When using TCCD for transtemporal insonation , firstly set the B-mode insonation depth at 16 cm and aim toward the contralateral window. Visualization of the contralateral concave-shaped hyperechoic skull may indicate a sufficient transtemporal bone window. Decrease the maximum depth to 10–12 cm and aim the probe slightly downward until the butterfly-shaped hypoechoic mesencephalic brainstem can be identified in the axial plane. While sweeping the ultrasound beam slightly up- and downward, color Doppler imaging now enables visualization of the major branches of the Circle of Willis in part and, in some cases, in whole (Fig. 15.1). Adjust the color box size to cover at least the ipsilateral portion of the Circle of Willis and the color velocity scale to ±10–20 cm/s. Increase the color gain until “bleeding” of color occurs into the surrounding tissue. Although the following steps refer to a complete TCD examination, these are also applicable to TCCD study.

On TCCD, the vertebrobasilar arteries are examined in the axial imaging plane. Patients should be placed in a sitting position with the head bent forward as much as possible. In patients not able to sit (e.g., due to an acute neurological deficit), the examination can be performed in the side posture instead, but the head still bent forward. Place the transducer approximately 2–3 cm below the occipital protuberance in the midline of the neck and slide the transducer’s sound beam slightly toward the bridge of the nose. Once the foramen magnum is visualized as hypoechoic rotund structure close to the transducer on B-mode, color Doppler imaging enables visualization of the vertebrobasilar vasculature (ideally in the form of a Y – “Y-sign”) (Fig. 15.2). Commonly, the VA cannot be visualized along its entire course on a single plane, thus, requiring stepwise adjustment of the transducer’s angulation and positioning by moving laterally to completely trace all segments of the vertebrobasilar arteries. If the distal BA cannot be detected with TCCD, TCD may facilitate examination of the BA along its rostral course.

The following steps refer to a complete TCD examination but are also applicable to TCCD study.

The TCD/TCCD interpretation consists of the assessment of:

A normal TCD/TCCD examination may reveal a wide range of depths of insonation, velocity values, and waveforms.

Transcranial Doppler constitutes the modality of choice to identify and monitor children who are at highest risk of incidental stroke and in need of blood transfusion for primary stroke prevention. In a pivotal trial by Adams et al., blood transfusion resulted in 90% relative risk reduction of first stroke in children with elevated TCD time-averaged mean of the maximum velocities [TAMM] (abnormal: TAMM ≥200 cm/s) on two separate examinations [24]. Moreover, long-term follow-up data from the Stroke Prevention Trial in Sickle Cell Anemia (STOP) trial indicated that persistent elevation in TCD velocities are associated with an ongoing stroke risk, and children who were initially selected by TCD for blood transfusion should stay on transfusion schedule to sustain the benefit in stroke risk reduction [25, 26]. However, previously published long-term data from the newborn-CHIC-Créteil-cohort indicated that in a subset of children on hydroxyurea treatment blood transfusions can be stopped when TCD velocities are normalized (normal: TAMM <170 cm/s) but should undergo trimestrial Doppler follow-up and receive transfusions in case of relapse into abnormal TCD findings [27]. Table 15.1 details normal TAMM velocity values in the cerebral arteries for children with sickle cell disease [28].

Up to 30% of patients with subarachnoid hemorrhage (SAH) experience clinical deterioration caused by delayed cerebral ischemia mostly between days 4 and 10 after the index event [29, 30]. Delayed cerebral ischemia usually occurs when arterial vasospasm results in a severe (≤1 mm) intracranial arterial narrowing producing flow depletion with extremely high velocities [31]. It may affect the proximal and distal segments of intracranial arteries with the most common locations being:

