History of Doppler Ultrasound

The origins of Doppler ultrasound can be traced back to the description of the Doppler effect by the Austrian physicist Christian Doppler. First presented to the Royal Bohemian Society of Sciences in May 1842, his work was titled “On the colored light of the double stars and certain other stars of the heavens.” This presentation described the Doppler effect as it subsequently became known, which explains the shift in the frequency of a wave when either the transmitter of the wave or the receiver of the wave is moving with respect to the wave-propagating medium. This effect applies to sound, and sound emanating from or reflected by an object moving toward an observer is characterized by a higher frequency in proportion to the speed of the moving object. Conversely, if sound emanates from an object moving away from an observer, the sound has a lower frequency in proportion to the speed of the moving object. According to this principle, ultrasound can be used to measure the velocity of flowing blood. Ultrasound is generated by a small crystal, emitted from a probe, and then reflected off the moving blood cells, and the reflected signal is also received by the probe. The shift in frequency between the emitted and the reflected ultrasound varies proportionally with the velocity of the flowing blood. Blood flowing toward the probe reflects the ultrasound at a higher frequency and produces a positive Doppler shift, whereas ultrasound reflected from blood flowing away from the probe is reduced in frequency or exhibits a negative Doppler shift. The signals are processed, and a spectral analyzer displays multiple spectral dots for the many reflections that are recorded.

The use of Doppler ultrasound to measure blood flow was initially reported by Satomora in 1959.¹ Satomora and Kaneko were originally interested in measuring cerebral blood flow; however, they concluded that the skull was an insurmountable barrier to the passage of ultrasound and focused on the extracranial carotid arteries in their initial investigations. After refinements in the equipment and advances in the technology, Doppler ultrasound was introduced as a clinical tool to examine blood flow velocity in the extracranial and peripheral arteries. Refinements in signal processing and the introduction of B-mode imaging, as well as duplex imaging (simultaneous display of B-mode tissue imaging and vascular flow velocity measurements), followed by the development of color flow ultrasound, have continued to improve its diagnostic capabilities for extracranial and intracranial vascular pathology. It has recently been demonstrated that sonothrombolysis (the use of ultrasound to help dissolve blood clots) can be used as a treatment of stroke and potential treatment of intracerebral hemorrhage. These observations have extended the applications of Doppler ultrasound from diagnostics to therapeutics in the brain.

B-Mode Ultrasonography

The basic principle underlying real-time brightness-mode (B-mode) imaging is the variable acoustic impedance that different body tissues naturally possess. When the technique was first developed to use ultrasound to image tissue, the intensity and time of flight of the reflected ultrasound signal (echo) were represented as a unidimensional tracing, with the amplitude of the wave representing intensity and the distance along the x-axis representing the reflector depth or distance from the transducer (known as amplitude modulation mode, or A-mode). The standard display now allows visualization of tissue interfaces when sound waves are spatially represented by picture elements (pixels) on a video display, with the brightness of each pixel correlating with the amplitude or intensity of the echo signal. Scanner screens use 256 shades of gray to represent the tissues’ different ability to absorb or reflect sound, which is displayed as a picture.

When the piezoelectric crystal in the probe emits a pulse, this focused beam travels along a single plane. Any sound reflected back along this plane is received by the probe, recorded, and presented on the display screen. By insonating adjacent segments of tissue with multiple crystals located within a sonographic head or with a rotating head, a two-dimensional representation of the object being insonated can be shown on the display screen. This B-mode display has become a standard mode of displaying the anatomy and differential densities of the insonated tissue. The rapid processing and display of these data allow “real-time” imaging in ultrasonography such that pulsations of vessels and cerebrospinal fluid spaces can be identified.

Duplex Ultrasonography

The combination of improved beam focusing and pulsed Doppler blood flow velocity measurements improved the ability to localize the source of the reflected signal within tissue. Doppler spectral analysis of this signal, through the use of fast Fourier transformations, allowed the complex reflected signal of each single-frequency component to be displayed visually. This resultant “power spectrum” for the Doppler signal could be used to distinguish the various flow characteristics that exist in normal and diseased vessels.

