Single-center study: The diagnostic performance of contrast-enhanced ultrasound (CEUS) for assessing focal splenic lesions compared to CT and MRI

BACKGROUND: Frequently focal splenic lesions (FSL) - cysts, hemangioma, hamartoma, metastases or infarction amongst others – are incidentally found within the scope of the sonographic examination of the abdomen. By using native B-mode and Color Doppler the underlying entity often is not elucidated. Thus, more elaborate imaging modalities like CT and MRI scans with their associated risks are used to clarify the entity of FSL. PURPOSE: The aim of the present retrospective single-center study is to evaluate the diagnostic performance of CEUS examination for assessing splenic focal lesions by comparison with findings from CT and MRI scans. MATERIALS AND METHODS: Between 2010–2018 46 patients were included in the study. All patients underwent native B-mode, Color Doppler and CEUS after given informed consent. The applied contrast agent was a second-generation blood pool agent (SonoVue^®, Bracco, Milan, Italy). CEUS examinations were performed and interpreted by a single experienced radiologist (EFSUMB Level 3). RESULTS: All patients were examined without occurrence of any side effects. In total, 53 FSL were investigated (9% traumatic vs. 91% non-traumatic). Compared to CT, CEUS showed a sensitivity, specificity, PPV, NPV of 100% for assessing infarction, hematoma, hamartoma, cystic and malignant lesions. In comparison with MRI, CEUS presented a sensitivity, specificity, PPV, NPV of 100% for evaluating pseudolesions, hemangioma, hamartoma, cystic and malignant lesions. CONCLUSION: With an excellent safety profile CEUS shows an equipollent diagnostic performance for differentiating FSL compared to CT and MRI scans.

Keywords: Spleen; tumor; focal splenic lesion; contrast-enhanced ultrasound; CEUS

The spleen rarely is the main focus when clinicians request imaging evaluation, but its analysis is included in the context of standard abdominal imaging by ultrasound, computed tomography (CT) or magnet resonance imaging (MRI). Nevertheless, the spleen is affected in a plethora of diseases of acquired or hereditary conditions [[1]]. Usually the spleen is discretely hyperechoic compared to renal cortex and is iso-/hyperechoic to liver parenchyma.

Unknown focal splenic lesions (FSL) often are incidentally found and their investigation in native B-mode and Color Doppler sonography frequently does not reveal their underlying entity [[2]]. The additional use of anamnestic, clinical and laboratory information can help to differentiate between different FSL. In case splenic lesions happen to be unifocal and depict to be hyperechoic on native B-mode, in asymptomatic patients those lesions normally are of benign origin. In contrast, if splenic lesions occur as multiple hypoechoic masses in underlying cancer disease, they are likely malignant [[3]]. Subsequent more elaborate imaging modalities like CT and MRI are critical to determine the distinct entity of the lesion.

Contrast-enhanced ultrasound (CEUS) depicts an alternative imaging tool to CT and MRI scans, complements findings from conventional ultrasound examinations and is especially eligible for highly vascularized organs. Likewise liver tissue, the spleen shows prolonged contrast enhancement due to the sequestration of microbubbles and allows for thorough scrutiny [[4]]. Absent or persistent late contrast enhancement is highly predictive for benign splenic lesions, whereas delayed wash-out is highly suspicious for malignancy [[7]]. Peripheral nodular enhancing pattern is characteristic for hemangioma.

The advantage of non-ionizing CEUS is its safe and immediately availability, repeatability and cost effectiveness [[7]].

In the present single-center study, we evaluated the diagnostic performance of CEUS in characterizing focal splenic lesions compared to findings from corresponding CT and MRI scans.

This retrospective single-center study was approved by the local institutional ethical committee of the institutional review board and all contributing authors followed the ethical guidelines for publication in Clinical Hemorheology and Microcirculation. All study data were gathered according to the principles expressed in the Declaration of Helsinki/Edinburgh 2002. Oral and written informed consent of all patients were given before CEUS examination and their associated risks and potential complications have been carefully described. All CEUS examinations were performed and analyzed by a single skilled radiologist with experience since 2000 (EFSUMB level 3). All included patients underwent native B-mode, Color Doppler and CEUS scans. Up-to-date high-end ultrasound systems with adequate CEUS protocols were utilized (GE Healthcare LOGIQ L9, Milwaukee, Wisconsin, USA; Siemens Ultrasound Sequoia, ACUSON Sequoia, Mountain View, California, USA; Philips Ultrasound iU22, EPIQ 7, Seattle, Washington, USA). A low mechanical index was used to avoid early destruction of microbubbles (<0,2). For all CEUS examinations, the second-generation blood pool contrast agent SonoVue® (Bracco, Milan, Italy) was used [[6]]. 1,2–1,5 ml of SonoVue® were applied. It is a purely intravascular contrast agent that does not diffuse into the interstitial space, thus allowing for dynamic assessment of microcirculation. After contrast agent was applied, a bolus of 5–10 ml sterile 0,9% sodium chloride solution was given. No adverse side effects upon administration of SonoVue® were registered. All CEUS examinations were successfully performed and image quality was sufficient in every single case. The patient files and imaging records were collected from the archiving system of our institution.

A total of 46 patients on whom CEUS was performed between 2010–2018 were included in this retrospective single-center study.

CEUS was successfully performed on all included 46 patients without occurrence of any adverse effects. The gender ratio was: 1:1. The mean age of the patients at the time of CEUS performance was 58 years (range: 19–83 years). In total, 53 splenic abnormalities were detected by CEUS of which 5 (9%) were traumatic and 48 (91%) non-traumatic lesions (Table 1). Findings from CEUS, CT and MRI scans were correlated.

