Abstract
Contrast-enhanced ultrasound (CEUS) has emerged as an additional modality to enhance color duplex ultrasound, with the potential to better detect and classify the type of endoleak and target-vessel patency. CEUS is the result of synergic integration between ultrasound contrast agents and dedicated hardware and software platforms. The endograft can be visualized with CEUS over approximately 5 to 10 minutes, imaging the endograft from different angles to assess the perfused lumen with high temporal resolution. Thrombotic material can be appreciated as a focal defect, located at the wall of the aneurysm sac or adjacent to the endograft. The European Federation of Societies for Ultrasound in Medicine and Biology has recommended CEUS for the detection, classification, and follow-up of abdominal aortic aneurysm (AAA) endoleaks. CEUS has some limitations as the sole imaging modality for EVAR surveillance, because of its “operator dependency” and certain patient characteristics, such as obesity (body mass index [BMI] >30), ascites, and conditions with abundant intestinal gas, which can create technical problems. Another potential disadvantage of CEUS is its relative inability to detect fractures or component separation of the metal skeleton of an endograft.
Keywords
contrast-enhanced ultrasound, contrast medium, endograft complications, endoleaks, EVAR
Acknowledgment
We would like to express our deepest appreciation to Ms. Angelica Pecchioli, who has helped us to coordinate the entire EVAR follow-up since 1999, and who embraced with the same enthusiasm and passion the CEUS project at our Vascular Unit.
The optimal protocol for imaging and timing of endovascular aortic aneurysm repair (EVAR) follow-up is still being developed. Various follow-up modalities are employed to measure aortic sac diameter, to detect and classify endoleaks, to detect morphologic details of the stent-graft (e.g., graft occlusion), and to detect imaging evidence of endograft infection and other details. A recent systematic review reported that more than 90% of EVAR patients undergoing follow-up do not benefit from surveillance, since imaging alone initiates asymptomatic secondary interventions (SIR) in only 1.4% to 9% of patients. Therefore the least invasive and safest EVAR follow-up protocol is needed so that radiation-induced and other complications from surveillance imaging do not exceed the risk of complications from EVAR itself. The “Achilles’ heel” of EVAR is the presence of endoleak and the indication/timing for SIR, especially for type II endoleaks, the most commonly encountered variety. This chapter examines the role of contrast-enhanced ultrasound (CEUS) in the follow-up of patients after EVAR.
Literature Review
A real-time imaging modality, CEUS is gaining popularity in different settings of vascular medicine because it has zero potential morbidity and no risk of contrast-induced nephropathy or radiation exposure. This is in marked contrast to the current “gold standard” technique of computed tomography angiography (CTA). CEUS has emerged as an additional modality to enhance color duplex ultrasound, with the potential to better detect and classify the type of endoleak and target-vessel patency. CEUS allows for superior visualization of the aorta and its main branches. CEUS is the result of synergic integration between ultrasound contrast agents and dedicated hardware and software platforms. The endograft can be visualized with CEUS over approximately 5 to 10 minutes, imaging the endograft from different angles to assess the perfused lumen and evaluate low-flow states with high temporal resolution. Thrombotic material can be appreciated as a focal filling defect, located at the wall of the aneurysm sac or adjacent to the endograft.
The agents used in CEUS are stabilized microspheres consisting of sulfur hexafluoride or perfluorocarbon encapsulated by a phospholipid shell. Ultrasound contrast agents are administered by intravenous injection and are strictly confined in the vascular space (blood-pool agents), where they strongly enhance the blood’s acoustic signal. Ultrasound microbubbles act similar to red blood cells. The effectiveness of these contrast agents depends on their echogenicity (ability of gas inside microbubbles to reflect ultrasound), concentration (number of bubbles), and harmonic answer (special behavior of bubbles when exposed to ultrasound beam). These microbubbles show nonlinear behavior when examined on an ultrasound machine with a low mechanical index.
Reports show that CEUS has high sensitivity and specificity in detecting endoleaks compared with CTA, with values of 92% to 100% and 82% to 100%, respectively. CEUS imaging has proved to be as good as CTA in detecting endoleaks because of its real-time dynamic nature. It is even better able to quantify flow and characterize the different endoleak types than CTA because of the latter’s limited ability to show the direction of flow. CEUS can be as sensitive as CTA in detecting the endoleaks that would normally warrant an immediate intervention (types I and III), as well as endoleaks (type II) that CTA might miss. CEUS can help determine the origin of these endoleaks and can provide ultrasound parameters of type II endoleaks that predict a high risk for aneurysm sac pressurization and rupture.
High-flow endoleaks are detected with simultaneous enhancement inside and outside the graft in types I and III ( Figs. 4.1 and 4.2 ). For type II endoleaks, the source of the nidus can be identified ( Fig. 4.3 ). With type IV endoleaks, however, no enhancement outside the graft is detectable, even in very late phase (>2 minutes) ( Fig. 4.4 ). An important role for CEUS is the follow-up of patients with previous EVAR who received SIR with coils, plugs, or glues. In this setting, CEUS is reliable for monitoring coil-embolized sacs containing tantalum-enhanced glues, avoiding artifacts inherent in CTA images. Moreover, Gargiulo et al. suggested the use of three-dimensional (3D) CEUS for follow-up of fenestrated EVAR, providing a reconstruction of the fenestrated endograft and its target vessels that is easier to interpret than CTA or two-dimensional (2D) CEUS.