These vascular diagnostic modalities were later integrated with B-mode imaging to produce duplex ultrasonography.¹⁰ Modern duplex scanning uses one transducer (5 to 7 MHz) to produce simultaneous B-mode images and pulsed Doppler waveform analysis. The screen of the display module provides real-time anatomic B-mode data and a graphic representation of the Fourier-transformed pulsed spectral analysis. An additional advantage of this diagnostic tool is that it has the ability to correct for variable angles of insonation, which if not kept between 55 and 65 degrees, could significantly alter the recorded frequencies (Fig. 347-1).

FIGURE 347-1 Effect of the insonation angle between the ultrasound beam and the artery on velocity values. The percentage of the actual velocity measured changes as a function of the cosine of the insonation angle (phi) according to the following formula: FV = v/cos(phi), where the true flow velocity (FV) equals the measured velocity (v) divided by the cosign (cos) of the angle of insonation (phi). The use of duplex imaging can determine this angle and correct for it, thereby increasing the accuracy of the velocity measurements.

One of the major limitations of duplex scanning is that just a small region of the artery can be studied at any one time. This technology is also only a two-dimensional representation of a three-dimensional dynamic process. Color flow imaging, which combines real-time, B-mode, gray-scale imaging with color encoding of multigated Doppler flow information, begins to address these issues by sampling the mean Doppler frequency shift at various depths over the entire scan area. The color assigned to the frequency data depends on the magnitude and direction of flow, with hue (red versus blue) depicting the direction of flow, the hue’s saturation denoting the magnitude of the frequency shift, and the brightness (luminance) demonstrating the variance in mean flow (i.e., the turbulence), which is superimposed on a gray-scale B-mode image depicting the surrounding anatomy. Color Doppler allows more rapid identification of the component vessels than duplex alone does, and it also provides rapid identification of laminar flow patterns for placement of a single pulsed Doppler gate for acquisition of spectral waveform data. Today, the combined use of B-mode two-dimensional imaging and the real-time, color-enhanced spectral analysis of pulsed wave Doppler have enabled experienced operators to recognize carotid stenosis with a sensitivity approaching 100% (Fig. 347-2).

FIGURE 347-2 Top, Color flow duplex scan of a normal right internal carotid artery (RICA) bifurcation showing the normal anatomy in gray scale, as well as the red color indicating blood flow at a peak systolic blood flow velocity of 59 cm/sec, indicative of no significant stenosis. Bottom, Color flow duplex scan of a significant (70% to 79%) stenosis of the RICA. The gray-scale picture indicates excess tissue in the intravascular space at the carotid bifurcation with a peak systolic blood flow velocity of 334 cm/sec and significant spectral broadening (increased gray color within the spectrum).

Transcranial Doppler

Aaslid and colleagues first reported the ability to record blood flow velocity in the intracranial arteries with Doppler ultrasound in 1982 and introduced TCD ultrasonography.¹¹ TCD ultrasonography used an optimized 2-MHz frequency with a pulsed Doppler range-gated design. The lower 2-MHz frequency allowed penetration through the cranium in the thin portions of the bone. The introduction of TCD ultrasound permitted examination of the intracranial vasculature, which has improved the diagnosis of intracranial disease. The technique of TCD ultrasound was initially used in the Department of Neurosurgery in Bern, Switzerland, for the diagnosis of vasospasm after subarachnoid hemorrhage.¹² Many subsequent uses have been described for this technology and are reviewed in this chapter.

A complete TCD examination normally includes examination through three transcranial windows: the transtemporal, transorbital, and transoccipital windows.¹³ Through these three windows, most of the basal intracranial arteries can be examined (Fig. 347-3). The transtemporal window is used to examine the middle cerebral artery, (MCA), anterior cerebral artery, intracranial internal carotid artery (ICA), and proximal posterior cerebral artery. The transorbital window is normally used to examine the ophthalmic artery and the intracavernous and supraclinoid ICA. The transoccipital window is used for examination of the posterior circulation, specifically the two vertebral arteries and the basilar artery. The origin of the posterior inferior cerebellar arteries can be examined in many patients.

FIGURE 347-3 The three windows for transcranial Doppler examination of the basal cerebral vessels. On the lateral portion of the skull, the transtemporal region (A and C) is used to examine the middle cerebral artery, proximal anterior cerebral artery, distal internal carotid artery, and proximal posterior cerebral artery. The spectral waveform of the middle cerebral artery (B) has a characteristic low-resistance profile. Anteriorly, the transorbital window is used to examine the carotid siphon, as well as the ophthalmic artery (C). The third window is the transforaminal window, which can be used to examine the posterior circulation vessels. The two vertebral arteries and the basilar artery are examined easily by this method. The posterior inferior cerebellar arteries can often be examined.

