THERAPEUTIC ULTRASOUND                     

The use of high frequency ultrasound (around 5MHz) in medical imaging is a routine part of antenatal medicine to obtain an ultrasonic scan of the foetus in the womb. Such "diagnostic" ultrasound uses a refined pulse echo technique based upon the fact that sound waves are reflected to varying degrees from the interfaces between different tissue, blood and bone in the body. The reflections are processed to give a visual image.

At lower ultrasonic frequencies energy inputs can be increased to a level where chemical effects become possible and this has given rise to a new field of medicine called therapeutic ultrasound.  Such is the interest and expansion in this field of medicine that a new society devoted to the promulgation of the general area of ultrasound in non-diagnostic medicine has been established under the title “International Society for Therapeutic Ultrasound”. The society has a scientific committee chaired by Dr. G. ter Haar, Head of Therapeutic Ultrasound, Royal Marsden Hospital, Sutton, UK and Professor Mason is a member of the committee.

Two purely mechanical applications of ultrasound have been in use for many years.

·                    In Dentistry a common piece of equipment is an ultrasonic device used for cleaning and descaling teeth. There has been research into the use of the same equipment for assisting in the curing of (glass ionomer) white filling material.

·                    In the hospital operating theatre another ultrasonic device is proving to be most useful – the ultrasonic scalpel. This device has a scalpel blade which vibrates ultrasonically and as a result reduces significantly the overall force required to cut. It also gives precise cutting and induces coagulation with minimal lateral tissue damage

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Sono-Dynamic Therapy (SDT)

Some chemicals e.g. porphyrins give out free radicals on treatment with light (Photo Dynamic Therapy) and so cancers which absorb the chemical can be treated wih light to accelerate kill. Ultrasound can do a similar job with the advantage that ultrasound can penetrate the body and so reach tumours without the need for them to be exposed directly to light. This is known as Sono-Dynamic Therapy (SDT). For such treatment the patient has a chemotherapy drug administered, the drug is taken up by the cancer cells and these are then targeted with therapeutic ultrasound to provide enhanced kill.

Transdermal drug delivery

Physiotherapists use ultrasound at frequencies of between 1 and 3 MHz to treat muscle injury because applying ultrasound to the skin surface provides a localised heating/massage effect to the injury site. However the accompanying vibration also causes a temporary weakening of the barrier formed by the stratum corneum.

Ultrasound can alter the barrier function of the skin to permit the administration of drugs not normally permeable through the skin layer. This approach to drug delivery shows potential for the transdermal delivery of:

•          antibiotics - where oral administration would not deliver the appropriate dose to the affected area, e.g. in severe acne or gangrene.

•          non-steroidal anti-inflammatory drugs - when taken orally over a long period may cause gastro-duodenal ulcers in many patients.

•          protein drug molecules - where enhancement of drug penetration through the skin could eliminate the need for injectable forms of insulin which currently 125 million people deal with on a daily basis.

•         Activation of dermal patches – for a rapid and instantaneous extra release of drugs through the skin

Improved uptake of drugs into cells

Several in vitro studies show that low-intensity ultrasound can increase the uptake of chemotherapeutic agents to cancer cells. This increased intracellular drug accumulation is believed to be due to an alteration in the cell membrane permeability mediated by ultrasound.

HIFU

The use of a focused array of transducers for use in cancer therapy (High-Intensity

Focused Ultrasound known as HIFU) has been under investigation for many years. In principal the array is constructed to produce a focus within the body in the

approximate shape of an elongated rugby football a few millimetres or so in cross

section and several millimetres long. The focus can be targeted accurately on

cancerous tissue within the body and, through the energy intensity generated at the

focus, thermally destroy it. In a sequence of exposures the focus can be moved to

cover the whole of the affected region. At lower powers the focused ultrasound can

also be used to enhance the action of chemotherapy agents such as a porphyrin which are known to be affected region and is thought to promote the types of radical reaction which are generally considered to be involved in chemotherapy.

To obtain an accurate focal point within the body which is accurately targeted at the correct point in space is not easy because the sound must pass through various different tissues.

“Review of research into the uses of low level ultrasound in cancer therapy” Tinghe Yu, Zhibiao Wang and T.J. Mason (2004) Ultrasonics Sonochemistry, 11, 95-103.

“The use of a microbubble agent to enhance rabbit liver destruction using high intensity focused ultrasound” Tinghe Yu, Shuhua Xiong, T.J. Mason and Zhibiao Wang (2006) Ultrasonics Sonochemistry 13, 143-149.

“Ultrasound: a chemotherapy sensitizer”, Tinghe Yu, Shugang Li, Jie Zhao and T.J.Mason (2006) Technology in Cancer Research and Treatment, (2006) 5, 51-60 .

Examples of Projects

“The influence of ultrasound on the uptake of chemotherapeutic agents into cells”

“Effect of ultrasound on transdermal drug delivery systems”

“Measurements of power output for therapeutic ultrasound devices”

“The effect of ultrasound on the permeability of diclofenac through cellulose membrane and EpiDerm tissue from a customized gel formulation in comparison to Voltarol Emugel”

“Ultrasonically assisted curing of glass ionomer cements”

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