Lung cancer is one of the commonest malignancies worldwide and necessitates both early and personalised treatment. A key requirement is histological sampling with immunohistochemistry obtained usually from percutaneous biopsy. Conventionally thoracic biopsies are performed using CT guidance, but more recently, there has been development of physician led ultrasound biopsy for pleural lesions. Contrast-enhanced ultrasound (CEUS) has been increasingly used in interventional procedures and is able to offer benefits for thoracic biopsies including improving lesional visualisation and characterisation, targeting viable tissue and avoiding critical vascular structures as well as evaluating for the presence of post-procedural complications. This educational review aims to benefits of the role of CEUS in thoracic biopsies.
Keywords: Lung cancer; Contrast-enhanced ultrasound; CEUS; Biopsy; Pleural
- CEUS allows improved lesional characterisation with detailed anatomy.
- CEUS allow accurate mapping for a biopsy path to avoid vasculature.
- Real time CEUS biopsy provides confidence for sampling viable tissue.
- Post procedure complications can be highlighted early through CEUS.
Lung cancer is one of the commonest malignancies worldwide with an estimated 2 million new cases in 2018, accounting for 20% of all cancer deaths [[
Managing oncological disease has now become personalised, relying on genetic and immunological profiling necessitating tissue sampling. Commonly tissue is obtained by percutaneous computed tomography guided biopsy (PCTB), which has superseded surgical biopsy in most cases, with decreased complication risk, length of stay and cost of procedure. Although usually a safe procedure, PCTB carries risk of pneumothorax, clinically significant haemorrhage or insufficient sampling [[
Ultrasound-guided biopsy (UGB) allows sampling of peripheral located lung and pleural lesions as an alternative to PCTB. UGB offers a real-time method of biopsy with excellent spatial resolution, lack of radiation exposure or use of iodinated contrast, with flexibility of performance in a variety of positions and at bedside. A study comparing UGB and PCTB showed ultrasound to have a decreased procedure time, fewer complications and a likely better pathological specimen, with UGB taking an average 14 min less time than PCTB [[
Contrast-enhanced ultrasound (CEUS) has become a well-recognised extension of conventional ultrasound with a myriad of utility [[
CEUS has a well-documented utility in interventional procedures including biopsies [[
CEUS-guided biopsies are still considered a novel technique, and this applies to using this procedure for thoracic lesions. As a consequence, no standardised protocols exist, but the authors describe their preferred approach to ensure safety and success.
Identification and localisation of a lesion is performed with an initial CT or positron emission tomography (PET-CT), often as part of disease staging. PET-CT is particularly helpful in aiding appropriate selection of the biopsy site, identifying metabolically active sites and components of lesions [[
The patient is positioned appropriately for sonographic evaluation of the lesion, this can often be performed in a sitting or semi-recumbent position. A curvilinear (3–6 MHz) or medium frequency linear transducer (9 MHz) can be used, the latter is of preference to allow better spatial resolution. Conversely, a curvilinear transducer allows better deep visualisation and can help in initial localisation of a lesion. Particularly with the wider field of view obtained.
After optimised B-mode and colour Doppler ultrasound imaging, two bolus injections of UCA are usually required to complete the biopsy procedure. CEUS is first performed for ascertaining the best site for a biopsy to be undertaken. The transducer should be positioned at the approximate tumour midline with an accessible window for a biopsy to be performed, followed by the intravenous administration of 2.4 ml of SonoVue/Lumason™ (Bracco, Milan) via a 21 g cannula ideally placed in antecubital fossa. Imaging of the tumour is undertaken until maximum diagnostic information regarding the tumour vascularity, areas of necrosis and access route are obtained. The bolus of UCA will allow at least 2–3 min to obtain this relevant information. Using a simultaneous imaging of B-mode and CEUS with a spit screen, local anaesthetic is administered and an incision through the skin is performed to allow the biopsy needle access. Then, a second bolus of 2.4 ml of the UCA is administered and in real time, a coaxial 18 g biopsy stylet and needle is advanced into a viable (i.e. vascularised) aspect of the lesion, avoiding any major vessels. The biopsy tract should not traverse aerated lung parenchyma as the needle would be poorly visualised, increasing the risk of procedure. After a sufficient sample is obtained, the needle and then stylet can be removed. An additional bolus of UCA injection can be administered to assess post-biopsy appearances and may identify any active bleeding points; several bolus disease of UCA is safe [[
