Content uploaded by Ryszard M Pluta
Author content
All content in this area was uploaded by Ryszard M Pluta
Content may be subject to copyright.
Reviews on Recent Clinical Trials, 2007, 2, 49-57 49
1574-8871/07 $50.00+.00 © 2007 Bentham Science Publishers Ltd.
Clinical Applications of Transcranial Doppler Sonography
Bawarjan Schatlo and Ryszard M. Pluta*
Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD, USA
Abstract: Transcranial Doppler sonography (TCD) is used to assess cerebral blood flow velocity in basal cerebral arteries
and is a common tool for the diagnosis and follow-up of cerebrovascular disease. With more than 200 clinical studies
using TCD published annually, indications for its use are expanding. The current article critically reviews standard and
recent clinical applications for TCD including delayed vasospasm after subarachnoid hemorrhage, sickle cell disease,
atherosclerosis of cranial vessels, ischemic stroke, brain trauma, brain death, carotid artery disease, cerebral venous
thrombosis, intraoperative TCD monitoring, arteriovenous malformations, cardiac shunts and preeclampsia.
Keywords: Autoregulation, Cerebral blood flow, Cerebrovascular disease, Chemoregulation, Transcranial Doppler
sonography, Stroke.
INTRODUCTION
Overview
Transcranial Doppler sonography (TCD) was first used in
1981 when Aaslid and coworkers assessed middle cerebral
artery (MCA) cerebral blood flow velocity (CBF-V) in
patients with subarachnoid hemorrhage (SAH) [1]. The main
difference between Aaslid’s “Ur-Doppler” and other,
conventional Doppler ultrasound devices at the time was that
the bidirectional probe was pulsed with a lower frequency of
2 MHz in order to sufficiently penetrate the temporal bone
window. Its main advantages compared to most other
neuroimaging methods are convenience, mobility, low cost,
non-invasiveness, and lack of side-effects. However, the
results of a TCD examination depend on the experience and
diligence of the examiner. More than 200 indexed clinical
studies published annually clearly show that applications for
TCD are rapidly expanding. Clinicians need to follow these
developments but should also beware of their often
somewhat limited practical value. To assess the usefulness of
TCD, it is impracticable or simply not applicable to perform
blinded, randomized or placebo-controlled studies. Yet,
guidance for using TCD should be obtained from prospective
studies with sufficiently large patient samples and with a
reasonably simple and reproducible technique. The TCD
report of the American Academy of Neurology attributed the
highest class rating to prospective studies fulfilling the
criteria of (1) broad study population, (2) validation of TCD
by comparison to the “gold standard”, (3) blinded evaluation
of the data and (4) statistically dependable diagnostic or
prognostic value [2]. The current paper reviews established
and pending clinically relevant indications for non-imaging
TCD and discusses the limitations of this diagnostic tool.
Specific reviews are available on applications for the not yet
universally established transcranial-color-coded sonography
[3, 4].
*Address correspondence to this author at the Surgical Neurology Branch,
NINDS, National Institutes of Health, 10 Center Drive, Room 5D37,
Bethesda, MD 20892, USA; Tel: 301-594-8117; Fax: 301-402-0380;
E-mail: rysiek@ninds.nih.gov
Technique
In addition to the medical indication to perform TCD,
subjects need a sufficiently thin temporal bone window to
enable penetration of the 2 MHz waves. The temporal
window is suitable for insonation in more than 90% of
patients [5], but may become more difficult to penetrate in
older patients, which prompted the development of a 1 MHz
probe [6]. TCD permits evaluation of the MCA, anterior
cerebral artery (ACA), posterior cerebral artery (PCA) and
terminal internal carotid artery (ICA). The suboccipital
(“transforaminal”) insonation can be performed on a supine
or sitting patient and yields good accessibility of the basilar
artery (BA) and possibly the vertebral arteries (VA). A trans-
orbital approach can be used to insonate the ICA in the
carotid siphon and the ophthalmic artery. Unless stated
otherwise, CBF-V indicates mean flow velocity in this
review. Ample reference values for CBF-V, proper angle and
depth of insonation are provided for healthy subjects [7],
including stratifications for age and sex [1, 8, 9]. CBF-V
obtained by TCD devices is a result of a spectrum of waves
reflected by erythrocytes, and thus depends particularly on
hematorheological conditions. In patients with very low
hematocrit (<30%), CBF-V is increased due to a decrease in
viscosity. Thus, TCD interpretation in patients with
abnormal blood viscosity requires caution. An insonation of
all accessible arteries can help distinguish between a
systemic cause of increased CBF-V (fever, hematocrit) or a
focal increase suggesting a local abnormality. Moreover,
sufficient time to perform a thorough examination and
experience are key factors contributing to its accuracy [10,
11]. Proper supervision and instruction of those new to the
technique is mandatory.
A recent report showed that careful routine adjustment of
CBF-V for sex and age can significantly increase the
predictive value of TCD to detect vasospasm [12]. It is
possible that “fixed reference values” may thus be replaced
by individually adjusted thresholds. However, because
confirming this type of adjusted threshold will require
prospective studies on very large patient samples with wide
50 Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 Schatlo and Pluta
distribution of strata, the available thresholds backed up by
current statistical conventions remain the reference.
Aside from CBF-V, TCD also detects inhomogeneities in
flow; for example when a solid thrombus passes through an
insonated part of a vessel. This causes a scattering and
deflection of the Doppler beam and results in a “high-
intensity transient signal”. As discussed in more detail
below, TCD microembolus detection is routinely used in
cerebrovascular disease [13]. Different types of emboli have
characteristic physical properties, and their characterization
by TCD as well as an industry standard for their detection is
still subject to development [14-16].
CBF-V and CBF
There still seems to be confusion among clinicians using
TCD and there are still studies published stating the
misconception that TCD reflects CBF [17]. Volume flow (Q)
in a rigid pipe system equals velocity (V) times the cross-
sectional area of the pipe (A) (Q = V · A). In peripheral
artery systems, the cross-sectional area of an artery can be
measured by super-imposing standard ultrasound on the
Doppler image. Thus, volume flow can be routinely
calculated to estimate blood supply to a certain organ or
extremity. However, using TCD, the diameter of the
insonated artery remains unknown and the following
simplified formula describes the relationship between CBF-
V and CBF:
CBF
KA
T
CBF V=
⋅⋅⋅
⋅
60
α
-
[18, 19]. CBF stands for
regional CBF measured in ml/l00g/min, α is the cosine of the
insonation angle, K is a constant, A is the cross-sectional area
of the vessel in cm
2
, T is the territory of vessel supply in l00g
of brain tissue and CBF-V is expressed in cm/sec. This
suggests a linear relationship between CBF and CBF-V only
if (1), vessel diameter remains constant, (2) the artery’s supply
territory remains constant, and (3) the angle of insonation is
less than 10 degrees (cosine > 0.985) [20]. Thus, because of
present regulatory mechanisms, e.g. in subjects with intact
autoregulation, CBF correlates poorly with CBF-V [21, 22].
Merely the percent changes in CBF-V and CBF correlate
during specific hypercapnic challenge tests in healthy
volunteers [23]. Data on a strong correlation of TCD with
absolute values of CBF are available for blood pressure
levels below autoregulation [22]. It can be assumed that
because of exhausted vasomotor motility, such as ischemic
vasoparalysis, TCD should reflect CBF [24]. This concept
may equally be applied to vasoparalysis following cerebral
ischemia, such as in transient ischemic attacks, carotid
endarterectomy or after resection of arteriovenous
malformations (AVM). However, robust evidence with the
necessary simultaneous assessment of CBF and TCD [25]
remains elusive [26]. Moreover, vessel diameter must be
known to calculate absolute CBF, which still represents a
technical difficulty. Color-coded duplex TCD may routinely
provide the possibility to measure vessel diameter of the
insonated artery. For further reading, the software
“Transcranial Doppler” by Rune Aaslid contains helpful
illustrations, equations and explanations concerning CBF
assessment by TCD [27].
