Individualizing Surveillance after Endovascular Aortic Repair Using a Modular Imaging Algorithm.

OBJECTIVES: Surveillance after endovascular aortic repair (EVAR) and fenestrated EVAR (FEVAR) is mainly directed by one-size-fits-all approaches instead of personalized decision making, even though treatment strategies and often endografts themselves are tailor-made to adjust for individual patients. We propose a modular imaging algorithm that escalates surveillance imaging based on invasiveness and need. MATERIALS AND METHODS: In this retrospective observational study of single-center data, results of a modular imaging algorithm were analyzed. The algorithm is characterized by initiating the examination with standard B-mode then transitioning to Duplex ultrasound, B-Flow, and CEUS. Additional CT(A) studies are conducted where required. The study population included both patients receiving EVAR or FEVAR. A comparative analysis was conducted regarding endoleak detection. RESULTS: The study population included 28 patients receiving EVAR and 40 patients receiving FEVAR. They accounted for 101 follow-up visits, which led to 431 distinct imaging studies. CEUS has the highest endoleak detection rate, followed by CTA and B-Flow. Duplex ultrasound and B-Flow resulted in 0 and 1 false positive cases, respectively, considering CEUS the reference standard. In a select group of six patients, CEUS was omitted after endoleaks were displayed by Duplex ultrasound or B-Flow, leading to a successful type II coiling and no aneurysm-related adverse events. CONCLUSIONS: The proposed modular algorithm showed great potential to incorporate principles of personalized medicine in surveillance after endovascular aortic treatment. Since Duplex ultrasound and B-Flow rarely cause false positive endoleaks, more resource-intensive and invasive imaging studies such as CEUS and CTA can be omitted after positive identification.

Ultrasound Coded-Excitation Imaging for Endoleak Detection After Complex Endovascular Aortic Repair.

OBJECTIVES: Several imaging modalities have been suggested for surveillance after fenestrated endovascular aortic repair in general and endoleak detection in specific. In the present project a coded excitation-based ultrasound (B-Flow) was investigated for endoleak detection after complex endovascular aortic repair. METHODS: Patients post complex endovascular aortic repair (FEVAR or T/FEVAR) undergoing follow-up appointments including ultrasonography of the aorta at a vascular and endovascular surgery outpatient center were included in the study. B-Flow was compared with computed tomography angiography (CTA), Duplex ultrasound (DUS), and contrast-enhanced ultrasound (CEUS) regarding agreement and reliability for endoleak detection and characterization. RESULTS: In total, 47 follow-ups were included. They accumulated in a total of 149 imaging investigations. Endoleaks were discovered in 44.7% of B-Flow studies and a majority of these endoleaks were classified as type II. Agreement between B-Flow and other imaging modalities was good (>80.0%) in general. However, with B-Flow 6 and 2 endoleaks would have been missed compared with CEUS and CTA, respectively. Regarding endoleak classification, B-Flow had a strong agreement (94.5%) with CEUS in detected cases. Furthermore, in a limited subset analysis, imaging findings were externally validated using findings from angiography. CONCLUSIONS: Ultrasonography allows for endoleak detection and characterization without an invasive procedure or the use of potentially nephrotoxic contrast medium and can reduce radiation exposure. While CEUS mitigates issues of radiation and nephrotoxicity it still requires the intravenous application of contrast enhancers. Ultrasound coded-excitation imaging such as B-Flow could therefore further simplify endoleak surveillance after fenestrated endovascular aortic repair.

Endoleak Detection after Endovascular Aortic Repair via Coded-Excitation Ultrasound-A Feasibility Study.

Endoleaks are the most common complication after endovascular aortic repair (EVAR). Their correct identification is one of the main objectives of surveillance protocols after EVAR. So far, computed tomography angiography (CTA), contrast-enhanced (CEUS) and Duplex ultrasound (DUS), as well as magnetic resonance angiography, have been investigated for their ability to detect endoleaks. In general, all technologies have distinct benefits and disadvantages, with CTA and CEUS emerging as the reference standard for surveillance after EVAR. However, they are both contrast-enhancer-dependent, and CTA additionally exposes patients to ionizing radiation. In the present study, we investigated B-Flow, a type of coded-excitation ultrasound that was specifically designed to optimize the visualization of blood flow, for its ability to detect endoleaks, and compared its performance to CEUS, CTA, and DUS. In total, 34 patients were included in the analysis that accumulated in 43 distinct B-Flow investigations. They underwent a total of 132 imaging investigations. Agreement between B-Flow and other imaging modalities was high (>80.0%), while inter-method reliability can be interpreted as good. However, with B-Flow, six and one endoleaks would have been missed compared to CEUS and CTA, respectively. Regarding endoleak classification, all metrics were lower but retained an adequate level of comparison. In a subset of patients requiring intervention, B-Flow had 100% accuracy regarding both endoleak detection and classification. Ultrasonography enables endoleak detection and classification without the need for pharmaceutical contrast enhancement or radiation. Ultrasound coded-excitation imaging in the application of B-Flow could further simplify surveillance after EVAR by offering adequate accuracy without requiring intravenous contrast enhancement. Our findings may promote subsequent investigations of coded-excitation imaging for endoleak detection and classification in the surveillance after EVAR.

