Intensive Care Med

https://doi.org/10.1007/s00134-019-05610-4

REVIEW

Brain ultrasonography: methodology,

basic and advanced principles and clinical
applications. A narrative review
Chiara Robba1*  , Alberto Goffi2  , Thomas Geeraerts3, Danilo Cardim4, Gabriele Via5, Marek Czosnyka6,
Soojin Park7, Aarti Sarwal8, Llewellyn Padayachy9, Frank Rasulo10  and Giuseppe Citerio11 

© 2019 Springer-Verlag GmbH Germany, part of Springer Nature

Abstract 
Brain ultrasonography can be used to evaluate cerebral anatomy and pathology, as well as cerebral circulation
through analysis of blood flow velocities. Transcranial colour-coded duplex sonography is a generally safe, repeatable,
non-invasive, bedside technique that has a strong potential in neurocritical care patients in many clinical scenarios,
including traumatic brain injury, aneurysmal subarachnoid haemorrhage, hydrocephalus, and the diagnosis of
cerebral circulatory arrest. Furthermore, the clinical applications of this technique may extend to different settings,
including the general intensive care unit and the emergency department. Its increasing use reflects a growing interest
in non-invasive cerebral and systemic assessment. The aim of this manuscript is to provide an overview of the basic
and advanced principles underlying brain ultrasonography, and to review the different techniques and different clini-
cal applications of this approach in the monitoring and treatment of critically ill patients.
Keywords:  Brain ultrasonography, Transcranial Doppler, Optic nerve sheath diameter, Neurosonology