TCD Indices
In addition to absolute values of systolic, diastolic and
mean CBF-V, the TCD waveform contains additional
information about vessel condition. Many variables and
measures have been developed for TCD, but their value is
often limited to a special application. The following
summary presents a few of these basic indices often
discussed in TCD studies.
Today’s TCD devices generate Gosling’s pulsatility
index (PI) automatically from the equation:
PI
Vsystolic V diastolic
Vmean
=
−()( )
()
, where V = CBF-V as obtained by
TCD
[28]. In the cerebral vasculature, PI can indicate higher
peripheral vessel resistance concomitant with increased
intracranial pressure (ICP). A rise in ICP affects the TCD
waveform, indicated by a rise in PI and later on, as ICP
continues to suppress perfusion, a subsequent decrease in
CBF-V. In a pooled neuro-intensive care unit (ICU) study
population, there was a strong correlation of PI and ICP
independent of cerebral pathology (r>0.9, p<0.0001) [29],
but sensitivity and specificity remain to be determined. PI is
further influenced by respiration, hemorheology and vessel
properties, and can also be increased in ketoacidotic
vasoparalysis [30] or angiopathy as in diabetes [31].
The simplest way to assess vasomotor reactivity (VMR)
of the cerebral vasculature is TCD recording during
breathholding for a few seconds. The duration of
breathholding (t) as well as the V
MCA
at the end of the
maneuver are recorded. A breath holding index (BHI) can be
calculated as
BHI
t
Vbreathholding V baseline
V base
=⋅
−100 ( ) ( )
( lline)
[32]. BHI
was found to correlate with standard CO
2
challenge
maneuvers and can be recommended to quickly obtain
information on VMR [33]. A plethora of other indices have
been developed to characterize VMR depending on
autoregulation [34], coherence of CBF-V changes [35] as
well as normalized VMR [36]. Rune Aaslid recently
dedicated an extensive review to the topic of VMR indices
[37].
The spectral waveform contains not only data about the
frequency of the reflected beam and thus the velocity of the
erythrocytes to or from the probe, but also with what
intensity a certain frequency is returned. This prompted the
establishment of a flow index (FI) as the product of the
returned Doppler frequencies and their respective signal
intensity. FI should tentatively correlate with the blood flow
passing through the insonated vessel. Analogous to the basic
relationship between flow (Q), velocity (V) and cross-
sectional vessel area (A) with Q = V · A ↔ A = Q / V, the
area index (AI) was defined as AI = FI / V
mean
. Changes in
this area index were indeed found to indicate vessel diameter
changes [38].
Cerebral circulation time is defined as the time that a
bolus of echo-contrast agent requires for one pass through
the cerebral circulation. It is measured as the time difference
of TCD registration between ICA and the jugular vein after
injection of a contrast bolus [39, 40]. Recent studies suggest
that in patients with intracranial AVMs, circulation time is
Clinical Applications of Transcranial Doppler Sonogragphy Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 51
dramatically decreased. Predictive values and thresholds are
not yet available because of the small studied populations,
but recent results with sensitivities of 1 and a specificity of
>0.9 support its potential usefulness [41]. Interestingly, in
patients with vascular dementia and Alzheimer’s disease,
cerebral circulation time as assessed by TCD is significantly
increased [42].
The spasm index (SI) was introduced by Jakobsen and
colleagues and CBF-V/CBF. SI is associated with severity of
vasospasm, clinical condition and a high arteriovenous
oxygen difference [43]. The index is used on occasion to
express the relationship of CBF-V and CBF in study
populations, but is not standard of care because of the lack of
a simple method to measure absolute CBF.
The difference between a right artery compared to the
respective left artery was expressed in the asymmetry index
as
AsymmetryIndex
V(right) V(left)
V(right)
=⋅
−
200
++V(left)
[44] and used to
characterize impairments in flow symmetry in stroke [45].
Crutchfield and coworkers have recently developed a
theoretical model for a comprehensive multifactorial
assessment of a patient’s hemodynamics using TCD [46].
After a TCD examination, this dynamic vascular analysis
(DVA) method performs an analysis of CBF-V, flow
acceleration and PI of all vessels. This should represent the
complex vascular status of a given patient and can be
compared to a large hemodynamic database. Future studies
will reveal the clinical usefulness of this interesting
approach.
Delayed Cerebral Vasospasm After SAH
Delayed cerebral vasospasm occurs mostly between days
3 and 13 after SAH and accounts for over 7% of deaths and
6% of disabilities [47]. With its delayed onset after a defined
event,
delayed vasospasm represents a potentially preventable
complication of SAH. The narrowing of the affected artery
segment is best visualized using digital subtraction
angiography [48]. On TCD, localized proximal vasospasm
leads to a focal acceleration of CBF-V [1], which
corresponded with angiographic vasospasm in most, but not
all studies [49]. For repetitive routine monitoring of SAH
patients, TCD as a non-invasive technique seems safer, but
has a lower sensitivity when a single examination is
compared to angiography [49]. Daily exams should be
performed and compared over time. A rise in CBF-V over
time is easier to appreciate and more sensitive than a single-
timepoint scan [50]. Current treatment modalities for SAH,
such as hemodilution, hypertension and hypervolemia
(triple-H therapy) may induce a rise in CBF-V, while the
occasionally routinely applied nimodipine for vasospasm
prevention induces peripheral vasodilation. These regimens
vary among centers, and recommendations and thresholds
given below are given regardless of the therapeutic
intervention.
MCA vasospasm can be diagnosed when mean
V
MCA
>200 cm/sec, while mean V
MCA
<120 cm/sec rules out
spasm [2, 48]. Additional extracranial flow velocimetry of
the ICA yields the Lindegaard-Index (V
MCA
/V
ICA
), with
values >6 suggesting severe MCA narrowing [51]. For ACA
and PCA vasospasm, no thresholds or indices have been
proven sufficient to reliably diagnose vasospasm [2, 52].
Although the Lindegaard-Index is widely used, recent
studies question its usefulness because (1) it does not
improve the predictive value of TCD for the diagnosis of
vasospasm [48] and (2) it does not aid in the prediction of
delayed neurologic deficits [53]. For the posterior window
concerning the understudied BA vasospasm after SAH, the
index V
BA
/V
extracranial VA
was established by Soustiel and
colleagues [54] and evaluated by others [55] in analogy to
the Lindegaard index. The preliminary result was promising
with good prognostic value for TCD to detect BA
vasospasm. Namely, V
BA
>85 cm/sec and a V
BA
/V
extracranial VA
ratio of >3 had a 92% sensitivity and 97% specificity to
detect a BA narrowing of >50%. A recent large prospective
large study successfully used a CBF-V threshold of 115
cm/sec to diagnose BA vasospasm which seems to be
independently associated with posterior circulation infarcts
[56].
Despite conflicting evidence on the degree of decreased
CO
2
-reactivity after SAH [57], VMR testing in patients after
SAH may contribute valuable information on vessel
condition. Frontera and colleagues recently showed that the
risk of vasospasm can be detected before its onset using
repeated CO
2
challenge at the bedside [58]. Although their
study was small (n=20) and only defined as a pilot study,
decreased CO
2
-reactivity was 100% sensitive for vasospasm
(p=0.011), with a specificity of 55%. Further prospective
studies using this diagnostic paradigm are expected.
