Ultrasound is a high frequency mechanical vibrations mechanical waves, which has an acoustic frequencies range from 2*104 to 1010Hz in the elastic medium of propagation. It propagates as a focused beam, so it can effectively detect human tissues. In addition, when ultrasound was stopped transmitting, there would be no energy accumulation on human, which is the ideal method of diagnosis and therapy. While in the ultrasonic applications, varies effects have appeared. One of the effects is physical aspects, containing thermal and non-thermal effects; the other is biological ones, such as tissue healing, hemostasis. Below, we discuss the effects of therapeutic ultrasound.
Non-thermal effects are composed of many mechanical effects, including the cavitation. The cavitation is described as the formation and the liquids that bubbles live in. Acoustic cavitation denotes the behavior of bubbles in an acoustic field.
Ultrasonic generated transformations of pressure and extension in flow, as a result bubbles filled with gas expand and compress. Cavitation appears at the same time. In general stable cavitation is benefit to injured tissue, while unstable cavitation is harmful to the tissue. The regular cavitation can be kept up at lower intensities and shorter pulses. At least 1000 cycles at 1 MHz are required to establish stable cavitation.
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Acoustic streaming is defined as a localized liquid flow around the vibrating bubble, which has been recognized as a primary effect of insonation. However, it should be kept in mind that the bulk streaming is essentially different with the microstreaming, while the latter is far more mechanically powerful than the former. Bulk streaming is generated by the propagation of an ultrasound beam inside a liquid which is moving along a single direction. On the other hand, microstreaming more likely appears with a form of flow eddies close to an oscillating object. In particular, the bulk streaming takes place in vivo but this is not the case for the microstreaming. The reason is that the microstreaming is usually related to cavitation that never exists in vivo except in gas-filled cavities. When the microstreaming occurs at the boundary of the cell membrane and tissue fluid, it would be the only form of acoustic streaming which has sufficient strength to alter membrane permeability and stimulate cell activity.
The movement of ultrasound waves through tissues, which produces small particle oscillation, is believed to take responsibility for other mechanical effects.
Red blood cells classify blood cell stasis, which is a non-thermal effect, in a standing wave field. This stasis is much stronger than any others, when the standing wave is not changing in a quite low acoustic medium, which has a satisfied reflector perpendicular to the ultrasound beam.
The degree of heating tissue depends on a large amount of inconstant, such as a rising temperature caused by insonation. Heating is intensity dependent. Decreased heating takes place for pulsed ultrasound as refuted to continuous ultrasound, the reduction being around relative to the on: off pulse ratio.
Homeostatic mechanisms will attend to contradict the increase in temperature of tissues uncovered to heating. The achiever of homeostasis in put back normal temperature depends on the balance between heat acquirement and heat loss. Any modification in temperature automatically starts a reaction in an attempt to renew normal temperature.
Regional and general homeostatic mechanisms are only partially prosperous in rapidly regress the effect of a gain in temperature. The consequent tissue temperature following heating will mainly depend on the extent of conduction into circumferent tissues and dissipation by blood perfusion.
A raise in blood flow provides a rapid overturn of warm blood, which supports cooling. In muscle, the use of radioactive tracers in human points illustrate that heating agents do not cause an advance in blood flow ,even by the conservative exercise.
Therapeutic eï¬€ects of normal ultrasound exposure have been defined for repairing destroyed ligaments, muscle spasms, inï¬‚amed tendons, stiï¬€ joints, fractured bones and cartilage. Associated eï¬€ects have also been used for debridement and speed up healing of bruises, skin rejuvenation, nerve stimulation [1-3], and improving the strength and elasticity of scar tissues. There are some distinguished applications of this therapy and their fundamental mechanisms.
Ultrasound participates in activating soft tissue healing. Tissues, especially densely-packed big protein molecules, can practice high temperatures resulting in various therapeutic satisfactions. These contain much more extensibility/ï¬‚exibility of collagen-rich scar tissues,  tendons and joints, pain and spasm relief due to heating of muscles and nerve roots, and probable raise in blood ï¬‚ow to help resolution of chronic inï¬‚ammatory processes. Function of non-thermal mechanisms in tissue regeneration and soft tissue restore  has also been widely proved. At a cellular-level, acoustic streaming and stable cavitation cause the changes in diï¬€usion rates and membrane permeability to ions , which can motivate cells by upregulation of signaling molecules. Speciï¬cally, ultrasound has been illustrated to add to protein synthesis, which is necessary to restore mechanisms in cells.
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During the inï¬‚ammation phase of the healing process, ultrasound can activate immune cells to move to the position of injury. Ultrasound also can assist in injure contraction and scar tissue remodeling by changes of the collagen ï¬ber pattern. These good eï¬€ects of ultrasound can be used in treating different skin situations such as varicose ulcers, skin lesions, pressure sores, acceptance of skin grafts, and sutured incised wounds.  Therapeutic eï¬€ects have been showed during regeneration of damaged muscle tissue, and peripheral and sciatic nerves.
