ULTRASOUND TRANSMISSION

All materials (tissues) present an impedance to the passage of sound waves. The specific impedance of a tissue will be determined by its density and elasticity. For the maximal transmission of energy from one medium to another, the impedance of the two media needs to be the same and thus the reflection that occurs at the interface will be minimized. Clearly, in the case of ultrasound passing from the generator to the body and then through the different tissue types, this cannot actually be achieved. The greater the difference in impedance at a boundary, the greater the reflection that will occur, and hence the smaller the amount of energy that will be transferred.

The difference in impedance is probably greatest for the steel–air interface, which is the first that the ultrasound has to overcome to reach the tissues. To minimize this difference, a suitable coupling medium has to be used. If an air gap exists between the transducer and the skin, the proportion of ultrasound that will be reflected approaches 99.998%, which means that there will be no effective transmission.

The coupling media used in this context include water, various oils, creams and gels. Ideally, the coupling medium should be sufficiently fluid to fill all available spaces; relatively viscous, so that it stays in place; have an impedance appropriate to the media it connects; and should allow transmission of ultrasound with minimal absorption, attenuation or disturbance (for extensive discussions regarding coupling media, see Casarotto et al 2004, Docker et al 1982, Klucinec et al 2000, Poltawski & Watson 2007a, Williams 1987). At the present time, the gel-based media are preferable to the oil- and cream-based media. Water is an effective medium and is a useful alternative but it fails to meet the above criteria in terms of its viscosity. A recent detailed study considering the effect of different coupling gels on ultrasound transmission demonstrated differences in transmission characteristics and absorption levels of commonly employed ultrasound gels, but there was no clinically significant difference between them (Poltawski & Watson 2007a).

In addition to the reflection that occurs at a boundary due to differences in impedance, there will also be some refraction if the wave does not strike the boundary surface at 90°. Essentially, the direction of the ultrasound beam through the second medium will not be the same as its path through the original medium – its pathway is angled. The critical angle for ultrasound at the skin interface appears to be about 15°. If the treatment head is at an angle of 15° or more to the plane of the skin surface, the majority of the ultrasound beam is predicted to travel through the dermal tissues (i.e. parallel to the skin surface) rather than penetrate the tissues as would be expected; it is therefore important to keep the treatment head as flat as possible to the skin surface.

PENETRATION AND ABSORPTION OF ULTRASOUND ENERGY

The absorption of ultrasound energy follows an exponential pattern, i.e. more energy is absorbed in the superficial tissues than in the deep tissues. For energy to have an effect, it must be absorbed. Transmission and attenuation of ultrasound energy are considered in detail in Chapter 2.

Because the absorption (penetration) of ultrasound energy is exponential, there is (in theory) no point at which all the energy has been absorbed, but there is certainly a point at which the energy levels are not sufficient to produce a therapeutic effect. As the ultrasound beam penetrates further into the tissues, a greater proportion of the energy will have been absorbed and therefore there is less energy available to achieve therapeutic effects.

The ‘half value depth’ is often quoted in relation to ultrasound. It represents the depth in the tissues at which half the surface energy is available. This will be different for each tissue and also for different ultrasound frequencies. As it is difficult (if not impossible) to know the thickness of each of these layers in an individual patient, average half value depths are employed for each frequency:

These values are not universally accepted (see Ward 1986) and ongoing research suggests that in the clinical environment they may be significantly lower. To achieve a particular ultrasound intensity at depth, account must be taken of the proportion of energy that has been absorbed by the tissues in the more superficial layers (Watson 2002).

As the penetration (or transmission) of ultrasound is not the same in each tissue type, it is clear that some tissues are capable of greater absorption of ultrasound than others. Generally, the tissues with the higher protein content will absorb ultrasound to a greater extent. This means that tissues such as blood and fat, which have a high water content and a low protein content, absorb little of the ultrasound energy, whereas those with a lower water content and a higher protein content will absorb ultrasound far more efficiently. It has been suggested that tissues can therefore be ranked according to their tissue absorption (Fig. 12.2). Although cartilage and bone are at the upper end of this scale, the problems associated with wave reflection at the tissue surface mean that a significant proportion of ultrasound energy striking the surface of either of these tissues is likely to be reflected. The best-absorbing tissues in terms of clinical practice are those with high collagen content: ligament, tendon, fascia, joint capsule and scar tissue (Frizzel & Dunn 1982, Nussbaum 1998, ter Haar 1999, Watson 2000, 2002).

Figure 12.2 Ranking of musculoskeletal tissues

The application of therapeutic ultrasound to tissues with a low energy-absorption capacity is less likely to be effective than the application of the energy into a more highly absorbing material. Recent evidence of the ineffectiveness of such an intervention can be found in Wilkin et al (2004), whereas application in tissue that is a better absorber will, as expected, result in a more effective intervention (Leung et al 2004a, Sparrow et al 2005).

