The use of CEUS in the assessment of uterine fibroids, a feasibility study

With Contrast Enhanced UltraSound (CEUS) the microvascularisation of uterine
leiomyomas can be visualized. In general practice we use color Doppler and
power Doppler to get an impression of the (macro) vascularity of fibroids and
to differentiate fibroids from other uterine abnormalities such as adenomyosis.
CEUS is able to present macro vascularity as well but it has additional
abilities to study the vascularity in more detail: 1) microvascularity can be
studied, 2) dynamic patterns that reflect vessel functionality can be studied
and 3) parameters for quantification of vascularization based on time-intensity
curves of regions of interest can be calculated (arrival-time, peak-time,
wash-in time, mean transit time, peak value, wash-in rate and area under the
curve). These parameters could replace (dynamic) MRI for the evaluation of
fibroids and its vascularity. We hypothesize that in the future these outcomes
could be useful for the prediction of fibroid responsiveness for specific
therapies and for the monitoring of therapeutical respons. So in theory it
could be advantages for the treatment choice and monitoring of uterine
leiomyomas.
In the past years numerous studies have been preformed with CEUS, but only a
few small series were reported on using CEUS in the assessment of uterine
leiomyomas. However it has not been compared to other sonographic modalities
such as 3D power Doppler in a structured way.
The aim of the current study is to compare CEUS outcomes with 3D power Doppler
parameters and to use dynamic MRI as a reference test. We will start with a
pilot study to test the feasibility of this technique in our hand and with our
software. Based on these outcomes a final study will be designed, including a
proper power calculation and optimalisation of the settings of the machine and
software used to analyze the images.

The objectives of the current pilot study are:
1 to test the feasibility of the used vaginal probe and machine, settings and
software that is currently used for the evaluation of prostates for uterine
fibroids and to see if we need any modifications of the settings and the
analyses.
2 to compare the main outcomes of vascularity with comparable outcomes of
dynamic MRI in order to calculate a mean difference and SD for future power
calculation.
3 to compare the outcome parameters of dynamic MRI with standard US power
doppler outcomes (i.e. 3D mean vascular index of the entire fibroid volume, the
mean vascular index of 2D surface of the plane with the largest diameter).
4 to learn and gain experience with the contrast enhanced ultrasound technique,
determine the optimal dosage of contrast agent required for optimal
visualization of fibroids and to standardize the settings of the machine and
software used to analyze the images.

A prospective observational pilot study of ten women who are clinically
suspected of having uterine leiomyomas who visit the outpatient department of
the VUmc or the AMC between March 2014 and June 2014. All patients with the
suspicion of uterine fibroids on conventional ultrasound that meet our
selection criteria will be asked to participate in the study. After informed
consent, a CEUS and a (dynamic) MRI will be performed according to a
standardized protocol. 3D US power Doppler sweep is stored of all women that
visit our outpatient department with a suspicion of fibroids are stored as a
part of our routine.
The contrast enhanced ultrasound will take place in the Academic Medical Centre
in Amsterdam, because they have the expertise and the equipment required to
make the contrast enhanced ultrasounds. The dynamic MRI will take place in the
VU Medical Centre.

The exclusion criteria of the current pilot study include:
- Postmenopausal woman
- Woman with an known allergy to SonoVue or any of its components
- Woman with an history of any clinically unstable cardiac condition including
class III/IV cardiac failure or right to left shunts
- Woman who have had a severe cardiac rhythm disorders within the last 7 days
- Woman with severe pulmonary hypertension of uncontrolled systemic
hypertension or respiratory distress syndrome
- Contra-indications for dynamic MRI

There is a small anticipated risk for participants. After the use of CEUS in
thousands of patients, adverse events appear to be transient, mild and rare.
The side effects mostly consist of transient alteration of taste, local pain at
the injection site and facial or general flush. In rare cases allergic reaction
to the contrast agent is described. Patients will be informed of the risk
during intake, and it will be described in the study information.
If the results of the study show that contrast enhanced ultrasound can provide
a precise depiction of the leiomyomas vascularisation this can be helpful for
the characterization, treatment choice and monitoring of fibroid treatment.