Introduction It can be applied in a range of settings, including neuro-

intensive and general intensive care units, the operating
The use of ultrasound imaging in intensive care and peri- room and the emergency department. At present, how-
operative medicine has increased enormously over the ever, brain ultrasonography is not routinely performed in
past decades. Brain ultrasonography, used to assess brain critical care settings. The aim of this review is to provide
parenchyma and cerebral blood flow (CBF), is a generally a brief overview of the physical and anatomical principles
safe, non-invasive and relatively low-cost neuromoni- underlying brain ultrasonography, and of its potential
toring method that is easily applicable at the bedside. clinical applications.
Potentially, it could provide crucially important informa-
tion in the early detection and monitoring of neurologi- The techniques
cal diseases, and to allow bedside assessment of cerebral Basically, two brain ultrasound techniques are currently
haemodynamics in critically ill patients. available: B-mode transcranial colour-coded duplex
(TCCD) and transcranial Doppler (TCD) sonogra-
phy. TCD, introduced in clinical practice approximately
*Correspondence: [email protected] 40 years ago [1], identifies the cerebral arteries “blindly”,
1
Department of Anaesthesia and Intensive Care, Ospedale Policlinico on the basis of the spectral display and standard criteria
San Martino IRCCS, San Martino Policlinico Hospital, IRCCS for Oncology,
University of Genoa, Largo Rosanna Benzi, 15, 16100 Genoa, Italy
(including arterial depth, arterial blood flow direction
Full author information is available at the end of the article and waveform analysis). It allows assessment and contin-
uous monitoring of CBF velocity, and is thus an excellent
technique for use in multimodal brain monitoring and
evaluation of basic and advanced parameters. Advanced
parameters such as cerebral autoregulation, critical
closing pressure and cerebral compliance can be assessed
with TCD, and it can also be used to perform functional Take‑home message 
tests for evaluating cerebrovascular reactivity [2].
TCCD, which combines colour-coded Doppler vessel Brain ultrasonography enables assessment of the main structures of the
brain, including the parenchyma and major cerebral vessels.
representation with bi-dimensional pulsed-wave Dop-
Brain ultrasonography can be performed using commonly used ultra-
pler ultrasound imaging, has further improved the above sound systems, through four main acoustic windows (transtemporal,
technique, allowing direct visualisation and better iden- occipital, submandibular and transorbital).
tification of the cerebral arteries. TCCD is therefore a Brain ultrasonography can be used for rapid bedside assessment of
newer, more technically advanced tool, and it is useful for pathological changes in neurocritically ill patients, allowing, for exam-
ple, evaluation of intracerebral haematomas, estimation of raised intrac-
high-precision freehand real-time scanning and haemo- ranial pressure, and detection of midline shift and intracranial masses.
dynamic assessment of the brain. While it permits direct Brain ultrasonography is not used exclusively in neurocritical care;
visualisation of the brain parenchyma and vessels, it does clinical applications have been described in different settings, including
not allow prolonged continuous monitoring of CBF. general intensive care and the emergency department.
TCCD is usually performed using a 2–2.5-MHz probe
that allows visualisation of the main cerebral structures
and vessels. On duplex imaging, the midbrain can be Intracranial haematomas
identified through the transtemporal window (Fig.  1), TCCD can identify and differentiate between intracranial
and individual arteries of the circle of Willis can be then haematomas and ischaemic strokes, with haematomas
visualised. Each artery is identified by its depth and being hyperechogenic and ischaemic lesions hypoecho-
blood flow direction in relation to the probe and other genic [1, 2]. In a cohort of 151 patients hospitalised
visualised arteries. TCCD can provide basic informa- with acute neurological deficits, TCCD, in comparison
tion regarding blood flow velocity (systolic, diastolic and with CT, proved able to correctly detect the presence of
mean values) in an insonated artery, as well as the pulsa- intracranial haemorrhage or ischaemic stroke (Fig.  3)
tility index (PI). [3]. A poor acoustic window was present in 12% of the
This review focuses mainly on the expanding clini- patients (n = 18). In 126 of the remaining 133 patients,
cal applications of TCCD. The basic conditions allowing brain ultrasonography was concordant with CT findings
a complete TCCD-based brain examination (including (haemorrhagic stroke, ischaemic stroke or neither), dem-
normal anatomy and insonation windows, and normal onstrating a sensitivity of 94% and a specificity of 95%.
blood flow velocity patterns of the cerebral arteries), TCCD has also been shown to reliably estimate haema-
as well as acquisition techniques and interpretation of toma volume and expansion in patients with hyperacute
images, are described in Figs. 1 and 2 and electronic sup- intracranial haemorrhage (i.e., TCCD performed within
plementalmaterial (ESM1a–e). Basic and advanced TCD- 3 h of onset of symptoms). In a cohort of 52 patients eli-
derived parameters are described in detail in ESM2. gible for TCCD assessment, 6 had a poor transtemporal
acoustic window, and in 8, TCCD was not able to detect
Clinical applications the intracranial haemorrhage (due to its small size as
Table  1 summarises all the clinical applications of brain measured on CT or its brainstem/cerebellar location). In
ultrasonography. Below, we analyse the most common the 34 patients who underwent TCCD both within 3 h of
ones in the neurocritical care, general intensivecare unit onset and at 6  h post-admission, the technique showed
(ICU), emergency department and prehospital medicine good correlation with CT for haematoma volume quan-
settings. tification (r = 0.85; p = 0.022) and for detection of early
haematoma expansion (r = 0.78; p = 0.03) [4]. We suggest
Brain ultrasonography in neurocritical care performing daily measurement of the volume of cerebral
Brain ultrasonography can be used in a wide range of haematomas for early detection of intracranial haemor-
clinical applications in neurocritical care, and the main rhage expansion.
ones are listed below. In general, although we recom-
mend implementation of this technique in clinical prac- Hydrocephalus
tice, we also suggest that it should not replace invasive Cerebrospinal fluid (CSF) is anechoic, whereas the
neuromonitoring techniques [such as invasive intracra- ependymal cells lining the cerebral ventricles are hyper-
nial pressure (ICP) monitoring] or substitute diagnostic echogenic. The third and lateral ventricles appear as dou-
tools such as computed tomography (CT) or magnetic ble hyperechogenic lines containing the anechoic CSF. An
resonance imaging (MRI). excellent correlation has been observed between TCCD
and CT measurements of the width of the third ventricle
(r = 0.83–0.95), right (r = 0.86) and left (r = 0.92) frontal
 Fig. 1  Acoustic windows for brain insonation. The temporal window extends from the cephalad to the zygomatic arch between the tragus and
lateral wall of the orbit. This area at the “temple” can be palpated as a 3–4-cm diameter depressed area in the skull. A phased-array transducer placed
in this area allows insonation of basal structures at the base of the brain and the cerebral arteries at the level of the circle of Willis, as shown in the
figure. By convention, the index marker points anteriorly towards the eyes. In the suboccipital window, the transducer is placed between the poste-
rior margin of the foramen magnum and the spinous process of the first cervical vertebra, at the midline (or in proximity to it), with the ultrasound
beam directed towards the bridge of the nose. The index marker points at the 3 o’clock position. This approach allows visualisation of the foramen
magnum and the distal segment of the vertebral arteries (proximal insonation field) and of the basilar artery (distal insonation field). Insonation
through the closed eyelid allows visualisation of the ophthalmic artery and the carotid siphon, as well as of the optic nerve sheath. Finally, a sub-
mandibular approach can be used to insonate the extra-cranial portion of the internal carotid artery (ICA) to calculate the mean flow velocity ratio
between middle cerebral artery and the ICA (Lindegaard index)