Although quantitative criteria have been studied extensively, grading arterial vasospasm severity remains difficult and the interpretation of TCD findings should be individualized. Daily TCD examinations (from the first day after SAH onward) may detect considerable flow velocity and pulsatility changes that may be attributed to early development of vasospasm and progression to a severe stage [23, 33–41]. For example, an MCA MFV increase by 50 cm/s may indicate a 20% diameter reduction of the vessel, and since flow velocity is inversely proportionate to the vessel radius, a 50% diameter reduction usually doubles the velocity on TCD [42]. Therefore TCD may be more sensitive to changes in intracranial artery diameter than angiography particularly at the early phases of vasospasm development. Since TCD is a screening tool, the criteria should be adjusted to a higher sensitivity to detect any degree of vasospasm in order to institute components of hemodynamic therapy (i.e., controlled hypervolemia and hypertension). At the same time, a higher specificity threshold should be used for severe vasospasm to minimize the number of false-negative angiograms, particularly if TCD is used to select patients for endovascular therapy. The use of Lindegaard ratio may help to minimize false-positive TCD results and predict better the diameter of the residual lumen on angiography [17, 42]. While TCD has its highest sensitivity f or detecting severe arterial vasospasm around 8 after SAH, its sensitivity for diagnosing delayed cerebral ischemia is lower [41]. However, TCD findings should be related to the patient clinical condition, medications, blood pressure, and time after day zero and ICP findings.

In general, we use the following criteria for arterial vasospasm grading:

Additional findings may include daily changes in velocities, ratios, and PIs during the first 2 weeks but are particularly pronounced during the critical days 3–7 after the onset of SAH. MCA vasospasm specific criteria are shown in Table 15.3. The differential diagnosis includes hyperemia, combination of vasospasm and hyperemia in the same vessel (particularly when SAH patients receive some part of hypertension-hypervolemia therapy), residual vasospasm, and hyperemia. Arterial vasospasm may also coexist with hydrocephalus and edema.

Prognostically unfavorable signs include an early appearance of MCA MFV ≥180 cm/s, a rapid (>20% or >65 cm/s) daily MFV increase during critical days 3–7, an MCA/ICA ratio ≥6, and the abrupt appearance of high-resistance PI ≥1.2 of flow in two or more arteries indicating increased ICP and/or distal vasospasm [30].

Grading vasospasm severity in the arteries other than MCA is difficult [22]. Sloan et al. showed that TCD is highly specific for VA and BA vasospasm when mean flow velocities are ≥80 and ≥95 cm/s, respectively, and suggested reporting vasospasm in these arteries as possible, probable, and definite (Table 15.4) [34]. Also, the use of the ratio >3 between the BA MFV and the extracranial VA MFV increases sensitivity and specificity for TCD detection of BA vasospasm [37–39].

Other hyperperfusion syndromes may occur after carotid endarterectomy (CEA) or carotid artery stenting (i.e., post-revascularization hyperemia) usually characterized by a ≥30% increase in MCA MFV unilateral to the reconstructed carotid artery and low-pulsatility waveforms compared with the contralateral side or >100% increase in MCA MFV from pre- to post-intervention, indicating decreased capacity of distal vasculature to regulate the reestablished flow [43–46]. Hyperemic reperfusion may also develop with intravenous thrombolysis and endovascular therapy for acute ischemic stroke [47].

Transcranial ultrasound may also play a role in monitoring of patients with cerebral vasoconstriction syndrome with elevated MFV >120 cm/s and Lindegaard index >3 being predictive of developing posterior leukoencephalopathy or ischemic strokes [48].

Primary findings for any significant ≥50% MCA stenosis include a focal significant MFV or PSV increase (≥100 cm/s or ≥140 cm/s, respectively), or interhemispheric MFV difference of 1:2 in adults free of cerebrovascular disease [59–68]. A ≥70% MCA stenosis could produce higher velocities, and in our laboratory we use an MFV cutoff >120 cm/s [69]. This velocity increase should be further associated with a ratio to a homologous segment of 1:3 or higher. If anemia, congestive heart failure, and other circulatory conditions associated with elevated or decreased velocities, a focal MFV difference ≥30% between neighboring or homologous arterial segments should be applied to see if the velocity increase reaches any significance. Adult patients with anemia or hyperthyroidism often have increased MCA mean flow velocities. In children with sickle cell disease, MCA TAMM ≥170–200 cm/s is considered conditional and ≥200 cm/s abnormal [22, 23].