Several harmful biological reactions of cells and tissues have been shown to ultrasound exposure comprising growth suppression, retarded protein synthesis, cytoplasmic vacuolation and disruption of intra-cellular components. However such eï¬€ects of ultrasound can be used to suppress or perhaps eliminate tumor in clinical train.
Another application of ultrasound is to influence non-necrotic and localized hyperthermia in tumor tissues. Keeping up heat the solid tumor tissues at temperatures of 42.5-43 C for 20-30 min causes benefical therapeutic eï¬€ect. Many clinical analyses have with success clarified tumoricidal eï¬€ects employing frequencies of ultrasonic hyperthermia in the range of 1-3 MHz. [8-10] Ultrasonic hyperthermia may clear its therapeutic eï¬€ects through apprehend cancer cells in the S phase of the cell cycle and may have advance eï¬€ects on hypoxic, acidic and mal-nourished tumor cells.
While instantaneous thermal ablation persist the authority mechanism of this treatment planning, up-to-date in vivo reports have show that ultrasound exposure can powerfully activate long-term antitumor immunity in the host.
Stimulation of immune response
Transcutaneous immunization (TCI) includes application of vaccines on the skin to induce immunization. Physiologically, skin demonstrates body's ï¬rst line of defense against pathogens and therefore it is an perfect location for inoculation due to the appearance of diverse immune cells, especially Langerhans cells (LCs) which are extremely strong antigen-presenting cells. However, simple topical application of vaccines does not give an enough immune reaction.For the purpose of complete a powerful immune response through TCI, skin tissue has to be fully invigorate with adjuvants to grow an inï¬‚ammatory kind response. In parallel to pro-inï¬‚ammatory noxious chemical adjuvants, ultrasound has been illustrated as a strong physical adjuvant for TCI.
Ultrasound exposure stimulated different immune cells in the skin, especially Langehans cells. Generally, these results advise that ultrasound, as a mechanical excitant, can enable upregulation of cytokines in the skin, activate immune cells and create an immune reaction against topically related vaccines.
Occlusive vascular disease, which supplies incomplete blood to organs, often leads to malnutrition and ischemic conditions, especially includes the myocardium and skeletal muscle tissue. Many methods for targeted stimulation of neovascularization have been followed in the past, containing delivery of growth factor proteins or genes.  In this condition, ultrasound begin to implose microbubbles in ischemic tissues, guiding to triggering of diverse angiogenic pathways .
High-intensity focused ultrasound (HIFU), at typical exposure settings of 1-5MHz and 1-10 kW/cm2 , has successfully achieved hemostasis in active bleeding from blood vessels [13-14] and organs such as liver spleen and lung.
Ultrasonic hemostasis uses a high-intensity beam of ultrasound, which is concertrate on the broken vasculature to perform speedy heating (tissue temperature surpassing 70 C), leading to coagulative necrosis of the tissue and hemostasis. Although this obvious cauterization of the tissue should be classiï¬ed as a direct thermal bioeï¬€ect of ultrasound, several post-exposure observations reveal active recovery of the injured site - a biological reaction of ultrasound exposure resulting in healing and lengthy hemostasis.
As early as 2 weeks after ultrasound exposure, the treatment can stimulate leukocytes and ï¬broblasts from surrounding regions to move and produce collagen, elastin and proteoglycans to improve healing. Additional studies have indicated that hemostasis may also be boosted by tissue thromboplastins released from ultrasonically heated endothelium. tissue recovery responses in hemostasis can be mediated by the non-thermal mechanisms of ultrasound, particularly acoustic cavitation. Further, ultrasound exposure was shown to disrupt platelets to release b-thromboglobulin, adenosine diphosphate and other chemical factors at the site of bleeding, which can induce clotting as well as recruitment of undamaged platelets for accelerated clot formation. [15-16]
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Ultrasound ï¬nds much of its therapeutic applications from thermal, physical and mechanical eï¬€ects on cells and tissues. Increasingly, such ultrasound-induced biological responses are being innovatively engineered to therapies including tissue healing and rejuvenation, cancer treatment, immune adjuvancy, arteriogenesis and hemostasis. At a tissue level, most of the observed ultrasonic therapeutic beneï¬ts are mediated by an inï¬‚ammatory response resulting in a coordinated recruitment of cells as seen in accelerated tissue regeneration, activation of immune cells in vaccination, or in stimulated growth of vasculature.
Although, ultrasonic therapy has yielded signiï¬cant clinical therapies since its initial investigations, more than 5 decades ago; an improved understanding of mechanisms instigating the ultrasonic biological responses will allow us a better handle over engineering these responses to the clinic.