Contrast-enhanced ultrasound of the spleen

Introduction

Examination of the spleen is a standard component of all abdominal ultrasound studies. Although some patients with splenic disease will present with symptoms related to the left upper quadrant (LUQ) of the abdomen, splenic pathology is often clinically silent. Therefore, it is important that ultrasound practitioners make a careful evaluation of the splenic parenchyma, rather than just undertake a perfunctory measurement of splenic size, to avoid missing significant pathology. Splenic abnormalities are uncommon in comparison with many of the other abdominal organs routinely assessed by ultrasound. ¹ However, if the spleen is always carefully assessed, significant findings will be regularly encountered in routine clinical practice. Focal splenic abnormalities are frequently difficult to characterise with grey scale and Doppler ultrasound. Benign lesions are slightly more common than malignant, ² but accurate diagnosis is often difficult and focal echo-poor lesions, in particular, have a wide differential diagnosis. Knowledge of the patient’s clinical presentation, past medical history, laboratory tests and review of previous imaging is often essential. Even with this information, a specific diagnosis may not be possible. The use of ultrasound contrast microbubbles can frequently provide valuable additional information to narrow the differential diagnosis and particularly to triage lesions that are likely to be benign from those that may be malignant.

Contrast-enhanced ultrasound (CEUS) is now routinely used for detection and characterisation of liver lesions. The spleen shares the property of sequestering and retaining ultrasound contrast microbubbles with the liver and is also ideally suited for ultrasound contrast imaging. The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines and Recommendations on the Clinical Practice of CEUS, updated in 2011, recommend several indications where CEUS may be utilised in the spleen. ³ These are: 1. To characterise splenic parenchymal inhomogeneity or suspected lesions on conventional US; 2. To confirm suspected splenic infarction; 3. To characterise accessory spleens or splenosis; 4. To detect splenic malignant lesions in oncologic patients when CT and/or MRI and PET are contraindicated or inconclusive; 5. To evaluate the spleen in selected patients following trauma.

This review article discusses the use and value of CEUS in imaging the spleen.

Normal findings and CEUS technique

The spleen is an intraperitoneal organ found in the left upper quadrant of the abdomen. It typically measures between 9 and 12 cm in its longest dimension; its size varies with body habitus and age. The spleen is usually easy to evaluate with ultrasound via an intercostal approach in suspended respiration; positioning the patient in the lateral decubitus position (right side down) may improve visualisation. Normal splenic parenchyma is more echogenic than both the liver and kidney.

In Europe, the second generation ultrasound contrast agent SonoVue (Bracco Imaging, Milan, Italy) is the most widely used contrast agent. This product does not have a license for splenic imaging and therefore use in the spleen is an ‘off label’ indication and should be administered after due consideration of the risks and benefits. SonoVue has an excellent safety profile in abdominal applications ⁴ and severe allergic events are very uncommon; resuscitation facilities should, however, be readily available in all areas performing CEUS studies. SonoVue may be contraindicated in some patients with pulmonary or cardiac disease. A written departmental operating policy for off label use of ultrasound contrast agents and a record of verbal patient consent for CEUS studies in the patient’s ultrasound report is recommended. A particular benefit of CEUS is the lack of renal toxicity, permitting its use in patients with renal failure, where the use of CT and MRI contrast media is undesirable.

Contrast microbubbles are administered as a rapid intravenous bolus followed by a bolus of 10 mL saline, usually through a cannula in an antecubital vein (20 G minimum size). Due to the avid enhancement of the splenic parenchyma, a smaller dose of contrast than that used for imaging the liver may be adequate and prevent the deeper aspects of the spleen being obscured by intense superficial enhancement; in practice, 2 mL of SonoVue is usually sufficient. Contrast specific abdominal presets, using low acoustic pressures (low mechanical index (MI)) and harmonic imaging, are employed that will almost completely suppress the native tissue image, leaving a virtually subtracted image generated by the contrast microbubbles. It is usually helpful to employ a split screen mode whereby a conventional grey-scale image (obtained at low MI) is displayed alongside the CEUS image. This allows the spleen, and any focal abnormality, to be kept within the ultrasound sector during the examination.