While TCD is helpful to detect angiographic vasospasm
of the MCA, there are suggestions [59], some evidence [60]
but no coherent proof [2] confirming that detection of
vasospasm using TCD improves patient outcome. This
controversy may partly be due to the lack of available
therapy against vasospasm, but also because some delayed
neurological deficits after SAH may be evoked by other
factors than vasospasm, such as cortical spreading ischemia
[61], reperfusion injury, acute hydrocephalus or blood brain
barrier opening. In a recent retrospective analysis, cerebral
infarction was associated with clinical symptoms as well as
abnormal TCD or angiography findings. While the positive
predictive value for detection of angiographic MCA spasm
lies above 95% [49], the positive predictive value for TCD to
indicate the development of cerebral infarction was
reportedly insufficient even when combined with CT [62]. In
a prospective study by Unterberg and colleagues, the
specificity for TCD to diagnose delayed neurological deficits
was only 0.63 [63]. Moreover, a positron emission
tomography-assisted study suggested that TCD indices
obtained from patients with delayed neurological deficits do
not correlate with absolute CBF, indicating that TCD alone
cannot detect possible low-perfusion states after SAH [64].
Finally, as many as 57% of patients after SAH may have
velocities in the “indeterminate range” between 120 to 200
cm/sec, in which even angiographic vasospasm may remain
undiagnosed by TCD alone [48].
Although TCD is useful to detect proximal vasospasm of
the MCA, its use to predict clinical outcome or even prevent
infarctions in the anterior circulation remains doubtful [50].
52 Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 Schatlo and Pluta
Sickle Cell Disease
Previously, patients with homozygous sickle cell disease
had a risk of 11% to suffer an ischemic stroke before the age
of 20 years [65]. TCD monitoring of children with sickle cell
disease performed every 6-12 months reliably detects those
at risk and guides transfusion therapy [66]. On TCD
examination, children are classified regarding the averaged
maximum CBF-V values (TAMMX). TAMMX should be
measured bilaterally in the MCA, its bifurcation, ICA, ACA,
PCA and BA. If all arteries have a TAMMX of ≤ 170
cm/sec, the examination is normal, while any TAMMX ≥
200 cm/sec indicates an abnormality which should prompt
transfusion treatment [67]. After introduction of preventive
practice guidelines, admissions of young sickle cell patients
for a first stroke have declined [68].
Despite the success in children, the thresholds for TCD
monitoring of adult patients with sickle cell disease remain
inconclusive because the CBF-V is lower than in children,
but higher than in the normal population. Thus, age-adjusted
TCD evaluation may be necessary to establish future
guidelines [69].
Intracranial Artery Stenosis
Atheromas of cerebral arteries represent an important risk
factor for stroke and contribute to more than 10% of cerebral
ischemic events [70]. To date, catheter angiography, e.g.
using CT, remains the gold standard for detection of cerebral
atherosclerosis and follow-up of patients with vascular risk
factors, among which a stenosis of over 70% is the most
important [71, 72]. Stenosis can be detected through an
increase or a severe decrease in mean CBF-V in the ICA,
ACA, MCA, PCA, BA and VA. Reference TCD criteria for
stenosis of over 50% in these patients are peak velocities of
≥155 cm/sec for the ACA, ≥220 cm/sec for MCA, ≥145
cm/sec for the PCA, ≥140 cm/sec for the BA and ≥120
cm/sec for the VA [73]. Moreover, a progression of CBF-V
over time suggests a higher risk of ischemic events [74].
However, strict operating guidelines with positive and
negative predictive values are still missing [2], and a trial is
underway to develop diagnostic thresholds and therapeutic
guidelines using magnetic resonance imaging (MRI) and
TCD [75].
Acute Ischemic Stroke
Depending on the center, patients with a clinical
diagnosis of stroke obtain either a cranial computed
tomography (CT) scan or MRI to exclude hemorrhage and
assess the extent an ischemic event [76]. MRI and CT
angiography represent the gold standard to locate the
affected vascular system. TCD can detect MCA occlusions
present on angiography with a sensitivity of 85% to 96%
[44, 73, 77-79]. In the case of MCA occlusion, the ratio of
ipsi- to contralateral mean CBF-V (V
MCA, occluded side
/ V
MCA,
contralateral side
) was suggested to (1) identify MCA occlusion if
the ratio was ≥ 0.6 and (2) to have a possible predictive value
on stroke severity, but limitations like the small size of the
study limit its usefulness [80]. Furthermore, TCD detected
occlusions of the ICA siphon, the VA and BA with
sensitivities ranging above 70% [81]. Clinical outcome
seems to be predicted by the presence of a pathological
finding on TCD examination of the anterior circulation [78,
82, 83].
Compared to CT and MRI, TCD has the unique
advantage that it can be applied repeatedly and, when fixed
to a patient’s head, continuously. Akopov and Whitman
advocated a superiority of multiple TCD recordings over a
single MRI angiography to monitor stroke patients [45]. It is
possible that with repeated recordings, TCD may obtain a
cumulative higher sensitivity to detect reocclusion than MRI.
Unfortunately, the study focused on occlusions of the MCA,
which narrows the suggested use of TCD to a subset of
patients and thus will not suffice to replace angiography.
For patients receiving thrombolytic tissue-plasminogen-
activator (tPA) therapy, TCD has recently been proposed as
a most promising monitoring and therapy-enhancing
measure [84]. TCD can be used to identify the exact location
of a partial or complete vessel occlusion [81]. The criteria to
identify the lesion site are based on the characteristic
“thombolysis in brain ischemia” (TIBI) spectral pattern [85]
and signs of collateral flow [86, 87]. Other changes
suggesting focal stenosis or thrombi include altered PI and
CBF-V indicative of stenosis, and microembolic signals
occurring focally [88, 89]. With a reported accuracy greater
than 90% (again for MCA and ICA only), the Doppler probe
can be fixed in place and kept focused on the lesion. There, it
serves as a monitor of CBF-V and, interestingly, as a catalyst
for re-canalization. In the “Combined Lysis of Thrombus in
Brain ischemia using transcranial Ultrasound and Systemic
tPA” (CLOTBUST) trial, continued application of the 2
MHz TCD beam dramatically improved re-canalization but
failed to produce significantly better outcome at three
months [90, 91].
In summary, TCD is a necessary part of a stroke unit [92]
and can detect occlusions, but with a high variability among
vessel systems in patient with acute ischemic stroke. Thus,
CT and MRI remain the imaging modalities of choice for
first admission. Regular TCD follow-up examinations are
recommended, although their effect on patient outcome
remains to be determined. Finally, further long term
evaluation the promising effect of TCD on acute occlusions
is expected.
Cerebral Vein Thrombosis
Despite reports of technical feasibility and the association
of increased venous flow velocities with the clinical picture,
the findings of correct TCD-based diagnoses such as sinus
thrombosis remain incidental [93]. TCD can access and
measure flow velocities in the straight sinus and possibly
deep cerebral veins, but has no diagnostic power for cerebral
venous afflictions [94].
Head Trauma
The use of TCD helped characterize the classic sequence
of changes in cerebral perfusion after severe head injury.
Directly after injury, V
MCA
remains stable (56.7±2.9 cm/sec)
but increases gradually around days 1-3 (86±3.7 cm/sec) in
the “hyperemic phase”. V
MCA
may increase further around
days 4-15 (96.7±6.3 cm/sec) [95]. Vasospasm is most likely
to occur around day 3 after head trauma with diagnostic
criteria similar to those applied to detect vasospasm after
Clinical Applications of Transcranial Doppler Sonogragphy Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 53
SAH [96]. Moreover, the PI as an indicator for increased ICP
is useful to detect brain swelling secondary to trauma.
