Contrast-enhanced ultrasound (CEUS) in the diagnostic evaluation of popliteal artery aneurysms, a single-center study

BACKGROUND: Popliteal artery aneurysms (PAA) are the most common peripheral artery aneurysms. Most common cause is arteriosclerosis. Acute thromboembolic limb ischemia and rupture of the PAA depict severe complications. Diagnostic tools for identifying PAAs are (Doppler) ultrasound, CT/MR angiography and DSA. PURPOSE: The aim of the present retrospective single-center study is to assess the application and safety of CEUS for assessing untreated and treated PAAs. MATERIALS AND METHODS: 13 patients were included in this study on whom CEUS was performed between 2007–2016. CEUS examinations were performed and interpreted by an experienced single radiologist (EFSUMB Level 3). RESULTS: CEUS allowed for the detection of PAAs in all cases. CEUS allowed for detection of partial thrombosis of PAA in 7/8 of untreated patients, proper exclusion of PAA upon femoro-popliteal bypass in 3 patients, incomplete exclusion of PAA upon femoro-popliteal bypass in 1 patient and ruling out of in-stent stenosis in 1 patient. CONCLUSION: CEUS is a useful and safe tool for in real-time evaluation of PAAs in the pre-/post-treatment status. In addition to conventional (Doppler) ultrasound and as an alternative tool to more elaborate imaging modalities, CEUS might be integrated in the future diagnostic work-up and follow-up of PAA patients.

Keywords: Popliteal arterial aneurysm; PAA; arteriosclerosis; ultrasound; CEUS

Although popliteal artery aneurysms (PAA) depict a rare form of peripheral aneurysms with an incidence of less than 1% [[1]], they are the most common of peripheral arterial aneurysms with a diameter >0.7 cm [[2]]. There is a predilection for men with a male: female-ratio ranging between 1:10–1:30, aged between 65–80 years [[3], [5]]. The aetiopathogenesis presumably is multifactorial. Besides arteriosclerosis as the main cause, other risk factors are smoking, familiar predisposition, trauma, Marfan's or Ehlers-Danlos syndrome and Behçet's disease [[6]]. Single or multiple aneurysms may occur along the popliteal artery.

PAAs often are associated with abdominal aortic aneurysms (AAA), in up to 30–50% of the cases, and are often being overlooked in the practical examination.

Many PAA patients are asymptomatic at the time of diagnosis and become symptomatic with a likeliness of 14% of cases/year [[8]]. More than half the patients present symptoms like acute thromboembolic limb ischemia, more moderate symptoms comprise pain, discomfort, calf claudication and swelling of the lower extremity due to displacement of adjacent nerves and veins, with risk of potentially resulting in deep vein thrombosis (DVT) in 5% of cases [[9]]. A severe complication is rupture of the PAA which occurs in 1–2.5% cases [[10]] and is associated with high morbidity and limb loss [[11]].

The non-invasive imaging modality of choice for identifying PAAs is Doppler ultrasonography [[13]]. MR and CT and digital substraction angiography (DSA) may complement the diagnostic work-up of PAAs [[15], [17]]. PAAs may be missed by conventional angiography in case of arterial occlusion. MRI helps to differentiate thrombotic material from aneurysmal sac [[2]].

Clinical management of PAA comprises conservative and surveillance concepts, open repair with bypass grafting preferably using veins and ligation of the aneurysm or endovascular repair (open vs. endovascular repair) [[19], [21], [23]]. The indication for treatment of asymptomatic PAAs is still a matter of debate.

In our present retrospective single-center study, we evaluated the use of CEUS in visualizing microperfusion of PAAs in the pre- and post-treatment status.

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, Chicago, Illinois, USA; Siemens Ultrasound Sequoia, ACUSON Sequoia, Mountain View, California, USA; Philips Ultrasound iU22, EPIQ 7, Seattle, USA). A low mechanical index was used to avoid early destruction of microbubbles (<0.2). For all CEUS examinations second-generation blood pool contrast agent SonoVue® (Bracco, Milan, Italy) was used [[24]]. It is a purely intravascular contrast agent that does not diffuse into the interstitial space, thus allowing for dynamic assessment of microcirculation [[25]]. 1.5–2.4 ml of SonoVue® were applied. 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 13 patients on whom CEUS was performed between 2007-2016 were included in this retrospective monocenter study.

CEUS was successfully performed on all included 13 patients without occurrence of any adverse effects (Table 1).

Table 1 Included PAA patients. AAA = abdominal aortic aneurysm, Fem.-pop. bypass = femoro-popliteal bypass, EVAR = endovascular aneurysm repair

The mean age of the included patients at the time of CEUS performance was 65 years (range: 44–81 years). All of the included patients were men. The mean diameter of PAAs was 2.7 cm (range: 1.5–3.8 cm), of which 8 were located left and 3 on the right side, in one case bilateral PAAs were registered. Nearly half of the patients (6/13) had concomitant AAA of whom 3 were treated before CEUS examination was performed.

7 of 8 (88%) untreated PAAs partially featured areas without contrast enhancement upon i.v. application of SonoVue® indicating partial thrombosis of the aneurysm (Fig. 1.A/B). 5/8 of the untreated patients with PAA also underwent CT or MRI scans by which partial thrombosis could be validated (Fig. 1.C).

Graph: Fig. 1 Partial thrombosis of popliteal artery aneurysm on the left side. A) CEUS image in longitudinal plane. B) CEUS image in transverse plane depicts circumferential partial thrombosis of the popliteal artery aneurysm. C) Corresponding CT scan in arterial phase shows circumferential thrombosis of PAA on the left side (red arrow), axial reformation.

