Ultrasound (US) has an ever-increasing role in the delivery of therapeutic agents including genetic material, proteins, and chemotherapeutic agents. Cavitating gas bodies such as microbubbles are the mediators through which the energy of relatively non-interactive pressure waves is concentrated to produce forces that permeabilize cell membranes and disrupt the vesicles that carry drugs. Thus the presence of microbubbles enormously enhances delivery of genetic material, proteins and smaller chemical agents. Delivery of genetic material is greatly enhanced by ultrasound in the presence of microbubbles. Attaching the DNA directly to the microbubbles or to gas-containing liposomes enhances gene uptake even further. US-enhanced gene delivery has been studied in various tissues including cardiac, vascular, skeletal muscle, tumor and even fetal tissue. US-enhanced delivery of proteins has found most application in transdermal delivery of insulin. Cavitation events reversibly disrupt the structure of the stratus corneum to allow transport of these large molecules. Other hormones and small proteins could also be delivered transdermally. Small chemotherapeutic molecules are delivered in research settings from micelles and liposomes exposed to ultrasound. Cavitation appears to play two roles: it disrupts the structure of the carrier vesicle and releases the drug; it also makes the cell membranes and capillaries more permeable to drugs. There remains a need to better understand the physics of cavitation of microbubbles and the impact that such cavitation has upon cells and drug-carrying vesicles.

/pdf/ultrasonic-drug-delivery-a-general-review-53bn9zfyxj.pdf

Ultrasonic Drug Delivery – A General Review

Almost 2 decades ago, it was pointed out that physical therapists tended to overlook the tenuous nature of the scientific basis for the use of therapeutic ultrasound. The purpose of this review is to examine the literature regarding the biophysical effects of therapeutic ultrasound to determine whether these effects may be considered sufficient to provide a reason (biological rationale) for the use of insonation for the treatment of people with pain and soft tissue injury. This review does not discuss articles that examined the clinical usefulness of ultrasound (see article by Robertson and Baker titled “A Review of Therapeutic Ultrasound: Effectiveness Studies” in this issue). The frequently described biophysical effects of ultrasound either do not occur in vivo under therapeutic conditions or have not been proven to have a clinical effect under these conditions. This review reveals that there is currently insufficient biophysical evidence to provide a scientific foundation for the clinical use of therapeutic ultrasound for the treatment of people with pain and soft tissue injury.

/pdf/a-review-of-therapeutic-ultrasound-biophysical-effects-38y2gtr660.pdf

A Review of Therapeutic Ultrasound: Biophysical Effects

Like nearly all biologic structures, the peripheral nervous system is remarkably temperature sensitive. Clinical neurophysiologists are most aware of the untoward effects of cooling on nerve conduction studies, including reduced conduction velocity, prolonged distal latency, and increased response amplitude and duration. However, familiarity with the effects of temperature variation on the peripheral nervous system can also provide a deeper understanding of the physiological mechanisms underlying the function of nerve, muscle, and neuromuscular junction in health and disease. Intentional temperature alteration can also improve the diagnostic accuracy of certain electrophysiologic tests, such as the use of heat when performing repetitive nerve stimulation in myasthenia gravis or the use of cold during needle electromyography in some of the myotonic disorders. Finally, extremes of temperature have long been known to produce permanent neuronal dysfunction; recent investigations are beginning to elucidate the mechanisms of such injury.

Effects of temperature on neuromuscular electrophysiology.

By doping an organic compound functioning as an electron donor (hereinafter referred to as donor molecules) into an organic compound layer contacting a cathode, donor levels can be formed between respective LUMO (lowest unoccupied molecular orbital) levels between the cathode and the organic compound layer, and therefore electrons can be injected from the cathode, and transmission of the injected electrons can be performed with good efficiency. Further, there are no problems such as excessive energy loss, deterioration of the organic compound layer itself, and the like accompanying electron movement, and therefore an increase in the electron injecting characteristics and a decrease in the driver voltage can both be achieved without depending on the work function of the cathode material.