Following decompressive craniectomy after trauma, TCD
confirms a decrease in intracranial pressure by rising CBF-V
and decreasing PI. Although these parameters fail to
correlate with recovery 6 months after injury, the cited study
was fairly small with only 19 patients [24]. Thus, large
prospective trials have yet to provide a stable diagnostic
threshold for TCD-guided therapy and to predict longterm
outcome based on CBF-V assessement.
Brain Death
Brain death is a clinical entity and includes the definition
of deep, unresponsive coma with absence of brain stem
reflexes. In light of ethical considerations evolving around
declaration of death and organ transplantation, additional
tests are suggested to confirm the diagnosis technically [97,
98]. In a series of 40 patients, Poularas and colleagues
confirmed a 100% agreement between the previous gold
standard of cerebral arteriography with TCD in the diagnosis
of brain death [99]. The TCD criteria of brain death are thus:
(1) brief systolic forward flow or systolic spikes and
diastolic reversed flow, (2) brief systolic forward flow or
systolic spikes and no diastolic reversed flow, or (3) no flow
in a patient in which flow had been documented on a
previous examination.
Extracranial ICA Stenosis
A recent meta-analysis revealed that the degree of an
ICA stenosis is best assessed using MRI angiography [100].
However, because extracranial ICA atherosclerosis can have
an impact on CBF hemodynamics, TCD should be used to
characterize its severity. On repeated examinations, TCD has
up to 95% sensitivity and 42% specificity to detect severe
ICA stenosis [101]. A lumen decrease of >70% is associated
with (1) ophthalmic and (2) ACA flow reversal, (3) low
MCA flow acceleration and (4) low PI. One of the
repercussions of chronic ICA disease is the decreased
cerebral VMR in response to CO
2
challenge, likely due to
continuous low perfusion and distal cerebrovascular dilation.
Patients with asymptomatic ICA disease and with an
impaired VMR seem to have a higher likelihood of
developing ischemic events [102].
Surgical TCD Monitoring
Intraoperative monitoring by TCD is justified when a
surgical intervention may release microemboli or influence
cerebral perfusion [103]. Because intraoperative TCD is
practicable, and fixation of the probe to the patient’s head is
easy to achieve, its clinical usefulness has been suggested
despite lack of large-scale evidence [2].
Coronary bypass graft surgery is associated with a high
risk of cerebrovascular complications, and TCD is both an
intraoperative CBF-V monitor as well as a tool in the
development of surgical approaches to minimize embolic
events [104, 105].
Carotid endarterectomy (CEA) is associated with a 5%
overall risk of peri- and postoperative mortality and stroke
[106] and TCD aids in reducing the incidence of stroke [107-
109]. CEA-related intraoperative stroke was found to be
associated with (1) TCD-detected microemboli, (2) a ≥90%
decrease in V
MCA
at cross-clamping, and (3) a ≥100%
increase in PI at clamp release [107]. Thus, continuous TCD
assessment is useful and can prompt an immediate
therapeutic increase in blood pressure [2]. Complementary to
TCD, intraoperative electroencephalography to detect
slowing of potentials may further improve monitoring [110].
Follow-up TCD assessment is similar to the management of
patients with ICA disease described above. CEA should
result in a normalization of CBF-V in the anterior
circulation, attenuation of flow asymmetry as well as
improvement of VMR [102].
Intracranial AVMs
Intracranial AVMs are complex vascular anomalies, and
angiography is necessary for their diagnosis and anatomical
delineation. Because AVMs are devoid of the small
resistance vessels and thus cannot modulate their vascular
tone, negative VMR testing by TCD can detect vessels
supplying an AVM (“feeders”) [111, 112]. Feeders seem to
have higher flow velocity and lower PI compared to healthy
vessels, facilitating their detection [113]. However, the
ability of TCD to detect feeders in small AVMs is limited
and has reportedly been low [94]. The therapeutic approach
to AVMs is complex, and the information obtained by TCD
can be valuable for the individual patient. More data is
necessary to issue definitive recommendations, but large
studies in AVM patients will remain scarce. The use of TCD
is thus recommended in addition to angiography, mostly
because it aids classification and detects flow direction in an
AVM [114]. The recently proposed TCD-index of “cerebral
circulation time” may further improve the management of
patients with AVM in the future, but remains investigational
[39, 40].
Thus, TCD should be used where surgical therapy is
advocated. The large-scale impact of the use of TCD on
outcome is difficult to assess. Although it has been suggested
that TCD may predict the risk of hemorrhage of an AVM,
the evidence has been classified as insufficient [94].
Moreover, clinically, TCD measures of AVM feeder showed
no relationship with the risk of stroke [115].
Normalization of flow dynamics after AVM resection
should lead to a normalization of CBF-V in former feeding
arteries [116]. In rare cases, patients may develop “perfusion
pressure breakthrough” [117]. Due to a loss of
autoregulation in the brain region neighboring the AVM,
CBF becomes pressure-passive. Consequently, edema and
hemorrhage can occur. Because of this vasoparalysis, TCD
values may be in close correlation with CBF and continuous
TCD monitoring may prove useful to monitor treatment in
the future.
Cardiac Shunts
Patency of the foramen ovale (PFO) with right-to-left
shunt (RLS) can solicit a thrombembolic event originating
from the right atrium [118]. In case of a RLS, right
intravenous injection of echo contrast such as agitated saline
or preferably specific ultrasound contrast like Echovist
[119], should lead to a shunt penetration of a certain amount
of microbubbles into the systemic circulation. Visualization
of bubbles in the left heart circulation on trans-esophageal
sonography allows for the diagnosis of RLS. Repeated
54 Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 Schatlo and Pluta
injections are suggested using Valsalva maneuvers and
patient position changes to avoid false-negatives [120].
Compared to transesophageal sonography, TCD
assessment of RLS by detecting contrast in the MCA using
standardized criteria has the same sensitivity [121], but is
more convenient and safer for the patient because of its non-
invasiveness. Maximum accuracy can be obtained using 10
ml of contrast medium and performing a Valsalva maneuver
at 5 seconds after injection in supine position [122, 123].
However, transesophageal sonography additionally provides
information on a patient’s anatomy and may be preferable in
case the cardiac pathology still needs to be characterized.
The risk for a second cerebrovascular incident due to
RLS at four years is 2.3% and increases to 15.2% for
patients with PFO and an atrial septal aneurysm [118].
Because the size of a PFO was suggested to correlate with
the risk of stroke [124] TCD-based risk stratification for
patients with a first stroke due to right-left-shunt was
developed. If more than 10 microbubbles were detected
during saline-enhanced TCD testing, suggesting a large atrial
shunt, patients had a higher risk of recurrent stroke [125].
This cutoff may prove highly useful in the future, but an
impact on guiding therapeutic measures has not yet been
confirmed.
Preeclampsia
Preeclampsia is defined as a new onset of elevated blood
pressure and proteinuria after 20 weeks of gestation [126].
An increase in CBF-V, possibly due to constriction of basal
arteries [127, 128] or because of distal arteriolar vasodilation
[129] is a regular finding in these patients [130]. Initially,
autoregulation [131] and chemoregulation [129] may still be
preserved. However, with increasing systemic blood
pressure, barotrauma may damage the reactively constricted
vasculature, leading to disruption of the blood brain barrier
[132] and a picture of hypertensive encephalopathy, seizures,
cerebral hemorrhage and death.