CEUS showed a 100% sensitivity in detecting partial thrombosis of untreated PAA compared to CT/MRI scans. 4 patients already underwent femoro-popliteal bypass surgery and 1 patient underwent endoluminal popliteal stent graft before CEUS was performed. In 3 of 4 of the patients who underwent femoro-popliteal bypass proper exlusion of the underlying popliteal artery aneurysm without any contrast enhancing spots could be visualized using CEUS. In patient #12 who underwent femoro-popliteal bypass surgery 15 months before, no hypervascularization could be detected in Doppler mode, whereas cranial and caudal poles showed dim contrast enhancement during CEUS indicating incomplete exclusion of the PAA by the bypass (Fig. 2.C).

Graph: Fig. 2 Incomplete exclusion of popliteal artery aneurysm by femoro-popliteal bypass.A) Native B-mode image illustrates 6.5 x 4.0 x 5.0 cm measuring popliteal artery aneurysm. B) No perfusion of the popliteal artery aneurysm is registered in Color Doppler. C) CEUS reveals incomplete exclusion of the PAA as microbubbles are seen in cranial and caudal poles after femoro-popliteal bypass was set.

Besides complete exclusion of the PAA after femoro-popliteal bypass, post-operative hematoma without any signs of active bleeding could be registered in patient #13 (Fig. 3.C).

Graph: Fig. 3 Popliteal stent graft with adjacent hematoma and without active bleeding. A) Native B-mode image depicts PAA (yellow arrow), stent graft (white arrow) and 6.0 cm measuring surrounding semiliquid hematoma (red arrow). B) Color Doppler image illustrates strong perfusion signal in popliteal stent graft (white arrow). C) CEUS image shows homogeneous contrast enhancement within the stent graft. No extravasating microbubbles in terms of incomplete exclusion of the popliteal aneurysm or active bleeding could be observed. D) Ultrasound-guided puncture (yellow arrow) and drainage of the hematoma (red arrow).

By means of CEUS, in-stent stenosis or endoleak could be excluded in patient #3 receiving intraluminal popliteal stent graft (Fig. 4.).

Graph: Fig. 4 Popliteal stent graft on the right side. A) Native B-mode image shows right-sided popliteal arterial stent graft (orange asterisk). B) Color Doppler image shows strong endoluminal perfusion signal in popliteal stent graft (orange asterisk). C) CEUS correlate depicts homogeneous distribution of the microbubbles without any perfusion deficit or thrombosis (orange asterisk).

Without doubt ultrasonography is indispensable in the daily clinical routine in angiology and vascular surgery and depicts the major non-invasive imaging modality in both specialties.

Ultrasound is the first imaging modality for pathologies of the carotid arteries like stenosis or dissection [[27]]. CEUS allows for evaluating microperfusion of carotid plaques, thereby distinguishing symptomatic vs. asymptomatic plaques [[29]]. In-stent stenosis of carotid stents can be identified by means of CEUS [[29]]. Of note, intratumoral microperfusion and devascularization after interventional embolization could be visualized by means of CEUS [[31]].

Doppler ultrasound is the mainstay of community-based or national routine screening programs for AAAs [[33]]. Recent and future portable and even fully-automated ultrasound devices will make ultrasonography a more powerful and widespread diagnostic tool for many different pathologies in many specialties that may also be performed by untrained personnel [[34], [36]]. Noteworthy, CEUS enables to dynamically detect endoleaks after endovascular aneurysm repair (EVAR) and shows similar to higher sensitivity and similar specificity than CT angiography [[37], [39]] without exposing the patient with ionizing radiation or application of iodinated contrast agents.

Screening for PAA especially in patients with risk factors such as concomitant AAA is of critical value. Particularly patients with PAA of 20 mm or more in diameter, accompanying atrial fibrillation and mural thrombosis in PAA ought to be screened regularly as those are associated with progression of PAA [[40]]. More, upon surgery for PAA, patients are at risk of developing new PAAs, thus lifelong surveillance is recommended [[41]]. Since arteriosclerosis, being mainly causative for PAA, often affects renal function and thus resulting in chronic kidney failure, i.v. application of contrast agents in CT an MRI should be well deliberated whether benefits outweigh potential risks like aggravated impairment of renal function. Here, the advantages of CEUS should be emphasized as a non-ionizing, cost-effective, easily accessible and repeatable imaging modality [[42]] that may be also used in patients with affected kidney function, hyperthyroidism [[24]] or even as recently shown in pregnant patients [[25]].

Besides the high diagnostic accuracy of CEUS for identifying PAAs, our findings indicate that CEUS is an eligible imaging modality for in real-time assessment of the status of PAAs post-treatment: in 1 patient incomplete exclusion of the PAA upon femoro-popliteal bypass could be visualized; in 2 patients who underwent bypass surgery and in 1 patient who received endoluminal stent graft proper post-treatment status could be ascertained. Of course, our findings need to be further validated in larger cohorts but suggest the possibility of CEUS being additionally used to Doppler ultrasound and reduce the necessity or even replace more elaborate imaging modalities as CT, MRI and DSA which are more frequently associated with adverse effects.

To our knowledge, this is the first study to assess the application of CEUS for evaluating PAA in the pre- and post-treatment situation.

High diagnostic accuracy of CEUS in addition to Doppler sonography, the ability of real-time imaging and less adverse effects compared to CT, MRI and DSA are convincing aspects and hold considerable promise that CEUS being prospectively integrated as a solid component within the clinical algorithm for management of PAAs.

Limitations of the present single-center study are its limited number of included patients and differing ultrasound systems as well as its retrospective character with only a single reader interpreting all examinations during a quite long period of time.