Ischemia/Reperfusion Injury Enhances Accumulation of Perfluoropropane Droplets.

Objective: Perfluoropropane droplets (PD) are nanometer-sized particles that can be formulated from commercially available contrast agents. The preferential retention of PDs in diseased microvascular beds can be detected by ultrasound imaging techniques after acoustic activation and offers an opportunity for the detection of such processes as scar formation or inflammation. We hypothesized that in the presence of ischemia/reperfusion (I/R) injury, retention of intravenously injected PDs would be enhanced.

Association of Gestational Diabetes With Subclinical Cardiovascular Disease.

Background: Gestational diabetes mellitus (GDM) is associated with increased long-term risk of cardiovascular disease but the cardiovascular structural and functional changes that contribute to risk are not well understood.

Objectives: The purpose of this study was to determine whether GDM is associated with adverse cardiac remodeling and endothelial dysfunction a decade after delivery, independent of type 2 diabetes.

Methods: Women with deliveries between 2008 and 2009 were initially selected from a prospective clinical cohort.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

Background: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling.

Ultrasound enhanced siRNA delivery using cationic liposome-microbubble complexes for the treatment of squamous cell carcinoma.

Microbubble () contrast agents combined with ultrasound targeted microbubble cavitation () are a promising platform for site-specific therapeutic oligonucleotide delivery. We investigated UTMC-mediated delivery of siRNA directed against epidermal growth factor receptor (), to squamous cell carcinoma () via a novel MB-liposome complex (). were constructed by conjugation of cationic liposomes to the surface of CF gas-filled lipid MBs using biotin/avidin chemistry, then loaded with siRNA via electrostatic interaction.

Acoustic Activation Imaging With Intravenous Perfluoropropane Nanodroplets Results in Selective Bioactivation of the Risk Area.

Background: Acoustically activatable perfluoropropane droplets (PD) can be formulated from commercially available microbubble preparations. Diagnostic transthoracic ultrasound frequencies have resulted in acoustic activation (AA) predominately within myocardial infarct zones (IZ).

Objective: We hypothesized that the AA area following acute coronary ischemia/reperfusion (I/R) would selectively enhance the developing scar zone, and target bioeffects specifically to this region.

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier.

The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for enhancing drug delivery to the brain. Here, we established a multicellular human brain spheroid model that mimics the BBB both architecturally and functionally.

Development of an In Vitro Model to Study Mechanisms of Ultrasound-Targeted Microbubble Cavitation-Mediated Blood-Brain Barrier Opening.

Objective: Ultrasound-targeted microbubble cavitation (UTMC)-mediated blood-brain barrier (BBB) opening is being explored as a method to increase drug delivery to the brain. This strategy has progressed to clinical trials for various neurological disorders, but the underlying cellular mechanisms are incompletely understood. In the study described here, a contact co-culture transwell model of the BBB was developed that can be used to determine the signaling cascade leading to increased BBB permeability.

Ultrasound-Induced Microbubble Cavitation for Targeted Delivery of MiR-29b Mimic to Treat Cardiac Fibrosis.

Objective: Cardiac fibrosis contributes to adverse ventricular remodeling and is associated with loss of miR-29b. Overexpression of miR-29b via plasmid or intravenous injection of microRNA mimic has blunted fibrosis, but these are inefficient and non-targeted delivery strategies. In this study, we tested the hypothesis that delivery of microRNA-29b (miR-29b) using ultrasound-targeted microbubble cavitation (UTMC) of miR-29b-loaded microbubbles would attenuate cardiac fibrosis and preserve left ventricular (LV) function.

Ultrasound-Targeted Microbubble Cavitation During Machine Perfusion Reduces Microvascular Thrombi and Graft Injury in a Rat Liver Model of Donation After Circulatory Death.

Background: Ischemic cholangiopathy is a process of bile duct injury that might result from peribiliary vascular plexus (PBP) thrombosis and remains a dreaded complication in liver transplantation from donors after circulatory death (DCD). The aim of this study was to propose a mechanical method of clot destruction to clear microvascular thrombi in DCD livers before transplantation.

Methods: Sonothrombolysis (STL) is a process by which inertial cavitation of circulating microbubbles entering an ultrasound field create a high-energy shockwave at a microbubble-thrombus interface, causing mechanical clot destruction.

Dynamic Behavior of Polymer Microbubbles During Long Ultrasound Tone-Burst Excitation and Its Application for Sonoreperfusion Therapy.

Objective: Ultrasound (US)-targeted microbubble (MB) cavitation (UTMC)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. Because of the potentially longer circulation time and relative ease of storage and reconstitution of polymer-shelled MBs compared with lipid MBs, we investigated the dynamic behavior of polymer microbubbles and their therapeutic potential for sonoreperfusion (SRP) therapy.

Methods: The fate of polymer MBs during a single long tone-burst exposure (1 MHz, 5 ms) at various acoustic pressures and MB concentrations was recorded via high-speed microscopy and passive cavitation detection (PCD).