Ultrasound microbubbles are unique amongst radiographic contrast agents in staying entirely within the intravascular space after injection. The spleen and liver, however, have the property of sequestering bubbles after injection with enhancement persisting long after the bubbles have cleared from other organs. This property is particularly marked in the spleen and enhancement often persists 5–7 minutes after injection, ⁵ making the spleen ideally suited for CEUS studies. After the administration of contrast, enhancement in the splenic arterial phase typically starts after approximately 12–18 seconds. The spleen should be continually scanned during this phase and it is desirable to record this arterial phase enhancement as a cine-clip for later review. During this phase, the spleen has a unique appearance described as the ‘zebra’ effect. The cause for this is thought to be due to the differential movement of blood through two circuits within the spleen, of the red pulp and white pulp. The same ‘zebra’ appearance is also seen on arterial phase post contrast series of the spleen in CT and MRI examinations. The heterogeneous appearance creates a potential pitfall to interpretation of the examination if the ultrasound practitioner is unfamiliar with this phenomenon and additionally, it may be difficult to identify a focal abnormality in this phase unless it has been accurately located on the grey-scale image. This inhomogeneity typically lasts for up to 1 minute. At this point, the parenchyma enhances avidly and homogenously with a long lasting late-phase enhancement, typically extending over 5 minutes. During this later phase, scanning should be intermittent, rather than continuous, to avoid the microbubble destruction that occurs even at low acoustic pressures and can lead to an artefactual appearance of late-phase contrast washout, particularly when the region of interest is located at the focal point of the ultrasound beam.

Focal splenic lesions

Most commonly, lesions found within the spleen are asymptomatic, incidentally discovered and may be solid or cystic. Cystic splenic lesions are uncommon; asymptomatic splenic cysts are usually pseudocysts secondary to trauma (which may or may not be recalled by the patient); congenital splenic cysts are less frequently encountered. Cystic lesions will not show enhancement in any CEUS phase and if asymptomatic can be safely monitored. In any immunocompromised patient, or patient with features of sepsis, splenic abscess formation must be considered in cystic lesions. Abscesses may show an enhancing rim or enhancing internal septation on CEUS. Ultrasound guided diagnostic aspiration and drainage can be safely performed in most patients when abscess formation is suspected. ⁶ In immunocompromised patients, atypical infection (including fungal) should be considered and, in endemic areas, echinococcal (hydatid) disease is a common cause of cystic splenic lesions.

Solid splenic lesions may be echogenic, echo-poor or mixed. Lesions may be single or multiple. Echogenic lesions are most commonly benign and an incidentally discovered, well-defined, echogenic lesion of less than 2 cm in diameter is likely to represent a haemangioma; interval ultrasound to confirm stability is usually sufficient for management. Focal, echo-poor, splenic lesions represent the greatest diagnostic challenge, as many of these lesions are malignant; however, some are benign. Conventional ultrasound frequently cannot make a diagnosis in this situation; review of the patient’s clinical and laboratory findings may help to narrow the differential diagnosis, but the addition of CEUS will often give an indication as to whether the lesion is likely to be benign or malignant. Occasionally, however, a tissue diagnosis is required. Fear of haemorrhage has traditionally led to reluctance to biopsy splenic lesions, but both fine needle aspiration and core biopsy procedures can be undertaken with a low probability of serious complications in most patients. ⁷ Trauma and vascular causes may also produce focal splenic lesions that can be evaluated by CEUS.

Indications for splenic CEUS and examination interpretation

Lesion detection

Isoechoic splenic lesions may be difficult to identify with conventional unenhanced ultrasound. In patients where an inhomogeneous splenic parenchyma is identified on conventional ultrasound, it will frequently be possible to identify discrete lesions with CEUS (Figure 1). ⁸ CEUS can also be a valuable addition to the ultrasound examination in patients presenting with left upper quadrant pain or with a history of localised trauma, demonstrating pathology that is not visualised on conventional ultrasound.

