brain receives a high proportion of the total cardiac output—in the order of 15–20%. The global cerebral blood flow (CBF) in an adult amounts to 700–800 mL/min, i.e., 13 mL/s or 55 mL/100 mg per minute assuming a brain weight of 1,400 g. About of 75% of the global CBF derives from the internal carotid arteries (ICAs) and the remaining 25% from both vertebral arteries (VAs) (Schöning et al 1994).

The ideal way to assess brain perfusion would be to analyze CBF directly. However, conventional Doppler flow velocity examination only generally permits flow velocity analysis of proximal arterial or venous vessel segments. CBF and flow velocity are not equal but correlate strongly with one other. A rising CBF causes rising blood flow velocities, and a low CBF correlates with low blood flow velocities. However, there are other important factors that have to be considered: Flow velocity correlates with the size of a vessel’s vascular territory despite the fact that the vessel’s diameter is adapted to it. For example, flow velocities in the middle cerebral artery (MCA), which supplies the largest cerebral territory, are higher than in the anterior cerebral artery (ACA) and posterior cerebral artery (PCA). In the anatomic variation with one A1-ACA segment providing blood supply to both ACA territories, its flow velocity is similar to or even higher than that of the ipsilateral M1-MCA.

Flow velocity also depends on vessel size. Local vessel narrowing will lead to increased velocities. Vessel dilatation, for example in hypertensive dilative vasculopathy or aneurysm formation, results in decreased flow velocities.

Other factors have more general effects. Anemia leads to a generalized increase of flow velocities. Flow velocities tend to decrease with increasing age, which is mainly attributed to brain parenchymal loss and subsequent reduction of CBF but also to vessel dilation. Under pathologic conditions chronological aspects have to be considered. For example, acute-phase flow assessment in ischemic stroke with intracranial large-vessel occlusion often shows reduced flow velocities in the preocclusive vessel segments. In the subsequent hyperemic phase after recanalization, increased velocities can be seen. However, the final or chronic state might show a reduction of flow velocity and an increase of pulsatility, depending on the extent of the remaining parenchymal defect (“no brain, no flow”).

As brain tissue has virtually no energy reserves, changes in perfusion lead to an immediate alteration in brain function. Therefore, many regulatory processes (these are listed and discussed below) exist to ensure a continuous and constant blood supply. Probably more than any other organ system, the brain needs to be constantly perfused for optimal function. However, the heart, which is responsible for blood supply and blood drainage, is a pulsatile pump. The arteries are the solution to this problem: with their elastic vessel walls they are capable of storing a considerable amount of blood during the systolic phase that is then released into the circulation during diastole (Windkessel function). This leads to an almost continuous blood flow in the periphery.

For easier understanding of the flow pattern seen during insonation of proximal arteries, we now introduce a simple model (Fig. A3.1). A filled rain barrel discharges water through a rigid pipe. To imitate the pulsatile action of the heart, a tap placed at the beginning of the pipe is repeatedly opened and closed. Flow analysis, in analogy to ultrasound analysis of proximal arterial blood vessels, is performed in the central segment of this pipe. The measured flow is pulsatile, with a high flow velocity when the tap is open (systole) and no flow when the tap is closed (diastole). If an elastic hose is used instead of a rigid pipe the flow profile will look different, i.e., more like the arterial blood flow profile in nonparenchymal organs (Fig. A3.2). When the tap is closed the elastic hose allows a continuous flow comparable with the arterial Windkessel function. If a second peripheral tap is added to the system, a microcirculation (as found in parenchymal organs such as the brain and kidneys) can be introduced into the model (Fig. A3.3): A reduction of outflow (microcirculation tap almost closed) will lead to reduced systolic flow velocities but distinctly lowered diastolic flow velocities and subsequently higher pulsatility. Opening of the microcirculation tap will lead to a reduction in peripheral resistance, resulting in slightly higher systolic flow velocities and distinctly higher diastolic velocities, i.e., reduced pulsatility.

Fig. A3.1 Model of the pulsatile pump function of the heart. A rigid pipe is connected to a filled water barrel. Opening (systole) and closing (diastole) of the tap results in a pulsatile flow within the pipe. Ultrasound analysis will detect flow in systole only and there will be an absence of flow in diastole.

Fig. A3.2 Model of the pulsatile pump function of the heart. A water hose is connected instead of the pipe, analogous to the arteries with their elastic vessel walls. During diastole, the diameter of the hose decreases (not shown), modeling the Windkessel function, thus leading to a detectable diastolic flow.

In addition to the mechanisms explained above, the Doppler waveform and pulsatility are also modulated by the quality of cardiac function, which can be altered by conditions like atrial fibrillation, congestive heart failure, aortic valve stenosis, insufficiency, or cardiomyopathy (Fig. A3.4 and Fig. A3.5).

Autoregulation

In contrast to other organ systems, but analogous to the kidney, the brain has an autoregulatory system that ensures constant tissue perfusion. Factors that influence cerebral perfusion are the cerebral perfusion pressure (CPP = mean arterial blood pressure [ABP] − intracranial pressure [ICP]) and the cerebrovascular resistance (CVR), determined by the functional status of the arteriolar vessels of the cerebral microcirculation. Under normal physiologic circumstances the ICP at rest is ~10–15 mm Hg and the resulting CPP is therefore only slightly lower than the ABP.