Table 1 Diagnostic performance of CEUS compared to CT, MRI. PPV = positive predictive value, NPV = negative predictive value. Malignant lesions: lymphomas and metastases

Compared to results from CT scans, for differentiating splenic infarction (representative case shown in Fig. 1) and hematoma CEUS presented a sensitivity of 100%, a specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100%.

Graph: Fig. 1 Splenic infarction. A. Color Doppler sonography shows homogenous perfusion signal of the spleen. B. Wedge-shaped hypoenhancing region as correlate of the splenic infarction is depicted via CEUS (yellow arrow).

In comparison with MRI, CEUS showed a sensitivity of 100%, s specificity of 100%, a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 100% for evaluating splenic infarctions, vascular pseudolesions, hemangioma and malignant lesions (metastases, lymphoma) (representing case shown in Fig. 2).

Graph: Fig. 2 Multifocal splenic lymphoma manifestation. A. Multiple hypoechoic round splenic lesions are shown in native B-mode sonography. B. Hypervascularization of the lesions are detected in Color Doppler. C. Early contrast enhancement of the lesions and venous wash-out in the delayed phase (D) is registered via CEUS.

For splenic rupture, CEUS had a sensitivity of 50%, a specificity of 100%, a PPV of 100% and a NPV of 0% compared to CT (case shown in Fig. 3). Compared with CT, CEUS had a specificity of 86% and a PPV of 86% for detecting hemangioma. The analysis of malignant lesions – metastases and lymphoma - via CEUS juxtaposed to CT showed a specificity of 100%, a sensitivity of 56%, a PPV of 64% and a NPV of 100%.

Graph: Fig. 3 Splenic rupture. A. Perisplenic hematoma (yellow arrows) is shown in native B-mode sonography. B. No vascular abnormality is detected in Color Doppler. C. CEUS reveals irregular non-enhancing splenic area with dehiscent splenic caspsule adjacent to the hematoma, depicting splenic laceration (red arrow). D. Corresponding CT-scan shows perihepatic hematoma (yellow arrows) and splenic laceration (red arrow), venous phase in coronal reformation.

Conventional ultrasound is the imaging modality of first choice when it comes to assessing abdominal status, including the spleen. Nevertheless, the diagnostic value of findings from conventional ultrasound often are limited.

The use of CEUS allows to identify splenic abnormalities in patients presenting with left upper quadrant (LUQ) pain and showing an inhomogenous splenic pattern in native B-mode [[13]]. CEUS enables to safely differentiate accessory splenic tissue (splenunculi/splenosis) from tumors of unknown origin since the former shares the typical sonomorphological "zebra"-like enhancing appearance of splenic tissue upon intravenous application of contrast and no venous wash-out likewise in contrast-enhanced CT or MRI scans [[14]]. In the setting of symptomatic acute infarction of the spleen, conventional B-mode and Doppler sonography often fail to elucidate the underlying pathology as splenic infarctions depicts faintly isoechoic. By CEUS, splenic infarction clearly demarcate as wedge-shaped and hypoenhancing areas in early arterial phase [[15]]. Furthermore, the distinct pattern of contrast-enhancement allows for discriminating between benign and malignant FSL [[16]]. In most major trauma cases the sonographic examination has been replaced by fast and more precise CT scans. Nevertheless, in hemodynamically stable patients with low-energy isolated abdominal trauma, the use of CEUS to identify damages of the visceral organs may be evaluated [[17]].

According to the guidelines of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) from 2017, applying CEUS is recommended to detect focal splenic abnormalities, diagnose splenic infarction, to detect suspected splenosis/accessory spleens and to identify benign splenic lesions [[2]].

Our results are in line with previous published results that using CEUS allows for differentiating benign from malignant splenic lesions [[21]]. Besides, CEUS shows similar diagnostic accuracy in differentiating non-traumatic FSL compared to CT [[15]]. In our retrospective single-center study, CEUS showed similar sensitivities for describing splenic infarctions, pseudolesions, hematoma, hamartoma, malignant and cystic lesions compared to findings from CT or MRI scans. In terms of splenic rupture and hemangioma, CEUS findings were less sensitive to those from corresponding CT scans, 50% and 86% respectively, which might be explained by the limited number of included patients (n = 2 for ruptures, n = 8 for hemangioma) and by delayed splenic ruptures which occur upon blunt abdominal trauma that might have not been detected by initial CEUS but by following corresponding CT scan [[24]].

The repeatability of CEUS application and its excellent safety profile are of high value. Particularly in multimorbid patients, renal impairment and thyroid hormone disturbances often depict contraindications for contrast-enhanced CT and MRI scans. Besides being safely performed in the those patients, the results from a retrospective single-center study showed that SonoVue® did not cross the blood-placental barrier and thus did not affect the fetus [[9]]. Thus, CEUS might also add a pivotal value in assessing spleens in pregnant patients. Furthermore, the safe use of non-ionizing CEUS in children had already been described in several clinical trials and led to its approval for pediatric liver imaging by the Food and Drug Administration (FDA) [[25]]. Consequently, CEUS depicts a powerful diagnostic tool for assessing FSL and can be applied with less hesitations during kidney failure, hyperthyroidism, pregnancy and in pediatric patients. Our results show that CEUS has a high diagnostic value for assessing and differentiating FSL with an excellent safety profile.