Still speculatively, there may be hemodynamic
repercussions heralding the onset of preeclampsia, and TCD
may be useful if the risk or onset could be assessed before
clinical manifestation. In an analysis of 40 pregnancies, 20
of which were complicated by preeclampsia, TCD changes
indicated increased vessel resistance at 28 to 32 weeks of
gestation [133]. The authors reported that the “time taken to
systole parameter” was changed significantly in the
preeclampsia group, but no changes were found in CBF-V or
PI to antedate preeclampsia. In order to make any statement
on future applications for TCD, this and other possible
methods needs to be evaluated further by prospective
studies.
CONCLUSION
Developed over 20 years ago, TCD has now become part
of the standard care in neuro-ICUs. TCD is of critical value
in
managing patients with sickle cell disease, thromboembolic
occlusion of a large conductance vessel, and cerebral
vasospasm of any etiology. Also, TCD is established for the
supportive diagnosis of brain death.
Staff performing TCD measurements should be trained
thoroughly to understand its limitations. TCD examination
should be performed in all accessible systems when possible.
While pathologies concerning the MCA and distal ICA are
well characterized, the ACA and vessels in the posterior
circulation, despite fair accessibility in most of the cases,
remain understudied.
In
summary, TCD is invaluable for daily neuromonitoring
of patients at risk of cerebrovascular accidents and more
indications for its use are to be expected with the next
technical assessment report of the American Academy of
Neurology. Further development of color-coded duplex TCD
devices will additionally enhance bedside monitoring of
CBF but will require wider distribution of the equipment and
more prospective data.
REFERENCES
[1] Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial
Doppler ultrasound recording of flow velocity in basal cerebral
arteries. J Neurosurg 1982; 57: 769-74.
[2] Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment:
transcranial Doppler ultrasonography: report of the Therapeutics
and Technology Assessment Subcommittee of the American
Academy of Neurology. Neurology 2004; 62: 1468-81.
[3] Krejza J, Baumgartner RW. Clinical applications of transcranial
color-coded duplex sonography. J Neuroimaging 2004; 14: 215-25.
[4] Jahromi AS, Cina CS, Liu Y, Clase CM. Sensitivity and specificity
of color duplex ultrasound measurement in the estimation of
internal carotid artery stenosis: a systematic review and meta-
analysis. J Vasc Surg 2005; 41: 962-72.
[5] Marinoni M, Ginanneschi A, Forleo P, Amaducci L. Technical
limits in transcranial Doppler recording: inadequate acoustic
windows. Ultrasound Med Biol 1997; 23: 1275-7.
[6] Klotzsch C, Popescu O, Berlit P. A new 1-MHz probe for
transcranial Doppler sonography in patients with inadequate
temporal bone windows. Ultrasound Med Biol 1998; 24: 101-3.
[7] DeWitt LD, Wechsler LR. Transcranial Doppler. Stroke 1988; 19:
915-21.
[8] Ackerstaff RG, Keunen RW, van Pelt W, Montauban van
Swijndregt AD, Stijnen T. Influence of biological factors on
changes in mean cerebral blood flow velocity in normal ageing: a
transcranial Doppler study. Neurol Res 1990; 12: 187-91.
[9] Babikian
VL, Wechsler LR. Transcranial Doppler Ultrasonography.
2 ed. Boston, Butterworth-Heinemann. 1999.
[10] Bouma GJ, Muizelaar JP. Relationship between cardiac output and
cerebral blood flow in patients with intact and with impaired
autoregulation. J Neurosurg 1990; 73: 368-74.
[11] Giller CA. The frequency-dependent behavior of cerebral
autoregulation. Neurosurgery 1990; 27: 362-8.
[12] Krejza J, Mariak Z, Lewko J. Standardization of flow velocities
with respect to age and sex improves the accuracy of transcranial
color Doppler sonography of middle cerebral artery spasm. AJR
Am J Roentgenol 2003; 181: 245-52.
[13] Markus HS, Harrison MJ. Microembolic signal detection using
ultrasound. Stroke 1995; 26: 1517-9.
[14] Markus H, Cullinane M, Reid G. Improved automated detection of
embolic signals using a novel frequency filtering approach. Stroke
1999; 30: 1610-5.
[15] Chung E, Fan L, Degg C, Evans DH. Detection of Doppler embolic
signals: psychoacoustic considerations. Ultrasound Med Biol 2005;
31: 1177-84.
[16] Chung EM, Fan L, Naylor AR, Evans DH. Characteristics of
Doppler
embolic signals observed following carotid endarterectomy.
Ultrasound Med Biol 2006; 32: 1011-23.
[17] Neu P, Heuser I, Bajbouj M. Cerebral blood flow during vagus
nerve stimulation--a transcranial Doppler study. Neuropsycho-
biology 2005; 51: 265-8.
[18] Sorteberg W, Lindegaard KF, Rootwelt K, et al. Blood velocity and
regional blood flow in defined cerebral artery systems. Acta
Neurochir (Wien) 1989; 97: 47-52.
[19] Sorteberg W. Cerebral Artery Blood Velocity and Regional
Cerebral Clood Flow in Normal Subjects. In: Newell D, Aaslid R,
editors. Transcranial Doppler. New York, Raven Press. 1992; 57-
66.
Clinical Applications of Transcranial Doppler Sonogragphy Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 55
[20] Kirkham FJ, Padayachee TS, Parsons S, Seargeant LS, House FR,
Gosling RG. Transcranial measurement of blood velocities in the
basal cerebral arteries using pulsed Doppler ultrasound: velocity as
an index of flow. Ultrasound Med Biol 1986; 12: 15-21.
[21] Jorgensen LG. Transcranial Doppler ultrasound for cerebral
perfusion. Acta Physiol Scand Suppl 1995; 625: 1-44.
[22] Larsen FS, Olsen KS, Hansen BA, Paulson OB, Knudsen GM.
Transcranial Doppler is valid for determination of the lower limit
of cerebral blood flow autoregulation. Stroke 1994; 25: 1985-8.
[23] Schreiber SJ, Gottschalk S, Weih M, Villringer A, Valdueza JM.
Assessment of blood flow velocity and diameter of the middle
cerebral artery during the acetazolamide provocation test by use of
transcranial Doppler sonography and MR imaging. AJNR Am J
Neuroradiol 2000; 21: 1207-11.
[24] Bor-Seng-Shu E, Hirsch R, Teixeira MJ, De Andrade AF, Marino
R, Jr. Cerebral hemodynamic changes gauged by transcranial
Doppler ultrasonography in patients with posttraumatic brain
swelling treated by surgical decompression. J Neurosurg 2006;
104: 93-100.
[25] Dahl A, Russell D, Nyberg-Hansen R, Rootwelt K. A comparison
of regional cerebral blood flow and middle cerebral artery blood
flow velocities: simultaneous measurements in healthy subjects. J
Cereb Blood Flow Metab 1992; 12: 1049-54.
[26] White H, Venkatesh B. Applications of transcranial Doppler in the
ICU: a review. Intensive Care Med 2006; 32: 981-94.
[27] Aaslid R. Transcranial Doppler Software (http://www.
transcranial.com), last access: 09/20/2006.
[28] Gosling RG, King DH. Arterial assessment by Doppler-shift
ultrasound. Proc R Soc Med 1974; 67: 447-9.
[29] Bellner J, Romner B, Reinstrup P, Kristiansson KA, Ryding E,
Brandt L. Transcranial Doppler sonography pulsatility index (PI)
reflects intracranial pressure (ICP). Surg Neurol 2004; 62: 45-51
discussion 51.
[30] Hoffman WH, Pluta RM, Fisher AQ, Wagner MB, Yanovski JA.
Transcranial Doppler ultrasound assessment of intracranial
hemodynamics in children with diabetic ketoacidosis. J Clin
Ultrasound 1995; 23: 517-23.