The original technique for examination was a handheld method in which manual manipulation of the probe with recordings of sample volumes at preselected depths was used to examine specific sites in the intracranial vasculature. Normally, as the distal intracranial arteries become vertically oriented in the sylvian and intrahemispheric fissures, they are considered beyond the scope of the normal TCD examination.¹⁴ The distal intracranial arteries can occasionally be examined in unusual circumstances, however, such as after craniotomy, when bone is removed and examination windows are created.

The Doppler signal reflected from intracranial arteries is used to measure ultrasound frequency shifts, which are converted into blood flow velocity in centimeters per second. To determine the actual blood flow in milliliters per minute, the total average velocity, vessel diameter, and angle of insonation need to be known precisely,¹⁵ and these parameters are not usually measured during routine TCD examinations. The angle of insonation (angle between the ultrasound beam and the vessel being recorded from) is important to consider when measuring TCD velocity. The true velocity and observed velocity are equal when the angle of insonation is zero, as often happens when examining the MCA trunk. As the angle of insonation increases, there is a reduction in the observed frequency as a function of the cosine of the angle (see Fig. 347-1). For example, if the angle between the ultrasound beam and the flow reflector is 30 degrees, 97% of the true velocity can be observed by the recording device. As the angle of insonation increases, the proportion of the true velocity observed decreases. If the angle of insonation is 60 degrees, 50% of the true velocity is observed by the recording equipment. TCD examination techniques incorporate this strategy to reduce the insonation angle to as low as possible when recording from different intracranial arteries. The introduction of color flow ultrasound adds the ability to determine the angle of insonation to some extent during the examination. Figure 347-3 illustrates a typical velocity recording from the MCA.

Since the introduction of TCD, the technology has undergone significant improvements as a result of technical advances in equipment and signal processing that allowed an increased capability of detecting abnormalities in intracranial vascular structure and function. TCD allows three-dimensional vessel maps to be constructed, and the recording site can be documented easily in most cases. Advantages of this technology include an easier learning curve for beginning examiners and positive identification of abnormal vascular anatomy, which can be due to anatomic variations, as well as pathologic changes from occlusion or displacement.

Advances in computerized recording devices and the miniaturization of computerized digital processing have allowed easier recording of Doppler signals for analyses. This development has permitted continuous recording of spectral outline and full spectral signals, which enables more detailed analysis of physiologic events.¹⁶ Digital recording with the capability of displaying continuous data over time has allowed calculation of changes in velocity secondary to alterations in blood flow evoked by physiologic stimuli, as well as analysis of cerebrovascular control mechanisms, such as CO₂ autoregulation and changes in flow caused by cortical activation. Two-channel TCD ultrasound was introduced to resolve physiologic questions regarding control of the cerebral circulation and to document simultaneous changes in venous and arterial flow.¹⁵ Subsequently, multichannel TCD has been used to register signals simultaneously from both cerebral hemispheres recorded from both MCAs.¹⁷ Multichannel TCD has allowed detection of emboli by recording from multiple sample volumes simultaneously.¹⁸ Reflected power recordings have enabled calculation of relative flow volume, which can be used for scientific purposes to calculate changes in cerebral blood flow.¹⁵ Power Doppler can be performed transcranially to provide further detail in imaging intracranial vascular structures, such as aneurysms and arteriovenous malformations. Miniaturization has allowed TCD units to become more portable, and in the future, battery-operated devices may serve as a neurovascular stethoscope to permit rapid determination of vessel patency and flow characteristics.

Intracranial Stenosis

TCD ultrasonography has extended the ability of Doppler ultrasound to diagnose intracranial arterial stenosis reliably, which may be caused by a variety of pathologic conditions other than vasospasm. A common cause of intracranial stenosis in patients with symptoms related to cerebrovascular disease is atherosclerosis involving the basal intracranial vessels. Other conditions can also cause intracranial arterial stenosis, including moyamoya disease, intracranial arterial dissection, vasculitis, preeclampsia, sickle cell disease, and arterial-to-arterial emboli undergoing various stages of recanalization.