THERMAL EFFECTS

When ultrasound travels through tissue a percentage of it is absorbed, and this leads to the generation of heat within that tissue. The amount of absorption depends upon the nature of the tissue, its degree of vascularization, and the frequency of the applied ultrasound. Tissues with a high protein content absorb ultrasound more readily than those with a higher fat content, and also the higher the ultrasound frequency, the greater the absorption rate. A biologically significant thermal effect can be achieved if the temperature of the tissue is raised to between 40 and 45°C for at least 5 minutes. Controlled heating can produce desirable effects (Lehmann & De Lateur 1982), which include pain relief, decrease in joint stiffness and increased local blood flow. The therapeutic benefits of tissue heating are well established (see Chapter 7 and 9) but ultrasound is relatively inefficient at generating sufficient thermal change in the tissues to achieve this therapeutic effect.

Historically, ultrasound has been widely employed for its thermal effects but it has been argued more recently that the ‘non-thermal’ effects of this energy form are more effective (Watson 2000, 2006a), and currently the majority of clinical applications focus on these. Gallo et al (2004) demonstrated that both continuous and pulsed ultrasound interventions generated measurable thermal changes in the tissues (muscle) but that, considering the temperature changes achieved, they would be expected to be of minimal therapeutic value. Garrett et al (2000) compared the heating effect of a pulsed shortwave treatment with an ultrasound treatment; the pulsed shortwave intervention was clearly more effective at achieving the required thermal change for therapeutic benefit. A patient treated with ultrasound in continuous mode at a relatively high dose will feel a temperature change (mainly in the skin, which is where thermal receptors are predominantly located) but this is not the same as achieving a clinically significant thermal change in deeper tissues.

A possible complication can occur when an ultrasound beam strikes bone or a metal prosthesis. Because of the great acoustic impedance difference between these structures and the surrounding soft tissues at least 30% of the incident energy will be reflected back through the soft tissue. This means that further energy is deposited as heat during the beam’s return journey. Therefore, heat rise in soft tissue could be higher when it is situated in front of a reflector. To complicate matters further, an interaction termed mode conversion occurs at the interface of the soft tissue and the reflector (e.g. bone or metal prosthesis). During mode conversion, a percentage of the reflected incident energy is converted from a longitudinal waveform into a transverse or shear waveform, which cannot propagate on the soft tissue side of the interface and is therefore absorbed rapidly, causing heat rise (and sometimes pain) at the bone-soft-tissue interface (periosteum). It is suggested that by maintaining a ‘moving’ treatment head approach and by using pulsed ultrasound, both of these effects will be minimized and will not constitute a clinical risk to the tissues. The greatest risk would be achieved with a high-dose, continuous ultrasound treatment using a stationary treatment applicator. The application of ultrasound over superficial bone or metal in the tissues is not contraindicated (see Chapter 21) although caution is advocated.

NON-THERMAL EFFECTS

There are many situations where ultrasound produces bioeffects and yet significant temperature change is not involved [e.g. low spatial-average temporal-average (SATA) intensity]. It is not strictly true to talk about ‘non-thermal’ mechanisms, in that the delivery and absorption of energy in the tissues will result in a temperature rise. The term ‘non-thermal’ in this context relates to the fact that there is no apparent thermal accumulation in the tissues (see Chapter 8) and is sometimes now referred to as a ‘microthermal’ effect. The term ‘non-thermal’ will be employed in the latter context throughout this section.

There is evidence indicating that non-thermal mechanisms play a primary role in producing a therapeutically significant effect: stimulation of tissue regeneration (Dyson et al 1968), soft-tissue repair (Dyson et al 1976, Watson 2006a), blood flow in chronically ischaemic tissues (Hogan et al 1982), protein synthesis (Webster et al 1978) and bone repair (Dyson & Brookes 1983, Malizos et al 2006).

The physical mechanisms thought to be involved in producing these non-thermal effects are one or more of the following: cavitation, acoustic streaming and standing waves (Baker et al 2001, ter Haar 1999, Williams 1987).

