260 Current Neurovascular Research, 2008, 5, 260-265
1567-2026/08 $55.00+.00 ©2008 Bentham Science Publishers Ltd.
Doppler Haemodynamics of Cerebral Venous Return
Erica Menegatti and Paolo Zamboni*
Vascular Diseases Center, University of Ferrara, Italy
Abstract: Physiologic functioning of the cerebrovenous system is indispensable for maintaining normal brain function.
However, in contrast to the cerebroarterial system, the cerebral venous return is not routinely investigated. Combined
high-resolution echo-colour-Doppler (ECD) and transcranial colour coded Doppler sonography (TCCS) represents an
ideal method to investigate the haemodynamics of cerebral venous return. TCCS-ECD is noninvasive, repeatable, cost-
effective and permits to investigate the cerebral venous outflow in its dependence upon changes in posture and the
alternating pressure gradients of the thoracic pump. Several authors reported normal parameters concerning related
aspects of cerebral venous return. However, there is no ECD-TCCS standardization of what can be considered a normal
venous return. The authors have summarized the current knowledge of the Doppler haemodynamics of the cerebrovenous
system and propose a list of reproducible clinical parameters for its sonographic evaluation. In future, the development of
this diagnostic technique could be of singular interest in iron-related inflammatory and neurodegenerative disorders like
role in ensuring the correct cerebrospinal venous outflow.
At the time of expiration, intrathoracic pressure is
approximately -5 cm H2O and forced inspiration generates
even lower intrathoracic pressures of about -8 cm H2O
(Schaller, 2004; Zamboni et al., 2007). The pressure
gradients favour venous return to the right heart, which fact
can be easily assessed with high-resolution ECD and
TCCS, which thus constitute an ideal method for
investigating the haemodynamics of cerebral venous return
(Schaller, 2004; Valdueza et al., 2000; Gisolf et al., 2004;
Schreiber et al., 2003; Doepp et al., 2004).
Posture and respiratory movements play a fundamental
extracranial outflow pathways, as follows: (Valdueza et al.,
2000) the IJV is the predominant venous pathway in the
supine position, as confirmed by an increased blood flow
in that posture; redirection of venous flow to the VVs
occurs in the upright position, with concomitant reduction
of blood flow in the IJVs.
To the contrary, MR and selective injection venography
are limited to evaluating cerebral venous haemodynamics
under different postural and respiratory circumstances.
Thereby, especially the
morphological but though exclusively static findings.
Several authors reported normal parameters after
investigating different aspects of cerebral venous Doppler
haemodynamics in the last decade. However, there is no
ECD-TCCS standardisation of what can be considered a
normal venous return. The authors have summarized the
current knowledge of the Doppler haemodynamics of the
cerebrovenous system and propose a list of parameters and
In addition, ECD showed a postural control of the
latter provides excellent
*Address correspondence to this author at the University of Ferrara,
44100 Ferrara, Italy; Tel: +390532236524; Fax: +390532237443;
Received: September 19, 08, Revised: September 23, 08, Accepted: September 25, 08
a clinical methodology for reproducibly assessing them, that
allow to tell whether cerebral venous outflow runs normally,
ECD-TCCS EQUIPMENT AND PATIENT POSITION
DURING THE INVESTIGATION
haemodynamics can envisage the contemporaneous analysis of
both the intracranial and extracranial pathways, by combining
with the same ultrasound machine respectively the
examination of the DCVs and main dural sinuses, by means of
the TCCS probe (Baumgartner et al., 1997; Stoltz et al., 1999;
Zamboni et al., 2007), with that of the IJVs-VVs by means of
the ECD probe (Schaller, 2004; Valdueza et al., 2000; Gisolf
et a.l, 2004; Schreiber et al., 2003; Doepp et al., 2004). The
transducer used at the intracranial level is at low frequency,
usually 2.5 Mhz, whereas at the cervical level it is at high
frequency, 7.5-10 Mhz or more, according to the different
depth of the veins respective to the body surface where the
transducer is placed.
Nowadays the investigation of the cerebral venous
indicated above, a crucial part determining the main route of
cerebral outflow. For this reason the subject should be
investigated at least in both supine and sitting position (0°and
90°), but it has further been proposed to assess venous flow
from the brain with the body positioned at 0°, +15°, +30°,
+45°, +90° in both the IJVs and VVs. (Valdueza et al., 2000).
This objective can be realized with the subjects being
positioned on a tilt bed.
