Contrast-Enhanced Ultrasound
Contrast enhanced ultrasound (CEUS) uses intravenous microbubble contrast agents that remain within the vascular space. They produce strong non-linear echoes at low mechanical index (0.05 to 0.2) with contrast specific imaging modes (pulse inversion, amplitude modulation).
The microbubbles have a gas core of sulphur hexafluoride or a perfluorocarbon, encapsulated in a phospholipid or albumin shell. They are 1 to 7 micrometres in diameter, similar in size to red blood cells.
Unlike iodinated CT contrast or gadolinium, ultrasound contrast agents are purely intravascular and are not nephrotoxic. They are not excreted by the kidney: the gas is exhaled by the lungs and the shell metabolised by the liver.
The agent is injected as a bolus (1.2 to 2.4 mL for liver, 2.4 mL for general use) followed by a 5 to 10 mL saline flush, or by infusion for left ventricular opacification. Enhancement is observed in real time for up to 4 to 6 minutes (longer for the liver).
The examination takes 20 to 40 minutes, with no radiation.
CEUS characterises focal lesions (notably in the liver, kidney, spleen and pancreas), shows vascularity and perfusion in real time, depicts bleeding and organ infarction, and assesses perfusion of transplants. It also directs biopsies and ablation, evaluates endoleaks after aortic stent grafting, and opacifies the left ventricle in echocardiography.
For indeterminate focal liver lesions, CEUS has a sensitivity of 90 to 95% and a specificity of 90 to 95% for differentiating benign from malignant lesions, comparable to contrast CT and MR in many series.
It has a sensitivity of over 90% for the diagnosis of hepatocellular carcinoma in cirrhosis, by typical arterial hyperenhancement followed by late and mild washout.
CEUS is safe: serious hypersensitivity type reactions occur in about 1 in 10 000 to 1 in 5000 examinations (anaphylactoid reactions, most within 30 minutes of injection), and nephrotoxicity or thyroid effects are not reported.
Indications. Characterisation of indeterminate focal liver lesions seen on B-mode ultrasound (haemangioma, focal nodular hyperplasia, adenoma, hepatocellular carcinoma, metastases, abscess, focal fatty change or sparing). Surveillance and diagnosis of hepatocellular carcinoma in cirrhosis. Post-treatment evaluation of tumour ablation (residual perfusion).
Control of biopsy to enhancing (viable) tumour and avoidance of necrosis. Assessment of complex renal cystic lesions and solid renal masses (when CT or MR contrast is contraindicated or inconclusive), renal infarction, pyelonephritis and abscess, renal trauma, renal transplant perfusion. Blunt abdominal trauma in children and young adults (solid organ injury, active bleeding).
Splenic lesions, infarcts and lacerations. Pancreatic focal lesions (differentiating solid from cystic lesions, and adenocarcinoma, which is hypoenhancing). Inflammatory bowel disease (bowel wall vascularity, abscess).
Vascular uses: endoleak after endovascular aneurysm repair, carotid plaque neovascularisation, and vascular patency. Echocardiography: left ventricular opacification in poor windows, assessment of endocardial border, left ventricular thrombus and apical hypertrophy. Breast, prostate, thyroid, lymph node and scrotal lesions in selected centres (vascularity).
Paediatric uses (intravesical contrast for voiding urosonography). Not for lesions that cannot be reached by ultrasound, or where whole body staging is required.
Contraindications and precautions. Known hypersensitivity to the agent or its components (sulphur hexafluoride, polyethylene glycol, phospholipids, albumin products depending on the agent).
Caution in patients with unstable cardiopulmonary conditions (acute coronary syndrome or recent myocardial infarction, acute heart failure, severe arrhythmia, severe pulmonary hypertension, right to left cardiac shunts, acute respiratory distress). Regulatory restrictions differ between countries, and labelled restrictions have been relaxed, but the agent should be used with monitoring in these groups.
Allergy to polyethylene glycol (check the specific agent). Pregnancy and breastfeeding: little data; use only if essential (breastfeeding can usually continue). Equipment for resuscitation must be at hand, the patient is observed for at least 30 minutes after injection, and intravenous access is secure.
Informed consent is obtained, and the operator is trained in the technique.
Preparation and technique. Fasting for 4 to 6 hours for abdominal studies. A baseline B-mode and colour Doppler study is made, and the lesion is located. A 20 to 22 G cannula (an antecubital vein) is placed, with a three way tap.
The contrast agent is prepared (agitation of the vial to form the microbubble suspension) and injected as a bolus followed by saline flush, and a timer is started. Low mechanical index contrast specific imaging is used, with the focus deeper than the lesion and a depth that allows visualisation of the lesion and the adjacent parenchyma.
The enhancement phases are observed as follows:
- the first 60 seconds continuously (arterial phase, usually 10 to 35 seconds in the liver);
- then intermittently every 30 to 60 seconds in the portal venous phase (30 to 120 seconds);
- and in the late phase (over 120 seconds up to 4 to 6 minutes).
Different phases and timing apply for each organ (kidney: cortical phase 10 to 20 seconds, medullary phase 30 to 60 seconds). A second injection may be needed to examine a second lesion. Images are stored as video clips for review. For endoleak and trauma, scanning is repeated from several windows.
