Cardiac allograft vasculopathy diagnosed by vasodilator myocardial contrast echocardiography perfusion imaging.

Cardiac allograft vasculopathy (CAV) remains a common long-term complication of cardiac transplantation. While invasive coronary angiography is considered the gold standard, it is also invasive and lacks sensitivity to detect early, distal CAV. Although vasodilator stress myocardial contrast echocardiography perfusion imaging (MCE) is used in the detection of microvascular disease in non-transplant patients, there is little data guiding its use in transplant recipients.

Contrast Ultrasound Assessment of Skeletal Muscle Recruitable Perfusion after Permanent Left Ventricular Assist Device Implantation: Implications for Functional Recovery.

Background: In heart failure with reduced ejection fraction (HFrEF), abnormal regulation of skeletal muscle perfusion contributes to reduced exercise tolerance. The aim of this study was to test the hypothesis that improvement in functional status after permanent left ventricular assist device (LVAD) implantation in patients with HFrEF is related to improvement in muscle perfusion during work, which was measured using contrast-enhanced ultrasound (CEUS).

Methods: CEUS perfusion imaging of calf muscle at rest and during low-intensity plantar flexion exercise (20 W, 0.

Echocardiographic Ischemic Memory Molecular Imaging for Point-of-Care Detection of Myocardial Ischemia.

Background: Noninvasive molecular imaging of recent ischemia can potentially be used to diagnose acute coronary syndrome (ACS) with high accuracy.

Objectives: The authors hypothesized that bedside myocardial contrast echocardiography (MCE) ischemic memory imaging could be achieved with phosphatidylserine microbubbles (MB) that are retained in the microcirculation via ischemia-associated endothelial activation.

Methods: A dose-finding study was performed in healthy volunteers (n = 17) to establish optimal MB dosing.

Plasma Lipidomic Patterns in Patients with Symptomatic Coronary Microvascular Dysfunction.

Coronary microvascular dysfunction (MVD) is a syndrome of abnormal regulation of vascular tone, particularly during increased metabolic demand. While there are several risk factors for MVD, some of which are similar to those for coronary artery disease (CAD), the cause of MVD is not understood. We hypothesized that MVD in symptomatic non-elderly subjects would be characterized by specific lipidomic profiles.

Flow Augmentation in the Myocardium by Ultrasound Cavitation of Microbubbles: Role of Shear-Mediated Purinergic Signaling.

Background: Ultrasound-mediated cavitation of microbubble contrast agents produces high intravascular shear. We hypothesized that microbubble cavitation increases myocardial microvascular perfusion through shear-dependent purinergic pathways downstream from ATP release that is immediate and sustained through cellular ATP channels such as Pannexin-1.

Methods: Quantitative myocardial contrast echocardiography perfusion imaging and in vivo optical imaging of ATP was performed in wild-type and Pannexin-1-deficient (Panx1) mice before and 5 and 30 minutes after 10 minutes of ultrasound-mediated (1.

Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation.

Objectives: The authors investigated ideal acoustic conditions on a clinical scanner custom-programmed for ultrasound (US) cavitation-mediated flow augmentation in preclinical models. We then applied these conditions in a first-in-human study to test the hypothesis that contrast US can increase limb perfusion in normal subjects and patients with peripheral artery disease (PAD).

Background: US-induced cavitation of microbubble contrast agents augments tissue perfusion by convective shear and secondary purinergic signaling that mediates release of endogenous vasodilators.

Limb Perfusion During Exercise Assessed by Contrast Ultrasound Varies According to Symptom Severity in Patients with Peripheral Artery Disease.

Background: In patients with peripheral artery disease (PAD), the severity of symptoms correlates poorly with ankle-brachial index (ABI). The aim of this study was to test the hypothesis that limb perfusion assessed using contrast-enhanced ultrasound (CEU) during contractile exercise varies according to functional class in patients with PAD, particularly those with ABIs in the 0.4 to 0.

Contrast Enhanced Ultrasound Perfusion Imaging in Skeletal Muscle.

The ability to accurately evaluate skeletal muscle microvascular blood flow has broad clinical applications for understanding the regulation of skeletal muscle perfusion in health and disease states. Contrast-enhanced ultrasound (CEU) perfusion imaging, a technique originally developed to evaluate myocardial perfusion, is one of many techniques that have been applied to evaluate skeletal muscle perfusion. Among the advantages of CEU perfusion imaging of skeletal muscle is that it is rapid, safe and performed with equipment already present in most vascular medicine laboratories.

Coronary Microvascular Dysfunction by Myocardial Contrast Echocardiography in Nonelderly Patients Referred for Computed Tomographic Coronary Angiography.

Background: Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. The authors hypothesized that nonelderly patients referred for computed tomographic angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of nonobstructive coronary artery disease (CAD) or reduced brachial flow-mediated dilation (FMD) predicted MVD.

Assessment of Novel Antioxidant Therapy in Atherosclerosis by Contrast Ultrasound Molecular Imaging.