Molecular imaging of chemokine-like receptor 1 (CMKLR1) in experimental acute lung injury.

The lack of techniques for noninvasive imaging of inflammation has challenged precision medicine management of acute respiratory distress syndrome (ARDS). Here, we determined the potential of positron emission tomography (PET) of chemokine-like receptor-1 (CMKLR1) to monitor lung inflammation in a murine model of lipopolysaccharide-induced injury. Lung uptake of a CMKLR1-targeting radiotracer, [Cu]NODAGA-CG34, was significantly increased in lipopolysaccharide-induced injury, correlated with the expression of multiple inflammatory markers, and reduced by dexamethasone treatment.

Acoustic Detection of Retained Perfluoropropane Droplets Within the Developing Myocardial Infarct Zone.

Perfluoropropane droplets (PDs) cross endothelial barriers and can be acoustically activated for selective myocardial extravascular enhancement following intravenous injection (IVI). Our objective was to determine how to optimally activate extravascular PDs for transthoracic ultrasound-enhanced delineation of a developing scar zone (DSZ). Ultrafast-frame-rate microscopy was conducted to determine the effect of pulse sequence on the threshold of bubble formation from PDs.

Ultrafast Microscopy Imaging of Acoustic Cluster Therapy Bubbles: Activation and Oscillation.

Acoustic Cluster Therapy (ACT®) is a platform for improving drug delivery and has had promising pre-clinical results. A clinical trial is ongoing. ACT® is based on microclusters of microbubbles-microdroplets that, when sonicated, form a large ACT® bubble.

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

Background: Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF).

Methods: We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale.

Association of Hypertensive Disorders of Pregnancy With Left Ventricular Remodeling Later in Life.

Background: Hypertensive disorders of pregnancy (HDP) are associated with short-term cardiac structure and function abnormalities, but later life changes are not well studied.

Objectives: This study aimed to determine if HDP history is associated with echocardiographic differences 8 to 10 years after delivery, and if subgroups with placental maternal vascular malperfusion (MVM) lesions or current hypertension may be particularly affected.

Methods: Women with pregnancies delivered from 2008 to 2009 were selected from a clinical cohort with abstracted pregnancy and placental pathology data to undergo transthoracic echocardiography (2017 to 2020).

STAT3 decoy oligonucleotide-carrying microbubbles with pulsed ultrasound for enhanced therapeutic effect in head and neck tumors.

Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis, tumor progression, and drug resistance in head and neck squamous cell carcinoma (HNSCC). A decoy oligonucleotide targeting STAT3 offers a promising anti-tumor strategy, but achieving targeted tumor delivery of the decoy with systemic administration poses a significant challenge. We previously showed the potential for STAT3 decoy-loaded microbubbles, in conjunction with ultrasound targeted microbubble cavitation (UTMC), to decrease tumor growth in murine squamous cell carcinoma.

Heme Induces IL-6 and Cardiac Hypertrophy Genes Transcripts in Sickle Cell Mice.

Emerging data indicate that free heme promotes inflammation in many different disease settings, including in sickle cell disease (SCD). Although free heme, proinflammatory cytokines, and cardiac hypertrophy are co-existing features of SCD, no mechanistic links between these features have been demonstrated. We now report significantly higher levels of IL-6 mRNA and protein in hearts of the Townes sickle cell disease (SS) mice (2.

Transendothelial Perforations and the Sphere of Influence of Single-Site Sonoporation.

Acoustically driven gas bubble cavitation locally concentrates energy and can result in physical phenomena including sonoluminescence and erosion. In biomedicine, ultrasound-driven microbubbles transiently increase plasma membrane permeability (sonoporation) to promote drug/gene delivery. Despite its potential, little is known about cellular response in the aftermath of sonoporation.

Commercial 4-dimensional echocardiography for murine heart volumetric evaluation after myocardial infarction.

Background: Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. New ECHO technology, including 4-dimensional ultrasound (4D-US), improves on these traditional models.

BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant vascular disorder characterized by development of high-flow arteriovenous malformations (AVMs) that can lead to stroke or high-output heart failure. HHT2 is caused by heterozygous mutations in ACVRL1, which encodes an endothelial cell bone morphogenetic protein (BMP) receptor, ALK1. BMP9 and BMP10 are established ALK1 ligands.

Ultrasound and Microbubble-targeted Delivery of a microRNA Inhibitor to the Heart Suppresses Cardiac Hypertrophy and Preserves Cardiac Function.

MicroRNAs (miRs) are dysregulated in pathological left ventricular hypertrophy. AntimiR inhibition of miR-23a suppressed hypertension-induced cardiac hypertrophy in preclinical models, but clinical translation is limited by a lack of cardiac-targeted delivery systems. Ultrasound-targeted microbubble cavitation (UTMC) utilizes microbubbles as nucleic acid carriers to target delivery of molecular therapeutics to the heart.