Standing waves

When an ultrasound wave hits the interface between two tissues of different acoustic impedances (e.g. bone and muscle), reflection of a percentage of the wave will occur. The reflected waves can interact with oncoming incident waves to form a standing-wave field in which the peaks of intensity (antinodes; see Chapter 2) of the waves are stationary and are separated by half a wavelength. Because the standing wave consists of two superimposed waves in addition to a travelling component, the peak intensities and pressures are higher than the normal incident wave. Between the antinodes, which are points of maximum and minimum pressure, are nodes, which are points of fixed pressure. Gas bubbles collect at the antinodes and cells (if in suspension) collect at the nodes (National Council on Radiation Protection (NCRP) 1983). Fixed cells, such as endothelial cells, which line the blood vessels, can be damaged by micro-streaming forces around bubbles if they are situated at the pressure antinodes. Erythrocytes can be lysed if they are swept through the arrays of bubblessituated at the pressure antinodes. Reversible blood cell stasis has been demonstrated, the cells forming bands half a wavelength apart centred on the pressure nodes (Dyson et al 1974). The increased pressure produced in standing-wave fields can cause transient cavitation and consequently the formation of free radicals (Nyborg 1977). It is therefore important to move the applicator continuously throughout treatment, and also use the lowest intensity required to cause an effect, to minimize the hazards involved in standing-wave field production (Dyson et al 1974).

The combination of stable cavitation and acoustic streaming is thought to be responsible for the cellular ‘upregulation’ that occurs during an ultrasound treatment. The therapeutic effects (see below) of this type of intervention arise as a consequence of this stimulated cellular activity and, strictly speaking, the ‘effects’ of ultrasound are at a cell membrane level (Fig. 12.3).

Figure 12.3 Summary of the mechanism by which ultrasound achieves therapeutic effects.

UNDERLYING REPAIR PROCESS

The major cellular components of the repair process include platelets, mast cells, polymorphonuclear leucocytes (PMNLs), macrophages, T lymphocytes, fibroblasts and endothelial cells. These cells migrate as a module into the injury site in a well-defined sequence that is controlled by numerous soluble wound factors. These wound factors originate from a various sources, such as inflammatory cells (e.g. macrophages and PMNLs), inflammatory cascade systems (e.g. coagulation and complement) and the breakdown products of damaged tissue.

For convenience, the whole repair process can be divided into several phases (Singer & Clark 1999, Watson 2006b), although it must be stated that these phases overlap considerably, lacking any distinct border between them. The three phases are:

There is now overwhelming evidence to show that the effectiveness of therapeutic ultrasound depends on the phase of repair in which it is used. This will be discussed in more detail in subsequent sections.

THE EFFECT OF ULTRASOUND ON THE INFLAMMATORY PHASE OF REPAIR

The inflammatory phase is extremely dynamic and numerous cell types (e.g. platelets, mast cells, macrophages and neutrophils) enter and leave the wound site. There is evidence to show that therapeutic ultrasound can interact with the above cells, influencing their activity and leading to the acceleration of repair (Fyfe & Chahl 1982, Maxwell 1992, Nussbaum 1997, ter Haar 1999, Watson, 2006a).

Acoustic streaming forces have been shown to produce changes in platelet membrane permeability leading to the release of serotonin (Williams 1974, Williams et al 1976). In addition to serotonin, platelets contain wound factors essential for successful repair (Ginsberg 1981). If streaming can stimulate the release of serotonin, it is proposed that it may also influence the release of these other factors.

One of the major chemicals that modifies the wound environment at this time after injury is histamine. The mast cell is the major source of this factor, which is normally released by a process known as mast cell degranulation. In this process, the membrane of the cell, in response to increased levels of intracellular calcium (Yurt 1981), ruptures and releases histamine and other products into the wound site. It has been shown that a single treatment of therapeutic ultrasound, if given soon after injury (i.e. during the early inflammatory phase), can stimulate mast cells to degranulate, thereby releasing histamine into the surrounding tissues (Fyfe & Chahl 1982, Hashish 1986). It is possible that ultrasound is stimulating the mast cell to degranulate by increasing its permeability to calcium. Increased calcium ion permeability has been demonstrated by a number of researchers. Calcium ions can act as intracellular messengers; when their distribution and concentration change in response to environmental modifications of the plasma membrane they act as an intracellular signal for the appropriate metabolic response (Leung et al 2004a, Mortimer & Dyson 1988, Nussbaum 1997).

Reversible membrane permeability changes to calcium have been demonstrated using therapeutic levels of ultrasound (Dinno et al 1989, Mortimer & Dyson 1988, Mummery 1978). The fact that this effect can be suppressed by irradiation under pressure suggests that cavitation is the physical mechanism responsible. Changes in permeability to other ions such as potassium have also been demonstrated (Chapman et al 1979). Work by Dinno et al (1989) demonstrated that ultrasound can modify the electrophysiological properties of skin; this study reported an ultrasound-induced reduction in the sodium/potassium ATPase pump activity. A decrease in pump activity, if it occurs in neuronal plasma membranes, may inhibit the transduction of noxious stimuli and subsequent neural transmission, which may account in part for the pain relief that is often experienced following clinical exposure to therapeutic ultrasound, although as a modality, ultrasound is not often applied with the primary intention of achieving pain relief, and is considered to be a secondary benefit rather than of primary importance. It should be noted, however, that the mechanism of ultrasound-induced pain relief is still not fully understood and that it may be attributed, in part at least, to placebo effects.

