For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords "HIFU" and "high intensity focused ultrasound". Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice.

High intensity focused ultrasound: surgery of the future?

For 50 years, high intensity focused ultrasound (HIFU) has been a subject of interest for medical research. HIFU causes selective tissue necrosis in a very well defined volume, at a variable distance from the transducer, through heating or cavitation. Over the past decade, the use of HIFU has been investigated in many clinical settings. This literature review aims to summarize recent advances made in the field. A Medline-based literature search (1965-2002) was conducted using the keywords ''HIFU'' and ''high intensity focused ultrasound''. Additional literature was obtained from original papers and published meeting abstracts. The most abundant clinical trial data comes from studies investigating its use in the treatment of prostatic disease, although early research looked at applications in neurosurgery. More recently horizons have been broadened, and the potential of HIFU as a non-invasive surgical tool has been demonstrated in many settings including the treatment of tumours of the liver, kidney, breast, bone, uterus and pancreas, as well as conduction defects in the heart, for surgical haemostasis, and the relief of chronic pain of malignant origin. Further clinical evaluation will follow, but recent technological development suggests that HIFU is likely to play a significant role in future surgical practice. The quest continues for a reliable and minimally-invasive alternative to open surgery. The endoscopic revolution is well underway and there is much research activity in other fields such as laser, radiofrequency, cryo-, thermo- and brachy-therapies. Lithotripsy is now an established treat- ment for stone disease, but currently, the only non-invasive modalities in mainstream use for cancer treatment are chemotherapy and radiotherapy, both of which carry significant side-effect profiles. High intensity focused ultrasound (HIFU) has the potential to provide the clinician with another truly non- invasive, targeted treatment option. Its scope is not, however, limited to the direct treatment of cancers. It may also be used in a palliative setting for relief of chronic pain of malignant origin, for haemostasis, or even for the treatment of cardiac conduction or congenital anomalies.

Review article High intensity focused ultrasound: surgery of the future?

This selective review of the biological effects of ultrasound presents a synopsis of our current understanding of how cells insonated in vitro are affected by inertial cavitation from the standpoint of physical and chemical mechanisms. The focus of this review is on the physical and chemical mechanisms of action of inertial cavitation which appear to be effective in causing biological effects. There are several fundamental conditions which must be satisfied before cavitation-related bioeffects may arise. First, bubbles must be created and then brought into proximity to cells. Exposure methods are critical in this regard, and simple procedures such as rotation of a vessel containing the cells during exposure can drastically alter the results. Second, once association is achieved between bubbles and cells, the former must interact with the latter to produce a bioeffect. It is not certain that the inertial event is the prime mechanism by which cells are lysed; there is evidence that the turbulence associated with bubble translation may cause lysis. Additionally, there appear to be chemical and other physical mechanisms by which inertial cavitation may affect cells; these include the generation of biologically effective sonochemicals and the apparent emission of ultraviolet (UV) and soft X-rays. The evidence for inertial cavitation occurring within cells is critically reviewed.

A review of in vitro bioeffects of inertial ultrasonic cavitation from a mechanistic perspective

Therapeutic ultrasound is an emerging field with many medical applications. High intensity focused ultrasound (HIFU) provides the ability to localize the deposition of acoustic energy within the body, which can cause tissue necrosis and hemostasis. Similarly, shock waves from a lithotripter penetrate the body to comminute kidney stones, and transcutaneous ultrasound enhances the transport of chemotherapy agents. New medical applications have required advances in transducer design and advances in numerical and experimental studies of the interaction of sound with biological tissues and fluids. The primary physical mechanism in HIFU is the conversion of acoustic energy into heat, which is often enhanced by nonlinear acoustic propagation and nonlinear scattering from bubbles. Other mechanical effects from ultrasound appear to stimulate an immune response, and bubble dynamics play an important role in lithotripsy and ultrasound-enhanced drug delivery. A dramatic shift to understand and exploit these nonlinear and mechanical mechanisms has occurred over the last few years. Specific challenges remain, such as treatment protocol planning and real-time treatment monitoring. An improved understanding of the physical mechanisms is essential to meet these challenges and to further advance therapeutic ultrasound.

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Physical mechanisms of the therapeutic effect of ultrasound (a review)

An interchangeable transducer for use with an ultrasound medical system having a keyless adaptor and capable of operating in a wet environment. The interchangeable transducer has an adaptor for engaging a medical system, an ultrasound transducer and additional electronics to provide a self-contained insert for easy replacement and usage in a variety of medical applications. A slip ring spacer is also disclosed, the slip ring spacer for use with a pancake slip ring having a base and flange configuration to form one or more channels around each contact ring of the pancake slip ring. The channels provide fluid isolation around each connector to help reduce electronic cross talk and contact corrosion between the connector pads of the slip ring while the slip ring is immersed in a wet environment.

