Analyzing Gene Expression After Administration of Low-Intensity Therapeutic Ultrasound in Human Islet Cells.

Objectives: Diabetes mellitus is a complex heterogenous metabolic disease that significantly affects the world population. Although many treatments exist, including medications such as metformin, sulfonylureas, and glucagon-like peptide-1 (GLP) receptor agonist, there is growing interest in finding alternative methods to noninvasively treat this disease. It has been previously shown that low-intensity ultrasound stimulation of pancreatic β-cells in mice can elicit insulin secretion as a potential treatment for this disease.

Therapeutic Ultrasound for Enhanced Corneal Permeability to Macromolecules.

Objectives: Topically applied macromolecules have the potential to provide vision-saving treatments for many of the leading causes of blindness in the United States. The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues.

Methods: Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70 kDa, or 150 kDa) and a receiver compartment.

Modeling of Ultrasound Stimulation of Adolescent Pancreas for Insulin Release Therapy.

Objectives: Our previous published studies have focused on safety and effectiveness of using therapeutic ultrasound (TUS) for treatment of type 2 diabetes mellitus (T2DM) in preclinical models. Here we present a set of simulation studies to explore potential ultrasound application schemes that would be feasible in a clinical setting.

Methods: Using the multiphysics modeling tool OnScale, we created two-dimensional (2D) models of the human abdomen from CT images captured from one normal weight adolescent patient, and one obese adolescent patient.

Therapeutic Ultrasound for Topical Corneal Delivery of Macromolecules.

Purpose: The objective of this study was to utilize therapeutic ultrasound in enhancing delivery of topical macromolecules into the cornea.

Methods: Rabbit corneas were dissected and placed in a diffusion cell with a small ultra-red fluorescent protein (smURFP; molecular weight of 32,000 Da) as a macromolecule solution. The corneas were treated with continuous ultrasound application at frequencies of 400 or 600 kHz and intensities of 0.

Therapeutic Ultrasound Effects on Human Induced Pluripotent Stem Cell Cardiomyocytes Measured Optically and with Spectral Ultrasound.

To the best of our knowledge, therapeutic ultrasound (TUS) is thus far an unexplored means of delivering mechanical stimulation to cardiomyocyte cultures, which is necessary to engineer a more mature cardiomyocyte phenotype in vitro. Spectral ultrasound (SUS) may provide a way to non-invasively, non-disruptively and inexpensively monitor growth and change in cell cultures over long periods. Compared with other measurement methods, SUS as an acoustic measurement tool will not be affected by an acoustic therapy, unlike electrical measurement methods, in which motion caused by acoustic therapy can affect measurements.

Feasibility of Therapeutic Ultrasound Application in Topical Scleral Delivery of Avastin.

Purpose: Macromolecules have been shown to be effective in vision-saving treatments for various ocular diseases, such as age-related macular degeneration and diabetic retinopathy. The current delivery of macromolecules requires frequent intraocular injections and carries a risk of serious adverse effects.

Methods: We tested the application of therapeutic ultrasound as a minimally invasive approach for the delivery of Avastin into the diseased regions of the eye.

Ultrasound-Enhanced Transcorneal Drug Delivery for Treatment of Fungal Keratitis.

Purpose: Transcorneal drug delivery is hindered by ocular physical and biochemical properties, such as tear production, the epithelial layer of the cornea, and blinking. The aim of this study was to determine whether ultrasound can be applied to increase the transcorneal drug delivery of natamycin used in the treatment of fungal keratitis without dangerously overheating the surrounding ocular tissues.

Methods: To verify the safety of various sets of ultrasound parameters, modeling studies were conducted using OnScale, an ultrasonic wave modeling software.

Effect of Therapeutic Ultrasound on the Release of Insulin, Glucagon, and Alpha-Amylase from Ex Vivo Pancreatic Models.

Objectives: Our previously published studies showed the potential of therapeutic ultrasound (US) as a novel non-pharmacological alternative for the treatment of secretory deficiencies in type 2 diabetes. Despite showing enhanced insulin release from beta cells, these studies did not explore the potential effects of US treatment on other cells in the islets of Langerhans such as glucagon-secreting alpha cells or acinar cells of the exocrine pancreas.

Methods: We applied US parameters found capable of safely stimulating insulin secretion from pancreatic beta cells (f = 800 kHz, I  = 0.

Therapeutic Ultrasound-Enhanced Transcorneal PHMB Delivery In Vitro.

Objective: Delivery of therapeutic agents to the cornea is a difficult task in the treatment of parasitic keratitis. In this study, we looked at using different combinations of ultrasound parameters to enhance corneal permeability to polyhexamethylene biguanide (PHMB), a clinically available ophthalmic antiparasitic formulation.

Methods: Permeability of PHMB was investigated in vitro using a standard diffusion cell setup.

Ex Vivo Imaging of Ultrasound-Stimulated Metabolic Activity in Rat Pancreatic Slices.

Ultrasound has previously been reported to produce a reversible stimulatory effect in cultured rat beta cells. Here, we quantified and assessed dynamic metabolic changes in an in situ pancreatic slice model evoked by ultrasound application. After plating, pancreas slices were imaged using a confocal microscope at 488 and 633 nm to image lipodamine dehydrogenase (Lip-DH) autofluorescence and a far red fluorescence, respectively.

Ultrasound-Enhanced Drug Delivery for Treatment of Acanthamoeba Keratitis.