As identified above, the evidence is clear: therapeutic ultrasound can alter membrane permeability to various ions. The ability to affect calcium transport through cell membranes is of considerable clinical significance as calcium, in its role as an intracellular or second messenger, can have a profound effect on cell activity, for instance by increasing synthesis and secretion of wound factors by cells involved in the healing process. This has been shown to occur in macrophages in response to therapeutic levels of ultrasound (Young & Dyson 1990a) and these are one of the key cells in the wound-healing system, being a source of numerous wound factors. This in-vitro study demonstrated that the ultrasound-induced change in wound factor secretion is frequency dependent. Ultrasound at an intensity of 0.5W/cm² (SATA) and a frequency of 0.75MHz appeared to be most effective in encouraging the immediate release of factors already present in the cell cytoplasm, whereas the higher frequency 3.0MHz appeared to be most effective in stimulating the production of new factors, which were then released some time later by the cells’ normal secretory processes. Therefore, there appeared to be a delayed effect when treating with the higher frequency; however, the resulting liberated factors, when compared with those liberated using 0.75MHz, were more potent in their effect on the stimulation of fibroblast population growth. One possible reason why these two frequencies induce different effects relates to the physical mechanisms involved. At each frequency the peak pressure generated by the ultrasound was that necessary for cavitation to occur (Williams 1987). Cavitation is more likely to occur at the lower frequency, whereas heating is more likely to occur at the higher one. Therefore, the differing proportions of non-thermal to thermal mechanisms present in each of the two treatments may explain the difference seen in the resulting biological effects.

Hart (1993) also found that following the in vitro exposure of macrophages to ultrasound, a wound factor was released into the surrounding medium that was mitogenic for fibroblasts.

It has often been thought that ultrasound is an anti-inflammatory agent (Reid 1981, Snow & Johnson 1988). When viewed from a clinical standpoint – that is, rapid resolution of oedema (El Hag et al 1985) – this conclusion is understandable. However, research has shown that ultrasound is not anti-inflammatory in its action (Goddard et al 1983, Watson 2006a); rather, it encourages oedema formation to occur more rapidly (Fyfe & Chahl 1985, Hustler et al 1978) and then to subside more rapidly than control sham-irradiated groups, so accelerating the whole process and driving the wound into the proliferative phase of repair sooner.

Further confirmation of this has been shown experimentally in acute surgical wounds (Young & Dyson 1990b). In this study, full-thickness excised skin lesions in rats were exposed to therapeutic ultrasound (0.1W/cm² SATA, 0.75MHz or 3.0MHz) daily for 7 days (5 minutes per day per wound). By 5 days after injury, the ultrasound-treated groups had significantly fewer inflammatory cells in the wound bed and more extensive granulation tissue than the sham-irradiated controls. Also, the alignment of the fibroblasts – parallel to the wound surface – in the wound beds of the ultrasound-treated groups was indicative of a more advanced stage of tissue organization than the random alignment of fibroblasts seen in the sham-irradiated control wounds. The results obtained suggest that there had been an acceleration of the wounds through the inflammatory phase repair in response to ultrasound therapy. It was also noted that there were no abnormalities such as hypertrophy of the wound tissue seen in response to ultrasound therapy.

Therefore, ultrasound therapy appears to accelerate the process without the risk of interfering with the control mechanisms that limit the development of repair materials. By increasing the activity of these cells, the overall influence of therapeutic ultrasound is certainly pro- rather than anti-inflammatory. The benefit of this mode of action is not to ‘increase’ the inflammatory response as such (although, if applied with too great an intensity at this stage, it is a possible outcome; Ciccone et al 1991), but rather to act as an ‘inflammatory optimizer’. The inflammatory response is essential to the effective repair of tissue, and the more efficiently the process can complete, the more effectively the tissue can progress to the next (proliferative) phase.

Employed at an appropriate treatment dose, with optimal treatment parameters (intensity, pulsing and time), the benefit of ultrasound is to make as efficient as possible the earliest repair phase, and thus have a promotional effect on the whole healing cascade. For tissues in which there is an inflammatory reaction, but in which there is no ‘repair’ to be achieved, the benefit of ultrasound is to promote the normal resolution of the inflammatory events, and hence resolve the ‘problem’ This will be most effectively achieved in the tissues that preferentially absorb ultrasound, i.e. the dense collagenous tissues.