Time Resolved Angiography in Cerebrovascular Shunts (TRACS)

The gold standard for intracranial vascular imaging has traditionally been
catheter angiography (CA), offering high
spatial and temporal resolution. In recent years, less invasive angiographic
techniques, e.g. magnetic resonance
angiography (MRA) and computed tomographic angiography (CTA), have replaced CA
for many clinical
indications. Aside from being less time consuming and less expensive, these
alternatives carry smaller procedural
risks, as they do not require arterial catheterization. In the diagnosis of
cerebral arterio-venous shunting lesions,
i.e. arterio-venous malformations (AVMs) or dural arterio-venous fistulae
(DAVFs), it is key to demonstrate the
actual shunting by showing premature filling of a vein. For this purpose, CTA
and MRA have thusfar not been able
to replace CA, as these are essentially 'vessel-cast' techniques lacking
important dynamic information.
The development of CT scanning equipment with 320 parallel detector arrays has
recently enabled non-invasive
dynamic visualization of the entire cranial circulation, maintaining spatial
resolution (4D-CTA). Our initial patient
data suggest its value in the diagnosis and classification of cerebral
arterio-venous shunting lesions. Especially in
DAVFs, lesion classification correlates to natural history (i.e. the risk of
intracranial hemorrhage) and determines,
to a large extent, which treatment strategy should be chosen.

The aim of this project is to assess whether 4D-CTA can generate 3D cranial
image data sets with sufficient spatial and temporal resolution to enable its
use as a diagnostic tool in cerebrovascular pathology and physiology such as
arteriovenous shunting lesions and hence to enable a change in routine clinical
practice, replacing CA and the risks it carries.

Hypothesis 1:
The negative predictive value of 4D-CTA for a cranial arterio-venous shunting
lesion is sufficient to rule out such a lesion with a reasonable level of
certainty.

Hypothesis 2:
When 4D-CTA detects a cranial arterio-venous shunting lesion, the detail is
sufficient for lesion classification and determination of treatment strategy.

Our study objective is to show the validity of the hypotheses, which would
indicate the value of 4D-CTA in the diagnostic work-up of patients suspected to
suffer from a cranial AV shunt.

Patients will be enrolled at the Leiden University Medical Centre (Leiden, the
Netherlands) as well as several international centers. We intend to cooperate
with at least 3 other centers to increase patient inclusion: Toronto (Canada,
co-investigator: K.G. terBrugge), Ottawa (Canada, co-investigator: M. Santos)
and Bangkok (Thailand, co-investigator: S. Pongpech). These centers are
specialized in neurovascular disorders, have the necessary equipment and
CTA-expertise and have indicated willingness to cooperate. Patients will be
recruited prior to CA imaging, either during their visit to the vascular clinic
or upon admission. After signing an informed consent, each patient will undergo
4D-CTA imaging within a week of undergoing CA imaging. To protect patient
identity, all imaging used for the purpose of this study will be stored and
presented on the basis of an assigned study ID number.

Imaging parameters will be compared in all patients undergoing both CA and
4D-CTA imaging. These parameters will include radiation burden, contrast
burden, time needed to perform the examination the necessary post-processing,
spatial resolution, temporal resolution and diagnostic value. The latter will
be assessed by having two observers score their ability to determine diagnosis,
classification, clinically relevant lesion details and proposed treatment
strategy.

Timeframe
The expected timeframe for the study is expected to be three years.
Yearly, our center typically finds 10 new DAVF patients and 15 AVM patients. To
diagnose these, we need to perform imaging in approx. 20 patients suspected of
a DAVF and 20 patients suspected of an AVM. We intend to cooperate with at
least 3 other centers to increase patient inclusion.
We expect the numbers in these centers to be either equal to ours or higher.
Thus, yearly, we expect to image a combined total of 80 patients to find 40
DAVFs and another 80 patients to find 60 AVMs. If 75% of patients comply with
our inclusion and exclusion criteria, 120 patients would be included with 75
positive findings (30 DAVFs and 45 AVMs). In two study years the total yield
would be 240 included patients with 150 positive findings. We believe this to
be an adequate number. A third year will be necessary to start-up and perform
post-close-out analysis.

There are two types of direct benefits to be gained for the patient by
participating. Firstly, the information acquired during a 4D-CTA examination
allows for the reconstruction of traditional axial cranial CT images and CT
perfusion maps, which may yield findings relevant to treatment planning.
Secondly, if the lesion is indeed demonstrated by 4D-CTA, follow-up imaging can
also consist of 4D-CTA rather than CA, thus reducing the number of invasive
procedures the patient needs to endure.

Benefits for this patient group in the future are related to a number of
definite drawbacks associated with CA, when compared to 4D-CTA. CA is an
invasive procedure with a high incidence of silent embolic events and a small
risk of transient or permanent neurological deterioration. The arterial
puncture and the post-procedural immobilization (at least 4 hours intramural)
to prevent arterial bleeding are associated with patient discomfort. Aside from
the patient, the radiologist and supportive staff are also exposed
to ionizing radiation. And even though post-processing of a 4D-CTA may take the
CT operator up to 30 minutes, a CA is considerably more time consuming for the
radiologist and the patient.
Due to its drawbacks, CA has been replaced by non-invasive alternatives for a
number of clinical questions regarding extracranial vascular pathology. If we
show the novel technique of 4D-CTA to be of sufficient diagnostic yield in
patients with an AVM or DAVF, this would result in a reduction of expenses,
time consumption and morbidity related to the diagnostic work-up of such
patients. Furthermore, such results would allow CA to be replaced by 4D-CTA
whenever repeat imaging is requested during follow-up.
On the other hand, if we show 4D-CTA to be insufficient to replace CA, this
will demonstrate the limitations of this new technique and prevent its
unjustified use in this patient category.

Patients participating in this study will be subjected to a single extra
examination, i.e. 4D-CTA, thus exposing them to an extra dose of contrast
material and radiation. The burden of contrast material will be comparable to
that involved with a routine cranial CT examination. The radiation burden will
be slightly higher than that of a routine cranial CT examination (approx. 4
mSv).
Specific CTA risks:
- Contrast Induced Nephropathy: in non-selected patients the incidence of
temporary hemodialysis is 0.2%. This is even lower when patients with
preexisting renal problems are excluded (as in our study).
- Allergic reactions to iodinized contrast media can occur but are usually
mild. In case of more severe reactions, qualified medical staff is always
present on site to intervene if necessary.
- Radiation hazard is far less than 1% with this amount (about 5.1 mSv)
additional radiation dosage.