Slip ring spacer and method for its use

High-intensity focused ultrasound (HIFU) has been used transrectally to induce intraprostatic coagulation necrosis lesion in the canine prostate. The device combines a firing system (power amplifier and therapy transducer) and a localization system (ultrasound scanner). Thirty-seven dogs have been treated with ultrasound intensity ranging from 720 W/cm2 to 2300 W/cm2 and shot durations ranging from 1 to 4 seconds. The threshold for focal ultrasonic lesions was determined to be 1000 W/cm2 with a 1-second shot duration. Intraprostatic lesions were obtained without any damage to the rectal wall. These lesions were homogeneous coagulation necroses and progressed first to an inflammatory fibrosis and then to sclerosis with cavity formation. Intraprostatic lesions also occurred with a combination of moderate acoustic intensity (720 W/cm2) and longer shot duration (4 seconds). The temperature reached at the focal point of the transducer was 85°C. The study confirms the possibility of creating irreversible lesion...

Prostatic Tissue Destruction by High-Intensity Focused Ultrasound: Experimentation on Canine Prostate1

The phenomenology of acousto-electric interaction signals in aqueous solutions of electrolytes

One of the well-known methods of ultrasound focusing is the use of a transducer having the form of a concave spherical cap In the theoretical analysis, O’Neil’s formula is widely used, which describes acoustic pressure on the axis of the transducer under the assumption that normal velocity of its surface is uniform Usually, it is believed that modern piezoelectric focused sources are very close to this theoretical model The paper presented describes results of experimental investigation which showed that there exists a significant disagreement between the observed acoustic field and that predicted by the theory of O’Neil Two types of measurements have been made to clarify this problem The acoustic pressure field of a focused piezoceramic transducer (with aperture diameter of 100 mm, radius of curvature of 100 mm, resonance frequency of 1 MHz) has been measured in a water tank using a miniature hydrophone In addition, the radiator surface vibration has been studied in air using an optical interferome

Lamb waves in piezoelectric focused radiator as a reason for discrepancy between O’Neil’s formula and experiment

In this work, a piezocomposite shock wave generator with electronic focusing capability is presented. The system is composed of a bidimensional array and its electronic hardware. The array is composed of 274 independent piezocomposite transducers arranged in a spherical shell of 280 mm in diameter and focused at 190 mm from its surface. The electronic hardware includes 274 x 6.6 kV distinct impulse generators. For the purpose of performing the electronic steering of shock waves, the delay time of each channel can be adjusted from 100 ns to 100 microseconds in steps of 100 ns. In order to enhance the effect of cavitation at the focus for the purpose of tissue destruction, the pressure-time waveform starts with a half cycle of negative pressure with a peak amplitude of about -150 x 10(5) Pa, followed by a very steep shock front with a positive peak pressure > 1000 x 10(5) Pa and a rise time of about 10 ns. Using this generator, the cavitation-induced lesions in rabbit liver were studied. To obtain a predefined lesion volume, two methods of scanning were used: mechanical and electronic. Comparison of the lesions obtained by these two methods shows that they have identical macroscopic and histological characteristics, which justify the feasibility of electronic beam steering of shock waves in tissue destruction applications.

A piezocomposite shock wave generator with electronic focusing capability: Application for producing cavitation-induced lesions in rabbit liver

Minimally invasive methods for the treatment of cancers, such as high-intensity focused ultrasound (HIFU) and high-energy shock waves (SW), have been proposed recently. Their feasibility for treatment of human cancer needs to be confirmed. A simplified model of isolated perfused pig liver that is close to the human liver in vivo has been proposed. The objective was to study the feasibility of deep focused tissue ablation with HIFU and SW in large organs approaching the size of the human liver. The model was demonstrated to be physiologically valid during the first 2 h of anoxic perfusion with a composite saline solution; arterial and portal pressure, enzymes, urea levels and bile secretion remained stable. It can simulate the major effects of perfusion and physical phenomena that occur in vivo during treatment. Histological analysis revealed no major changes. Previous results obtained in vivo in animal models at a depth of 2-3 cm were successfully reproduced and deeper lesion arrays at 4, 6, 8 and 9 cm from the surface were produced using the same principles. The depth of 9 cm from the liver surface is consistent with an extracorporeal treatment of most of the liver segments in man. Other applications of the model are proposed, particularly for the study of the role of interferences such as ribs and intestinal gas, blood perfusion and respiratory movements.

D. Cathignol

Papers

Prostatic Tissue Destruction by High-Intensity Focused Ultrasound: Experimentation on Canine Prostate1

The phenomenology of acousto-electric interaction signals in aqueous solutions of electrolytes

Lamb waves in piezoelectric focused radiator as a reason for discrepancy between O’Neil’s formula and experiment

A piezocomposite shock wave generator with electronic focusing capability: Application for producing cavitation-induced lesions in rabbit liver

Ultrasound-induced tissue ablation: studies on isolated, perfused porcine liver.