horns, and middle part (r = 0.73) of the lateral ventricles simple sonographic method for determining the presence
[5, 6]. In patients with post-haemorrhagic hydrocepha- of MLS: it involved measuring, bilaterally, the distance
lus undergoing an external ventricular drain clamping between the skull and the third ventricle. MLS can be cal-
trial, changes greater than 5.5 mm in the size of the lat- culated as the difference between the two sides divided by
eral ventricles as assessed by TCCD were correlated with two (Fig. 3, ESM3). Ultrasound MLS correlates well with
the need to reopen the drain (sensitivity 100%, specificity findings on CT, and it is an early outcome predictor in
83%) [7]. Therefore, ventricular width monitoring with acute stroke patients [10, 11]. Good agreement between
TCCD may, in selected patients and in the hands of expe- CT and sonography for MLS assessment was recently
rienced operators, represent a valid alternative to CT confirmed in neurocritical care patients (Pearson’s cor-
scans. Finally, TCCD can also visualise the position of the relation coefficient 0.65; p < 0.001) [12]. Most study of
external ventricular drain tip, especially in patients who ultrasound assessment of MLS has been conducted in
have been submitted to decompressive craniectomy [8]. malignant stroke and supratentorial intracerebral haem-
TCCD can be useful to assess bedside the diameter of the orrhage [13]. In a mixed population with a majority of
third ventricle and the position of the external ventricular traumatic brain injury (TBI) patients, a good correlation
drain, and to detect early the development of hydroceph- was found between ultrasound-measured MLS and CT
alus and ventricular drain displacement. scan measurement at the level of the third ventricle [area
under the receiver operating curve (AUC) for 0.5-cm
Brain midline shift CT shift: 0.85, 95% confidence interval (CI): 0.73‒0.94%]
Brain midline shift (MLS) is a life-threatening condition and at the level of the septum pellucidum (AUC for 0.5-
that requires urgent diagnosis and treatment. In 1996, cm CT shift: 0.86, 95% CI: 0.74‒0.94%) [12]. Bedside
Seidel et al. [9] in ischaemic stroke patients, described a assessment of MLS can be useful to detect early cerebral
 Fig. 2  Transtemporal axial insonation planes: brain ultrasonography images at three different insonation planes (mesencephalic, diencephalic,
ventricular) in patients without and with decompressive craniectomy (DC). The mesencephalic plane is the most basal plane; the identification of
the contralateral skull (usually at 12–15 cm) confirms the presence of an adequate insonation window; the midbrain is usually easily identified at
the midline, and it resembles a butterfly with the wings directed anteriorly. Diencephalic plane—from the mesencephalic plane, an approximate
10° cranial tilting of ultrasound beam allows identification of the third ventricle, seen as two pulsating parallel lines (usually less than 10 mm apart)
positioned slightly more cranial and anterior to the midbrain. Ventricular plane—further cranial tilting of the ultrasound beam allows visualisation of
the thalami and frontal horns of the lateral ventricles

complications and the need for further imaging or neuro- dilation of the orbital perineural subarachnoid space
surgical intervention. However, these results suggest that has been confirmed by several studies using ultrasound
MLS assessed using ultrasound should not be considered [14, 15]. ICP changes, as detected by intraparenchymal
as an “absolute” number, but more as a trend. probes, are followed very rapidly (within seconds) by
changes in optic nerve sheath diameter (ONSD) [10,
Optic nerve sheath diameter 12]. According to a recent systematic review and meta-
CSF circulates in the optic nerve sheath space, from the analysis of seven studies (320 patients), performed
posterior to the anterior part. Due its particular tra- to evaluate the diagnostic accuracy of sonographic
becular architecture, the anterior (or retrobulbar) part ONSD measurements in adults [16], thresholds in the
of the optic nerve sheath is more distensible than the range of 4.80–6.30  mm were found to demonstrate
posterior part. Providing there is no CSF flow obstruc- robust prediction ability (AUC of 0.94) for the assess-
tion, a rise in CSF pressure is transmitted along the ment of intracranial hypertension (applying a threshold
optic nerve sheath. Due to this “cul-de-sac” anatomy of > 20  mmHg or > 25 ­cmH20). The pooled diagnostic
of the optic nerve sheath, in the event of an increase odds ratio, and positive and negative likelihood ratios
in ICP, CSF will accumulate in its retrobulbar part were 67.5 (95% CI: 29‒135), 5.35 (95% CI: 3.76‒7.53)
(Fig. 4, ESM5). This close relationship between ICP and and 0.088 (95% CI: 0.046‒0.152), respectively.
Table 1  Clinical applications of brain ultrasonography (morphological findings and basic/advanced TCCD-/TCD-derived
parameters)

BA basilar artery, Ca compliance of the cerebral arterial bed, CBF cerebral blood flow, Ci compliance of the intracranial space, CPP cerebral perfusion pressure, CrCP
critical closing pressure, CT computed tomography, DNC death by neurological criteria, ECMO extracorporeal membrane oxygenation, ER emergency room, FV
cerebral blood flow velocity (m mean, d diastolic, s systolic), ICA internal carotid artery, ICP intracranial pressure, MCA middle cerebral artery, MLS midline shift, ONSD
optic nerve sheath diameter, PaCO2 partial pressure of carbon dioxide, PCA posterior cerebral artery, PI pulsatility index, SAH subarachnoid haemorrhage, Tau
cerebrovascular time constant, TBI traumatic brain injury, TCD transcranial Doppler ultrasonography

