Ultrasound

What Does Ultrasound Do?

At low power levels essentially nothing.

This is fundamentally how diagnostic ultrasound works it simply bounces back. It has so little effect on tissues it is used world wide to scan even in pregnancy.

Ultrasound used in treatment is higher power and simply moves molecules and hence gives up energy.

This movement may be in a straight line, round in a circle or by puling molecules out of shape. The amount of energy given up will vary until it is all gone.

This movement and transfer of energy can be great enough to cause heat. This is how high power machines can target and destroy cells.

In therapy there are 2 main ways of treating using ultrasound:

  1. Thermal
  2. Non Thermal

Before we look at the thermal and non thermal effects we have to at least consider the thermal vs non thermal debate:

In any given treatment it is argued there will always be some thermal and some non thermal effects. This would make sense and has ‘face validity’. Not every structure would be sufficiently heated to meet the parameters of a thermal effect but they would be affected by the ultrasound. Conversely even when trying for only non thermal effects there is the likelihood that some tissues would be heated to the required threshold and so would receive a thermal effect.

Some tissues have such a good blood supply that a large amount of ultrasound energy could be given to them and the heat would just be dissipated by the blood flow, and hence the effects would be non thermal even at high doses.

When treating deeper tissues you might find, as an example, the subcutaneous fat is heated but the underlying ligaments receive a non thermal effect and vice versa.

Thermal:

Ultrasound delivered in a continuous mode has been shown to have thermal effects such as increased blood flow and volume along with resolution of chronic inflammatory states (Dyson and Suckling 1978).

Together these have the effect of:

  • Reduction of pain (Soren 1965)
  • Increased blood flow (Lehman et al. 1966)
  • Reduction of muscle spasm (Draper et al. 1993)
  • Decreased joint stiffness (Draper et al. 1993)
  • Increased collagen tissue extensibility (Draper et al. 1993)
  • Increased elasticity of fibrous tissues (less stiffness) (Lehmann 1982)
    • e.g. Joint capsule, ligaments, tendons, scar tissue
  • Tissue healing (Dyson 1978)

Many years ago an upper limit was described (this is argued about but is essentially true) where increasing the heat in tissues was beneficial and beyond that became destructive. Lehman and Guy (1972) said up to 45 degrees Celsius (40-450C) was beneficial and beyond 450C was destructive. Later Lehman and deLateur (1982) said that the increase in temperature needed to be maintained for 5 minutes to achieve a beneficial effect. Based on the results of Forest and Rosen’s (1989), ultrasound must heat tissues to at least 400C in order for them to receive therapeutic effects. In 1993 Draper et al. showed temperatures could be increased safely in tissues to 400C using gel application through the skin.

Non Thermal:

Cavitation

There are 2 main types of cavitation both of which rely on the same fundamental process – the production of gas bubbles in the tissues. These gas bubbles are formed when the static pressure of the liquids within tissues reduce to below the liquid’s vapour pressure, leading to the formation of small vapor-filled cavities. This can then take 2 main forms:

1. Transient (or collapsing) cavitation:

With the right conditions these cavities, (people refer to them as bubbles or voids), collapse and can move rapidly (and unpredictably) potentially damaging tissues. The physical process of transient cavitation is similar to boiling. Boiling occurs when the local temperature of the liquid reaches the saturation temperature, and further heat is supplied to allow the liquid to sufficiently phase change into a gas. Cavitation occurs when the local pressure falls sufficiently below the saturated vapor pressure. The application of ultrasound forces microscopic gas bubbles (that are generally present in any liquid) to oscillate due to an applied acoustic field. If the acoustic intensity is sufficiently high, the bubbles will first grow in size and then rapidly collapse (Brennen 2015). High-power ultrasonics usually utilize the inertial cavitation of microscopic vacuum bubbles for treatments (including the destruction of tissues for removal purposes – like fat removal with ultrasound).

2. Acoustic Streaming:

Non-inertial cavitation (acoustic streaming) occurs when a bubble is created in a fluid which is then maintained. This will forced the molecule to oscillate in size or shape (or both) due to the ongoing ultrasound energy input. This leads to fluid movement around the oscillating bubble known as microstreaming. 

This streaming has been said to alter the permeability of cell membranes (Mortimer and Dyson 1988) as the effects are particularly marked near boundaries. When the ultrasound reaches the cell membrane this can act as a boundary, or the cell it’s self can act as a boundary by vibrating within the extra cellular matrix. A cell wall vibrating parallel to itself generates a shear wave. This effect is localised to a few micrometres in fluids at 1 MHz. The streaming flow generated due to the interaction of sound waves and microbubbles within biological cells (Salari et al. 2019) are examples of boundary driven acoustic streaming. 

Altering the cell membrane can alter the diffusion of ions across the membrane (Low and Reed 1995). Ultrasound can affect the permeability of different cells which have unique properties that affect the body. For example mast cells that have their calcium ion permeability changed affect inflammation (Leung, Ng,  and Yip 2004) . Whilst nerve cells that have their sodium ion permeability changed can lead to pain reduction. A commonly quoted change is that of calcium ion permeability in bone/muscle/tendon etc. which can affect the proliferation of those cells and hence healing rate (Sparrow et al. 2005). 

