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Lower limb contrast venography: A modified technique for use in

thromboprophylaxis clinical trials for the accurate evaluation of deep vein
thrombosis

Article  in  The British journal of radiology · December 2007

DOI: 10.1259/bjr/15041517 · Source: PubMed

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The British Journal of Radiology, 80 (2007), 859–865

REVIEW ARTICLE

Lower limb contrast venography: a modified technique for use in

thromboprophylaxis clinical trials for the accurate evaluation of
deep vein thrombosis
1 2 1
P S SIDHU, BSc, MRCP, FRCR, R ALIKHAN, MD, MRCP, T AMMAR, MBBS, MRCP and 1D J QUINLAN, MBBS

1
Department of Radiology, King’s College Hospital and 2Department of Haematology, John Radcliffe Hospital, Oxford,
UK

ABSTRACT. Lower limb venography remains the imaging modality of choice for
detection of asymptomatic deep vein thrombosis (DVT) in clinical trials of anticoagulant
agents. A variety of techniques of venography have been described. Here, we describe
a modified technique (the ‘‘King’s’’ technique) developed to increase the overall
adequacy of identification of lower limb veins and detection of small asymptomatic Received 2 May 2006
DVT. Essential elements include proper preparation of patients prior to their arrival in Revised 3 December 2006
the radiology department, intermittent use of tourniquets to ensure complete and Accepted 7 January 2007
adequate deep vein filling, use of a consistent image acquisition sequence and
DOI: 10.1259/bjr/15041517
visualization of all veins in at least two different planes. Use of this technique
minimizes technical difficulties, provides improved patient through-put in ‘‘busy’’ ’ 2007 The British Institute of
fluoroscopy units and, ultimately, improves ‘‘off-site’’ levels of adjudication. Radiology

Contrast venography has traditionally been the
accepted reference imaging examination for the diag-
nosis of deep vein thrombosis (DVT) [1, 2]. Although
now commonly replaced by ultrasound for the initial
diagnosis of symptomatic DVT, venography remains
widely used in clinical trials investigating anticoagulant
therapies [3]. Owing to its high sensitivity for the
detection of small asymptomatic lower limb DVT,
venography enables clinical trials to be conducted with
smaller sample sizes than those evaluating clinical
outcomes [3–7].
With the development of B-mode and colour Doppler
compression ultrasound as a non-invasive imaging
modality for symptomatic DVT, the technique of
venography is now practised less often and, more
importantly, taught to fewer radiology trainees [2].
Doppler ultrasound has limitations for the detection of
asymptomatic DVT, particularly calf vein thrombi [8, 9].
These asymptomatic (silent) DVTs are often non-occlu-
sive, small (1–2 cm) and are usually not associated with
venous distension or impaired blood flow, factors
important for the ultrasonographic diagnosis of sympto-
matic DVT [10, 11]. Anatomical variations in venous
anatomy are well documented and are often not
apparent on an ultrasound examination [12]. In addition,
Doppler ultrasound is heavily examiner dependent, and
does not lend itself to ‘‘off-site’’ blinded adjudication of
thrombotic events. Although ultrasound has both a
sensitivity and specificity approaching 95% for the
detection of symptomatic proximal DVT, this sensitivity
Address correspondence to: P S Sidhu, Department of Radiology,
King’s College Hospital, London, UK. E-mail: paul.sidhu@kingsch.
nhs.uk
falls to 26–40% for asymptomatic DVT [6, 9, 13–15].
Conversely, contrast venography maps out and records
venous anatomy in a form readily interpretable off-site
and has a far higher rate of detection of asymptomatic
distal DVT.
Although various techniques of venography have been
described, the most widely used remains the technique
described by Rabinov and Paulin over 30 years ago [16],
representing a modification of the technique described
by Greitz in 1954 [17]. A further technique described by
Thomas differs in its use of tourniquets, smaller contrast
volumes and the degree of semi-upright tilt on the
fluoroscopy table [18, 19].
Having participated in a large number of clinical trials
involving the use of venography for detection of
asymptomatic DVT, we developed a modified technique
in an attempt to improve overall standards, minimize
technical difficulties, improve patient through-put in
‘‘busy’’ fluoroscopy units and, ultimately, improve ‘‘off-
site’’ levels of adjudication.
The ‘‘King’s’’ technique
Using electronic databases (MEDLINE and EMBASE,
1980–1996) and clinical trial venography protocols, a
review of various venography techniques was under-
taken. A protocol for a modified venography technique,
described here as the ‘‘King’s’’ technique, was developed
and then implemented (from 1997 onwards) in our
department. Since then, the technique has been used in
clinical trials involving patients undergoing joint replace-
ment (hip/knee) [20–23], surgery for hip fracture [24, 25],
surgery for cancer [26], abdominal surgery [27] and

