Craig Weinkauf

Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress

The aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO). Histology was performed on carotid endarterectomy samples from patients undergoing surgery for unstable atherosclerosis to assess target expression in humans. In DKO mice, CEUS signal for all four targeted MBs was significantly higher than that for control MBs, and was three to sevenfold higher than in wild-type mice, with the highest signal achieved for VCAM-1 and VWF. All molecular targets were present on the patient plaque surface but expression was greatest for VCAM-1 and VWF. We conclude that ultrasound contrast agents bearing small peptide ligands feasible for human use can be targeted against endothelial cell adhesion molecules for inflammatory cells and platelets for imaging advanced atherosclerotic disease.

Perigraft air mimicking infection on CT angiography following open abdominal aortic aneurysm repair

Aortic graft infection is a feared complication after open abdominal aortic aneurysm repair secondary to its high mortality. Perigraft air is a common finding after open aortic aneurysm repair; however, it is also associated with aortic graft infection. Delineating between graft infection and common postoperative finding is a challenge. This is further complicated by use of hemostatic agents such as Gelfoam, which is also documented to cause perigraft air. Correct diagnosis has crucial implications in management of potential aortic graft infection, which is a vascular emergency. We report a case of perigraft air in a patient status after open aortic aneurysm repair with associated clinical manifestations of infection in whom conservative management and surveillance was selected for treatment. We then discuss the timeline of perigraft air, potential causation, importance of history, and physical examination, and finally, we discuss how specific findings on computed tomography imaging for infection in other areas may be useful in aortic graft infection.

PC068. Factors Associated With Microembolization After Carotid Intervention

infarction rates were similar among the groups. However, the matched groups revealed TCAR was associated with a decreased rate of mortality at 30 days (0.0% vs 2.3%; P 1⁄4 .026). Conclusions: These early data suggest that patients undergoing TCAR, even those with high-risk comorbidities, achieve similar neurologic outcomes compared with patients undergoing CEA while mitigating perioperative mortality.

Endothelial vascular cell adhesion molecule 1 is a marker for high-risk carotid plaques and target for ultrasound molecular imaging

Background: Molecular imaging of carotid plaque vulnerability to atheroembolic events is likely to lead to improvements in selection of patients for carotid endarterectomy (CEA). The aims of this study were to assess the relative value of endothelial inflammatory markers for this application and to develop molecular ultrasound contrast agents for their imaging. Methods: Human CEA specimens were obtained prospectively from asymptomatic (30) and symptomatic (30) patients. Plaques were assessed by semiquantitative immunohistochemistry for vascular cell adhesion molecule 1 (VCAM‐1), lectin‐like oxidized low‐density lipoprotein receptor 1, P‐selectin, and von Willebrand factor. Established small peptide ligands to each of these targets were then synthesized and covalently conjugated to the surface of lipid‐shelled microbubble ultrasound contrast agents, which were then evaluated in a flow chamber for binding kinetics to activated human aortic endothelial cells under variable shear conditions. Results: Expression of VCAM‐1 on the endothelium of CEA specimens from symptomatic patients was 2.4‐fold greater than that from asymptomatic patients (P < .01). Expression was not significantly different between groups for P‐selectin (P = .43), von Willebrand factor (P = .59), or lectin‐like oxidized low‐density lipoprotein receptor 1 (P = .99). Although most plaques from asymptomatic patients displayed low VCAM‐1 expression, approximately one in five expressed high VCAM‐1 similar to plaques from symptomatic patients. In vitro flow chamber experiments demonstrated that VCAM‐1‐targeted microbubbles bind cells that express VCAM‐1, even under high‐shear conditions that approximate those found in human carotid arteries, whereas binding efficiency was lower for the other agents. Conclusions: VCAM‐1 displays significantly higher expression on high‐risk (symptomatic) vs low‐risk (asymptomatic) carotid plaques. Ultrasound contrast agents bearing ligands for VCAM‐1 can sustain high‐shear attachment and may be useful for identifying patients in whom more aggressive treatment is warranted. Clinical Relevance: A noninvasive method for stroke risk assessment in patients with asymptomatic carotid atherosclerosis is long overdue and key to improving treatment. Our data are the first to show that vascular cell adhesion molecule 1 expression is significantly increased in high‐risk compared with low‐risk carotid plaques in humans (P = .0005), and they demonstrate a novel targeted ultrasound agent that could be used for noninvasive vascular cell adhesion molecule 1 evaluation in patients. Furthermore, these data build on our understanding of carotid plaque biology and define tools for in vivo molecular analysis of atherosclerosis in animal models as well as in humans. This ultrasound technology would be easily translatable to a vascular outpatient setting.