[31] Lee KY, Sohn YH, Baik JS, Kim GW, Kim JS. Arterial pulsatility
as an index of cerebral microangiopathy in diabetes. Stroke 2000;
31: 1111-5.
[32] Markus HS, Harrison MJ. Estimation of cerebrovascular reactivity
using transcranial Doppler, including the use of breath-holding as
the vasodilatory stimulus. Stroke 1992; 23: 668-73.
[33] Muller M, Voges M, Piepgras U, Schimrigk K. Assessment of
cerebral vasomotor reactivity by transcranial Doppler ultrasound
and breath-holding. A comparison with acetazolamide as
vasodilatory stimulus. Stroke 1995; 26: 96-100.
[34] Soehle M, Czosnyka M, Pickard JD, Kirkpatrick PJ. Continuous
assessment of cerebral autoregulation in subarachnoid hemorrhage.
Anesth Analg 2004; 98: 1133-9, table of contents.
[35] Giller CA, Iacopino DG. Use of middle cerebral velocity and blood
pressure for the analysis of cerebral autoregulation at various
frequencies: the coherence index. Neurol Res 1997; 19: 634-40.
[36] Widder B, Paulat K, Hackspacher J, Mayr E. Transcranial Doppler
CO2 test for the detection of hemodynamically critical carotid
artery stenoses and occlusions. Eur Arch Psychiatry Neurol Sci
1986; 236: 162-8.
[37] Aaslid R. Cerebral Autoregulation and Vasomotor Reactivity. In:
Baumgartner RW, editor. Handbook on Neurovascular Ultrasound
Front Neurol Neurosci Basel 2006; 216-28.
[38] Giller CA, Hatab MR, Giller AM. Estimation of vessel flow and
diameter during cerebral vasospasm using transcranial Doppler
indices. Neurosurgery 1998; 42: 1076-81 discussion 81-2.
[39] Schreiber SJ, Kauert A, Doepp F, Valdueza JM. Measurement of
global cerebral circulation time using power duplex echo-contrast
bolus tracking. Cerebrovasc Dis 2003; 15: 129-32.
[40] Schreiber SJ, Franke U, Doepp F, Staccioli E, Uludag K, Valdueza
JM. Dopplersonographic measurement of global cerebral
circulation time using echo contrast-enhanced ultrasound in normal
individuals and patients with arteriovenous malformations.
Ultrasound Med Biol 2002; 28: 453-8.
[41] Schreiber SJ, Diehl RR, Weber W, et al. Doppler sonographic
evaluation of shunts in patients with dural arteriovenous fistulas.
AJNR Am J Neuroradiol 2004; 25: 775-80.
[42] Schreiber SJ, Doepp F, Spruth E, Kopp UA, Valdueza JM.
Ultrasonographic measurement of cerebral blood flow, cerebral
circulation time and cerebral blood volume in vascular and
Alzheimer's dementia. J Neurol 2005; 252: 1171-7.
[43] Jakobsen M, Enevoldsen E, Dalager T. Spasm index in
subarachnoid haemorrhage: consequences of vasospasm upon
cerebral blood flow and oxygen extraction. Acta Neurol Scand
1990; 82: 311-20.
[44] Zanette EM, Fieschi C, Bozzao L, et al. Comparison of cerebral
angiography and transcranial Doppler sonography in acute stroke.
Stroke 1989; 20: 899-903.
[45] Akopov S, Whitman GT. Hemodynamic studies in early ischemic
stroke: serial transcranial Doppler and magnetic resonance
angiography evaluation. Stroke 2002; 33: 1274-9.
[46] Crutchfield KE, Razumovsky AY, Tegeler CH, Mozayeni BR.
Differentiating vascular pathophysiological states by objective
analysis of flow dynamics. J Neuroimaging 2004; 14: 97-107.
[47] Kassell NF, Torner JC, Haley EC, Jr., Jane JA, Adams HP,
Kongable GL. The International Cooperative Study on the Timing
of Aneurysm Surgery. Part 1: Overall management results. J
Neurosurg 1990; 73: 18-36.
[48] Vora YY, Suarez-Almazor M, Steinke DE, Martin ML, Findlay
JM. Role of transcranial Doppler monitoring in the diagnosis of
cerebral vasospasm after subarachnoid hemorrhage. Neurosurgery
1999; 44: 1237-47 discussion 47-8.
[49] Lysakowski C, Walder B, Constanza MC, Tramer MR.
Transcranial Doppler Versus Angiography in Patients With
Vasospasm due to a Ruptured Cerebral Aneurysm: A Systematic
Review. Stroke 2001; 32: 2292-8.
[50] Aaslid R. Transcranial Doppler assessment of cerebral vasospasm.
Eur J Ultrasound 2002; 16: 3-10.
[51] Lindegaard KF, Nornes H, Bakke SJ, Sorteberg W, Nakstad P.
Cerebral vasospasm after subarachnoid haemorrhage investigated
by means of transcranial Doppler ultrasound. Acta Neurochir Suppl
(Wien) 1988; 42: 81-4.
[52] Wozniak MA, Sloan MA, Rothman MI, et al. Detection of
vasospasm by transcranial Doppler sonography. The challenges of
the anterior and posterior cerebral arteries. J Neuroimaging 1996;
6: 87-93.
[53] Chieregato A, Sabia G, Tanfani A, Compagnone C, Tagliaferri F,
Targa L. Xenon-CT and transcranial Doppler in poor-grade or
complicated aneurysmatic subarachnoid hemorrhage patients
undergoing aggressive management of intracranial hypertension.
Intensive Care Med 2006; 32: 1143-50.
[54] Soustiel JF, Shik V, Shreiber R, Tavor Y, Goldsher D. Basilar
vasospasm diagnosis: investigation of a modified "Lindegaard
Index" based on imaging studies and blood velocity measurements
of the basilar artery. Stroke 2002; 33: 72-7.
[55] Sviri GE, Britz GW, Douville CM, Lam A, Newell DW.
Transcranial Doppler grading criteria for basilar artery vasospasm.
9th international conference on cerebral vasospasm; 2006; Istanbul;
2006.
[56] Sviri GE, Lewis DH, Correa R, Britz GW, Douville CM, Newell
DW. Basilar artery vasospasm and delayed posterior circulation
ischemia after aneurysmal subarachnoid hemorrhage. Stroke 2004;
35: 1867-72.
[57] Voldby B, Enevoldsen EM, Jensen FT. Cerebrovascular reactivity
in patients with ruptured intracranial aneurysms. J Neurosurg 1985;
62: 59-67.
[58] Frontera JA, Rundek T, Schmidt JM, et al. Cerebrovascular
reactivity and vasospasm after subarachnoid hemorrhage: a pilot
study. Neurology 2006; 66: 727-9.
[59] Jarus-Dziedzic K, Juniewicz H, Wronski J, et al. The relation
between cerebral blood flow velocities as measured by TCD and
the incidence of delayed ischemic deficits. A prospective study
after subarachnoid hemorrhage. Neurol Res 2002; 24: 582-92.
[60] Lee JH, Martin NA, Alsina G, et al. Hemodynamically significant
cerebral vasospasm and outcome after head injury: a prospective
study. J Neurosurg 1997; 87: 221-33.
[61] Dreier JP, Sakowitz OW, Harder A, et al. Focal laminar cortical
MR signal abnormalities after subarachnoid hemorrhage. Ann
Neurol 2002; 52: 825-9.
[62] Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of
cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke
2004; 35: 1862-6.
[63] Unterberg AW, Sakowitz OW, Sarrafzadeh AS, Benndorf G,
Lanksch WR. Role of bedside microdialysis in the diagnosis of
56 Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 Schatlo and Pluta
cerebral vasospasm following aneurysmal subarachnoid
hemorrhage. J Neurosurg 2001; 94: 740-9.