Reaching sufficient amounts of therapeutic agents in ocular tissues is a major challenge in ophthalmology. In this study, we examined the effects of ultrasound application for delivery of polyhexamethylene biguanide for treatment of Acanthamoeba keratitis. Ultrasound intensities of 0.

Therapeutic Ultrasound-Induced Insulin Release in Vivo.

The tolerability and efficacy of low-frequency, low-intensity therapeutic ultrasound-induced insulin release was investigated in a pre-clinical in vivo murine model. The treatment groups received a single 5-min continuous sonication at 1 MHz and 1.0 W/cm.

Optimization of Ultrasound-Mediated Drug Delivery for Treatment of Onychomycosis.

Background: Onychomycosis is a fungal nail disorder that does not have a successful cure due to the poor permeability of topical anti-fungal drugs through the nail. This study utilizes ultrasound to increase the permeability of the nail to the topical drugs currently used in clinic. The first aim of this study was to optimize ultrasonic parameters within the temperature increase limits set by the American Institute of Ultrasound in Medicine (AIUM) and the British Medical Ultrasound Society (BMUS).

Therapeutic Systems and Technologies: State-of-the-Art Applications, Opportunities, and Challenges.

In this review, we present current state-of-the-art developments and challenges in the areas of thermal therapy, ultrasound tomography, image-guided therapies, ocular drug delivery, and robotic devices in neurorehabilitation. Additionally, intellectual property and regulatory aspects pertaining to therapeutic systems and technologies are addressed.

Ultrasound-Induced Insulin Release as a Potential Novel Treatmentfor Type 2 Diabetes Mellitus.

Therapeutic ultrasound presents a potential novel treatment for type 2 diabetes mellitus that utilizes the non-invasive application of ultrasound energy to treat secretory defects in the earlier stages of the disease. Our previous studies have shown that ultrasound is capable of stimulating insulin release from pancreatic beta cells, safely and effectively. This study aims to both examine the calcium-dependent mechanisms of ultrasound-mediated insulin release from pancreatic beta cells using three complementary modalities - carbon fiber amperometry, ELISA studies, and Ca2+ fluorescence imaging - and to study the translational potential of therapeutic ultrasound using transgenic hyperglycemic mice for safety and efficacy studies.

Ultrasound-Enhanced Drug Delivery for Treatment of Onychomycosis.

Objectives: The aim of our study was to determine the effectiveness of using ultrasound (US) to increase the permeability of the nail, with the goal of improving outcomes in the treatment of onychomycosis.

Methods: Porcine nails were used because of their similarity to human nails. A hydrophilic blue dye was used as a drug-mimicking compound.

Calcium-dependent ultrasound stimulation of secretory events from pancreatic beta cells.

Background: Our previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes. The purpose of this study was to explore the temporal dynamics and Ca-dependency of ultrasound-stimulated secretory events from dopamine-loaded pancreatic beta cells in an in vitro setup.

Methods: Carbon fiber amperometry was used to detect secretion from INS-1832/13 beta cells in real time.

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes.

Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time.

Model for Porosity Changes Occurring during Ultrasound-Enhanced Transcorneal Drug Delivery.

Ultrasound-enhanced drug delivery through the cornea has considerable therapeutic potential. However, our understanding of how ultrasound enhances drug transport is poor, as is our ability to predict the increased level of transport for given ultrasound parameters. Described here is a computational model for quantifying changes in corneal porosity during ultrasound exposure.

Therapeutic Modulation of Calcium Dynamics using Ultrasound and Other Energy-based Techniques.

Ultrasound, along with other types of energy-based methods, has been widely investigated for use in various therapeutic applications because of its ability to stimulate specific biological processes. Many of these processes are mediated by calcium (Ca2+) signaling, thus making modulation of Ca2+ dynamics an evident therapeutic target for energy-based techniques. Various diseases have been associated with abnormal Ca2+ signaling and could therefore benefit from therapeutic approaches trying to regulate the transport of Ca2+ across cell membranes.

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study.

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors' previous in vitro and in vivo studies.

Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software.

Ultrasound-enhanced ocular delivery of dexamethasone sodium phosphate: an in vivo study.

Background: The eye's unique anatomy and its physiological and anatomical barriers can limit effective drug delivery into the eye.

Methods: An in vivo study was designed to determine the effectiveness and safety of ultrasound application in enhancing drug delivery in a rabbit model. Permeability of a steroid ophthalmic drug, dexamethasone sodium phosphate, was investigated in ultrasound- and sham-treated cases.

Development of novel imaging probe for optical/acoustic radiation imaging (OARI).

Purpose: Optical/acoustic radiation imaging (OARI) is a novel imaging modality being developed to interrogate the optical and mechanical properties of soft tissues. OARI uses acoustic radiation force to generate displacement in soft tissue. Optical images before and after the application of the force are used to generate displacement maps that provide information about the mechanical properties of the tissue under interrogation.

Ultrasound-enhanced delivery of antibiotics and anti-inflammatory drugs into the eye.

Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3-1.

Mechanical bioeffects of pulsed high intensity focused ultrasound on a simple neural model.

Purpose: To study how pressure pulses affect nerves through mechanisms that are neither thermal nor cavitational, and investigate how the effects are related to cumulative radiation-force impulse (CRFI). Applications include traumatic brain injury and acoustic neuromodulation.

Methods: A simple neural model consisting of the giant axon of a live earthworm was exposed to trains of pressure pulses produced by an 825 kHz focused ultrasound transducer.