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Reactive oxygen species (ROS) are hypothesized to play a role in the sonoporation mechanisms. Sofar, the production of ROS has been mainly reported inside the cytoplasm of cells after sonoporation. However, the acoustical phenomenon triggering the production of ROS is unknown. In this context, we investigated whether the interaction between microbubbles (MBs) and ultrasound (US) induce the production...
Microbubble (MB) contrast agents are widely used in diagnostic and therapeutic ultrasound (US) applications. However, due to their 1–10 μm size range, MBs are constrained to the vasculature and thus this limits applications in cancer diagnosis and therapy. To expand contrast enhanced US capabilities, we have developed sub-micron contrast agents, nanobubbles (NB), stabilized with Pluronic, a nonionic...
Perfluorocarbon nanodroplets (PFCnDs) are emerging ultrasound (US) contrast agents that seek to enable contrast-enhanced imaging of extravascular spaces and offer increased biological stability and circulation times compared to traditional microbubbles (MBs). However, rigorous studies have not analyzed the impact of shell composition on PFCnDs. In particular, lipid-shell PFCnD formulations borrow...
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and can often lead to fibrosis, cirrhosis, cancer and complete liver failure. Liver biopsy is the current standard of care to quantify hepatic steatosis but it comes with increased patient risk and only samples a small portion of the liver. Imaging approaches to assess NAFLD include proton density fat fraction...
Photoacoustic microscopy (PAM) is promising for label-free histology of lipid-rich tissue. Lipids have optical absorption peaks at 1.2 and 1.7 μm, but these wavelengths are typically produced with expensive optical parametric oscillator (OPO) lasers. We have been exploring nonlinear fiber optics to convert inexpensive pulsed lasers into multi-wavelength sources for PAM. Photonic crystal fibers (PCFs)...
Lipid-coated microbubbles are being researched as agents for ultrasound imaging and ultrasound-assisted drug delivery. It is well known that lipid shell composition of a microbubble affects the acoustic response. However, the effect of temperature on lipid shell viscoelasticity has not yet been fully established. The goal of this study was to determine the effect of temperature on the viscoelastic...
Clinical translation of targeted contrast agents for molecular imaging of disease precludes the use of the biotin-avidin cross linking strategy due to the immunogenicity of avidin. Our objective was to cross link targeting ligands to ultrasound contrast using non-immunogenic covalent chemistry, and to validate the resulting targeted contrast agents using a binding assay to cultured cells.
Microbubbles (MBs) excited by ultrasound (Us) are used as contrast agents for the detection of blood vessels. MBs can also be used to enhance drug delivery. However, the usage of MBs is limited to the blood pool due to their large size; where detection of biomarkers on tumor cells and effective drug delivery, requires MBs to reach the tumor tissue outside of the vasculature.
Intravascular photoacoustic (IVPA) imaging is being developed to improve and guide treatment of atherosclerotic vulnerable plaques. While lipid has been successfully imaged, current studies have not determined how many or which optical wavelength(s) will accurately characterize atherosclerotic plaques. We leverage Monte Carlo (MC) optical modeling to determine the optimal dual-wavelength combination...
Prostate cancer biopsies are increasingly guided by ultrasound (US) imaging, yet poor soft tissue contrast makes delineation between normal/abnormal tissue difficult. There is growing interest in US contrast agents (USCA) to improve differentiation of tumors within the prostate gland and facilitate US-guided biopsies. The most widely used formulations are lipid or protein-stabilized perfluorocarbon...
With its thickness decreasing down to 60 μm, the (K0.45Na0.55)0.96Li0.04NbO3 (KNLN) single crystals maintains superior piezoelectric constant (d33 = 675 pC N−1). In combination with a 200 μm core multimode fiber, the successful fabrication of a tiny intravascular photoacoustic probe with a 1 mm outside diameter is achieved. The intravascular photoacoustic imaging of the atherosclerotic lesion of a...
Microbubble (MB) contrast agents are widely used in diagnostic and therapeutic ultrasound (US) applications. However, due to their 1–10 μm size range, MBs have limited use in cancer detection and treatment. To expand contrast enhanced US capabilities, we have developed sub-micron contrast agents, nanobubbles (NB), via the addition of Pluronic, a nonionic triblock copolymer surfactant, to the phospholipid...
Photoacoustic microscopy (PAM) is promising for label-free histology of lipid-rich tissue. Lipids have optical absorption peaks at 1.2 and 1.7 μm, but these wavelengths are typically produced with expensive optical parametric oscillator (OPO) lasers. Photonic crystal fibers (PCFs) have nonlinear optical properties that enable a single-wavelength laser to produce an ultra-broadband supercontinuum spanning...
Background: Sonodynamic therapy is a cancer treatment using drugs called “sonosensitizers” which, upon exposure to ultrasound (US), generate reactive oxygen species (ROS), thereby causing cell death. Despite the potential of sonodynamic therapy, many ideal sonosensitizers, such as protoporphyrin IX (PpIX), are hydrophobic compounds; poor water solubility limits systemic delivery and constrains clinical...
Sonophoresis which utilizes ultrasound for transdermal drug delivery (TDD), can increase the skin permeability and improve the efficiency of drug delivery to various drugs. In addition, the addition of microbubbles in sonophoresis accelerate and increase an efficiency of drug delivery. The cavitation induced by sonophoresis with microbubbles on the skin surface may cause disordering of the lipid bilayers...
Sonodynamic therapy is a cancer treatment using drugs called “sonosensitizers” which, upon exposure to ultrasound (US), generate reactive oxygen species (ROS), thereby causing cell death. Despite the potential of sonodynamic therapy, many ideal sonosensitizers, such as protoporphyrin IX (PpIX), are hydrophobic compounds; poor water solubility limits systemic delivery and constrains clinical translation...
The dissipation of ultrasound (US) signal from microbubble contrast agents has been linked to their fragmentation, jetting or sonic cracking, leading to a loss of gas. With strong interest in the use of bubbles as drug delivery vehicles, their ultimate fate is of great importance. It has been hypothesized that remnant shells shed into the surround aqueous medium, folding into liposomes or micelles...
Localizing tumors and securing resection margins are sometimes difficult especially during laparoscopic surgery for malignant diseases. Therefore, we have developed a tissue marker, which is composed of giant cluster-like vesicles (GCVs) encapsulating near-infrared (NIR) fluorescent liposomes and X-ray contrast agents coated with lipids. The GCVs facilitate localizing tumors preoperatively and intraoperatively...
Non-invasive diagnosis of non-alcoholic steatohepatitis (NASH) can be achieved by quantitative ultrasound (QUS), which requires a detailed understanding tissue-specific acoustic microstructure at cellular scale (i.e., 10 μm). This study focuses on obtaining speed of sound (c) of organelles (i.e., nucleus, cytoplasm, and fibers) using 250-MHz ultrasound in rat livers. Three different pathological stages...
Sub-micron bubbles have recently gained interest in cancer imaging and therapy for their ability to enter the tumor parenchyma through the enhanced permeability and retention (EPR) effect. It remains unclear whether nanoscale lipid-stabilized bubbles can produce the observed enhanced acoustic backscatter at clinically relevant frequencies. Because NB polydispersity is high, micron sized bubbles are...
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