Over the last two decades, contrast-enhanced ultrasound (CEUS) has gained popularity as a potent diagnostic tool for detecting and characterizing liver focal lesions. Its primary advantages include real-time examination, safety, and the ability to be performed in patients with renal impairment [1, 2]. More recently, attention has been directed towards CEUS applications in percutaneous interventional procedures such as liver biopsy, liver tumor ablation [3–7], and the intracavitary use of contrast agent (IC-CEUS) [6–12]. A significant benefit of CEUS-guided liver biopsy is the enhancement of diagnostic accuracy by selecting viable areas in complex focal liver lesions (FLL) with necrotic areas and targeting poorly visualized or invisible FLL [13]. In liver ablation, in addition to its well-known role in immediate post-ablation assessment [14], CEUS allows for the targeting of poorly visible FLL on B-Mode US [15]. CEUS may also play a role in detecting complications after interventional liver procedures (biopsy and ablation) [16].

IC-CEUS involves the injection of a diluted contrast solution directly into the catheter or needle to visualize the exact location of the cavity or tissue around the catheter or needle tip. This relatively new CEUS application has primarily been used in the management of abscess drainage, percutaneous nephrostomy, and biliary interventions [6–12].

Pyogenic liver abscess (PLA) is an uncommon but potentially life-threatening disease, with its incidence rapidly increasing in recent decades [17–19]. Causative agents include bacteria, fungi, and parasites, and the etiology is extremely variable, with the most frequent causes being biliary stone disease, post-surgical or post-interventional radiologic maneuvers, underlying malignancy, and hematogenous spread from intestinal infections [17–19]. Percutaneous drainage (PD) under US or computed tomography (CT) guidance combined with targeted antimicrobial therapy has long been recognized as the first-line therapy for PLA [20–22]. Surgery is generally considered when PLA fails to respond to PD, or the patient has concomitant abdominal diseases [23].

Two types of PD are available for PLA treatment: percutaneous catheter drainage (PCD) and percutaneous needle aspiration (PNA), both demonstrating overlapping results in terms of technical and clinical success rates [24, 25].

The aim of this study is to assess the role of the combined use of CEUS and IC-CEUS in the management of percutaneous treatment of PLA, with special reference to the decision-making process by a single operator caring for patients with PLA.

52 patients with 64 PLAs were treated at our Interventional Ultrasound Unit between January 2019 and December 2023. From this population, 36 patients (23 males and 13 females; mean age 64 ± 13.9 years) with 39 PLAs were selected for inclusion in the study if CEUS and IC-CEUS were used in combination to manage the clinical case.

This study was approved by the institutional review board and conducted in accordance with the ethical standards outlined in the Helsinki Declaration of 1975 and its later amendment. Signed informed consent was obtained from all patients before US-guided interventional procedures and the administration of US contrast media.

Table 1 presents the main characteristics of the PLAs, which were mostly polymicrobial, primarily attributed to E. Coli, Streptococcus, and Klebsiella pathogens. The differentiation between single and multiple abscesses was based on the presence of normal intervening liver parenchyma separating multiple abscesses and/or evidence that the abscesses were in different segments of the liver. Unilocular and multilocular abscesses were defined based on CEUS findings, considering the presence or absence of enhancing internal septations.

B-Mode US, CEUS, and contrast-enhanced examinations were performed before interventional procedures in all patients. Contrast-enhanced CT and/or contrast-enhanced magnetic resonance imaging (MRI) were available in 19 cases before US-guided procedures, while the remaining 17 patients were evaluated in an emergency setting, and PD was promptly performed based on B-Mode US and CEUS results.

CEUS was conducted following a standardized protocol: SonoVue (sulfur hexafluoride with a phospholipid shell; Bracco SpA, Milan, Italy) was administered intravenously as 2.4 mL boluses through the antecubital vein in 2–3 seconds, followed by a 5 mL flush of normal saline (0.9%).

State-of-the-art US machines (Resona 7 system, Mindray Bio-Medical Electronic Co, Shenzhen, People’s Republic of China; GE Logiq E10, GE Healthcare) were used in all cases. For IC-CEUS images, diluted SonoVue (0.1–0.5 mL of medium contrast in 20 mL of saline) was injected through needles during the interventional procedures, including needle aspiration and before passing the guidewire during the Seldinger maneuver. This method highlighted the internal abscess structure, distinguishing single vs multiple cavities and revealing communication either between liquified cavities in multilocular PLA or between PLA and adjacent anatomic structures (e.g., biliary ducts, hollow viscera, thorax). IC-CEUS was also performed just after catheter deployment to confirm correct positioning in all cases of PCD.

In addition to clinical and laboratory findings, CEUS and IC-CEUS were repeated every 2–3 days in all patients with the catheter left in place for continuous drainage to monitor PLA evolution in terms of morphology, providing useful information on the proper timing of catheter removal and patient discharge. All patients with uneventful outcomes were followed with imaging (prevalently US) up to three months after discharge to verify complete healing or relapse.

To assess the clinical impact of contrast-based techniques in the therapeutic management of PLA, CEUS and IC-CEUS results were considered clinically relevant findings (CRF) if they modified one of the following therapeutic choices in comparison with pre-operative imaging (B-Mode US, CT/MRI) results: 1) PCD vs PNA; 2) a combination of PNA and PCD; 3) the use of single vs multiple catheters according to the presence or absence of communication between compartments of complex abscess cavities; 4) additional therapeutic measures required (e.g., biliary stenting).