Since 2011, the European Federation of Societies for Ultrasound in Medicine and Biology has recommended CEUS for the detection, classification, and follow-up of abdominal aortic aneurysm (AAA) endoleaks. CEUS has some limitations as the sole imaging modality for EVAR surveillance, however, because of its “operator dependency” and certain patient characteristics, such as obesity (body mass index [BMI] >30), ascites, and conditions with abundant intestinal gas, which can create technical problems. Another potential disadvantage of CEUS is its relative inability to detect fractures or component separation of the metal skeleton of an endograft.
San Giovanni di Dio Hospital Experience
The CEUS experience at the San Giovanni di Dio Hospital, Florence, Italy, is one of the largest for EVAR follow-up. We have performed CEUS routinely for EVAR follow-up since 1999, when the first EVAR procedure was performed at our center.
At the beginning, EVAR surveillance at our tertiary referral center was based on plain abdominal radiography (RX), color duplex ultrasound (CDU), and CTA. From 2012, CEUS was performed for the following indications:
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Detection of an endoleak
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Significant aneurysm expansion (e.g., sac growth >5 mm within 6 months)
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Patient with renal insufficiency (e.g., ≥stage 3 chronic kidney disease [CKD] classification)
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Patient with iodine contrast allergy
Our current postoperative EVAR protocol is a 1-month follow-up consisting of CTA, CDU, plain RX, and clinical checkup. CEUS is performed selectively, based on the four indications. Thereafter, clinical checkup, CDU, and plain RX are performed every 6 months. Currently, CTA is reserved in our center for any abnormalities or nondiagnostic imaging, or to plan SIR.
A standard CDU is always performed before CEUS. After overnight fasting, a sagittal or transverse scan of the supine patient is performed using the probe. B-mode imaging is used initially to identify the aorta, while the maximum diameter of the aneurysmal sac is measured in the transverse plane. The patency of renal arteries is confirmed using spectral Doppler ultrasound. The aorta is scanned from the proximal attachment site of the endograft to the distal point. Using color and spectral Doppler ultrasound, the stent is assessed for perigraft flow, graft stenosis, thrombosis, kinking, and endoleaks, according to the reporting standards for EVAR.
CEUS is then performed with the same ultrasound machine; always by an experienced vascular surgeon. A low mechanical index (varying from 0.2 to 0.30) is used to avoid early destruction of the microbubbles. A 2.5- to 5-MHz probe (Esaote, Genoa, Italy) is employed. The contrast used is a second-generation agent (SonoVue; Bracco, Milan, Italy) made of sulfur hexafluoride–filled microbubbles with flexible lipid shells, eliminated through the respiratory system. Its use is contraindicated in patients with unstable angina, recent episode of acute coronary syndrome (<14 days), or severe chronic obstructive lung disease with a recent exacerbation. As such, all patients are screened for the contraindications before contrast administration.
Contrast techniques apply a low acoustic pressure to produce images based on nonlinear acoustic interaction between the ultrasound system and the microbubbles. The microbubbles oscillate and resound, allowing continuous display of contrast enhancement on gray-scale images. A single bolus of 5 mL is administered through an 18-gauge cannula placed in the antecubital fossa, followed by 5 mL of normal saline flush. We prefer to inject this larger amount of contrast agent to increase both sensitivity and specificity of the examination in detecting endoleaks; literature reports a dose of 1 to 2.5 mL for the first bolus, generally with a similar amount of contrast for the second bolus. Immediate endoleak enhancement would suggest a graft-related type I or III endoleak, whereas a delay of greater than 5 seconds suggests a type II endoleak. Indeed, in all patients in this study in whom a type I endoleak was observed, contrast enhancement was seen arriving in the aneurysm and stent-graft simultaneously (see Fig. 4.1 ).
Findings are reviewed and discussed at a multidisciplinary team meeting of vascular radiologists and vascular surgeons, to arrive at a diagnosis and formulate an appropriate management plan.
Between 2012 and 2016, EVAR surveillance prompted 318 CEUS scans (median age, 78; range, 67-92; 255 males). The main indications for CEUS were the presence of any endoleak ( n = 160; 50%); significant aneurysm expansion, with sac growth greater than 5 mm within 6 months ( n = 34; 11%); and patients with renal insufficiency (≥stage 3 CKD: n = 91; 29%) or iodine contrast allergy ( n = 33; 10%) ( Fig. 4.5 ). Median follow-up after EVAR was 78 months (range, 0-207 months). CEUS was compared to CTA in the first 100 patients and had 100% sensitivity and 100% specificity for classification of endoleaks. Moreover, CTA misclassified two type II endoleaks (one as type I and one as type III). In all cases, CEUS was able to detect and classify endoleaks. The frequency of type I, II, III, and IV endoleaks was 16 (10%), 139 (86%), 3 (2%), and 3 (2%), respectively ( Table 4.1 ). During the 4-year period since CEUS introduction, the rate of SIR for screened patients was 11% (36). Need for SIR was prompted by CEUS when all the following three criteria occurred:
- 1.
Sac growth greater than 5 mm within 6 months
- 2.
Presence of any endoleak
- 3.
Contrast enhancement persisting longer than 60 seconds