Nevertheless, the possible ONSD cut-off value for the such as venous transcranial Doppler assessment of the
detection of intracranial hypertension is still under straight sinus, may provide better prognostic accuracy
debate, with most studies reporting an optimal cut-off for the detection of intracranial hypertension than ONSD
in the 5.0‒6.0-mm range [17]. measurement alone. In a study by Robba et  al. [18], the
Moreover, it has been demonstrated that combining combination of ONSD and straight sinus systolic flow
ONSD measurement with other ultrasound modalities, velocity showed a statistically significant improvement of
 Fig. 3  Clinical applications of brain ultrasonography in neurocritical care

AUC values compared with the use of ONSD alone (0.93 relationship between ICP and CBF velocity-derived indi-
and 0.91, respectively, p = 0.01). ces. Because of the physiological relationship between
Although ultrasound-based methods have several blood flow velocity and pressure in cerebral vessels with
limitations (ESM16) and should not substitute invasive compliant walls, increased ICP will affect CBF velocity
methods, they may help physicians to estimate high ICP, measured by TCD, producing changes in the flow veloc-
monitor treatment response, and manage ICP after TBI ity waveform, such as low diastolic flow velocity, peaked
[through assessment of fluid loading effect, carbon diox- waveform and a higher pulsatility index (PI) [20]. These
ide optimisation by assessing cerebral resistance and “markers” of disturbed CBF have been applied in a vari-
TCCD waveform, vasopressor dose adjustment to obtain ety of methods for describing cerebral haemodynam-
an appropriate cerebral perfusion pressure (CPP) etc.]. ics, as well as in nICP monitoring [21]. nICP estimation
methods can be divided into three categories (see ESM4
TCCD‑ and TCD‑based methods for non‑invasive
for more details):
intracranial pressure assessment
Intracranial pressure (ICP) evaluation and management I. Methods based on the TCCD-/TCD-derived PI,
is crucial in many neurological diseases. The currently defined as the difference between maximum and
available ICP monitoring methods require invasive pro- minimum blood flow velocity normalised to the
cedures, and carry inherent risks such as haemorrhage, average velocity. The usefulness of this index for pre-
haematoma and infection [19]. dicting ICP is controversial, as changes in PI are not
CBF velocity waveform analysis is a widely explored dependent solely on changes in ICP, but also on cere-
non-invasive ICP (nICP) estimation technique. TCCD-/ bral perfusion pressure (CPP), arterial blood pressure
TCD-derived nICP estimation methods are based on the and its pulsatility, and variations in partial pressure of
­CO2;
 Fig. 4  Optic nerve sheath diameter (ONSD). a Axial image of the optic nerve sheath in a patient without increased ICP. The ONSD is measured
perpendicularly to an electronic caliper positioned 3 mm behind the retina. b Axial image of the optic nerve sheath in a patient with increased ICP,
demonstrating both bulging of the optic nerve disc in the vitreal space, consistent with papilloedema and widening of the ONSD