Near-instant noninvasive optical imaging of tissue perfusion for vascular assessment

Background Noninvasive vascular tests are critical for identifying patients who may benefit from surgical revascularization, but current tests have significant limitations in people with diabetes. This study aimed to evaluate the ability of spatial frequency domain imaging (SFDI), an optical imaging method capable of measuring tissue oxygen saturation (StO2) and tissue hemoglobin, to assess lower extremity blood supply. Methods Ankle‐brachial index, toe‐brachial index, pedal Doppler waveforms, and SFDI images were prospectively evaluated in 47 consecutive patients with and without diabetes in whom there was concern for peripheral artery disease (PAD). SFDI is a noncontact optical imaging technology that uses structured illumination to quantify subsurface (2‐3 mm in depth) StO2 and tissue hemoglobin in the dermal microcirculation (HbT1) and macrocirculation (HbT2) over a large field of view (15 × 20 cm) within 10 seconds. Results This demonstrates the ability of SFDI to capture reliable clinical measurements of perfusion in plantar aspects of the feet. SFDI StO2 values differentiate nondiabetic patients with and without arterial disease, defined as ankle‐brachial index <0.9 (P = .06), but are limited in those with diabetes (P = .43). An elevated StO2 and reduced HbT1 are observed in people with diabetes compared with nondiabetic patients (P < .05). An SFDI‐derived HbT2/HbT1 index differentiates diabetics with PAD vs no PAD (P < .01) using toe‐brachial index <0.7 as a cutoff for PAD in diabetes. Conclusions SFDI is a feasible, rapid, and easy to use widefield measurement of perfusion in a clinical setting. This first‐of‐use study suggests that the technology has potential to evaluate lower extremity perfusion in people with and without diabetes. Further studies with increased numbers of patients and end points including wound healing will need to be designed to fully evaluate the applicability of this new technology.

Open versus endovascular aneurysm repair trial review

&NA; The Open versus Endovascular Aneurysm Repair trial is the only randomized controlled trial that is funded by the federal government to evaluate the treatment outcomes of infrarenal abdominal aortic aneurysms. Since the initial publication, multiple post‐hoc analyses have become available. This review summarizes these data, focusing on the primary outcome measures (ie, overall survival) and several key secondary outcomes including aneurysm‐related death, age consideration, secondary procedures, and endoleaks. Cost‐effectiveness of each treatment modality and the limitations of OVER trial also are discussed critically in this review.

In Patients with Limb-Threatening Ischemia Who Are Not Candidates for Revascularization Do Non-operative Options Improve Outcomes Compared to Amputation?

Patients with critical limb ischemia (CLI) or limb-threatening ischemia comprise a heterogenous population with varying co-morbidities that strongly influence outcomes after therapeutic intervention. Broadly, there are three treatment strategies for patients with limb-threatening ischemia: direct revascularization (open or endovascular), amputation and medical treatment with local wound care. Although many affected patients do well with surgical revascularization, disease recurrence brings many patients back with ever-diminishing surgical options. This review discusses clinical decision-making, and particularly evaluates options for patient care when arterial anatomy or patient co-morbidities do not support surgical revascularization. This topic is an increasingly important one as data indicate direct intervention is not always a reasonable clinical option and as definitions for therapeutic success progress beyond graft/stent patency and limb salvage and non-surgical options to promote wound healing improve.

Technological Advances in Endovascular Surgery

The twentieth century witnessed a tremendous explosion in the application of minimally invasive, catheter-based interventions in virtually all vascular bed territories, surpassing the number of performed open surgical cases by the end of that time period. This fact allowed a greater number of patients to be candidates for potentially life-saving surgical interventions, many of whom could not have tolerated the superior stresses of an open surgical procedure. The development of such technological advances that can provide significant benefits to our patients does require the participation of both industry and physicians; neither group by themselves could achieve these goals in isolation. Such cooperation is a new paradigm, first tested during the development of laparoscopy in the general surgery specialty and clearly expanded in vascular surgery. Whereas no major technological advances have been reported during the beginning of the twenty-first century in open vascular surgery techniques, major improvements in the endovascular arena have been described, from the technological and technical points of view. This chapter is a concise review of the most recent and important techniques and device developments involved in vascular interventions.