Atherosclerotic disease of the intracranial vessels has received much less attention than similar lesions of the extracranial cerebral vessels.²⁴ Although intracranial arterial stenosis secondary to atherosclerosis is less common than extracranial stenosis in Western populations, intracranial atherosclerotic lesions can be a significant cause of stroke and transient ischemic attacks. Bogousslavsky and coworkers analyzed the natural history of patients with MCA stenosis or occlusion entered into the Extracranial-Intracranial Bypass Study Group.²⁵ During a follow-up period of 42 months, 11.7% of the patients per year experienced recurrent cerebrovascular events (transient ischemic attack or stroke).

Several early studies reviewed the accuracy of TCD for the diagnosis of intracranial stenosis secondary to atherosclerosis.^26–28 Spencer and Whisler compared carotid siphon stenosis assessed by angiography and TCD.²⁷ In a group of 33 carotid siphons visualized angiographically, 11 showed stenosis ranging from 30% to 75%. Comparison of TCD with angiography revealed a sensitivity of 73% and specificity of 95%. Ley-Pozo and Ringelstein compared intra-arterial digital subtraction angiography with TCD in detecting occlusive disease of the carotid siphon and MCA.²⁸ Sixteen of 17 cases of carotid siphon stenosis were identified correctly with TCD. Rorick and colleagues compared TCD with angiography for the diagnosis of intracranial stenosis.²⁹ These investigators found that the presence of coexisting extracranial stenosis can be a confounding variable affecting the accuracy of TCD in detecting intracranial lesions. It has been useful to examine the intracranial arteries with TCD in patients with cerebrovascular symptoms who are not found to have significant pathology in the extracranial arteries.

Intracranial Hemodynamics

Evaluation of intracranial hemodynamics with TCD has allowed assessment of vascular control of the cerebral circulation, as well as identification of patients with cerebrovascular occlusive disease who are at higher risk for stroke. In patients with occlusive disease, the two most useful capabilities of TCD with regard to hemodynamic parameters are evaluation of collateral patterns and cross-flow and direct assessment of hemodynamic changes in the distal vascular territories caused by proximal occlusive lesions.

Maintenance of adequate cerebral blood flow depends on sufficient cerebral perfusion pressure through the inflow vessels along with adequate blood pressure, intact anatomy of the extracranial and intracranial vasculature, and compensatory mechanisms when the vasculature or blood pressure becomes compromised. The normally configured circle of Willis functions as a manifold to normalize perfusion pressure to the distal cerebral vessels if one or more extracranial vessels becomes occluded or hemodynamically compromised secondary to stenosis. The circle of Willis normally allows nearly complete compensation in the event of carotid occlusion.³⁰

Compensation for carotid occlusion usually occurs via (1) crossover through the anterior communicating artery and reversed flow in the proximal anterior cerebral artery (A₁) ipsilateral to the occlusion, (2) forward flow in the posterior communicating artery ipsilateral to the occlusion, or (3) reversed flow in the ipsilateral ophthalmic artery.³¹ Major differences in the functional capacity of the circle of Willis are found in the general population, however, and some patients cannot recruit sufficient flow to maintain adequate cerebral perfusion pressure.

The use of TCD to evaluate vasomotor reserve (VMR) is based on the principle that changes in velocity are proportional to changes in flow through a vessel if the vessel diameter is constant. Changes in blood flow velocity through the MCA can be used to reflect relative changes in blood flow in that artery as a result of alterations in CO₂ concentration or acetazolamide or moderate changes in arterial blood pressure (autoregulation). By using these principles, the functional capacity of the distal regulating vessels in the cerebral circulation can be assessed with TCD.

When cerebral perfusion pressure decreases as a result of proximal arterial stenosis or occlusion, the distal cerebral regulatory vessels become dilated maximally and exceed their functional capacity to autoregulate and respond to CO₂. Acetazolamide has been used to induce distal cerebral vasodilation and probably works by a similar pH-dependent mechanism as inhalation of CO₂. Lack of responsiveness to CO₂ or to acetazolamide can be used to indirectly detect reduced cerebral perfusion pressure in the MCAs as a result of the effects of proximal occlusive disease.