II. Methods based on non-invasive estimation of CPP in the anterior circulation, and can also be used to assess
(nCPP) and subsequent calculation of ICP, using the cerebral autoregulation and its role as a predictor of the
formula ICP = MAP − nCPP; development of VSP and delayed cerebral ischaemia [24,
III.
Methods based on mathematical models associat- 25]. Indeed, a clear correlation has been found between
ing CBF velocity and arterial blood pressure (only for increased CBF velocity and reduced artery diameter on
TCD, see ESM2, 4). angiography [26–28]. TCCD can help to guide imag-
ing decisions, and when tested directly against TCD,
Schmidt et  al. [22], using the formula the sensitivity of TCCD CBF velocity measurement for
nCPP = MAP ∗ FVm FVd + 14 mmHg, demonstrated a good detecting VSP was found to be higher [29]. There are four
correlation between nCPP estimation and invasive CPP reasons why TCCD may be more sensitive to VSP detec-
measurement (R = 0.61; p = 0.003), with a 95% confidence tion than TCD. First, colour-coded Doppler sonography
limit range no greater than ± 12  mmHg, and with CPP allows the vessel of interest to be visualised, which can
ranging from 70 to 95 mmHg. allow the sonographer to select the site of highest veloc-
Non-invasive methods should not replace the use of ity acceleration rather than discover it by trial and error
invasive tools for invasive ICP estimation. However, as with “blind” TCD. Second, misinterpretation of the
when invasive ICP monitoring is not available or con- vessel source of the Doppler signal is a common error in
traindicated (in patients with severe coagulopathy, such conventional “blind” TCD [30]. Third, the guidance for
as hepatic encephalopathy), a reliable alternative nICP imaging decisions provided by TCCD enables a higher
estimation method may be helpful for the screening of rate of complete exams [bilateral middle cerebral artery
patients and for assessing their evolution and response to (MCA), anterior cerebral artery (ACA), posterior cer-
treatment interventions. ebral artery] [31]. Fourth, CBF velocity measurement is
dependent upon the angle between the ultrasound beam
and the direction of blood flow (Fig. 3, ESM6). The per-
Vasospasm
formance of TCD/TCCD has been tested against angio-
Although vasospasm (VSP) and delayed cerebral ischae-
graphic detection of VSP (generally defined as a > 25%
mia should not be considered synonymous [23], TCD-/
narrowing of the artery) [32]. In an updated meta-anal-
TCCD-based methods can provide an indication of vessel
ysis of high-quality TCD/TCCD studies (n = 18) [33],
narrowing (i.e., VSP) on the basis of elevated blood flow
pooled sensitivities for the MCA (66.7%, 55.9–75.9)
velocity, as first described by Aaslid, Huber and Nornes
and the basilar arteries (62.1%, 33.3–84.3) were higher suspected DNC, allowing evaluation of cerebral circula-
than for the ACA (32.7%, 10.9–65.7). The pooled spe- tory arrest patterns.
cificities were very similar for these three arteries: MCA
89.5% (80.3–94.7), basilar 84.5% (71.1–92.3), ACA 89.6%
(48.2–98.7). For each artery there was great heteroge- Stroke
neity across the studies, with wide CIs. TCCD studies The use of brain ultrasonography for the diagnosis of
showed less heterogeneity than TCD ones for the MCA, arterial stenosis is being more frequently applied during
and resulted in a better pooled estimate [sensitivity 81.5% the very early phase following stroke symptom onset.
(67.5–90.3); specificity 96.6% (93.2–98.3)], but this result In patients with acute stroke, TCCD is used mainly for
was not statistically significant. Notably, only three stud- diagnostic purposes, along with classical imaging tech-
ies using TCCD were included, and these did not include niques such as CT and MRI (see ESM8), and specifically
any head-to-head comparison [33]. TCD/TCCD is more for:
specific than sensitive for detecting VSP. There are many
possible reasons for the wide range of sensitivity, both ••  Monitoring arterial recanalization and complications
sonographer-related (wrong vessel, missing peak veloc- (mainly haemorrhagic) after thrombolytic therapy.
ity, inter-operator variability) and/or technology-related During this acute phase, ultrasound imaging would
(inability to visualise peak velocity, inability to correct be helpful for defining successful recanalization and
for angle of insonation). In patients at risk for VSP, we for evaluating complications as haemorrhagic con-
suggest performing daily TCD/TCCD for the early and version of an ischemic lesion.
bedside detection of patients at risk for neurological ••  Evaluating the evolution of brain shift in malignant
complications and requiring further imaging/treatment. MCA infarction. Brain ultrasonography can help
verify the efficacy of blood pressure augmentation
of CBF through the assessment of adequate cer-
Brain death ebral perfusion. Cerebrovascular autoregulation is
Clinical examination of the patient is the mainstay for frequently compromised in the early phase of acute
determining death by neurological criteria (DNC). How- stroke [39], and this has led to the current treatment
ever, clinical examination can be confounded by several guidelines of permissive hypertension in the hypera-
factors, including metabolic disturbances, ocular injuries cute phase [40]. However, stroke patients with com-
or pupillary paralysis, heavy sedation, and trauma to the promised cerebrovascular autoregulation are more
middle or inner ears [34]. In this context, ancillary imag- prone in developing either hypoperfusion or hyper-
ing techniques capable of demonstrating the absence of perfusion, both of which can lead to brain oedema
CBF have been proposed in order to complement the and increased ICP. Furthermore, cerebral infarcts
clinical assessment [35]. Robust techniques like angiog- may also be complicated to haemorrhagic infarc-
raphy and radionuclear studies are currently the standard tion of the ischemic area. This later may also lead to
options for diagnosing cerebral circulatory arrest and the intracranial hypertension [41–43].
state of brain death. Nevertheless, such techniques might ••  Diagnosing large vessel occlusion or stenosis and
not be the most practical options in unstable patients evaluating collateral circulation.
who cannot easily be moved outside the ICU. By con-
trast, compared with these techniques, brain ultrasonog- TCCD is complementary to CT angiography and
raphy using TCD/TCCD may constitute a simpler, faster angio-MRI and it is an exam that can be repeated at the
and more effective technique for demonstrating intracra- bedside.
nial flow patterns compatible with DNC [36, 37].
Devastating brain injuries cause a significant increase Other applications
in ICP and subsequent decrease in CPP; these intracra- Use of TCD/TCCD has been described in other condi-
nial haemodynamic changes are associated with char- tions managed in the neurointensive care unit, such as
acteristic, progressive changes in the cerebral vessel central nervous system infections [8] and cerebral sinus
waveform spectrum [38] (Fig.  3, ESM7a, b). A recent thrombosis [44].
meta-analysis exploring the accuracy of TCD for diag-
nosing DNC found pooled sensitivity and specificity Brain ultrasonography in the general ICU
estimates of 0.90 (95% CI, 0.87–0.92) and 0.98 (95% CI, Although most of the applications of brain ultrasonogra-
0.96–0.99), respectively [37]. These results suggest that phy in critically ill patients are derived from “traditional”
TCD is a highly accurate ancillary test in the context of neurocritically ill patients, other potential uses of TCCD
have been described in medical ICU patients at high risk
 Fig. 5  Clinical applications of brain ultrasonography in the general ICU and in the emergency room

