Ultrasonography has become one of the basic diagnostic tools for vascular diseases of the central nervous system (CNS). Due to the widespread availability of ultrasound, it seems necessary to define standards for equipment requirements, the scope of ultrasound and the experience of the person performing the procedure. The goal of this paper is to standardize the testing protocol in all neurosonology laboratories. We hope that the presented standards will prove useful in everyday patient management as well as will become the basis for discussion and comments to be taken into account in subsequent versions. The paper further describes different types of neurosonological tests, such as cerebral circulatory arrest or diagnostics of right-to-left shunts.
The proposed diagnostic criteria should be standardized in all neurosonology laboratories due to differences between ultrasonographic devices, particularly in relation to velocity calibration.
An assessment of the competence of the circle of Willis (The Matas Test)
The Matas test is performed in situations when it is necessary to determine the competence of the circle of Willis, e.g. in the case of necessary ligation of the internal carotid artery due to the presence of a large cavernous segment aneurysm.
The evaluation is performed using an ultrasound device equipped with a linear probe with a frequency of 7.5–13 MHz and a 2–3.5 MHz sector probe (transcranial color-coded duplex, TCCD) or an ultrasound device equipped with a linear probe with a frequency of 7.5–13 MHz and “blind” Doppler ultrasound device equipped with 2 MHz probe with pulse wave (PW) Doppler (transcranial Doppler, TCD).
The test is performed in a patient lying in supine position.
The procedure is preceded by the examination of the extracranial carotid arteries, as in accordance with the protocol, and the exclusion of atherosclerotic plaques in the common and internal carotid arteries. It should not be performed if atherosclerotic plaques are present in the extracranial carotid arteries.
The evaluation can be performed using transcranial Doppler ultrasound (TCD) or transcranial color-coded Doppler ultrasonography (TCDD). A firm compression of the ipsilateral common carotid artery, as far as possible from the bulb, should be performed during insonation of the internal carotid artery bifurcation (insonation depth: 60– 65 mm). Under no circumstances should be the carotid artery compressed in the vicinity of the bulb due to the risk of cardiac arrest (irritation of the carotid body). If the anterior communicating artery (the most important route for collateral circulation within the circle of Willis) is patent, then a reversal of the flow in the anterior cerebral artery will occur after several seconds (there will be two TCD spectra directed towards the probe or the blue colored TCCD flow ‘away from the probe’ in the anterior cerebral artery will change into red colored flow directed towards the probe, and there will be two overlapping spectra for the flow towards the probe in spectral Doppler). The absence of a change in the direction of flow in the anterior cerebral artery and a reduction in blood flow velocity of >30% in the middle cerebral artery as well as delayed systolic peak indicate very poor competence of the circle of Willis and the risk of ischemic complications in the case of ligation of the ipsilateral internal carotid artery(1–4).
The documentation should include the recorded flow spectra from the vicinity of intracranial internal carotid artery bifurcation at rest and after common carotid artery compression.
The results should contain the name of the method used (Duplex scan of the extracranial carotid arteries and TCD or TCCD), the name of the devices and the frequency of the probe. It is necessary to report the absence of atherosclerotic lesions in the compressed common carotid artery. If bilateral atherosclerotic lesions are found in the common carotid artery, this fact should be reported as the reason for withdrawing from further testing. It should also be reported whether a reversal in the direction of blood flow in the ipsilateral anterior cerebral artery occurred (good collateral circulation, competent circle of Willis) or not, or whether there was a reduction in blood flow velocity and a delayed systolic peak in the ipsilateral middle cerebral artery following common carotid artery compression (poor collateral circulation in the circle of Willis) (4).