The posture of the subject under examination obtains, as
TCCS VENOUS INVESTIGATION
intracranial veins are the diameter of the third ventricle (III V),
and flow parameters which include direction, velocity and
The main parameters of the TCCS investigation of the
Doppler Haemodynamics of Cerebral Venous Current Neurovascular Research, 2008, Vol. 5, No. 4 261
Assessment of Third Ventricle Diameter
volume plus cerebro-spinal fluid (CSF), plus cerebral
blood volume (CBV) always remains constant (Schaller,
2004). Therefore, an increase in venous pressure/volume
determines a volume compensation achieved by changes in
both extra- and intracellular cerebral fluid volume
(Carmelo et al., 2002; Wey and Kontos, 1982). From this
point of view, the assessment of the diameter of the III V is
an important parameter, easy and rapid to assess by B-
mode TCCS, for its being, interestingly, related to both
CBV and CSF volume. In addition, III V measured by B-
mode TCCS closely and significantly correlates with MRI
assessment (Kallmann et al., 2004).
According to the Monro-Kellie law, the sum of brain
temporal bone window, and the depth of the insonation is
adjusted to 10 cm. At an insonation depth of about 7 cm it
is possible to consistently identify the echo-lucent III V,
limited by two echogenic bright margins, as well as the
two comma-shaped frontal horns of the lateral ventricles
(Kallmann et al., 2004; Zamboni et al., 2007). In normal
subjects III V diameter is about 4 mm in the supine
position (Kallmann et al., 2004), (Fig. 1).
The transducer is placed at the level of the trans-
wider, and an increased diameter corresponds to an
increased disability score. This finding is of course related
to the tissue loss and a compliant reduced brain volume
(Kallmann et al., 2004). However, it suggests, according to
the Monro-Kellie hypothesis, also a relationship with
modifications of CBV, which was found in multiple
sclerosis (Wuerfel et al., 2004; Rashid et al., 2004).
Interestingly in multiple sclerosis it is significantly
Intracranial Venous Flow Direction
directional, and characterized by low velocity and low
resistance index. It can be recorded again through the
trans-temporal approach, but the trans-occipital or the
trans-ophthalmic windows can be used as well
(Baumgartner et al., 1997; Stoltz et al., 1999; Zamboni et
Physiological intracranial venous flow is mono-
al., 2007; Zipper and Stoltz, 2002; Valdueza et al., 1996).
Subjects can be examined in both sitting and supine positions
and the venous flow is enhanced by inviting the subject to
breathe (Zamboni et al., 2007). Using the trans-temporal
acoustic bone window, it is highly probable to insonate at least
one of the DCVs, including basal veins of Rosenthal, great
vein of Galen, and internal cerebral veins, according to criteria
previously described (Valdueza et al., 1996; Stolz et al. 1999;
Zipper et al., 2002).
In a study, patients affected by multiple sclerosis were
examined in both sitting and supine positions, demonstrating
reflux flow. The reflux in the intracranial veins is defined as a
flow recorded in a direction opposite to the physiologic one for
a duration > 0.5 sec., a finding significantly different from the
mono-directionality registered on normal volunteers.
demonstrated pathological venous reflux within DCVs and
transverse sinuses during the activity of the thoracic pump.
Such refluxes were absent in the DCVs in healthy subjects and
while only 7% of healthy individuals exhibited venous
refluxes in the transverse sinus (Zamboni et al., 2007).
In about 50% of multiple sclerosis patients TCCS
EXTRACRANIAL DOPPLER VENOUS INVESTIGA-
as above reported. Subjects should be examined at least in
sitting and supine positions, or better on a tilting bed with the
body positioned at 0°, +15°, +30°, +45°, +90°(Valdueza et al.,
2000). Either the IJVs and the VVs can be examined by using
both the transversal and/or the longitudinal cervical access.
The operator uses minimal pressure over the skin in order to
prevent compressing the vein and thereby affecting the
measurement, as previously reported (San Millan Ruiz et al.,
2002; Valdueza et al., 2000; Gisolf et al., 2004; Schreiber et
al., 2003; Doepp et al., 2004).
Examination is performed with high frequency transducers
velocity, competence of the IJV valve, cross sectional area in
relation to change in posture, duplex derived flowmetry, and
The operator can assess the following: flow direction, flow
Fig. (1). A: TCCS through the ventricular plane of the trans-temporal window, axial section. At an insonation depth of about 7 cm the echo-
lucent third ventricle is seen (IIIV), limited by two echogenic bright margins; B: by using the zoom function is easier to measure the III V
diameter in the magnification of the image.