Testing of VMR with TCD can provide valuable physiologic information regarding prognosis in patients with certain vascular lesions. Kleiser and Widder reported the results of a natural history study of patients with unilateral carotid occlusion after VMR testing.³⁰ In a group of 86 patients with unilateral carotid occlusion, 11 had exhausted their VMR and had an increased ipsilateral stroke rate (17% per year for 3 years as compared with an ipsilateral stroke rate of 3% per year for the entire group, which is comparable to previously published series). Similar findings of increased stroke risk in patients with carotid occlusion and impaired vascular reserve, measured with other methods, including xenon-enhanced computed tomography (CT) with acetazolamide challenge and positron emission tomography (PET), have been reported.^32,33 Patients with impaired vascular reserve and recent symptoms distal to ICA occlusion are the subject of an ongoing randomized clinical trial comparing extracranial-to-intracranial bypass surgery with medical therapy for prevention of stroke (Carotid Occlusion Surgery Study [COSS]).

The prognosis of patients with carotid stenosis may be influenced by VMR. Gur and associates reported that patients with asymptomatic carotid stenosis and impaired VMR had a worse prognosis than did those with intact VMR.³⁴ With the use of VMR testing it appears possible to identify patients with poor hemodynamic reserve and carotid stenosis or occlusion who have a high risk for stroke and may benefit from medical or surgical therapy to improve cerebral perfusion.

Cerebral Autoregulation

Cerebral autoregulation is the ability of the brain to maintain constant cerebral blood flow despite changes in cerebral perfusion pressure. The methodology for determining cerebral autoregulation in the past was cumbersome and invasive and required radioisotopes for cerebral blood flow measurement and vasoactive medication to change the blood pressure. TCD can be used to determine autoregulation noninvasively in the MCA perfusion territories.^35,36 Preliminary clinical testing in patients with cerebrovascular occlusive disease indicates that cerebral autoregulation is absent in patients with severely impaired CO₂ reactivity.^36,37 Noninvasive testing of cerebral autoregulation with TCD may prove useful in the complete hemodynamic evaluation of patients with cerebrovascular occlusive disease and may also be helpful in managing patients after head injury.

Positional Vertebral Artery Obstruction

Cerebrovascular insufficiency can sometimes occur in the posterior circulation secondary to positional obstruction of one or both vertebral arteries in the setting of impaired collateral pathways from the anterior circulation. Several reports have found TCD monitoring of the posterior cerebral arteries bilaterally during various head positions to be useful in detecting transient hemodynamic insufficiency in this condition.^38,39 The most common cause of positional vertebral artery obstruction is cervical spondylosis, which can be treated surgically by anterolateral removal.³⁹ The essential diagnostic findings on TCD are a transient drop in posterior cerebral artery velocity signals with head turning and rebound hyperemia on return to a neutral position. Examination with TCD is helpful in differentiating true positional ischemia from positional vertigo and can identify patients who require angiography to define the location and nature of the obstruction.

Intracranial Emboli

Interest has developed in the ability of TCD to directly detect intracranial microemboli in the basal cerebral vessels and their relationship to stroke and ischemic symptoms in patients with occlusive vascular disease. Doppler ultrasound was previously used clinically to detect intravascular air microemboli audibly during cardiac surgery⁴⁰ and during neurosurgical procedures in the sitting position.⁴¹ The ability of TCD to detect intracranial microemboli was first recognized by monitoring MCA velocity during carotid endarterectomy (CEA) and cardiac surgery.^42,43

Clinical correlation of detection of intracranial and extracranial microemboli has been described.⁴⁴ Intracranial microemboli have been detected in patients with atrial fibrillation, prosthetic heart valves,⁴⁵ carotid stenosis,^46,47 fibromuscular dysplasia, arterial dissection,^48,49 and intracranial stenosis, as well as during invasive procedures such as angiography,⁵⁰ angioplasty,⁵¹ and vascular and heart surgery⁵² and after aneurysm treatment.⁵³ Monitoring for intracranial air microemboli after venous injection has been helpful in identifying patients with cardiac and pulmonary defects causing right-to-left circulation shunts.⁵⁴ Most microemboli do not cause overt symptoms; however, multiple microemboli have been associated with impaired neuropsychological function after cardiac surgery.⁵⁵ The clinical utility of intracranial monitoring of emboli is still being established, but much has been learned with TCD about microembolism to the brain. Monitoring of emboli with TCD has played a useful role in identifying the site of active embolization in the arterial system in patients with transient ischemic attack or recent stroke, distinguishing embolic versus hemodynamic causes of stroke and transient ischemic attack, identifying high-risk stages of neurovascular and surgical procedures, and detecting patients with vascular lesions at higher risk for ischemic events.