The British Journal of Radiology, November 2007 859


non-surgical patients who were acutely immobilized
[28, 29]. All trials had received ethics committee
approval for bilateral venography and patients gave
written informed consent for the procedure. The mod-
ified technique is described below.
Preparation of the patient
Prior to venography, patients are reviewed either on the
ward or in the out-patient department. Adequate prepara-
tion of patients prior to arrival in the radiology department
allows greater time for the identification of suitable venous
access in an environment that is more comfortable for the
patient. Swollen oedematous feet are wrapped in firm
compression bandages and then elevated for at least one
hour before venous cannulation is attempted prior to
arrival in the fluoroscopy unit. This assists in identification
of large easily accessible veins, thereby reducing the
possibility of failed venous access. The majority of patients
undergoing venography are elderly with thin skin, but in
those with thicker skin the use of EmlaH cream
(AstraZeneca, Luton, UK) may be beneficial to reduce
patient discomfort upon venous cannulation. Before
cannulation, the feet are bathed in warm water for
5 min, allowing the veins to become dilated and more
prominent. The warm water has the additional effect of
softening the skin and may also provide a mild analgesic
effect. For venous cannulation, the patient then sits on the
edge of the bed or chair with the legs dependent.
Venepuncture is performed via the dorsal vein of the
great toe using a size 22-gauge cannula (VenflonH;
Ohmeda, Helsingborg, Sweden). The cannula is secured
with adhesive tape. If a patient has undergone an
orthopaedic procedure, then cannulation of the operated
leg is attempted first, as 80% of thrombi usually occur in
this limb [30]. The dorsal vein of the great toe has the
advantage of being easily located, even in an oedematous
foot, by gently squeezing the dorsum of the toe with both
thumbs. Compared with a ‘‘butterfly needle’’, the
advantage of using a cannula is that extravasation of
contrast into the subcutaneous tissues is rare and can be
detected promptly because of the thin layer of skin and
adipose tissue in the area of cannulation.
If it is not possible to cannulate the dorsal vein, then an
attempt at cannulation is made at the most distal and
medial vein on the dorsum of the foot. Personal
experience has shown that a more proximally and
laterally located venous cannulation results in inade-
quate filling and opacification of the deep venous
system; with contrast more likely to pass into the dorsal
venous arch, which then drains into the long and short
saphenous veins. If distal veins are not available for
cannulation, more proximally located veins may be
utilized, although the venous cannula is now sited in
an antegrade direction, i.e. pointing towards the toes
(Figure 1). Contrast medium is then injected in a down-
stream direction, where it communicates with the deep
plantar arch of the foot before flowing in a retrograde
direction into the posterior tibial veins [18, 31]. In
patients with very small foot veins, a 23-gauge ‘‘butterfly
needle’’ or a 25-gauge cannula may need to be used;
however, warm contrast is required for prompt and
adequate injection volumes.
860
P S Sidhu, R Alikhan, T Ammar and D J Quinlan
Figure 1. Antegrade cannulation in the dorsum of the left
foot and dorsum of the right great toe. A Foley catheter is
shown in situ above the left malleolus with a tourniquet
above the left knee.
Contrast medium
A non-ionic iodinated contrast medium is routinely
used in venography. Our practice is to use OmnipaqueH
(Iohexol; Nycomed Amersham Imaging AS, Norway)
with an iodine content of 350 mg ml21. Two 50 ml
syringes containing 35 ml of OmnipaqueH diluted with
15 ml of 0.9% saline, for each limb under investigation,
are prepared. A large volume (100 ml) of dilute contrast
results in better deep venous filling and improved image
quality [16, 18, 31].
Radiographic equipment
A fluoroscopy unit with a real-time television monitor
and tilting table is required for adequate lower limb
venography. Although other venography techniques
without fluoroscopy, e.g. the long leg technique, have
been described [8, 32, 33], visualization of specific veins
is not guaranteed, as it is not possible to accurately
predict contrast flow along the deep veins in order to
calculate image acquisition. Furthermore, it is often
impossible to distinguish between artefacts resulting
from flow or underfilling, which may be confused with
thrombosis or post-thrombotic syndrome [19]. Our
venography studies are performed on a digital fluoro-
scopic imaging system (Siemens Medical Engineering,
Erlangen, Germany). Tube voltages of 65–70 kV are used
for the lower leg, 80–90 kV for the thigh, and 100 kV for
the pelvic region. At the end of the procedure, all images
are displayed on a monitor, which allows for immediate
assessment of venography quality and diagnosis of
venous thrombus. Digital imaging has the advantage of
post-procedure manipulation, such as windowing, edge
enhancement and correction using the video-enhancer