Additional findings may include turbulence (occasionally a low-frequency noise produced by non-harmonic co-vibrations of the vessel wall and musical murmurs due to harmonic co-vibrations producing pure tones can be heard) or disturbed flow distal to the stenosis or presence of characteristic flow voids on PMD-TCD indicating a low-frequency bidirectional turbulent flow during systole; an increased unilateral ACA MFV may indicate compensatory flow diversion or A1 ACA or ICA bifurcation stenosis and microembolic signals (MES) found in the distal MCA.

If MFVs are increased throughout the M1 MCA, the differential diagnosis includes MCA stenosis, terminal ICA or siphon stenosis, hyperemia, or compensatory flow increase in the presence of contralateral ICA stenosis, ACA occlusion, and incorrect vessel identification.

A critical stenosis or obstruction with near-occlusive thrombus or embolus can either produce a focal velocity increase or a blunted MCA waveform with slow or delayed systolic acceleration, slow systolic flow deceleration, low velocities, and lower MFVs in the MCA than ACA or any other intracranial artery [53, 55]. Decreased or minimal flow velocities with slow systolic acceleration can be also found due to a tight elongated MCA stenosis. These focal lesions should be differentiated from a proximal ICA obstruction that can also produce delayed systolic flow acceleration in the MCA [49–56]. To confirm the presence of a flow-limiting lesion, arterial branches need to be evaluated. Note that an M1-M2 MCA near-occlusion is usually accompanied by flow diversion to the ACA and/or compensatory flow increase in the PCA, indicating transcortical collateralization [55, 70].

Primary findings for any significant ACA stenosis include a focal significant mean flow velocity increase (ACA > MCA) and/or a ≥30% difference between the proximal and distal ACA segments and/or interhemispheric ACA MFV difference of ≥30% (these are the original criteria, but in reality ACA MFV velocity should at least double the velocity of the reference vessel) [53, 65, 70]. According to a recent TCD validation study, a PSV of 120 cm/s combined with additional parameters (e.g., abnormal spectrum, side-to-side difference) was the most accurate criterion for detecting substantial ACA stenosis [71]. Collateralization via the anterior communicating artery (AComA) can be excluded by a normal contralateral ACA flow direction. The differential diagnosis includes anterior cross-filling due to a contralateral proximal carotid artery obstruction [49–52].

Additional findings may include turbulence and a flow diversion into the MCA and/or compensatory flow increase in the contralateral ACA. Decreased or minimal flow velocities at the A1 ACA origin may indicate a suboptimal angle of insonation from the unilateral temporal window, an atretic or tortuous A1 ACA segment, or A1 ACA near-occlusion. Since the A2 ACA segment cannot be assessed directly by TCD, its obstruction can be suspected only if a high-resistance flow is found in the distal dominant A1 ACA segment.

Common errors include incorrect vessel identification (terminal ICA vs. ACA), velocity underestimation (suboptimal angle of insonation, poor window, weak signals), and inability to differentiate a collateral flow from the stenosis.

A terminal ICA (traceable through the temporal window) and ICA siphon (traceable through the transorbital window) stenosis produces a focal significant MFV increase (ICA > MCA, and/or an ICA MFV ≥70 cm/s, and/or ≥30% difference between arterial segments) [53, 65, 72, 73].

The differential diagnosis includes moderate proximal ICA stenosis and/or compensatory flow increase with contralateral significant ICA obstruction. Additional findings in the presence of an ICA stenosis may include turbulence, blunted unilateral MCA, OA MFV increase, and/or flow reversal with low pulsatility. The ICA siphon MFV may decrease due to siphon near-occlusion (a blunted siphon signal) or distal obstruction (i.e., MCA occlusion or increased ICP).

Common errors include incorrect vessel identification such as MCA versus terminal ICA via transtemporal approach or ACA versus ICA with deep transorbital insonation and consequently collateralization of flow via the anterior cross-filling misinterpreted as an arterial stenosis. In the absence of temporal windows, these findings may be the only yet confusing indicators of a significant carotid artery lesion.