[64] Minhas PS, Menon DK, Smielewski P, et al. Positron emission
tomographic cerebral perfusion disturbances and transcranial
Doppler findings among patients with neurological deterioration
after subarachnoid hemorrhage. Neurosurgery 2003; 52: 1017-22;
discussion 22-4.
[65] Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular
accidents in sickle cell disease: rates and risk factors. Blood 1998;
91: 288-94.
[66] Adams R, McKie V, Nichols F, et al. The use of transcranial
ultrasonography to predict stroke in sickle cell disease. N Engl J
Med 1992; 326: 605-10.
[67] Adams RJ. TCD in sickle cell disease: an important and useful test.
Pediatr Radiol 2005; 35: 229-34.
[68] Fullerton HJ, Adams RJ, Zhao S, Johnston SC. Declining stroke
rates in Californian children with sickle cell disease. Blood 2004;
104: 336-9.
[69] Sampaio Silva G, Vicari P, Figueiredo MS, Filho AC, Valadi N,
Massaro AR. Transcranial Doppler in adult patients with sickle cell
disease. Cerebrovasc Dis 2006; 21: 38-41.
[70] Sacco RL, Kargman DE, Zamanillo MC. Race-ethnic differences in
stroke risk factors among hospitalized patients with cerebral
infarction: the Northern Manhattan Stroke Study. Neurology 1995;
45: 659-63.
[71] Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic
stroke in the territory of a symptomatic intracranial arterial
stenosis. Circulation 2006; 113: 555-63.
[72] Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of
warfarin and aspirin for symptomatic intracranial arterial stenosis.
N Engl J Med 2005; 352: 1305-16.
[73] Baumgartner RW, Mattle HP, Schroth G. Assessment of >/=50%
and <50% intracranial stenoses by transcranial color-coded duplex
sonography. Stroke 1999; 30: 87-92.
[74] Wong KS, Li H, Lam WW, Chan YL, Kay R. Progression of
middle cerebral artery occlusive disease and its relationship with
further vascular events after stroke. Stroke 2002; 33: 532-6.
[75] Warfarin Aspirin Symptomatic Intracranial Disease Trial W. Stroke
outcome and neuroimaging of intracranial atherosclerosis
(SONIA): design of a prospective, multicenter trial of diagnostic
tests. Neuroepidemiology 2004; 23: 23-32.
[76] Kidwell CS, Chalela JA, Saver JL, et al. Comparison of MRI and
CT for detection of acute intracerebral hemorrhage. JAMA 2004;
292: 1823-30.
[77] Razumovsky AY, Gillard JH, Bryan RN, Hanley DF, Oppenheimer
SM. TCD, MRA and MRI in acute cerebral ischemia. Acta Neurol
Scand 1999; 99: 65-76.
[78] Camerlingo M, Casto L, Censori B, Servalli MC, Ferraro B,
Mamoli A. Prognostic use of ultrasonography in acute non-
hemorrhagic carotid stroke. Ital J Neurol Sci 1996; 17: 215-8.
[79] Fieschi C, Argentino C, Lenzi GL, Sacchetti ML, Toni D, Bozzao
L. Clinical and instrumental evaluation of patients with ischemic
stroke within the first six hours. J Neurol Sci 1989; 91: 311-21.
[80] Saqqur M, Shuaib A, Alexandrov AV, et al. Derivation of
transcranial Doppler criteria for rescue intra-arterial thrombolysis:
Multicenter experience from the Interventional Management of
Stroke study. Stroke 2005; 36: 865-8.
[81] Demchuk AM, Christou I, Wein TH, et al. Accuracy and criteria
for localizing arterial occlusion with transcranial Doppler. J
Neuroimaging 2000; 10: 1-12.
[82] Kushner MJ, Zanette EM, Bastianello S, et al. Transcranial
Doppler in acute hemispheric brain infarction. Neurology 1991; 41:
109-13.
[83] Baracchini C, Manara R, Ermani M, Meneghetti G. The quest for
early predictors of stroke evolution: can TCD be a guiding light?
Stroke 2000; 31: 2942-7.
[84] Alexandrov AV. Ultrasound identification and lysis of clots. Stroke
2004; 35: 2722-5.
[85] Demchuk AM, Burgin WS, Christou I, et al. Thrombolysis in brain
ischemia (TIBI) transcranial Doppler flow grades predict clinical
severity, early recovery, and mortality in patients treated with
intravenous tissue plasminogen activator. Stroke 2001; 32: 89-93.
[86] Kaps M, Damian MS, Teschendorf U, Dorndorf W. Transcranial
Doppler ultrasound findings in middle cerebral artery occlusion.
Stroke 1990; 21: 532-7.
[87] Ley-Pozo J, Ringelstein EB. Noninvasive detection of occlusive
disease of the carotid siphon and middle cerebral artery. Ann
Neurol 1990; 28: 640-7.
[88] Alexandrov AV, Demchuk AM, Felberg RA, Grotta JC, Krieger
DW. Intracranial clot dissolution is associated with embolic signals
on transcranial Doppler. J Neuroimaging 2000; 10: 27-32.
[89] Demchuk AM, Christou I, Wein TH, et al. Specific transcranial
Doppler flow findings related to the presence and site of arterial
occlusion. Stroke 2000; 31: 140-6.
[90] Alexandrov AV, Molina CA, Grotta JC, et al. Ultrasound-enhanced
systemic thrombolysis for acute ischemic stroke. N Engl J Med
2004; 351: 2170-8.
[91] Labiche LA, Al-Senani F, Wojner AW, Grotta JC, Malkoff M,
Alexandrov AV. Is the benefit of early recanalization sustained at 3
months? A prospective cohort study. Stroke 2003; 34: 695-8.
[92] Alberts MJ, Latchaw RE, Selman WR, et al. Recommendations for
comprehensive stroke centers: a consensus statement from the
Brain Attack Coalition. Stroke 2005; 36: 1597-616.
[93] Valdueza JM, Hoffmann O, Weih M, Mehraein S, Einhaupl KM.
Monitoring of venous hemodynamics in patients with cerebral
venous thrombosis by transcranial Doppler ultrasound. Arch
Neurol 1999; 56: 229-34.
[94] Babikian VL, Feldmann E, Wechsler LR, et al. Transcranial
Doppler ultrasonography: year 2000 update. J Neuroimaging 2000;
10: 101-15.
[95] Martin NA, Patwardhan RV, Alexander MJ, et al. Characterization
of cerebral hemodynamic phases following severe head trauma:
hypoperfusion, hyperemia, and vasospasm. J Neurosurg 1997; 87:
9-19.
[96] Oertel M, Boscardin WJ, Obrist WD, et al. Posttraumatic
vasospasm: the epidemiology, severity, and time course of an
underestimated phenomenon: a prospective study performed in 299
patients. J Neurosurg 2005; 103: 812-24.
[97] Shemie SD, Doig C, Dickens B, et al. Severe brain injury to
neurological determination of death: Canadian forum
recommendations. CMAJ 2006; 174: S1-13.
[98] Kerridge IH, Saul P, Lowe M, McPhee J, Williams D. Death, dying
and donation: organ transplantation and the diagnosis of death. J
Med Ethics 2002; 28: 89-94.
[99] Poularas J, Karakitsos D, Kouraklis G, et al. Comparison between
transcranial color Doppler ultrasonography and angiography in the
confirmation of brain death. Transplant Proc 2006; 38: 1213-7.
[100] Wardlaw JM, Chappell FM, Best JJ, Wartolowska K, Berry E.
