Magnetic Resonance Direct Thrombus Imaging for Suspected Thrombosis of Upper Extremity Diagnostic Evaluation (Selene Study)

The clinical diagnosis of upper extremity thrombosis (UE-DVT) alone is
inaccurate. Therefore accurate objective imaging is required to avoid
incorrectly concluding that thrombosis is present or absent placing the patient
at risk for a pulmonary embolism at the one hand or a *potentially fatal-
bleeding at the other hand. Although a clinical algorithm has been created, the
diagnosis of UE-DVT poses a clinical challenge. Contrast venography is
considered the reference standard for diagnosing UE-DVT. However this technique
is invasive and requires radiation exposure. Furthermore in 18% of the patients
contrast venography could not be performed. Ultrasonography is noninvasive and
does not expose the patients to radiation and intravenous contrast. Compression
ultrasonography (CUS) as diagnostic modality for suspected UE-DVT is reliable
in anatomic places where compression is
possible with a sensitivity of 96% and specificity of 94%. However if the
thrombosis is more centrally located, the accuracy of CUS is poor due to
overlying anatomical structures which limit the possibility of applying
compression. Doppler ultrasonography could be used in these area, but
visualization of the thrombus is often difficult. Therefore contrast venography
is still recommended as diagnostic modality in these patients. CT venography
and MR-venography may serve as alternative modalities; however CT still
requires contrast medium and exposes the patient to radiation.
Furthermore only limited studies have been performed with the use of MR
venography and the studies which evaluated the use of MR venography in
suspected UE-DVT were gadolinium enhanced techniques. Magnetic Resonance Direct
Thrombus Imaging (MRDTI) has been shown a highly accurate diagnostic method for
a first deep vein thrombosis of the legs. The method is based on measurement of
the T1 signal which shortens as a result of the formation of methemoglobin in a
fresh thrombus. This technique does not require the administration of
gadolinium and the acquisition time is short, making this a patient friendly
technique. The sensitivity was 97% and specificity 100% for diagnosis of DVT in
the legs. However studies have never assessed the reliability of MRDTI in
patients with a suspected UE-DVT.

Before embarking on a study using MRDTI as sole test to manage clinically
suspected UE-DVT, we need to perform a study to determine whether the test has
the potential to be useful in patients with suspected UE-DVT. This study has
the objective to estimate the sensitivity of MRDTI by examining patients with a
clinically suspected UE-DVT. We reason that since MRDTI has already been
sensitive for DVT of the legs, it should be sensitive for the arms too, since
formation of methemoglobin in a thrombus is common to both conditions and
normal MRDTI should rule out UE-DVT. On the other hand, if there were few false
positive results in patients with definitively ruled out UE-DVT by contrast
venography an abnormal result would be diagnostic of UE-DVT.

The Selene study is a prospective diagnostic proof of concept study. The
diagnostic management of suspected UEDVT will be according to the usual
clinical practice at the enrolling site. All patients with suspected acute
UEDVT will be managed according to a standardized protocol, starting with
calculation of the clinical decision rule by Constans, followed by a D-dimer
test in case of an unlikely clinical probability. In case of unlikely clinical
probability and normal D-dimer test, UEDVT is considered to be ruled out. In
case of elevated D-dimer concentration or likely clinical probability CUS will
be performed. A positive CUS is diagnostic for UEDVT, an inconclusive CUS or
negative CUS is followed by venography to definitely rule out UEDVT. All
enrolled patients will receive a MRDTI examination within 48 hours of their
initial diagnostic testing. In addition, D-dimer tests will be assessed in
patients with a likely clinical probability as well. All patients will be
followed for a 90-day (+/-7 days) period for the occurrence of symptomatic
venous thromboembolism.
Two groups of consecutive patients will be compared: those with confirmed UEDVT
('group 1') and those in whom suspected UEDVT is ruled out by the algorithm and
who had an uneventful follow-up ('group 2'). Before including patients in the
two study groups we will include 3 pilot patients with CUS proven UEDVT to
optimize the MRDTI sequences used in previous studies for MRDTI of the lower
extremities.

Patients receive as extra examination the MRI. There are no known side-effects
of MRI examination.