Background: Ultrasound molecular imaging was used to evaluate the therapeutic effects of antioxidant therapy with EUK-207, which has superoxide dismutase and catalase activities, on suppressing high-risk atherosclerotic features.

Methods: Mice with age-dependent atherosclerosis produced by deletion of the low-density lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207 or vehicle was administered for the preceding 8 weeks.

Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia.

Objectives: This study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations.

Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol.

Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia.

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).

Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation.

Background: Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging.

Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling.

Background: Augmentation of tissue blood flow by therapeutic ultrasound is thought to rely on convective shear. Microbubble contrast agents that undergo ultrasound-mediated cavitation markedly amplify these effects. We hypothesized that purinergic signaling is responsible for shear-dependent increases in muscle perfusion during therapeutic cavitation.

Functional adaptations of the coronary microcirculation to anaemia in fetal sheep.

Key Points: In fetuses, chronic anaemia stimulates cardiac growth; simultaneously, blood flow to the heart muscle itself is increased, and reserve blood flow capacity of the coronary vascular bed is preserved. Here we examined functional adaptations of the capillaries and small blood vessels responsible for delivering oxygen to the anaemic fetal heart muscle using contrast-enhanced echocardiography. We demonstrate that coronary microvascular flux rate doubled in anaemic fetuses compared to control fetuses, both at rest and during maximal flow, suggesting reduced microvascular resistance consistent with capillary widening.

Echocardiographic Ischemic Memory Imaging Through Complement-Mediated Vascular Adhesion of Phosphatidylserine-Containing Microbubbles.

Objectives: This study hypothesized that microvascular retention of phosphatidylserine-containing microbubbles (MB-PS) would allow detection of recent but resolved myocardial ischemia with myocardial contrast echocardiographic (MCE) molecular imaging.

Background: Techniques for ischemic memory imaging which can detect and spatially assess resolved myocardial ischemia are being developed for rapid evaluation of patients with chest pain.

Methods: MCE molecular imaging with MB-PS was performed 1.

Molecular Imaging of Platelet-Endothelial Interactions and Endothelial von Willebrand Factor in Early and Mid-Stage Atherosclerosis.

Background: Nonthrombotic platelet-endothelial interactions may contribute to atherosclerotic plaque development, although in vivo studies examining mechanism without platelet preactivation are lacking. Using in vivo molecular imaging at various stages of atherosclerosis, we quantified platelet-endothelial interactions and evaluated the contribution of major adhesion pathways.

Methods And Results: Mice deficient for the low-density lipoprotein receptor and Apobec-1 were studied as an age-dependent model of atherosclerosis at 10, 20, 30, and 40 weeks of age, which provided progressive increase in stage from early fatty streak (10 weeks) to large complex plaques without rupture (40 weeks).

Contrast-enhanced ultrasound assessment of impaired adipose tissue and muscle perfusion in insulin-resistant mice.

Background: In diabetes mellitus, reduced perfusion and capillary surface area in skeletal muscle, which is a major glucose storage site, contribute to abnormal glucose homeostasis. Using contrast-enhanced ultrasound, we investigated whether abdominal adipose tissue perfusion is abnormal in insulin resistance and correlates with glycemic control.

Methods And Results: Contrast-enhanced ultrasound perfusion imaging of abdominal adipose tissue and skeletal muscle was performed in obese insulin resistance (db/db) mice at 11 to 12 or 14 to 16 weeks of age and in control lean mice.

Real-time contrast ultrasound muscle perfusion imaging with intermediate-power imaging coupled with acoustically durable microbubbles.

Background: There is growing interest in limb contrast-enhanced ultrasound (CEU) perfusion imaging for the evaluation of peripheral artery disease. Because of low resting microvascular blood flow in skeletal muscle, signal enhancement during limb CEU is prohibitively low for real-time imaging. The aim of this study was to test the hypothesis that this obstacle can be overcome by intermediate- rather than low-power CEU when performed with an acoustically resilient microbubble agent.

Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume.

Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects.

Quantification of residual limb skeletal muscle perfusion with contrast-enhanced ultrasound during application of a focal junctional tourniquet.

Objective: Focal junctional tourniquets (JTs) have been developed to control hemorrhage from proximal limb injuries. These devices may permit greater collateral perfusion than circumferential tourniquets. We hypothesized that JTs eliminate large-vessel pulse pressure yet allow a small amount of residual limb perfusion that could be useful for maintaining tissue viability.

Ischemic memory imaging in nonhuman primates with echocardiographic molecular imaging of selectin expression.

Background: Selectins are adhesion molecules that are expressed by the vascular endothelium upon activation and may be an imaging target for detecting myocardial ischemia long after resolution. The aim of this study was to test the hypothesis that molecular imaging of selectins with myocardial contrast echocardiographic (MCE) molecular imaging could be used to detect recent brief ischemia in closed-chest nonhuman primates.

Methods: Myocardial ischemia was produced in anesthetized adult rhesus macaques (n = 6) by percutaneous balloon catheter occlusion of the left anterior descending or circumflex coronary artery for 5 to 10 min.