[34].
Positioning of patient
Ideally, the procedure should be carried out with the
patient in the erect position to allow maximum mixing of
contrast and blood, with subsequent filling of the deep
The British Journal of Radiology, November 2007
Review article: Lower limb contrast venography
venous system. To attain the fully erect position,
specialized equipment is required and many patients,
especially the elderly and those who have had recent
surgery, are unable to tolerate or sustain this position for
any length of time. A compromise is to allow a 30–40 ˚ tilt
on the fluoroscopy table. The patient’s head and body
are kept flat against the table in order to prevent a
hypotensive or vasovagal circulatory reaction. Support is
provided by handgrips on both sides. The limb not being
examined is allowed to weight bear on a specially
constructed box (measuring 20610610 cm), allowing
for free movement and rotation of the contralateral limb
under investigation (Figure 2). It is important that the
limb under investigation is kept relaxed without exces-
sive strain or calf muscle contraction during the
procedure, which might result in contrast being expelled
from the region of interest.
To prevent superficial vein filling and to aid deep vein
filling, two tourniquets are used. The first tourniquet is
placed tightly above the ankle malleoli, whereas the
second is placed 5–10 cm above the patella, where it is
useful in delaying the emptying of contrast from the calf
veins, thereby allowing improved deep venous filling.
The best tourniquet for this purpose is a rubber tube,
such as a size 16 Foley catheter (Bard Limited, Crawley,
UK), which allows a greater degree of force per unit area;
this is held in place with a pair of artery forceps.
Sequence of image acquisition
The examination is most efficient when performed by
a radiologist and an assistant; the assistant injects the
contrast and rotates the limb, leaving the radiologist free
to check the position of the limb and obtain the relevant
images at the optimum time.
The first syringe containing contrast is connected to
the cannula via a 50 cm infusion line (Connecta Plus 3;
Becton Dickinson Infusion Therapy AB, Sweden) and is
injected by hand as rapidly as possible (approximately
50 ml at 2 ml s21) to produce a dense bolus. During
injection, the left hand of the assistant is placed over the
injected vein to reduce mechanical over-distension and
also to palpate for contrast extravasation.
Figure 2. Fluoroscopy table tilted to 30 ˚ with contrast
injected by the assistant who also compresses the calf prior
to the tilting the table into the horizontal position.
The British Journal of Radiology, November 2007
The radiologist obtains a screening image at the level
of the knee joint and allows time for the distal deep calf
veins to fill. The posterior tibial veins, which arise from
the deep plantar foot vein, are usually the first to fill,
followed by the peroneal veins arising from the lateral
region of the foot. The anterior tibial veins originating
from the dorsal vein of the foot are commonly the last
and most difficult veins to fill. If the anterior tibial vein
does not fill with contrast following administration of the
first 50 ml syringe, the table is then tilted to 50–60 ˚, the
ankle tourniquet is removed and sufficient time allowed
for these veins to fill. If filling still does not occur, a
further 25 ml of contrast is administered, with additional
time allowed for filling.
12 images are routinely obtained. When the three pairs
of calf veins have filled, and with the leg in the neutral
position, the first image obtained is of the upper calf,
including the knee joint (Figure 3a). The assistant then
rotates the leg, and images are obtained with the leg in
internal (Figure 3b) and then external rotation
(Figure 3c). It is important to take these three images,
as the deep veins often overlie one another and can make
separation and interpretation difficult. A screening
image is then obtained above the ankle, making sure
that there is overlap with the previous images. Similar to
the procedure above, three images are obtained: in
neutral, internal rotation and external rotation. Removal
of the ankle tourniquet at this stage allows further filling
of the more distal veins without vein compression
caused by the tourniquet.
The radiologist obtains two images at the level of the
popliteal fossa, where the junction of the anterior and
posterior tibial veins forms the popliteal vein. The first
image is taken in the neutral position (Figure 4a) and the
second in external rotation. In those patients with knee
prostheses, it may be necessary to take a third image
with the patient rolled onto his or her side to fully
visualize the popliteal vein (Figure 4b). If the image
intensifier has a rotating C-arm, this can be used to
achieve proper visualization of the popliteal vein.
The leg is then kept in external rotation and the above-
knee tourniquet is removed as the second syringe of
(a) (b) (c)
Figure 3. Venography images of the upper calf in three
separate views: (a) neutral position; (b) internal rotation; and
(c) external rotation.
861