of developing brain injury (e.g., those with severe respira- cerebral haemodynamic (hyperaemia and impaired
tory failure) or with secondary brain injury related to the cerebral autoregulation) and metabolic changes con-
primary insult (e.g., in patients presenting acute liver fail- tribute to the development of encephalopathy, oedema
ure or post-cardiac arrest syndrome). Literature on these and raised ICP. Hyperaemia is found in 80% of patients
applications is still limited, and the studies described in with ALF, and it seems to precede and contribute to the
this section should be seen more as hypothesis-generat- rise in ICP. Loss of cerebral autoregulation is also well-
ing literature rather than standard-of-care recommenda- known in ALF patients. Interestingly, it can be promptly
tions (Fig. 5). restored after improvement of hepatic function, whether
spontaneous or post-liver transplant [49, 50]. It has
Acute liver failure also been shown that moderate hyperventilation may
Acute liver failure (ALF), a life-threatening multisys- restore cerebral autoregulation in most patients with
tem critical illness caused by severe acute liver injury, is ALF, although concerns have been raised over the risk
associated with encephalopathy and coagulopathy [45]. of hypoperfusion of certain areas, especially in patients
Despite significant improvements in incidence rates with associated intracranial hypertension and when
and outcome, intracranial hypertension is still detected hyperventilation is performed in the absence of ade-
in approximately 50% of comatose ALF patients [2, 46, quate monitoring of cerebral metabolism [51]. The use
47] and it accounts for 20–25% of deaths in this popu- of nICP estimation in ALF is challenging due to the role
lation [48]. Due to the significant risks associated with simultaneously played in ICP by many physiological fac-
invasive ICP monitoring in the context of ALF-asso- tors of sometimes unknown magnitude [e.g., mean arte-
ciated coagulopathy [47], non-invasive techniques, rial pressure (MAP), ­CO2, vessel elasticity and volume,
including brain ultrasonography for monitoring CBF intracranial volume and temperature]. For example, the
and ICP, may constitute a useful option. In ALF, both PI [20] reflects distal vascular resistance and vessel wall
elasticity and size, and it is influenced by heart rate, sys- The study showed a linear relationship between ICP
tolic blood pressure, and ­PaO2 and ­PaCO2 levels [52–54]. and nICP both when using ONSD (r = 0.53, p < 0.0001)
This could explain why, in a retrospective cohort study and when using TCD (r = 0.30, p < 0.01). The ability of
of patients with ALF undergoing invasive ICP monitor- both ONSD and TCD to predict intracranial hyperten-
ing, PI did not adequately discriminate ICP > 20  mmHg sion (ICP ≥ 20  mm Hg) in this population was strong
(AUC 0.55; 95% CI 0.34–0.75; p = 0.70) [46]. Conversely, [AUC = 0.96 (95% CI: 0.90–1.00) and AUC = 0.91 (95%
in the same study, another commonly used TCD-derived CI: 0.83–1.00), respectively].
parameter, CPPe/ICPtcd [i.e., ICP calculated from TCD TCCD is an option in patients following cardiac arrest
flow velocities using the estimated cerebral perfusion since, by allowing bedside monitoring of cerebral haemo-
pressure (CPPe) technique] [55], demonstrated a good dynamic status, it may be used both for early identifica-
intraclass correlation coefficient for IICP and ICPtcd tion of patients at higher risk of cerebral oedema and for
(0.66; 95%CI: 0.31–0.85) and good discrimination for haemodynamic/metabolic optimisation purposes.
detection of concurrent IICP > 20 mmHg (AUC 0.90; 95% TCCD during cardiac arrest has been shown to be
CI 0.72–0.98; p < 0.00001). Importantly, the TCD CPPe feasible, especially insonation of the ICA through the
method was excellent in excluding elevated ICP (negative transorbital window [65]. However, due to challenges in
predictive value 100% for invasive ICP > 20 mmHg when image acquisition, it cannot easily be implemented dur-
ICPtcd ≤ 18.55  mmHg), and its use as a screening tool ing cardiac arrest scenarios, except in  situations (e.g.,
may be considered. Similarly, an increased ONSD in liver cardiac and aortic procedures) in which there is thought
failure patients may be associated with high mortality to be a high risk of cerebral hypoperfusion [66, 67], and
(8/10; 80%) [56]. However, the largest published (n = 23) should not be routinely used in this phase.
study correlating invasive ICP monitoring with ONSD TCCD after cardiac arrest has been used in several
measurements in ALF patients did not find the tech- studies (ESM11.Table 2b) [68–77], which have confirmed
nique to adequately discriminate ICP > 20  mmHg (AUC the presence of significant alterations of cerebral haemo-