262 Current Neurovascular Research, 2008, Vol. 5, No. 4 Menegatti and Zamboni
Assessment of Flow Direction and Doppler Flow
be measured during inspiration and/or expiration, but it is
recommended to measure it in the respiratory pause
(Valdueza et al., 2000); flow direction can be measured
also with Valsalva for testing the competence of the
jugular valve but this will be treated separately. The
direction of flow can be analyzed either with the pulsed
wave sample placed in the vessel, at a 60° angle, or with
the Colour Coded Mode, by comparing the colour of the
flow in the IJVs/VVs with that of the satellite carotid
and/or vertebral artery, respectively (Fig. 2A,B).
According to consensus statements on peripheral vein
ECD investigations, we define as monodirectional a flow
always directed toward the heart. Flow is considered
bidirectional when, in at least one of such conditions, we
detect a flow reversal from its physiological direction for a
duration < 0.5 sec. When the phase of reverse flow is > 0.5
sec, it is defined as venous reflux (Nicolaides et al., 2000;
Coleridge-Smith et al., 2006).
The flow direction, in either the IJVs or the VVs, can
the softwares included in the package of the ultrasound
equipment, is performed at the level of the thyroid gland
for the IJVs and at the level of C5-C6 for VVs (Valdueza et
al., 2000). Therefore, it has been suggested to record flow
measurement beginning two minutes after the change in
posture and after several deep breaths in order to permit
blood redistribution in the venous system.
It is well apparent in Table 2 that predominance of the
IJV in cerebrovenous drainage is limited to the supine
position. In the erect position, the vertebral venous system
represents the major outflow pathway. Moreover, in the
Assessment of Doppler flowmetry in ml/min by using
supine position, a duplex derived-flowmetry of 700±270 ml/m
was measured in normal volunteers. This was found to change
completely, however, when the subject changed to the upright
position, as the IJV flow fell to 70±100 ml/m, whereas in the
VV it rose from 40±20 to 210±120 ml/m (Valdueza et al.,
Table 1. Duplex Derived Flowmetry and CSA Recorded in
Normal Subjects (Data Derived from (Valdueza et al.,
(mean ± SD)
700±270 40±20 106±37 10.6±2.8
(mean ± SD)
70±100 210±120 17±8 11.9±3.6
standing posture represents the gravitational effect of the
hydrostatic pressure, which causes the displacement of 70% of
the total volume of blood below the heart level (Folkow and
From this point of view, the higher hydrostatic column in
the valveless vertebral-azygos system in the erect position
favours venous drainage through this route, rather than through
The apparent unexplained rest of about 450 ml/min in the
Competence of the Jugular Valve
IJVs has been widely described by anatomists and
pathologists, they can be even absent. IJVs valves were found
in 93 % of the post-mortem studies, and in 87 % of patients by
Although the presence of valves in the distal portion of the
Fig. (2). The longitudinal cervical access in supine position (SUP), left side (L) A: red flow directed toward the brain depicts the common
carotid (CC), whereas blue colour depicts the outflow in the IJV; B: with transducer placed just above the supraclavicular fossa, through a
more posterior longitudinal access, the left IJV together with respectively the vertebral artery in red (VA) and the vertebral vein in blue (VV)
Doppler Haemodynamics of Cerebral Venous Current Neurovascular Research, 2008, Vol. 5, No. 4 263
means of high resolution B-mode ultrasounds; the majority
of unilateral valve were found on the right side (Lepori et
concerned, it is well established in Doppler haemo-
dynamics to test it by means of the Valsalva manoeuvre.
According to a recent study on reflux time cut-off values,
we can consider reflux a flow reversal from its
physiological direction for a duration > 0.88 sec across the
IJVs valve (Nedelmann et al., 2005). It has been reported
that 33% of healthy individuals showed unilateral or
bilateral IJVs valve incompetence. However, reflux
recorded in accordance to this condition of measurement is
strongly associated with transient global amnesia, in 68%
of cases, with significantly higher prevalence as compared
to controls (Sander and Sander, 2005; Schreiber et al.,
As far as the competence of the venous valve is
B-Mode Detection of Anomalous IJVs Morphology
stenosis and, in contrast, also IJVs aneurysms. An
asymmetry, defined as a cross sectional area (CSA) at least
twice that of the contralateral IJV was noted in 62.5% of
cases. In addition, stenosis of the IJVs with a CSA of 0.4
cm2 or less was measured in 23% of cases (Lichtenstein et
It has been reported that it is possible to observe IJVs
the absence of trauma, AV fistula and thoracic malformation
have been described.