A focally significant PCA stenosis results in an MFV increase PCA > ACA or ICA and/or a PCA MFV ≥50 cm/s in adults [56, 66, 74]. Additional findings may include turbulence and a compensatory flow increase in the MCA.

The differential diagnosis includes collateral flow via the posterior communicating artery (PComA) either toward the posterior circulation in case of BA occlusion or toward the anterior circulation in case of MCA, TICA or tandem extracranial ICA/MCA occlusions, and siphon obstruction. Of note, PComA is a tortuous vessel, and its flow direction on TCD does not necessarily indicate where the lesion is that requires collateralization. Using TCCD, it may be possible to differentiate PCA stenosis from collateralization of flow using PSV [75]. Common sources of error include unreliable vessel identification and a top-of-the-basilar stenosis.

Primary findings in the presence of a BA stenosis include a focal significant MFV increase BA > MCA or ACA or ICA, and/or an MFV BA ≥60 cm/s in adults, and/or a ≥30% difference between arterial segments [56, 66]. The findings of the Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial indicate that a BA stenosis of ≥50% can be more reliably identified when BA MFV exceeds 80 cm/s [68]. To detect ≥70% intracranial vertebrobasilar stenosis, we use MFV increase >110 cm/s and a stenotic-pre-stenotic ratio ≥3 [69].

The differential diagnosis includes a terminal VA stenosis if elevated velocities are found proximally, i.e., at a depth of 70–80 mm. If elevated velocities are found throughout the entire BA course, the differential diagnosis includes a compensatory flow velocity increase, i.e., in case of a carotid artery obstruction. With the latter, velocities are increased in at least one of the VAs.

Basilar artery near-occlusion produces a focal MFV decrease (≤30% difference between neighboring arterial segments, and/or BA < VA) resulting in a blunted waveform [56]. The differential diagnosis includes a fusiform (dolichoectatic) BA with or without thrombus since an enlarged vessel diameter may reduce flow velocities. If the end-diastolic flow is absent, the differential diagnosis includes BA occlusion or tortuosity with branch insonation at a suboptimal angle.

Additional findings may include turbulence and disturbed flow signals distal to the stenosis, compensatory flow increase in VAs and posterior cerebellar inferior arteries indicating cerebellar collateralization, and a collateral supply via PComA to PCA with a reversed flow in the distal BA.

Common sources of error include a tortuous basilar (“not found” does not always mean obstructed), elongated BA obstruction, and distal BA lesions that were not reached by TCD or identified due to flow presence to the superior cerebellar arteries producing false-negative results. Application of ultrasound contrast and TCCD may help the detection of the distal BA segment, tortuosity, and distal branches [7, 56, 76, 77]. A collateral flow from the posterior to the anterior circulation in the presence of carotid lesions may increase flow velocity changes associated with mild stenosis and/or tortuosity. In the case of flow collateralization, the dominant VA velocities are also increased [78]. Reversed flow in the BA (low-resistance flow toward the probe) is characteristic for a proximal BA occlusion with retrograde filling of the distal BA through the PComA [56, 79]. The origin of the collateral flow in the anterior circulation can be confirmed with carotid artery tapping that can be transmitted to the reversed flow.

Primary findings of an intracranial VA stenosis include a focal MFV increase VA > BA, and/or MFV VA ≥50 cm/s in adults, and/or a ≥30% difference between VAs or its neighboring segments [66, 80]. Recent findings have indicated that a ≥50% VA stenosis can be more reliably identified when VA MFV exceeds 80 cm/s and when the stenotic-to-normal MFV ratio is ≥2 [68]. A ≥70% VA stenosis could produce higher velocities, and in our laboratory we use a MFV cutoff >110 cm/s and a stenotic-to-normal MFV ratio of ≥3 [69]. On TCCD, minimal flow on color imaging with otherwise good visualization of the contralateral VA and significant reduction of the PSV as compared with the contralateral segment may indicate critical stenosis of the VA [81]. The differential diagnosis includes proximal BA or contralateral terminal VA stenoses and a compensatory flow increase in the presence of a contralateral VA occlusion or carotid lesion.