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Figure 1.

Melanoma metastases. In this split screen image, the spleen has an inhomogeneous appearance on the low MI grey-scale image (to the readers’ right). On the late-phase CEUS image (readers’ left), contrast has washed out of the metastatic lesions and they are easily visualised within the enhanced splenic parenchyma.

Ectopic splenic tissue: splenunculi and splenosis

CEUS is useful in cases where there is doubt over the origin of a perisplenic mass. Characterisation of an accessory spleen (splenunculus) or of tissue that has arisen as post-splenectomy or trauma (splenosis) is aided by CEUS.

A splenunculus is typically found alongside the normal spleen in the LUQ. It is usually less than 3 cm in size, round or oval in shape and isoechoic with adjacent splenic parenchyma; a pedicle of flow from the splenic artery may be demonstrated with color Doppler ultrasound. In most cases, the diagnosis is straightforward and CEUS is not required; however, large or atypically located splenunculi can cause diagnostic uncertainty. Splenosis is auto transplantation of splenic tissue following trauma or surgery; splenic implants are most commonly found in the abdomen or pelvis and may easily be misinterpreted as pathological masses if the history of splenic trauma or surgery is not appreciated.

CEUS can confirm that a mass represents ectopic splenic tissue for both splenunculi and splenosis by demonstrating an enhancement pattern typical of normal spleen. A ‘zebra pattern’ may be seen in the parenchymal phase but, most importantly, the tissue will display persistent late-phase enhancement, differentiating the mass from other lesions such as pancreatic tail tumors, splenic hilar lymph nodes, adrenal lesions, ovarian masses and metastatic deposits, which do not have the characteristic of sequestrating contrast microbubbles and will show late- phase contrast washout (Figures 2 and 3). ⁹

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Figure 2.

Splenunculus. (a) An incidental finding of a soft tissue mass interposed between the spleen and left diaphragmatic crus (arrow) in this abdominal CT scan was interpreted as representing a left adrenal mass. Biochemical investigations for adrenal hyper-function were negative. (b) Grey-scale ultrasound demonstrates the mass deep to the spleen of similar echogenicity to splenic parenchyma (arrow). (c) Late-phase CEUS image shows that the mass remains avidly enhanced (identical to splenic parenchyma – arrows) indicating that this is a large unusually located splenunculus, not an adrenal mass.

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Figure 3.

Splenosis. (a) This patient has a history of splenectomy for trauma. As an incidental finding on CT, there is a large mass in the pancreatic tail showing rim calcification (arrow). (b) CEUS shows that the mass shows avid late-phase (7 min) enhancement indicating splenic tissue (arrows). (c) A nuclear medicine heat damaged red-cell scan image shows uptake of the radiopharmaceutical in the mass (arrow) confirming that it represents implanted splenic tissue (splenosis).

Differentiating benign from malignant splenic masses

Benign splenic lesions typically demonstrate no enhancement in any phase (Figure 4) or rapid enhancement followed by persistent late-phase enhancement.^3,10 Malignant splenic lesions characteristically demonstrate low level early diffuse or peripheral enhancement followed by washout of microbubbles in the late phases and become progressively hypo-enhancing.^3,11 CEUS can significantly improve the accuracy of diagnosis of focal splenic lesions. ¹² If a lesion has benign characteristics on CEUS, further evaluation with CT is of limited additional value. ¹³

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Figure 4.

Splenic haematoma. (a) In this patient with severe acute pancreatitis, conventional ultrasound demonstrates an echogenic mass at the splenic hilum (adjacent to the pancreatic tail). (b) Late-phase CEUS study demonstrates that the mass demonstrates no enhancement, consistent with a perisplenic haematoma complicating pancreatitis.