Light Emitting Device

Objective To present the frequency resonance hypothesis, a possible mechanical mechanism by which treatment with non-thermal levels of ultrasound stimulates therapeutic effects. The review encompasses a 4-decade history but focuses on recent reports describing the effects of nonthermal therapeutic levels of ultrasound at the cellular and molecular levels. Data sources A search of MEDLINE from 1965 through 2000 using the terms ultrasound and therapeutic ultrasound. Data synthesis The literature provides a number of examples in which exposure of cells to therapeutic ultrasound under nonthermal conditions modified cellular functions. Nonthermal levels of ultrasound are reported to modulate membrane properties, alter cellular proliferation, and produce increases in proteins associated with inflammation and injury repair. Combined, these data suggest that nonthermal effects of therapeutic ultrasound can modify the inflammatory response. Conclusions The concept of the absorption of ultrasonic energy by enzymatic proteins leading to changes in the enzymes activity is not novel. However, recent reports demonstrating that ultrasound affects enzyme activity and possibly gene regulation provide sufficient data to present a probable molecular mechanism of ultrasound's nonthermal therapeutic action. The frequency resonance hypothesis describes 2 possible biological mechanisms that may alter protein function as a result of the absorption of ultrasonic energy. First, absorption of mechanical energy by a protein may produce a transient conformational shift (modifying the 3-dimensional structure) and alter the protein's functional activity. Second, the resonance or shearing properties of the wave (or both) may dissociate a multimolecular complex, thereby disrupting the complex's function. This review focuses on recent studies that have reported cellular and molecular effects of therapeutic ultrasound and presents a mechanical mechanism that may lead to a better understanding of how the nonthermal effects of ultrasound may be therapeutic. Moreover, a better understanding of ultrasound's mechanical mechanism could lead to a better understanding of how and when ultrasound should be employed as a therapeutic modality.

/pdf/nonthermal-effects-of-therapeutic-ultrasound-the-frequency-38yq0qx7mn.pdf

Nonthermal effects of therapeutic ultrasound: the frequency resonance hypothesis.

To achieve the thermal effects of ultrasound, the tissue temperature must be raised from 1 to ≥4°C, depending on the desired outcome of the treatment. In the past 25 years, there have been no in vivo studies that have measured rate of change in temperature during 1-MHz ultrasound treatments, and none have ever been performed with the 3-MHz frequency. Thus, we are left to pure speculation regarding how long to administer an ultrasound treatment. We performed this study to plot the rate of temperature increase during ultrasound treatments delivered at various intensities and frequencies. We inserted two 23-gauge thermistors into each subjects' medial triceps surae at the following depths: 1 MHz at depths of 2.5 and 5.0 cm (12 subjects) and 3 MHz at depths of .8 and 1.6 cm (12 subjects). Each subject received a total of four 10-minute treatments, one each at .5, 1.0, 1.5, and 2.0 W/cn2, and temperature was measured every 30 seconds. No significant difference was found in the rate of heating at the two depths...

https://www.jospt.org/doi/pdf/10.2519/jospt.1995.22.4.142

Rate of temperature increase in human muscle during 1 MHz and 3 MHz continuous ultrasound.

A back support brace for supporting the back of a wearer of the brace for preventing injuries and reinforcing proper lifting mechanics during lifting activities comprises a back panel, a left side panel and a right side panel wherein the left and right side panels are secured at opposite ends of the back panel and are wrappable around the waist of a wearer and adjustably securable thereto. Aligned pairs of belt loops are provided on an inner surface of the brace and are adapted to receive a belt for holding up the pants of the wearer of the brace therethrough so as to prevent the brace from being advanced out of a preset position during lifting activities. A lower edge of the brace includes cutout portions generally positioned above the thighs of the wearer such that the lower edge is contoured to conform to the shape of the wearer throughout lifting activities. Elastic insets extend over the cutout portions to increase tension across the back panel.

Back support belt

A device for delivering light and/or ultrasound across a skin surface is provided. The device has a layered structure comprising a light source and/or an ultrasonic transducer. In one embodiment, the light source comprises an organic light emitting diode or a plurality of printed light emitting diodes and the ultrasonic transducer comprises a piezoelectric coating. The device is electrically coupled to a controller, which is electrically coupled to one or more sensors in contact with the skin surface. The controller is operable to receive sensor data from the sensor and dynamically control the device in response to the received sensor data. The device may be provided with a therapeutic or cosmetic composition to be applied to the skin surface, wherein the light and ultrasound emitted from the device cause transdermal transport of the composition through the skin surface.

Light and ultrasonic transducer device

Low-Watt Pulsed Shortwave Diathermy and Metal-Plate Fixation of the Elbow

A system for delivering light and/or ultrasound across a skin surface is provided. The system includes a device having a layered structure comprising one or both of a light source and an ultrasonic transducer. The light source comprises a flexible light emitter layer electrically coupled to a first conductive layer and a second conductive layer, wherein at least one of the first and second conductive layers is transparent. The ultrasonic transducer comprises a flexible ultrasound emitter layer electrically coupled to a third conductive layer and a fourth conductive layer. The system also includes one or more sensors in contact with the skin surface and a controller electrically coupled to the device and the sensor. The controller is operable to receive sensor data from the sensor and dynamically control the device in response to the received sensor data.

Dawn Castel

Papers

Rate of temperature increase in human muscle during 1 MHz and 3 MHz continuous ultrasound.

Back support belt

Light and ultrasonic transducer device

Low-Watt Pulsed Shortwave Diathermy and Metal-Plate Fixation of the Elbow

Light and/or ultrasonic transducer device with sensor feedback for dose control