CeVUS With Intravesical Administration of OPTISON TM (Trademark) in Children

Contrast enhanced Voiding Urosonography (ceVUS) is a radiation free, highly sensitive imaging
modality for vesicoureteral reflux (VUR) and urethral imaging in children. It employs
ultrasound technology in combination with ultrasound contrast agent, which is administered
intravesically via a bladder catheter. Currently, second generation ultrasound contrast
agents are commercially available, comprising of gas-filled microbubbles. CeVUS in children
is being widely practiced, primarily in Europe, despite the fact that none of the
commercially available ultrasound contrast agents are yet approved for clinical applications
in pediatric population. In the United States, there is limited clinical experience with
ceVUS in children. Among the currently commercially available ultrasound contrast agents,
OPTISON has already been used in research and off-label in clinical settings involving adults
and children. One in-vitro study has been conducted aiming to optimize the ultrasound
technical parameters and the dose of OPTISON for intravesical administration in children. In
this clinical trial the investigators aim to evaluate the diagnostic feasibility and safety
of ceVUS with the intravesical use of OPTISON for vesicoureteral reflux detection and
urethral imaging in children.

Inclusion criteria:

1. Children 2-18 years (first age cohort).

2. Children 0-18 years (second age cohort).

3. Referred to the Children's Hospital of Philadelphia (CHOP) for the performance of the
clinically indicated Voiding Cystourethrography (VCUG) examination.

4. Parental/guardian permission (informed consent) and if appropriate, child's assent for
additional performance of contrast enhanced Voiding Urosonography (ceVUS) examination.

Exclusion criteria:

1. Hypersensitivity to perflutren, blood, blood products or albumin.

2. Children requiring sedation for VCUG or ceVUS examinations.

3. Parents/guardians or subjects who, in the opinion of the principal investigator, may
be non-compliant with study schedules or procedures.