(a) (b)
Figure 4. Venography images of the popliteal fossa of a
patient with a total knee replacement: (a) neutral position;
and (b) external rotation.
contrast is slowly administered (approximately 35 ml at
1 ml s21). The superficial femoral vein is the direct
continuation of the popliteal vein and passes upwards
and medially across the lower third of the femur through
the adductor canal towards the groin. Below the inguinal
ligament, it receives the profunda femoris (deep femoral)
vein, which is often visualized in its proximal segment
only when there is retrograde contrast flow. The
common femoral vein is formed by the confluence of
the superficial femoral and profunda femoris veins and
continues above the inguinal ligament as the external
iliac vein. As with the knee, a hip prosthesis (especially
when surgical cement is used) may obscure a full view of
the vein, and therefore an image of the common femoral
vein is obtained by either rolling the patient onto his or
her side or by the use of a rotating C-arm. Tilting the
table towards the horizontal position at this stage enables
a good bolus of contrast to pass through the common
femoral vein.
For the final image, the image intensifier is placed over
the abdomen. A fast bolus of the remaining contrast is
injected (approximately 15 ml at 3 ml s21). As the table
is lowered back to the horizontal position, the assistant
gently squeezes the calf with the palms of both hands,
enhancing the filling of the external iliac vein, common
iliac vein and inferior vena cava. This can be followed by
passive elevation of the legs, which assists in visualiza-
tion of the iliac veins and inferior vena cava (Figure 5).
Sufficient attention to detail is required in visualization
of the common femoral and iliac veins, as both are
subject to flow defects that produce false visualization of
a thrombus.
If poor deep venous filling occurs in the proximal
veins, the valsalva manoeuvre may be attempted by
asking the patient to take a deep breath in and to blow
862
P S Sidhu, R Alikhan, T Ammar and D J Quinlan
Figure 5. Venography images of the common iliac vein and
inferior vena cava. The image intensifier is placed over the
abdomen and the remaining 15 ml of contrast injected as a
fast bolus, while the calf is gently squeezed and the lower
leg elevated.
out with the mouth closed and nose pinched. The effect
of blowing out against a closed glottis causes a rise in
intra-thoracic pressure that is transmitted to the inferior
vena cava, producing a reflux of blood down towards the
limb veins and an increase in opacification with contrast.
If this proves to be difficult, a similar effect can be
obtained if the patient forcefully coughs.
To decrease any potential for post-venography throm-
bosis, the venography study is performed in a swift
manner in order to decrease the amount of time contrast
remains in contact with the vein wall. Once all of the
images have been obtained, the infusion line is flushed
with 25 ml of 0.9% saline and the limb is elevated to help
clear the veins of contrast material. A screening image of
each limb is obtained at the end of the examination to
ensure dispersal of contrast from the deep veins.
In the clinical diagnosis of deep vein thrombosis, it
may be possible to exclude some of the images to
produce a diagnostic venography study of the lower
limb. In order to confirm the presence of a thrombus, an
intra-luminal filling defect or vein occlusion must be
visible in at least two images obtained in different
planes. Therefore, in the context of a clinical trial, at least
12 images are taken to be confident of providing a
complete examination suitable for evaluation by an
independent ‘‘off-site’’ adjudication committee.
Discussion
Here, we describe a modified venography technique
that may potentially improve the adequacy of visualizing
veins within the deep venous system of the lower limbs.
Although this technique is most suited to use in clinical
trials where bilateral venography is performed to detect
The British Journal of Radiology, November 2007
Review article: Lower limb contrast venography
asymptomatic DVT, adoption of the technique can have
advantages whenever venography must be performed,
especially in difficult patients in whom ultrasound
provides an inconclusive result.
In clinical trials of anticoagulant agents, the overall
adequacy of venography is reported to range between
70% and 90% [4, 5, 35, 36], despite apparent strict
adherence to established venography protocols. In order
to assess the efficacy of an anticoagulant, it is of
paramount importance to visualize the entire deep
venous system so that it is possible to identify or exclude
the presence of thrombus. An inadequate venography
examination invalidates the data for that individual
patient and, by implication, has subjected the individual
patient to unnecessary investigation and treatment.
Furthermore, as venography is included in the primary
efficacy outcome of many clinical trials, this results in up
to 30% of patients being non-evaluable for the primary
efficacy outcome [36]. Indeed, clinical trial protocols
incorporate this venogram failure rate in their sample
size calculations. These issues led to our development of
a modified technique to improve venography examina-
tion adequacy rates.
Kälebo et al [35] highlighted the two most common
reasons for inadequate venography examinations in
multicentre clinical trials: insufficient contrast filling