Below are examples of how ultrasound interacts with the cells involved in the various stages of healing:

Acute Phase (from the time of injury):

The main effects of ultrasound during the acute phase are considered to be in altering inflammation. Ultrasound affects many of the cells involved in inflammation the most important are listed below.

  • Mast cells:
    • Mortimer and Dyson (1988), Fyfe (1982) and (Leung, Ng,  and Yip 2004) described ultrasound affecting the calcium ion diffusion across the cell membrane in mast cells causing degranulation. This in turn leads to the release of histamine and arachidonic acid which affects the amounts of prostaglandins and leukotreine (and the presumption is other growth factors) all together this results in earlier resolution of inflammation. In reality this may seem counter intuitive as ultrasound increases the release of these inflammatory mediators which would make ultrasound a pro not an anti inflammatory treatment.  Although this would be true and ultrasound has been described as pro inflammatory it is actually a net reducer of inflammation in rehabilitation.
  • White blood cells:
    • Evans (1980) and Maxwell (1992) said ultrasound increased phagocytosis due to the agitation of the fluids under treatment.

Please Note:

  • There is literature to suggest ultrasound in not effective at reducing long term inflammation (ElHag et al. 1985, Hashish et al. 1986 and 1988). It is best used to move the patient from the inflammatory phase to the next phase and not as a treatment for long term inflammation where it has not been shown to be effective.

Granulation Phase (day 3 of injury onwards):

Ultrasound affects the connective tissue framework by altering the permeability of several types of cells:

  • Fibroblasts:
    • Once again ultrasound increases the permeability of calcium ions (Harvey et al 1975) which controls cellular activity in fibroblasts. This leads to increased collagen synthesis which is also stronger than without ultrasound (Mortimer and Dyson 1988).
  • Angiogenesis:
    • Mortimer and Dyson (1988) and Young and Dyson (1990) showed ultrasound could increase angiogenesis with increased angiogenetic growth factors, which in turn induce neovascularization and improve blood supply.
  • Growth factors:
    • Young (1988) Observed that ultrasound released proliferating factors including eNOS, VEGF, and PCNA.
    • Reher et al. (1999) showed the effect of ultrasound on the production of IL-8, basic FGF and VEGF. Cytokine. 

Remodelling (can last years in some cases):

In the remodelling phase ultrasound can help to produce more fibroblasts (needed for healing). Move collagen fibres move from one type to another (normally type III to type I according to Wang 1988 and Nussbaum 1988) whilst improving circulation (which may or may not be desirable e.g. in the Achilles tendon) and releasing growth factors needed for repair. It does this by affecting the following cells.

  • Fibroblasts:
    • Fibroblasts continue to be affected (as above) and the now mature collagen becomes more extensible (flexible) according to Lehman and deLateur (1982). The primary reason for this is the re orientation of the fibres which leads to greater flexibility without a loss of strength.
  • Macrophages:
    • Young and Dyson (1990) showed an increase in macrophage activity
  • Endothelial cells:
    • Maxwell (1992) described an increase in the activity of endothelial cells (involved in clotting, wound healing and angiogenesis).
  • Protein Synthesis and Growth Factors:
    • The growth factors shown above continue to be stimulated particularly those shown by Reher et al. (1999) with increased production of IL-8, basic FGF and VEGF.
    • Tsai et al. (2006) showed upregulation of transforming growth factor β which is important in the development of types I and III collagen.
  • Heat Shock Proteins or Stress Proteins:
    • In a study in 2007 Nussbaum and Locke found increased heat shock protein expression in rat skeletal muscle after repeated applications of pulsed and continuous ultrasound. The term ‘heat’ may be misleading in this case as neither ultrasound method actually created any appreciable heat (average muscle temperatures were 38.71°±0.30°C continuous and 38.16°±0.57°C pulsed). They found  significantly increased HSP 25, in the plantaris and soleus muscles and HSP 72 content in the plantaris muscles. Continuous ultrasound significantly increased HSP 72 content in the white gastrocnemius muscle. Heat-shock proteins are named according to their molecular weight. For example, Hsp60, Hsp70 and Hsp90 (the most widely studied HSPs) refer to families of heat shock proteins on the order of 60, 70 and 90 kilodaltons in size. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including stressful enough exercise and during wound healing or tissue remodelling. They help by stabilizing new proteins to ensure correct folding or by helping to refold proteins that were damaged by the cell stress.

Other lesser considered effects:

  • Micromassage
    • This is a stated effect of ultrasound therapy postulated to reduce oedema by Summer and Patrick (1964) however, it is not a well recognised effect of ultrasound in modern use.
  • Standing Waves
    • As described in the effects of ultrasound section refracted waves can be superimposed on each other known as standing waves. This produces stationary waves with peaks of high pressure and subsequent zones of no pressure. Dyson and Pond (1973) showed this could have an effect on blood vessels creating clots (thrombus formation). This is avoided in normal treatments by keeping the head moving or by pulsing the wave.