Recognition of a lung or pleural lesion is normally straightforward appearing hypoechoic often with distinct delineation from the adjacent aerated lung or thoracic wall. With an underlying collapsed or consolidated lung, the lesion may be ill defined, with difficulty in assessing the lesion borders. Differentiating thoracic wall lesions may be more problematic (Fig. 1) due to the complexity of striated muscle, and similarly, pericardial lesions or lesions within collapsed or consolidated lung may be inconspicuous (Fig. 2). One of the uses of CEUS is to increase conspicuity of pathological tissue from the background normal tissue, a phenomena dependent on altered vascular perfusion of pathological tissue. The lung parenchyma is predominantly supplied by pulmonary arteries, whereas neovascularity of tumours arises from bronchial arteries [[
Graph: Fig. 1 Patient with pleural mesothelioma. a B mode ultrasound shows a relatively ill-defined lesion (arrow), which is difficult to differentiate from the striated muscle at some points (arrowheads). b CEUS shows clear hyperenhancement of the lesion (arrow) defining the borders and necrotic component (thin arrow) from the straited muscle layer (arrowhead) allowing accurate targeting for an optimal biopsy sample
Graph: Fig. 2 Male patient with persistent cough. a A CT examination showed focal anterior pleural thickening (arrow). b PET-CT examination demonstrated a small focus of avidity within the pleura thickening. c B mode ultrasound defines the area of pleural thickening but not the smaller focus of avidity seen on PET-CT (d) simultaneous CEUS showed the subpleural area to be hypoenhancing (thick arrow) with a 4-mm focus of hyperenhancement (thin arrows) suggestive of the pathological tissue. e, f Simultaneous B mode and CEUS imaging with an 18-gauge biopsy needle (thin arrows) traversed through the enhancing focus (thick arrow). Histology revealed pleural adenocarcinoma
Many tumour types outgrow the neovascularity progression, resulting in areas of necrosis within the tumour, seen in up to 42% of cases [[
A CT examination may not have sufficient microvascular detail of lesions in a peripheral location and the snapshot nature of contrast enhancement does not allow for full assessment. As such a PET-CT examination is often required to delineate active disease prior to biopsy [[
Graph: Fig. 3 Male patient with recent chest drainage catheter insertion. a A CT examination showed focal heterogenous density (arrow) within a pleural effusion, thought to be a haematoma secondary to the drainage catheter insertion (thin arrow). b B mode ultrasound of the lesion (arrow) is of a predominantly solid appearance. c CEUS defines the large avascular necrotic central component (arrowhead) and a thick enhancing periphery (arrow), indicating that the biopsy had to be taken from the periphery. Histology revealed sarcomatoid mesothelioma
Graph: Fig. 4 Patient with squamous cell carcinoma. a CT examination shows a solid appearing lung lesion (arrow). b PET-CT suggests small areas of necrosis (thin arrow) within the avid lesion (arrow). c, d Simultaneous B mode and CEUS images show the hyperenhancing lesion (arrow) with better appreciation of the complexity and volume of necrosis (thin arrows) indicating a deep eccentric portion required targeting for biopsy (arrow)
Graph: Fig. 5 Patient with squamous cell carcinoma. a PET-CT shows a peripherally avid lesion with no central avidity (arrow). b, c Simultaneous B mode and CEUS images as the biopsy is performed. B mode demonstrates a hypoechoic lesion (thick arrow) with the biopsy needle within the lesion (thin arrow). The contrast image (c) shows the biopsy (thin arrows) is taken from the deep area of enhancement and therefore viable tissue (thick arrow)
Graph: Fig. 6 Patient with (a) CT examination showing an indeterminate rib lesion (arrow) and clinical sepsis. b, c Simultaneous B mode and CEUS better defined the lesion which was not well seen on B-mode ultrasound imaging (arrow) into a solid hyperenhancing component (thin arrow) and central avascular component (thick arrow). Fluid aspiration yielded pus of the fluid component and the biopsy was inflammatory indicating osteomyelitis