Measurement of the cerebral vasomotor reserve
The measurement of vasomotor reactivity (VMR) is the most commonly used ultrasonography technique assessing the competence of mechanisms underlying the autoregulation of cerebral blood flow. VMR evaluation involves the measurement of changes in the mean blood flow velocity in the circle of Willis, usually in the middle cerebral artery, caused by changes in the volume of the vascular bed of the cerebral microcirculation (increased or decreased blood flow) induced by a vasoactive agent. Carbon dioxide is a substance that has the most profound effect on cerebral microcirculation. Physiological (respiratory tests) and pharmacological provocation can be used for the assessment. VMR evaluation is currently used mainly for scientific research as well as in clinical practice as a method assisting the qualification for carotid artery repair(2, 3, 5, 6).
The study is performed using “blind” Doppler ultrasound equipped with 2 MHz probe with pulse wave Doppler. The use of a monitoring headband significantly facilitates the examination (it also allows to maintain a constant insonation angle), and the sensitivity may be increased by simultaneous bilateral monitoring, i.e. dual-channel monitoring (if the apparatus features this option). Dual-channel monitoring also allows to shorten scanning duration(2, 6).
The test is performed in a patient in a lying supine or sitting position and wearing a monitoring headband. The test is performed under the same conditions (temperature, light, humidity), after a 10-minute rest period. The end-tidal CO2 concentration (ETCO2) should be monitored using capnograph (lateral stream measurement) and the blood pressure (BP) should be monitored, preferably using continuous non-invasive measurement techniques. Significant changes in the BP values should be avoided during the measurement(2, 3, 6).
The examination is performed by insonating the middle cerebral artery at a depth of 50–60 mm through the temporal window. It is advisable to use a headband and set a dual-channel monitoring (bilateral monitoring of the middle cerebral arteries). Provocation tests are preceded by the measurement of the mean blood velocity at rest (Vmean rest) (1-minute registration) in the middle cerebral artery. Further stages involve performing provocation tests and tracing provocation-induced changes in the mean blood flow velocity.
Provocation methods include:
Breath-holding test(1–3, 5, 6)
The method allows to assess the degree of microcirculatory vasodilatation induced by hypercapnia. The patient is asked to hold their breath for 30 minutes to achieve hypercapnia (tBH = 30 s). Breath hold should not be preceded by an additional, deeper inhalation, which may provoke the Valsalva mechanism. The maximum mean blood flow velocity (Vmean end BH) is measured immediately after the end of breath-hold (a minimum of 4–5 full cardiac cycles with the highest blood flow velocity). The breath-holding index (BHI) is calculated from the following formula:
[Vmean end BH – the mean middle cerebral artery (MCA) blood flow velocity at the end of breath-hold; Vmean rest – the mean middle cerebral artery (MCA) blood velocity at rest; tBH – breath-hold duration in seconds].
The measurement of vasomotor reserve(1–3, 5, 6)
Vasomotor reactivity reserve/range (VMRr) reflects the full range of changes in blood flow parameters: from resistance vessel stenosis due to hypocapnia to resistance vessel dilation induced by hypercapnia. It is measured based on hyperventilation provocation test (during which hypocapnia occurs). The patient should take regular, deep breaths with a full exhalation for 2 minutes at a rate of about 12 breaths per minute. The next stage involves a breath-hold (see above). The breathing tests are performed consecutively at 4-minute intervals, which are necessary for the normalization of blood flow parameters. The minimum mean blood flow velocity during hyperventilation (Vmean hyperventilation) is calculated as a mean for the last three breathing cycles during hyperventilation. The VMRr is calculated from the following formula:
[Vmean BH – mean MCA velocity at end breath hold; Vmean hyperventilation – mean MCA velocity during hyperventilation; Vmean rest – mean MCA velocity at rest].