The abnormal dilatation was related to a fibrotic wall with
absence or reduction of smooth muscle cells suggesting a
congenital/developmental malformation (Zamboni et al.,
To the contrary, in Sardinia frequently, IJVs aneurysms in
Flow not Doppler Detectable in the IJVs and/or VVs
Doppler detectable venous flow in the IJVs and/or VVs despite
numerous deep inspirations. In normal subjects this finding
was never observed with the head in any position but the
supine, in 6 % of cases (Doepp et al., 2004).
It has been described that there occurs the absence of a
CSA Variation According to the Predominant Pathway of
Cerebral Venous Drainage
? ? CSA in the IJVs, obtained by subtracting the CSA
measured in the supine from that in the sitting position, is a
positive value in normal subjects, as clearly shown in Table 1
(Schaller, 2004; Valdueza et al., 2000; Gisolf et al., 2004;
Schreiber et al., 2003).
In Fig. (3) the change in CSA in response to the change in
posture, and the corresponding ?CSA, are apparent: CSA is
wider in the supine position and reduced in the sitting. It can
be considered a pressure/volume relationship, in practice a
Fig. (3). The increase of CSA observed while passing from sitting to supine position in the IJV reflects the variation of blood volume; the
latter is maximum when the subject lying down and the hydrostatic pressure is around zero. In contrast, in up-right position it has been there
resulted a proportional reduction in volume with a negative hydrostatic pressure. From this point of view such a curve represents a rough
estimation of the compliance of the given jugular system, representing a pressure/volume relationship. (Data derived from a personal
observation on 60 healthy subjects).
264 Current Neurovascular Research, 2008, Vol. 5, No. 4 Menegatti and Zamboni
non-invasive compliance curve of the jugular system. In
fact, CSA variation reflects the variation of blood volume
which flows in the IJV (Table 1) in response to changes in
hydrostatic pressure determined by the different bodily
positions (Zamboni et al., 1997; Zamboni et al., 1998).
CONCLUSIONS AND PERSPECTIVES
may be one of the most important factors indispensable for
the maintenance of a normal brain function (Schaller,
2004). Still, in contrast to the cerebroarterial system, the
cerebral venous return is not routinely investigated. This
review marks the combination of ECD and TCCS as the
ideal method for tracing individual variations and
anomalies in the haemodynamics of cerebral venous return.
The adequate functioning of the cerebrovenous system
the assessment of transient global amnesia and in multiple
sclerosis, but this imaging technique might as well be used
for elucidating further clinical conditions.
As yet TCCS-ECD has only been taken advantage of in
for monitoring the progression of the disease through a
faster and cheaper assessment of the diameter of the III V
as compared to MRI. In perspective, it seems also
promising to study the topographic relationship between
the cerebral veins exhibiting reflux at TCCS together with
the location of plaques found at MRI; particularly, MR
susceptibility weighted imaging, which allows contempo-
raneous imaging of veins and plaques, offers even greater
promise (Koopmans et al., 2008). Finally, in view of the
increased iron deposits forming a constant feature of either
chronic venous disorders or multiple sclerosis (Zamboni,
2006; Zivadinov and Bakshi, 2004), it should be interesting
to measure, by means of MR susceptibility weighted
imaging (Haacke et al., 2007), the amount of iron in
plaques of multiple sclerosis, evaluating the plaques’
topographic correspondence with the refluxing cerebral
In multiple sclerosis, TCCS-ECD recommends itself
University and Scientific Research and by the Foundation
Cassa di Risparmio di Ferrara. The open access to the
article has been generously offered by the Hilarescere
Research supported by the Italian Ministry for
GLOSSARY AND ABBREVIATIONS
Transcranial color-coded Doppler
Internal Jugular Vein
Deep cerebral veins, including
internal cerebral vein, basal vein,
Cross sectional area of the IJV
Difference in CSA assessed in
supine and sitting posture in the
= To permit, by a mono-directional
flow, a drainage of a volume of
blood per unit of time adequate to a
certain territory. This assumption has
to be valid in all conditions.
Reflux = Venous
physiologic direction for a duration >
0.88 sec in the extracranial pathways,
and > 0.50 sec in the DCVs.
flow reversal to the
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