Dedicated colour Doppler imaging prior to biopsy often delineates vascular anatomy, most importantly the identification of regional arteries i.e. intercostal or internal mammary arteries. An artery may be difficult to appreciate on B mode ultrasound imaging alone, and the use of colour Doppler during a biopsy creates distracting artefact and is profoundly affected by motion. Colour Doppler ultrasound may be inaccurate in depiction of low flow, particularly if settings are not optimised. Diagnostic CEUS prior to intervention allows identification the micro- and macro-vasculature, and the truly intravascular nature of the UCA ensures recirculation and continued arterial visualisation. At present, no studies have identified a significant difference in bleeding rate post-biopsy with CEUS compared to CT or conventional ultrasound. Typically, intercostal and internal mammary arteries present the most significant risk. Imaging in real time allows avoidance of these vessels (Fig. 7), and it is suggested that CEUS results in improved selection of a needle path [[
Graph: Fig. 7 Male patient with chest wall swelling. a A CT examination showed focal soft tissue thickening (arrow) encasing the internal mammary artery (IMA) (thin arrow). b On the B mode ultrasound, the lesion (arrow) blends with striated muscle but the IMA is not seen. c CEUS defines the hypoenhancing pathological tissue (arrow) encasing the IMA (thin arrow). d, e Simultaneous B mode and CEUS imaging with an 18-gauge biopsy needle (thin arrows) advanced to the lesion avoiding the IMA (arrow). The lesion was histologically proven lymphoma
Graph: Fig. 8 Patient with Pancoast adenocarcinoma of the lung. Coronal (a) and axial (b) views show soft tissue density (thick arrows) encasing the left carotid artery and subclavian artery (thin arrows). c The tumour is seen as a hypoechoic area, ill-defined on B mode ultrasound with the subclavian artery visible on the periphery (thin arrow). d Simultaneous CEUS clearly defines the hypoenhancing lesion and the previously unseen carotid artery and subclavian artery (thin arrows). e, f Simultaneous B mode ultrasound and CEUS with the biopsy needle (thin arrows) within the hypoenhancing lesion avoiding the critical arterial structures (arrow)
Complications from thoracic biopsy are usually restricted to either haemorrhage or pneumothorax. A pneumothorax is usually readily visible on ultrasound, particularly given the known site of iatrogenic injury. Conventional B mode ultrasound shows the absence of normal pleural sliding and a lung edge may also be seen where a transition point ("lung point") occurs [[
Haemorrhage may be clearly evident with backflow of blood through a coaxial needle stylet, or may be seen on a post-procedural CT. The post-procedure CT requires a repeat injection of contrast media and may be impractical. CEUS can help in the detection of a focus of haemorrhage, in particular, the presence of a bleeding intercostal or internal mammary artery. The ability of CEUS to define microvacuolar low flow enables accurate depiction of trauma in many organs and has proven utility in identification of active bleeding and pseudoaneurysm formation similar to CT [[
Graph: Fig. 9 Patient with metastatic squamous cell carcinoma. a PET-CT examination shows a peripherally avid lesion in the costophrenic angle (arrow) with an associated pleural effusion (thin arrow). b, c Simultaneous B mode and CEUS images post-biopsy shows pooling of the UCA within the pleural effusion (thick arrow) which was static on dynamic imaging and single microbubbles (thin arrow) within the otherwise anechoic effusion. The findings are of post-biopsy haemorrhage which ceased without intervention
CEUS presents an additional tool for an ultrasound-guided thoracic biopsy, from a diagnostic and interventional perspective. Histological yield can be maximised whilst making fewer biopsy passes and choosing an optimised path for intervention, avoiding markedly vascularised and obvious necrotic areas. Diagnostic CEUS prior to the procedure can help in characterisation of the lesion, recognising additional features to guide the procedure and reduce complications as well as providing assessment of potential complications post-procedure.
GTY performed procedures and designed the manuscript. GTY, CF, ST, DR, SBP, KS, DYH and PSS all contributed to the writing and editing of the manuscript. All authors read and approved the final manuscript.
None.
Not applicable.
Not required.
Author consent, patient consent not required.
GTY has received honoraria for Siemens and Bracco. PSS has received honoraria from Siemens, Samsung, Hitachi and Bracco, and consulting fees from ITREAS. DYH, DR, SBP, KS have no disclosures.
• CEUS
- Contrast-enhanced ultrasound
• CT
- Computed tomography
• PCTB
- Percutaneous computed tomography-guided biopsy
• PET
- Positron emission tomography
• UCA
- Ultrasound contrast agents
• UGB
- Ultrasound-guided biopsy
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
By Gibran T. Yusuf; Cheng Fang; Sa Tran; Deepak Rao; Sam Bartlett-Pestell; Konstantinos Stefanidis; Dean Y. Huang and Paul S. Sidhu
Reported by Author; Author; Author; Author; Author; Author; Author; Author