All US-guided interventional maneuvers were performed through transhepatic route access and with a biopsy guiding system. For continuous drainage, 8–12 French pigtail catheters with thread locks were placed into PLAs using the Seldinger technique, followed by vigorous irrigation with multiple boluses of 10–20 mL of saline until the returning material was clean. Multiple catheters were always deployed in the same session. PNA was carried out with 18-gauge Chiba needles in single or multiple sessions as needed. PLAs equal to or smaller than 3 cm did not undergo PD.

Aspirated pus was immediately sent to the laboratory for culture. Broad-spectrum antibiotics were usually administered to all patients before PD until the results of the laboratory tests were available, and the treatment was modified according to the causative organisms.

A single physician with more than 30 years of experience performed all interventional maneuvers, CEUS, and IC-CEUS and followed up on the clinical and imaging evolution of all patients. Adverse events after CEUS and IC-CEUS were recorded.

In total, 23 patients with 24 PLAs (mean size 8.5 ± 2.7) underwent PCD using 8–10F catheters in size, except for one case where a 12F catheter was utilized. PNA was associated with PCD in 5 patients to drain small cavities not in communication with major ones in the context of multilocular PLAs. In the remaining 8 patients with 10 PLAs (mean size 6.4 ± 2.3 cm) underwent single or multiple PNA using 18-gauge Chiba needles.

Out of 36 patients, 24 (66.7%) with 26 PLAs had an uneventful outcome after percutaneous treatment and complete resolution of the PLA and without relapses as assessed during follow-up after discharge. 11 patients did not benefit from interventional procedures due to the progression of their underlying neoplastic disease. In one patient, a large pseudo-tumoral mass remaining after PCD of the initial multilocular PLA was resected along with a metachronous right-sided colon cancer. Histology revealed only inflammatory features without neoplastic foci in the excised liver mass.

In this study, we aimed to assess the clinical utility of the combined use of CEUS and IC-CEUS in the daily practice of a single operator managing patients with PLA amenable to percutaneous treatment. The therapeutic decisions were modified and better tailored to individual patients in 58.4% of cases after CEUS. The demonstration of real PLA echostructure, accurate measurement of liquified areas, and determination of the presence or absence of communication between abscessed loculi assisted the operator in the decision-making process. Specifically:

1.

PNA was favored as the sole therapy when a small (< 4 cm) liquified area, even in large abscesses, was observed.

In a minority of cases (11.1%), CEUS was also crucial for guiding needles in the largest liquified compartment of multilocular PLAs that appeared poorly defined on B-Mode US.

During the initial phase of the therapeutic plan decision-making process, IC-CEUS provided a limited contribution. It helped in tailoring the therapeutic approach in 8.3% of cases by demonstrating, contrary to all pre-operative imaging techniques, real communication between the largest necrotic area and multiple tiny cavities inside PLA.

Overall, the combination of CEUS and IC-CEUS guided PD options in 66.7% of our patients. The added value of IC-CEUS was particularly evident in cases where fistulous communication with adjacent anatomic structures (the biliary tree/pleural cavity) was demonstrated, prompting additional therapeutic measures (biliary stenting/thoracic drainage). Throughout patients’ follow-up during hospital stay, the combination of CEUS and IC-CEUS facilitated the monitoring of morphology and size (of both the entire PLA and the liquified component) and optimized the timing of catheter removal in cases of continuous drainage, along with clinical and laboratory findings. Moreover, IC-CEUS revealed occlusion or dislodgement of catheters, necessitating immediate catheter withdrawal.

It is noteworthy that, despite a relatively short drainage duration (one week on average), none of our patients with an uneventful outcome experienced a PLA relapse, confirming that catheters had been removed at the right time. This is crucial, as premature catheter removal may worsen prognosis and increase the risk of treatment failure [23, 26].

In our series, clinical success was independent of the multilocular structure and size (> 7 cm) of PLA, contrary to some reports associating these characteristics with PD failure [27]. This aligns with the majority of findings reported by other authors [28–30].

The absence of adverse events after intravenous and intracavitary injection confirms the high tolerability profile of the US contrast agent [2, 6, 7, 10]. Due to its safety and non-invasiveness, CEUS and IC-CEUS can be liberally used to follow-up patients according to operator’s judgment even at the bedside. Only conventional US could be an alternative to monitor PLA evolution but limits of B-Mode US in recognizing catheter tip inside or outside (in case of dislocation) drained cavities are well known. CT and/or MRI expose patients to radiations, are more expensive, and are not invariably available in all geographical areas.

Limitations of our study include: 1) the lack of randomization to a control group (managed by either CT or CEUS and IC-CEUS), which is challenging to implement in real-life scenarios; 2) the absence of radiological verification in some cases, but exhaustive imaging studies might not have necessarily added value to diagnosis and treatment; 3) the potential non-reproducibility of a single operator’s experience elsewhere.

In conclusion, the combined use of CEUS and IC-CEUS proved to be a powerful and safe tool for a single operator managing patients with PLA. It enabled the tailoring of treatment approaches to individual cases, facilitated the monitoring of PLA evolution over time, and provided decisive information, especially with IC-CEUS, on the optimal timing of catheter removal.