Haemangiomas are the most common benign splenic mass. Typically, haemangiomas are echogenic and measure less than 2 cm in diameter. In this situation, particularly when the patient does not have a known malignancy, these features are reassuring and CEUS is usually not required; interval imaging will be appropriate. Some splenic haemangiomas, however, have atypical features, including low echogenicity, cystic spaces or calcifications and therefore are not able to be characterised by conventional ultrasound. ¹⁴ Even when the grey-scale features are consistent with a haemangioma, but where it measures above 2 cm, where multiple lesions are identified or in a patient with a known malignancy, CEUS can provide additional reassurance that the lesion is benign by demonstrating a persistent late-phase enhancement pattern (Figure 5). However, it should be noted that the characteristic benign CEUS features may be less frequently seen in the more typical echogenic lesions than in lesions that are atypical on grey-scale imaging; CEUS is thus more reliable in the iso or hypoechogenic lesions. The nodular, peripheral arterial ehanancement pattern with gradual centripetal filling seen in many liver haemangiomas is uncommon in splenic haemangiomas, ¹⁵ and a subset of haemangiomas may be less well enhanced than splenic parenchyma in the late phase and cannot therefore be definitely distinguished from malignant lesions by their CEUS behaviour, ¹⁰ although the absence of large intra-lesional vessels makes a benign lesion more likely. ¹¹

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Figure 5.

Splenic haemangioma. (a) Incidentally discovered echogenic splenic mass. The grey-scale appearances are consistent with a haemangioma but it measures well over 2 cm in diameter. (b) In the arterial phase the mass is avidly enhanced and slightly hypervascular relative to adjacent splenic tissue (arrow). (c) In the late phase, the mass remains enhanced and is difficult to identify. The enhancement characteristics are those of a benign lesion and consistent with a haemangioma.

Hamartomas are uncommon benign splenic masses; they are sometimes grouped with haemangiomas as ‘benign vascular tumours’ and will also typically show persistent late-phase enhancement. ¹¹

Hyper or isoenhancement of a splenic mass in the arterial phase has also been shown to be an independent benign feature and is particularly valuable, as this characteristic is usually seen in the atypical iso or hypoechoic subset of benign vascular tumours. ¹⁶ Primary (non-lymphoma) malignant splenic tumours are exceptionally uncommon. Malignant splenic lesions are almost always either lymphoma or metastases. Splenic lymphoma is usually part of secondary disease and focal splenic lymphoma deposits are most commonly seen in non-Hodgkin’s lymphoma. Lesions may be single or multiple and are invariably echo-poor. The spleen is an uncommon site for non-lymphomatous metastases and, when metastases are present, there is usually disseminated malignancy; lung, breast and melanoma are the most common primary sites. Lesions may show a variety of appearances on conventional grey-scale ultrasound.

Both lymphoma and non-lymphomatous metastases are typically hypoenhancing in the arterial phase, often with visible intralesional vessels and perfusion defects, ¹⁶ characteristically show progressive microbubble washout during the CEUS study and are usually conspicuous during the late phase (Figures 1 and 6).

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Figure 6.

Large B cell lymphoma. (a) Incidental finding of a large echo-poor mass within the spleen. (b) Early-phase CEUS shows some enhancement predominantly within the periphery of the mass. (c) Late-phase CEUS shows that the bubbles have washed-out and the mass is almost completely unenhanced. In view of the malignant appearances a biopsy was performed showing large B cell lymphoma. (d) PET CT scan demonstrates that the lesion is intensely metabolically active and was shown to be the only site of disease.

Splenic infarction

The vascular supply to the spleen is via the splenic artery, a branch of the coeliac axis. It is an end artery with terminal branches. The spleen may become infarcted due to an embolic event or due to a thrombus of the splenic artery or one of these terminal branches. Potentially, this could result in global infarction of the organ, but more commonly, a segment of the spleen is affected. Venous infarction may also occur, secondary to splenic or portal vein thrombosis. Splenic infarction frequently presents with LUQ pain. With conventional sonography, the region of infarction is frequently isoechoic and difficult to identify in the acute phase. As the infarct matures, its appearances becomes more hypoechoic and conspicuous. The typical appearance is that of a wedge-shaped lesion, apex pointing toward the hilum and its base parallel with the splenic capsule, showing no internal flow with conventional colour Doppler ultrasound. ⁸ The boundaries of an infarct may be more clearly seen with CEUS and it can demonstrate the shape and extent of the lesion more accurately than with grey-scale sonography alone. Microbubbles will not be taken up in the region of infarct and typically, a geographic or wedge-shaped area of non-perfusion will be seen, most easily appreciated in the late phase of the examination (Figure 7). ¹³

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Figure 7.