0.59; 95% CI: 0.37–0.79; p = 0.54). Altogether, TCCD dynamics after cardiac arrest. Although TCCD does not
and ONSD can be useful tools to monitor non-invasively seem to be a tool allowing accurate neuroprognostica-
ICP in this cohort of patients where the risk for intrac- tion, it may still have a role in haemodynamic and ven-
ranial hypertension is high and invasive methods are not tilatory optimisation, i.e., ensuring adequate cerebral
indicated. perfusion and blood flow [71, 78]. TCD parameters may
also be used to assess the safety of rewarming after tar-
Post‑cardiac arrest syndrome geted temperature management by measuring ICP and
Global cerebral ischaemia–reperfusion injury caused CBF [69, 75, 79]. Finally, diffuse, severe TCCD signs of
by cardiac arrest has a complex and still only partially hypoperfusion (e.g., reversal of diastolic flow or unde-
understood pathophysiology [57, 58]. Prognostication tectable flow patterns) seem to be highly specific for
after cardiac arrest can be challenging, and no single bad neurological outcome [69], whereas regional asym-
test has been shown to have a 0% false positive rate [59]. metries may predict the occurrence of stroke after car-
The role of TCCD as part of a whole-body ultrasound diac arrest [80].
approach in cardiac arrest and post-resuscitation syn-
drome is described in detail in ESM9–10.
Four studies (185 patients) have investigated the rela- Severe respiratory failure
tionship between ONSD measured on ultrasound after Severe respiratory failure is not uncommon in patients
cardiac arrest and outcome (survival or neurological with acute brain injury [81, 82], and cognitive impair-
outcome) [60–63] (ESM11.Table  2a), and they all dem- ment is frequent in acute respiratory distress syndrome
onstrated a significantly larger ONSD in poor-outcome/ survivors, being present in 70–100% of patients at hospi-
non-surviving patients compared with good-outcome/ tal discharge and in 20% at 5 years [83]. Commonly used
surviving patients. However, optimal cut-offs spanned ventilatory (e.g., high positive end-expiratory pressure,
a wide range (5.11 to 6.7  mm), and prognostic perfor- recruitment manoeuvres, lung-protective ventilation
mances were only moderate and therefore insufficient to with permissive hypercapnia) and non-ventilatory strat-
warrant use of this parameter as an accurate prognostic egies (e.g., prone positioning, extracorporeal membrane
tool. oxygenation) may affect cerebral perfusion and cerebral
More recently, Cardim et  al. [64] measured ICP, both oxygen delivery [84–86]. Therefore, the use of ultrasound
invasively and non-invasively, using both ONSD and techniques aimed at monitoring CBF at the bedside, and
a TCD-based method in a population of patients with the response to therapeutic interventions in patients
hypoxic ischaemic brain injury after cardiac arrest. with severe respiratory failure, is appealing. A lung- and
neuroprotective ventilatory strategy may be considered scenario and the emergency department share a lack of
not only in patients with acute brain injury, but also in information on ICP. TCCD screening for signs of intracra-
those without evidence of primary brain insult. How- nial hypertension could potentially fill this gap.
ever, evidence is still lacking in this context and further In a prospective multicentre study, TCD upon emer-
research is warranted to test our hypothesis. gency department admission was able to predict neuro-
logical worsening after mild to moderate TBI with good
sensitivity and specificity [92]. Although evidence on the
Sepsis prehospital feasibility and benefits of brain ultrasonogra-
Neurological dysfunction is a frequent complication dur- phy is still lacking, its role within the multi-organ PoCUS
ing sepsis; 70% of patients with bacteraemia manifest approach to trauma, namely to determine the need for
symptoms of septic encephalopathy [87]. Its pathophysi- neurosurgical care and allow the early implementation
ology is poorly understood, with cytokine-induced dam- of neuroprotective strategies, is noteworthy. Preliminary
age of the blood–brain barrier, microvascular damage data suggest that high-quality measurements of ONSD in
and impairment of cerebral autoregulation being some of the ambulance or helicopter, conducted to estimate the
the most commonly described contributory factors [88]. risk of raised ICP in TBI, are feasible [93]. In TBI patients,
Brain ultrasonography might be helpful to optimise the TCCD-estimated MLS demonstrated a mean difference
haemodynamic management of these patients, by allow- of 0.12 ± 1.08  mm (95% CI, 0.15–0.41  mm, p = 0.36), a
ing the identification of MAP values associated with best linear correlation of 0.88 (p < 0.0001), no significant bias
cerebral autoregulation, and non-invasively providing and limits of agreement of +2.33 to −2.07  mm when