(16%) and unilateral examination (4%). Other reasons
include obscuring of veins by metallic materials, a
missing part on films, poor exposure, missing films
and incomplete labelling [35]. These findings are
consistent with our experience, with the most common
reason for an inadequate venography examination being
insufficient contrast filling of veins, especially of the
anterior tibial veins. Many clinical trial venography
protocols allow for the non-visualization of the anterior
tibial vein [37–39], as isolated thrombi in this location are
thought to be extremely rare and usually occur in
combination with other calf vein thrombi [40–42]. Rose
et al [11], however, demonstrated that two out of five
asymptomatic anterior tibial vein thrombi detected by
venography were isolated to this segment.
Performing a unilateral venogram may occur as a
result of patient refusal, failure of adequate venous
cannulation, blood vessel rupture during contrast injec-
tion or movement of a butterfly needle [35]. Therefore,
proper preparation of patients before their arrival in the
radiology department remains an essential component of
a successful examination. Despite having a reputation as
a painful and difficult procedure, application of the
preparation phase we describe will ensure the procedure
can take place in a timely fashion with reduced patient
discomfort. In those patients undergoing venography
following lower-limb joint replacement, cannulation
should be first attempted on the operated limb, as the
majority of thrombi will occur ipsilateral to the surgical
site [10]. If a patient then refuses to have a cannula
placed in the other foot, at least the side most likely to be
affected by thrombus will have been assessed. In our
experience, with adequate preparation, successful can-
nulation can be achieved in 90–95% of patients. The other
advantage of preparing patients in advance is that only
patients in whom a successful procedure can be
performed are brought to the fluoroscopy unit, thereby
reducing the pressure of obtaining venous access in the
The British Journal of Radiology, November 2007
fluoroscopy unit, which should in turn allow for ease of
imaging and rapid movement of patients through the
examination without disruption to working practices of
the radiology department.
Metallic prostheses, which can obscure the opacified
vein, are another cause of inadequate venography
examinations [35]. Being alert to this problem and pre-
empting it by placing the patient onto his or her side and
taking extra images or using a rotating C-arm will avoid
this problem.
In line with other interventional procedures, non-ionic
contrast medium is used, which eliminates the majority
of complications and contraindications, including ana-
phylactic reactions and discomfort along the injection
line of the vein [43, 44]. In addition, the non-ionic
medium has less thrombogenic effect on vessel walls,
such that thrombosis related to endothelial damage is
virtually eliminated [45]. Although it is appreciated that
contrast-induced nephrotoxicity has been associated
with non-ionic contrast, especially in patients with
diabetes and pre-existing renal insufficiency, adherence
to adequate patient hydration significantly reduces any
potentially harmful effects caused by these disorders.
The use of tourniquets remains a contentious issue,
with disagreement between authors and practitioners of
venography [5, 19]. We have found tourniquets to be
useful in ensuring the initial opacification of the deep
veins without superficial vein opacification. Opacifi-
cation of superficial veins often obscures images of the
deep veins, and causes difficulties in interpretation and
assessment. However, application of an ankle tourniquet
may result in failure to opacify the anterior tibial vein [5].
A compromise would therefore be to allow images of the
deep veins of the calf to be obtained with the ankle
tourniquet in situ. If the anterior tibial veins do not fill,
the tourniquet is removed with further tilt of the
fluoroscopy table in conjunction with administration of
further contrast.
So far, this technique has been performed only by a
select group of individuals interested in obtaining good
examinations for clinical trials. More widespread evalua-
tion of the technique is required with further validation
in clinical trials. Similarly, blinded comparison of the
technique with traditional venography methods requires
further evaluation.
In summary, venography will remain the imaging
modality of choice for accurate visualization of the deep
calf veins and detection of asymptomatic DVT in clinical
trials. We describe a successful modified technique that
demonstrates a high venography adequacy rate for
visualization of the veins. In addition, this technique
allows for the rapid processing of patients with minimum
disruption to the daily routine of the fluoroscopy unit.
Acknowledgments
P Sidhu and D Quinlan developed the technique and
wrote the protocol; P Sidhu, R Alikhan and D Quinlan
refined the technique and performed the venograms;
P Sidhu and T Ammar implemented the technique
within the department; P Sidhu, T Ammar, R Alikhan
and D Quinlan contributed to the writing of the paper.
We thank all the radiographers and study coordinators
863

involved in performing this technique and caring for the
patients undergoing these procedures.
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