CBF = ABP/CVR (Ohm’s law of hemodynamics).

Fig. A3.3 Model of the pulsatile pump function of the heart. A second tap is introduced to simulate the microcirculation. While tap 1 is open, closing tap 2 reduces the systolic flow but to a larger extent the diastolic flow, resulting in high-pulsatility signals. Opening tap 2 increases the diastolic flow to a larger extent than the systolic flow, resulting in low-pulsatility signals.

The above formula shows that CBF can be kept almost stable during changes in ABP if compensatory alterations are made in the cerebrovascular resistance, i.e., the microcirculation. Low blood pressure requires a reduction of resistance, i.e., a dilation of the peripheral arterial vessels. High blood pressure requires peripheral vasoconstriction. As CBF is closely related to the blood flow velocities in the main arteries supplying the brain, the above mechanism will result in stable flow velocities during changes in blood pressure (Diehl 2002). However, this mechanism only works under physiologic conditions within a certain range of blood pressure (autoregulatory plateau), as changes in the diameter of the peripheral arterial vessels only occur over a certain range. Above and below this range the mechanism fails and blood pressure and CBF are directly coupled (Fig. A3.6). If regional autoregulation is abolished or impaired, for example in ischemic stroke, this also implies direct coupling of cerebral perfusion and blood pressure. Therefore, a reduction in blood pressure in impaired autoregulation will lead to a reduction of brain perfusion, which should be avoided. Conversely, in acute stroke normal or slightly raised blood pressure is desired. For further reading see also Chapter 5, “Collateral Pathways.”

Fig. A3.4 Doppler spectra selection of a patient with a high-grade aortic valve stenosis (valve opening area 0.8 cm²). Note the delayed systolic flow rise in all brain-supplying arteries, highlighted by red bars (examples are given for the extracranial and intracranial anterior and posterior circulation).

Testing of Autoregulation

For cerebral functional and regulatory testing, the transcranial Doppler (TCD) method is preferred; ultrasound probe holding systems are commercially available which permit continuous monitoring over time without the risk of change in probe position. In contrast with current duplex ultrasound systems, TCD permits simultaneous measurement in more than one blood vessel, i.e., bilateral monitoring is possible (Fig. A3.7).

Several methods of autoregulatory testing by means of blood pressure alteration have been proposed. Aaslid and coworkers (1989) published a thigh-cuffmethod in which sudden blood pressure drops can be induced. Two thigh cuffs are inflated above systolic blood pressure values for more than 2 minutes, causing temporary leg ischemia. A sudden cuff release results in leg hyperemia and an ~20% systemic blood pressure drop lasting 10 seconds. In normal autoregulation, this maneuver leads to an initial reduction of blood flow velocity within the MCA. Compensatory autoregulatory flow increase starts after 1 second and flow velocities reach normal values after 5 seconds. Other published methods are the performance of a standardized Valsalva maneuver and the analysis of spontaneous blood pressure oscillations. The former test comprises expiration into a tube containing a closed pressure valve over 15 seconds, resulting in a transient blood pressure reduction as well as a less pronounced temporary reduction of blood flow velocity within the MCA, caused by the autoregulatory response (Tiecks et al 1996). The latter method analyzes spontaneous blood pressure oscillations (M-waves) or oscillations induced by slow breathing. High frequencies of more than 0.2 Hz were found to result in virtually direct changes of MCA flow velocity. Blood pressure oscillations at lower frequencies led to phase-shifted MCA velocity changes of up to 70°, i.e., an autoregulatory response was observed (Diehl 2002, Diehl et al 1995).

Fig. A3.5 Doppler spectra selection (common carotid artery [CCA], ECA, and MCA) of a patient with atrial fibrillation. Note the different flow velocities in each cardiac cycle caused by varying left heart filling and subsequently varying left cardiac output. Right: Example of blood flow in the MCA in a patient with a ventricular assist device (VAD). Note the loss of pulsatility (68/54 cm/s) caused by the constant flow of the VAD, modulated by the patient’s heartbeat.

Fig. A3.6 The relation of blood pressure (BP) and cerebral blood flow (CBF) under physiologic conditions (red lines) and pathologic conditions (blue lines). Intact autoregulation leads to a constant CBF over a wide pressure range (autoregulatory plateau) caused by a continuous decrease of small artery diameter with increasing BP. In impaired autoregulation, BP directly translates into CBF, because the small arteries do not constrict with increasing BP. Continuous lines, BP/CBF relation; dashed lines, BP/small arterial diameter relation.

Fig. A3.7 Example of a holding device for continuous bilateral TCD monitoring with two 2-MHz probes.

Fig. A3.8 TCD, transtemporal approach, distal P2-PCA segment insonation. (A) Flow velocity with the subject’s eyes closed (TAV_max 36 cm/s, PI 0.78). (B) Flow in the same vessel segment after eye opening (TAV_max 56 cm/s, PI 0.5).

All three reported methods have been shown to detect impaired autoregulation in patients with, for example, a high-grade ICA stenosis. So far, these methods are mostly used in specialized centers either because additional continuous blood pressure monitoring is required (thigh-cuffand Valsalva method) or because commercial evaluation software is not available (spontaneous oscillation method).