information about cerebral perfusion and cerebrovascu- compared with CT scan images [94]. TCD may also allow
lar resistance. Cerebral autoregulation is often impaired early detection of low CBF by detecting low MCA dias-
in patients with septic shock, and low CPP significantly tolic flow velocities and high PI values. In a pilot feasibil-
correlates with elevated levels of protein S-100β, a bio- ity study, Tazarourte et  al. [95] performed prehospital
marker of brain injury [89]. Furthermore, abnormal PI MCA TCD in severe TBI patients with the aim of improv-
values and the presence of cerebral oedema are associ- ing cerebral perfusion by using an early goal-directed
ated with severity of clinical symptoms and might show a approach (norepinephrine infusion if PI was > 1.4 and
correlation with the development of delirium. TCCD can MAP was  < 80  mmHg; mannitol administration if PI
be used as part of multimodal neuromonitoring to assess was > 1.4 and MAP was > 80 mmHg). Although no statisti-
cerebrovascular resistance, as well as the optimal CPP to cally significant conclusions can be drawn from this small
apply to this group of patients. prospective study (nine patients with PI > 1.4), normali-
sation of TCD flows was obtained in the majority of the
Brain ultrasonography in the emergency treated patients. Finally, a recently published multicentre
department and prehospital medicine prospective pilot study conducted in 38 ICU patients sug-
The bedside availability and dynamic nature of ultra- gested that TCD could be used as an early tool to rule out
sound techniques are two features that make them raised ICP in severe TBI. In this study, Rasulo et al. [96], by
appealing in the emergency department and/or in pre- comparing TCD-estimated ICP with invasive ICP moni-
hospital scenarios as potential sources of real-time infor- toring, showed that TCD can detect ICP > 20 mmHg with
mation on cerebral physiology. high sensitivity. According to these results, TCCD can be
useful not to assess ICP as a number, but to safely exclude
Brain ultrasonography within the whole‑body ultrasound patients with intracranial hypertension.
approach in multiple trauma In all the above-mentioned settings, standardisation of
Ever since the introduction, in the prehospital setting and clinical practice of brain ultrasonography and research is
emergency room, of the focused assessment with sonogra- warranted. Data on clinical studies regarding the ultra-
phy for trauma (FAST) protocol [90] and the further devel- sound-based management of patients are lacking, as is a
opment of its paradigm into a multi-organ approach [91, standardised training and certification process. A panel
92], point-of-care ultrasound (PoCUS) has become a widely of neurointensive care experts is currently finalising a
used and extensively taught approach for the rapid evalua- consensus aimed at providing recommendations that
tion of acute trauma patients. PoCUS involves multi-site will pave the way for standardisation of minimal require-
investigation, and includes cardio-thoracic, abdominal, vas- ments for brain ultrasonography and of the different lev-
cular and skeletal scans (Fig.  6), and it aims to detect life- els of skills required. Also, several teaching programmes
threatening lesions and provide immediate assessment of and courses are now being developed.
the pathophysiology of the haemodynamic impairment [91]. Other specific considerations, including application in
Due to obvious technical limitations, both the prehospital the paediatric setting and in pregnancy, are described in
Fig. 6  Brain ultrasonography for the assessment of multi-system trauma. Implementation of brain ultrasonography in the context of extended
focused assessment with sonography in trauma (E-FAST) in the emergency room for multi-system trauma patients, as part of both the primary
and the secondary survey. Brain ultrasonography (using optic nerve sheath diameter measurement and either TCD or TCCD) can be applied for the
non-invasive assessment of ICP and cerebral perfusion pressure, and for the assessment of flow patterns suggesting increased ICP, as well as for the
assessment of brain anatomy, including the identification of midline shift and intracranial haemorrhage
ESM12–15. Possible pitfalls and artefacts of brain ultra- Publisher’s Note
sonography, as well as its safety limitations, are described Springer Nature remains neutral with regard to jurisdictional claims in pub-
lished maps and institutional affiliations.
in ESM16.
Received: 18 January 2019 Accepted: 26 March 2019

Conclusions
Brain ultrasonography is a non-invasive, low-cost, gen-
erally safe and readily available technique, which can
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