SonoVue®-Enhanced Ultrasound Versus Unenhanced US for Focal Liver Lesion Characterization

Unit of analysis for the outcome measures was the lesion, equivalent to the subject, since
each subject had a single lesion that was to be characterized.

Inclusion Criteria:

- Male/female.

- Provides written Informed Consent and is willing to comply with protocol requirements.

- Is at least 18 years of age.

- Has at least 1 focal liver lesion (FLL) (target lesion) requiring work-up for
characterization. Target lesions may include those:

- Incidentally detected,

- In subjects with chronic hepatitis or liver cirrhosis,

- In subjects with known history of malignancy.

- Is scheduled for surgical removal or biopsy of the target lesion from 24 hours to 30
days after the SonoVue® administration OR

- In case tissue biopsy is not indicated nor surgery planned, is scheduled for or has
performed a contrast-enhanced (CE) CT and/or CE-MRI of the target lesion from 30 days
to 48 hours prior to or from 24 hours to 30 days after the administration of SonoVue®.

Exclusion Criteria:

- Has an acoustic window insufficient for adequate ultrasound examination of the liver.

- Has a FLL that cannot be identified with unenhanced ultrasound.

- Has received or is scheduled for antineoplastic chemotherapy or an invasive procedure
in the time period between test procedures and truth standard assessments which may
have modified the target lesion.

- Is receiving any other contrast medium, within the 48 hours before and up to 24 hours
following the administration of SonoVue®.

- Has previously been enrolled in and completed this study.

- Known right to left cardiac shunt, bidirectional or transient.

- Has any known allergy to 1 or more of the ingredients of the investigational product
(sulfur hexafluoride or to any components of SonoVue®).

- Has any contraindication to 1 of the planned imaging procedures (ultrasound, CT or
MRI), e.g., implants, claustrophobia, inadequate medical conditions etc.

- Has received an investigational compound within 30 days before admission into this
study.

- Has any medical condition or other circumstances which would significantly decrease
the chances of obtaining reliable data, achieving study objectives, or completing the
study and/or post-dose follow-up examinations.

- Is determined by the Investigator that the subject is clinically unsuitable for the
study.

- Is a pregnant or lactating female. Exclude the possibility of pregnancy by:

- testing on site at the institution serum beta-human chorionic gonadotropin (βHCG)
within 24 hours prior to the start of SonoVue® administration,

- surgical history (e.g., tubal ligation or hysterectomy),

- post menopausal with a minimum 1 year without menses.