Ventilation with 5% CO2(3, 5, 6)
A test with carbogen ventilation may be performed to induce hypercapnia. A patient wearing a respiratory mask (half-open circuit) is exposed to a mixture of 5% CO2 and 95% O2 (carbogen) for 90 minutes. Optionally, closed-circuit ventilation using breathing bags may be used. The maximum mean blood flow velocity (Vmean post-ventilation) is calculated as a mean value recorded during at least 5 seconds after the end of ventilation with the mixture. The VMR is calculated from the following formula:
4) Pharmacological provocation methods
The acetazolamide test(5, 6):
The method allows to assess the degree of microcirculatory vasodilatation. Acetazolamide, a carbonic anhydrase inhibitor, induces transient hypercapnia and, consequently, vasodilatation (blood flow maximization). The assessment of vasomotor reactivity based on the acetazolamide testing (e.g. Diamox 1 g – 15 mg/kg body weight IV) involves the measurement (within 1 minute) of blood flow velocity at rest (Vmean rest) and 10 minutes after infusion (a slow 2–5-minute IV infusion of solution of 5 mL of the drug) (Vmean ACE).
The range of VMR assessed based on acetazolamide testing is calculated from the following formula:
Infusion of L-arginine, an amino acid involved in the endogenous nitric acid synthesis, induces transient vasodilation in the microcirculation. The mechanism allows for a selective measurement of endothelium-dependent vasomotor reactivity. The test involves an infusion of 30 g L-arginine (usually in 100 mL 0.9% NaCl solution) for 30 minutes. Registration of blood flow parameters begins 10 minutes before infusion and ends 10 minutes after infusion. VMRr is calculated from the following formula:
The documentation includes the recorded curve for the mean blood flow in the middle cerebral artery (or both middle cerebral arteries using dual-channel monitoring) during hypercapnia and hypocapnia testing.
The result should include the name of the device and the frequency of the probe used for testing, as well as a statement whether it was one or dual-channel examination and the applied method for the provocation of changes in carbon dioxide pressure. The result should further include the percentage range of changes in the vasomotor reserve (hyperventilation and breath-hold) or the BHI in the case of breath-hold testing. The range of vasomotor reserve is more than 80% in healthy individuals, and the normal BHI value is 1.2 (±0.4). VMR below 50%, and MHI below 0.6 (±0.1) are considered pathological(2, 3, 6).
Substantia nigra hyperechogenicity assessment
The test is performed using a high-resolution ultrasound device equipped with a sector probe with a frequency of 1.6–2.5 MHz.
The test is performed in a patient lying in supine position.
The evaluation is performed through the temporal window, as in the case of TCCD, in an axial insonation plane. Ultrasound penetration depth of 14–16 cm, and a dynamic range of 45–55 dB should be set. The brightness of the image should be adjusted; low-echoic signal reduction should be used, if possible. Once a cross-sectional image of the brain stem at the level of midbrain (butterfly shaped) is obtained, 1.5–4 times magnification of the image is performed in the axial plane and a planimetric measurement of the area of potential hyperechogenicity is performed. Cut-off values should be defined in each laboratory and for each apparatus to determine hyper- and normal echogenicity of the substantia nigra. Then, the hyperechogenic area should be outlined manually and its area should be measured. An area of hyperechogenicity exceeding the 90th percentile in a healthy population is considered a significant hyperechogenicity of the substantia nigra (≥0,25 cm2 for most apparatuses). If the area of hyperechogenicity is between the 70th and the 90th percentile (≥0.2 and <0.25 cm2 for most apparatuses), the hyperechogenicity is defined as moderate. An area of substantia nigra hyperechogenicity of up to 70th percentile is considered a normal echogenicity. Although most authors report the lager of the two bilaterally measured substantia nigra hyperechogenicity areas, the mean value of the bilaterally measured hyperechogenic areas can also be reported. A uniform system of reporting results should be used in every laboratory(7, 8).
The documentation should include images of the brain stem at the level of the midbrain without measurements as well as images from the planimetric measurement of the outlined hyperechogenic area of the substantia nigra with values in cm2(8).
The results should contain the name of the device, the frequency of the probe as well as data on the echogenicity of substantia nigra (normal echogenicity, moderate hyperechogenicity, severe hyperechogenicity). The area of the potential hyperechogenicity and the ranges of norm/ pathology specific for a given laboratory and apparatus, should be reported(8).
Conflict of interest
Authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication