Iezzi 2009.

Clinical features and settings	People who underwent endovascular repair of an unruptured infrarenal AAA. Type of stents received: 81 aorto‐bi‐iliac stent grafts, consisting of 43 Talent (Medtronic AVE), 28 Excluder (WL Gore & Associates), 8 Zenith (Cook), 1 Vanguard, and 1 AneuRx (Medtronic AVE); and 3 aortomonoiliac stent grafts (Talent, Medtronic, AVE). Aneurysm diameter: 5.3 cm. Setting: department of radiology.
Participants	84 consecutive participants; 69 men; mean (± SD) age: 79.6 ± 5.2 years; range: 62‐89 years; mean (± SD) BMI: 27.4 ± 3.5 kg/m2; range: 22‐34.2 kg/m2. Comorbidities: not reported. Geography: Italy.
Study design	Prospective single centre cross‐sectional study.
Target condition and reference standard(s)	Target condition: endoleak. Definition of endoleak: persistent perigraft flow within aneurysmal sac excluded by stent graft. Endoleaks classified according to size and aetiology. Endoleak (absolute n): 40. Prevalence of endoleak: 47.6% (40/84). Reference standard: multidetector row helical CT scanner. Image acquisition: "unenhanced images were obtained with a slice collimation of 2.5 mm, whereas a 1‐mm slice collimation was used for contrast‐enhanced acquisitions, obtained after bolus intravenous injection of 120 mL of iodinated nonionic contrast medium (Iomeprol 300 mg/mL, Iomeron; Bracco) at a flow rate of 3 mL/s through an antecubital vein. Delayed‐phase acquisition, focused on the endovascular graft, was performed 60 seconds after contrast medium injection;" thickness: unenhanced images were obtained with a slice collimation of 2.5 mm, whereas a 1‐mm slice collimation was used for contrast‐enhanced acquisitions. Type of CT scanner: Somatom Plus 4 Volume Zoom (Siemens, Forchheim, Germany). Use of contrast: 120 mL iodinated non‐ionic contrast medium (Iomeprol 300 mg/mL, Iomeron; Bracco).
Index and comparator tests	Index test: CDUS. Image production: axial and longitudinal and acquisition scans used for US imaging. CEUS scans performed after administration of bolus of 2 different doses of contrast agent dissolved in 0.9% saline solution (1.2 mL and 2.4 mL), each followed by flushing with 5 mL bolus of saline solution through an 18‐ to 20‐gauge cannula placed in arm vein. A minimum interval of 10 minutes and complete bubble destruction, which was achieved by scanning entire abdominal aorta at a high mechanical index, required between the 2 injections to avoid carryover effects. Scanning started at beginning of contrast agent injection and sweep was usually completed within 5 minutes. Phases of CE‐CDUS defined as arterial (10‐40 s after contrast agent injection) and late (90‐300 s after injection). Type of US: convex multi‐frequency 5 to 2 MHz probe, Philips HDI 5000 scanner (Philips Medical Systems, Bothell, WA, USA). Use of contrast: second‐generation contrast agent (SonoVue, Bracco, Milan, Italy) made of sulphur hexafluoride‐filled microbubbles with flexible shells that allow real‐time imaging at low acoustic pressure (mechanical index range: 0.12‐0.14). Operator: 2.
Follow‐up	"All patients completed the protocol, and no adverse events were recorded during CEUS or multidetector CT examinations."
Notes	Secondary objective: to define optimal dose of second‐generation contrast agent to routinely use in CEUS examinations for endoleak detection. Readers independently assigned a confidence level for endoleak diagnosis using 5‐point scale: 1, certainly absent; 2, probably absent; 3, possibly present; 4, probably present; and 5, certainly present. Readers were informed that a confidence level ≥ 3 represented positive diagnosis of endoleak. Test analysis showed excellent interobserver agreement (analysis value ≥ 0.89) in all reading sessions for endoleak detection. Mean (± SD) follow‐up after EVAR: 8.6 ± 5.4 months; range: 1‐24 months. US assessors "reviewed videotapes of each patient during three different sessions: (1) the baseline unenhanced US scan ‐ session A (CDUS), (2) CEUS after the administration of 1.2 mL of the contrast agent ‐ session B, low‐dose contrast‐enhanced (LDCE) US imaging, (3) CEUS after the administration of 2.4 mL contrast medium ‐ session C, high‐dose contrast‐enhanced." "Patients with unstable general conditions, such as heart failure (New York Heart Association class IV), severe chronic bronchopulmonary disorders, severe pulmonary hypertension, or uncontrolled hypertension were excluded."
Table of Methodological Quality
Item	Authors' judgement	Description
Representative spectrum? All tests	Yes	Participants represented average patients that after receiving EVAR are exposed to endoleak surveillance. "The study enrolled all patients treated with EVAR who underwent CTA as part of a routine surveillance programme at 1, 6, and 12 months after the procedure and annually thereafter. They underwent CTA and CDUS and CEUS imaging on the same day. To avoid selection bias in favor of patients who were 'easy to scan', patients were recruited before undergoing a baseline US scan. No patient was excluded on the basis of poor technical quality of the baseline US study."
Acceptable reference standard? All tests	Yes	Reference standard was CTA.
Acceptable delay between tests? All tests	Yes	Index test and reference standard performed on same day.
Partial verification avoided? All tests	Yes	All study participants accounted for and results of reference standard reported for all.
Differential verification avoided? All tests	Yes	All participants who received index test subjected to same reference standard.
Incorporation avoided? All tests	Yes	Index test not part of reference standard.
Reference standard results blinded? All tests	Yes	"US examinations were randomly reviewed independently by two radiologists not involved in the imaging, one radiologist specialized in vascular radiology (D. P. with 10 years of experience) and the other in CEUS (R. B. with 15 years of experience), and neither was aware of the CTA outcomes or dose of contrast used for CEUS."
Index test results blinded? All tests	Yes	"The radiologist was blinded to all other imaging findings at the time of examinations."
Relevant clinical information? All tests	Yes	Yes.
Uninterpretable results reported? All tests	Yes	"None of the CTAs resulted in an uncertain diagnosis (score 2)". "Endoleaks classification: two large endoleaks were not clearly classified by CTA (differential diagnosis between type II and type III endoleak). These two patients underwent selective conventional angiography that detected two type II endoleaks due to retrograde flow into the aneurysm sac through lumbar arteries. Five small type II endoleaks were detected only on delayed phase and were classified as low‐flow leaks."
Withdrawals explained? All tests	Yes	"All patients completed the protocol, and no adverse events were recorded during CEUS or multidetector CT examinations."