4 The diagnostic tests

4 The diagnostic tests


4.1 SonoVue is a second-generation contrast agent that uses sulphur hexafluoride microbubbles for contrast-enhanced ultrasound imaging in adults. SonoVue is a low solubility gas contrast agent that allows imaging at low mechanical index, which leads to effective suppression of the tissue signal. It is used to enhance the echogenicity of the blood and can thus improve the signal to noise ratio in ultrasound. SonoVue has a UK marketing authorisation for diagnostic use only. The summary of product characteristics states that SonoVue improves display of the blood vessels in liver lesions during doppler sonography, allowing more specific characterisation of lesions. The summary of product characteristics also states that SonoVue should only be used in people in whom unenhanced ultrasound is inconclusive.

4.2 SonoVue consists of a kit containing a vial of sulphur hexafluoride gas and phospholipid powder, a prefilled syringe of solvent (sodium chloride solution) and a transfer and ventilation system (mini spike). The saline is introduced into the vial by the mini spike delivery system and once reconstituted, microbubbles are formed. These microbubbles are the contrast agent which is injected into a peripheral vein at the antecubital fossa. When the ultrasound probe is placed on the abdomen, ultrasound waves cause the microbubbles to resonate so that a signal is picked up by a transducer and an image is formed on a screen.

4.3 SonoVue remains within the blood vessels and, depending on the type of lesion, it shows a pattern of uptake similar to that of contrast agents used for imaging blood vessels in CT or MRI. The contrast agent is broken down by the body after a few minutes. The sulphur hexafluoride gas is exhaled through the lungs and the phospholipid component of the microbubble shell is metabolised (re-entering the endogenous phospholipid metabolic pathway).


4.4 People with inconclusive unenhanced ultrasound are currently referred for contrast-enhanced CT and/or contrast-enhanced MRI. These are the comparators for this assessment. Contrast-enhanced MRI generally uses gadolinium-based vascular contrast agents. These can differentiate between benign and malignant focal liver lesions by vascular enhancement patterns in a similar way to contrast agents used for contrast-enhanced CT and contrast-enhanced ultrasound. However, contrast-enhanced MRI of the liver can also use hepatocyte-specific contrast agents. These include superparamagnetic iron oxide (SPIO) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA).

4.5 Expert opinion indicated that biopsy would not be performed as the next test when unenhanced ultrasound was inconclusive. Therefore, biopsy was not considered a relevant comparator in this assessment.

4.6 The comparators used in the model were:

  • contrast-enhanced CT

  • contrast-enhanced MRI using gadolinium as the contrast agent

  • contrast-enhanced MRI using SPIO as the contrast agent.

  • National Institute for Health and Care Excellence (NICE)