Splenic infarction. (a) Grey-scale ultrasound shows an inhomogeneous splenic parenchyma with a lower echogenicity region in the middle third. (b) Late-phase CEUS split screen image shows a geographic region of reduced perfusion representing a large area of focal splenic infarction.

Splenic trauma

CT is the most appropriate imaging modality for most patients with major trauma, due to its speed, accuracy and ability to comprehensively image the entire body. Although focused ultrasound is sometimes used in the initial triage of patients with abdominal trauma (FAST ultrasound), predominantly to detect haemoperitoneum, conventional ultrasound is known to miss many parenchymal injuries and significant injury may be present in the absence of free-intraperitoneal fluid. ¹⁷ Ultrasound has been superseded by CT in most trauma settings.

Splenic lacerations and haematomas may be difficult to identify with conventional ultrasound, particularly when they are isoechoic. Splenic injuries are, however, usually easily identified using CEUS showing reduced or absent perfusion in the late phase (Figure 8). In one study of patients with solid-organ injuries detected by CT, using the ultrasound contrast agent Definity (Bristol Myers Squibb Imaging, Massachusetts, USA), CEUS successfully identified all the splenic injuries. ¹⁸ In patients with splenic trauma, CEUS may also be used to detect delayed splenic pseudo-aneurysms. ¹⁹

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Figure 8.

Splenic trauma. (a) Late-phase CEUS image demonstrating multiple splenic lacerations and intraparenchymal haematomas. (b) Corresponding CT image demonstrating splenic lacerations and perisplenic haematoma.

The EFSUMB guidelines ³ recommend the use of CEUS as an alternative to CT in stable patients with isolated moderate-energy abdominal trauma to rule out solid organ injuries (especially in children), to further evaluate equivocal CT findings and for the follow-up of injuries that are managed conservatively. CEUS has been shown to have high sensitivity and accuracy in identifying and grading traumatic abdominal organ injuries in patients with low-energy isolated abdominal trauma, ²⁰ and its use can be considered in patients who are haemodynamically stable. ²¹ The use of CEUS may be particularly beneficial in trauma patients where administration of iodinated contrast medium is undesirable. Occasionally, splenic rupture may occur in the absence of trauma. There is usually an underlying haematological disease or infection and splenomegaly is frequently present. ²² CEUS may help to demonstrate splenic lacerations and haematoma.

Conclusion

Splenic abnormalities are uncommon and often clinically silent. It is important that the spleen is carefully evaluated in all abdominal ultrasound examinations and splenic abnormalities will then be occasionally encountered. Conventional grey-scale ultrasound has a limited ability to characterise focal splenic lesions; the addition of CEUS will significantly improve the accuracy of detection and characterisation of focal splenic lesions. The absence of enhancement in any phase and persistent late-phase enhancement (particularly when accompanied by arterial phase hyperenhancement) are features that are associated with benign lesions. Arterial phase hypoenhancement followed by microbubble washout in the last phase is a feature of malignancy but is sometimes seen in atypical benign lesions, this enhancement pattern will usually indicate the need for further imaging and possibly biopsy.

CEUS is also a valuable technique in confirming the nature of accessory splenic tissue and for confirming splenic infarction in patients presenting with LUQ pain. It has a valuable role in selected patients with blunt abdominal trauma for diagnosis and follow-up of splenic injury. Contrast ultrasound is easy to perform, inexpensive and safe. It provides an invaluable additional to conventional and Doppler ultrasound of the spleen.