Non-invasive imaging compared with intra-arterial angiography in
the diagnosis of symptomatic carotid stenosis: a meta-analysis.
Lancet 2006; 367: 1503-12.
[101] Wilterdink JL, Feldmann E, Furie KL, Bragoni M, Benavides JG.
Transcranial Doppler ultrasound battery reliably identifies severe
internal carotid artery stenosis. Stroke 1997; 28: 133-6.
[102] Russell D, Dybevold S, Kjartansson O, Nyberg-Hansen R,
Rootwelt K, Wiberg J. Cerebral vasoreactivity and blood flow
before and 3 months after carotid endarterectomy. Stroke 1990; 21:
1029-32.
[103] Doblar DD. Intraoperative transcranial ultrasonic monitoring for
cardiac and vascular surgery. Semin Cardiothorac Vasc Anesth
2004; 8: 127-45.
[104] Bowles BJ, Lee JD, Dang CR, et al. Coronary artery bypass
performed without the use of cardiopulmonary bypass is associated
with reduced cerebral microemboli and improved clinical results.
Chest 2001; 119: 25-30.
[105] Harrison MJ, Pugsley W, Newman S, et al. Detection of middle
cerebral emboli during coronary artery bypass surgery using
transcranial Doppler sonography. Stroke 1990; 21: 1512.
[106] Louridas G, Junaid A. Management of carotid artery stenosis.
Update for family physicians. Can Fam Physician 2005; 51: 984-9.
[107] Ackerstaff RG, Moons KG, van de Vlasakker CJ, et al. Association
of intraoperative transcranial doppler monitoring variables with
stroke from carotid endarterectomy. Stroke 2000; 31: 1817-23.
[108] Ackerstaff RG, Vos JA. TCD-detected cerebral embolism in
carotid endarterectomy versus angioplasty and stenting of the
carotid bifurcation. Acta Chir Belg 2004; 104: 55-9.
[109] Spencer MP. Transcranial Doppler monitoring and causes of stroke
from carotid endarterectomy. Stroke 1997; 28: 685-91.
[110] Arnold M, Sturzenegger M, Schaffler L, Seiler RW. Continuous
intraoperative monitoring of middle cerebral artery blood flow
velocities and electroencephalography during carotid
Clinical Applications of Transcranial Doppler Sonogragphy Reviews on Recent Clinical Trials, 2007, Vol. 2, No. 1 57
endarterectomy. A comparison of the two methods to detect
cerebral ischemia. Stroke 1997; 28: 13245-50.
[111] De Salles AA, Manchola I. CO
2
reactivity in arteriovenous
malformations of the brain: a transcranial Doppler ultrasound
study. J Neurosurg 1994; 80: 624-30.
[112] Lindegaard KF, Grolimund P, Aaslid R, Nornes H. Evaluation of
cerebral AVM's using transcranial Doppler ultrasound. J Neurosurg
1986; 65: 335-44.
[113] Grolimund P, Seiler RW, Aaslid R, Huber P, Zurbruegg H.
Evaluation of cerebrovascular disease by combined extracranial
and transcranial Doppler sonography. Experience in 1,039 patients.
Stroke 1987; 18: 1018-24.
[114] Massaro AR, Young WL, Kader A, et al. Characterization of
arteriovenous malformation feeding vessels by carbon dioxide
reactivity. AJNR Am J Neuroradiol 1994; 15: 55-61.
[115] Mast H, Mohr JP, Osipov A, et al. 'Steal' is an unestablished
mechanism for the clinical presentation of cerebral arteriovenous
malformations. Stroke 1995; 26: 1215-20.
[116] Tyagi SK, Mahapatra AK, Mishra NK. Transcranial Doppler
evaluation of blood flow velocity changes in basal cerebral arteries
in cerebral AVMs following embolisation and surgery. Neurol
India 2000; 48: 112-5.
[117] Spetzler RF, Wilson CB, Weinstein P, Mehdorn M, Townsend J,
Telles D. Normal perfusion pressure breakthrough theory. Clin
Neurosurg 1978; 25: 651-72.
[118] Mas JL, Arquizan C, Lamy C, et al. Recurrent cerebrovascular
events associated with patent foramen ovale, atrial septal aneurysm,
or both. N Engl J Med 2001; 345: 1740-6.
[119] Droste DW, Lakemeier S, Wichter T, et al. Optimizing the
technique of contrast transcranial Doppler ultrasound in the
detection of right-to-left shunts. Stroke 2002; 33: 2211-6.
[120] Telman G, Kouperberg E, Sprecher E, Yarnitsky D. The positions
of the patients in the diagnosis of patent foramen ovale by
transcranial Doppler. J Neuroimaging 2003; 13: 356-8.
[121] Droste DW, Lakemeier H, Ritter M, et al. The identification of
right-to-left shunts using contrast transcranial Doppler ultrasound:
Performance and interpretation modalities, and absence of a
significant side difference of cardiac micro-emboli. Neurol Res
2004; 26: 325-30.
[122] Albert A, Muller HR, Hetzel A. Optimized transcranial Doppler
technique for the diagnosis of cardiac right-to-left shunts. J
Neuroimaging 1997; 7: 159-63.
[123] Schwarze JJ, Sander D, Kukla C, Wittich I, Babikian VL,
Klingelhofer J. Methodological parameters influence the detection
of right-to-left shunts by contrast transcranial Doppler
ultrasonography. Stroke 1999; 30: 1234-9.
[124] Steiner MM, Di Tullio MR, Rundek T, et al. Patent foramen ovale
size and embolic brain imaging findings among patients with
ischemic stroke. Stroke 1998; 29: 944-8.
[125] Anzola GP, Zavarize P, Morandi E, Rozzini L, Parrinello G.
Transcranial Doppler and risk of recurrence in patients with stroke
and patent foramen ovale. Eur J Neurol 2003; 10: 129-35.
[126] Wagner LK. Diagnosis and management of preeclampsia. Am Fam
Physician 2004; 70: 2317-24.
[127] Will AD, Lewis KL, Hinshaw DB, Jr., et al. Cerebral
vasoconstriction in toxemia. Neurology 1987; 37: 1555-7.
[128] Lewis LK, Hinshaw DB, Jr., Will AD, Hasso AN, Thompson JR.
CT and angiographic correlation of severe neurological disease in
toxemia of pregnancy. Neuroradiology 1988; 30: 59-64.
[129] Zatik J, Aranyosi J, Settakis G, et al. Breath holding test in
preeclampsia: Lack of evidence for altered cerebral vascular
reactivity. Int J Obstet Anesth 2002; 11: 160-3.
[130] Franco-Macias E, Quesada CM, Cayuela-Dominguez A, Miranda-
Guisado ML, Stieffel Garcia-Junco P, Gil-Peralta A. Anomalies in
brain haemodynamics in pre-eclamptic expectant mothers. Rev
Neurol 2003; 37: 615-8.
[131] Belfort MA, Varner MW, Dizon-Townson DS, Grunewald C,
Nisell H. Cerebral perfusion pressure, and not cerebral blood flow,
may be the critical determinant of intracranial injury in
preeclampsia: A new hypothesis. Am J Obstet Gynecol 2002; 187:
626-34.
[132] Zunker P, Happe S, Georgiadis AL, et al. Maternal cerebral
hemodynamics in pregnancy-related hypertension. A prospective
transcranial Doppler study. Ultrasound Obstet Gynecol 2000; 16:
179-87.
[133] Williams KP, Moutquin JM. Do maternal cerebral vascular changes
assessed by transcranial Doppler antedate pre-eclampsia?
Ultrasound Obstet Gynecol 2004; 23: 254-6.
Received: August 14, 2006 Revised: September 15, 2006 Accepted: September 27, 2006