Clinical Applications of B-Flow Ultrasound: A Scoping Review of the Literature.

Coded excitation ultrasound investigations have the potential to augment the resolution, increase the efficiency, and expand the possibilities of noninvasive diagnostic imaging. B-Flow ultrasound, a type of digitally encoded imaging, was developed more than 20 years ago with the aim to optimize the visualization of blood flow. It has been investigated for a plethora of applications so far. A scoping review regarding its clinical applications was conducted based on a systematic literature research. B-Flow has been investigated in various anatomic locations and pathologies. However, previous research is limited by small sample sizes, the rare occurrence of elaborate study designs, the reliance on subjective reports and qualitative data, as well as several potential biases. While results are in general promising, it should therefore still be considered an emerging technology. Nevertheless, the limitations can be addressed in future research and the potential to expand its applications make B-Flow an interesting candidate for further investigations.

Degree of contralateral carotid stenosis improves preoperative risk stratification of patients with asymptomatic ipsilateral carotid stenosis.

OBJECTIVE: The benefit of carotid surgery in asymptomatic patients with high-grade internal carotid artery stenosis (ICAS) is subject of intense debate, and thus improved preoperative risk stratification is mandatory. This study aimed to investigate the predictive value of contralateral ICAS (cl-ICAS) for the preoperative clinical presentation of patients with ipsilateral ICAS (primary outcome). METHODS: This study was a post hoc analysis of a prospective cohort comprising 485 consecutive patients undergoing carotid endarterectomy for high-grade ICAS. Patients were classified by their clinical presentation, ie, asymptomatic (n = 213) or symptomatic (within 6 months of surgery; n = 272, comprising both transient ischemic attack [TIA; n = 163] and stroke [n = 109]). We investigated the association of cl-ICAS with the primary outcome in adjusted regression models. RESULTS: Mean ipsilateral degrees of ICAS were similar in both groups (84% ± 10% vs 84% ± 11%; P = .92), whereas contralateral degrees were significantly higher in the symptomatic group (29% ± 34% vs 38% ± 39%; P = .008). After multivariable regression analysis, cl-ICAS >60% conferred a three times higher preoperative stroke risk (odds ratio, 3.31; 95% confidence interval, 1.98-5.54; P < .001). Inclusion of cl-ICAS significantly improved (P = .001) ipsilateral combined TIA and stroke risk prediction based on established risk factors (area under the curve, 0.66; 95% confidence interval, 0.60-0.72; P < .001). CONCLUSIONS: Our study identifies a high contralateral degree of ICAS as an independent predictor of preoperative ipsilateral TIA and stroke in patients with ipsilateral high-grade ICAS. Therefore, such patients might rather benefit from elective carotid surgery and intensive postoperative medical care.

The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury.

In the event of a myocardial infarction, current interventions aim to reopen the occluded vessel to reduce myocardial damage and injury. Although reperfusion is essential for tissue salvage, it can cause further damage and the onset of inflammation. We show a novel anti-inflammatory effect of a fibrin-derived peptide, Bbeta15-42. This peptide competes with the fibrin fragment N-terminal disulfide knot-II (an analog of the fibrin E1 fragment) for binding to vascular endothelial (VE)-cadherin, thereby preventing transmigration of leukocytes across endothelial cell monolayers. In acute or chronic rat models of myocardial ischemia-reperfusion injury, Bbeta15-42 substantially reduces leukocyte infiltration, infarct size and subsequent scar formation. The pathogenic role of fibrinogen products is further confirmed in fibrinogen knockout mice, in which infarct size was substantially smaller than in wild-type animals. Our findings conclude that the interplay of fibrin fragments, leukocytes and VE-cadherin contribute to the pathogenesis of myocardial damage and reperfusion injury. The naturally occurring peptide Bbeta15-42 represents a potential candidate for reperfusion therapy in humans.

Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a "humanized" SCID mouse model.

Paclitaxel is an alkaloid that inhibits endothelial cell proliferation, motility, and tube formation at nanomolar concentrations. Cationic liposome preparations have been shown to target blood vessels. We wished to explore the possibility that paclitaxel encapsulated in cationic liposomes carries paclitaxel to blood vessels and thereby provides an antiangiogenic effect. We used a humanized SCID mouse melanoma model, which allowed us to analyze tumor growth and tumor angiogenesis in an orthotopic tumor model. Here, human melanoma cells grow on human dermis and are in part nourished by human vessels. We show that paclitaxel encapsulated in liposomes prevents melanoma growth and invasiveness and improves survival of mice. Moreover, liposome-encapsulated paclitaxel reduces vessel density at the interface between the tumor and the human dermis and reduces endothelial cell mitosis to background levels. In contrast, equimolar concentrations of paclitaxel solubilized in Cremophor EL(R) had only insignificant effects on tumor growth and did not reduce the mitotic index of endothelium in vivo, although the antiproliferative effect of solubilized paclitaxel in Cremophor EL(R)in vitro was identical to that seen with liposome-coupled paclitaxel. In conclusion, we present a model of how to exploit cytotoxic effects of compounds to prevent tumor growth by using cationic liposomes for targeting an antiproliferative drug to blood vessels.