Annemarie Oesterle, head of medical technology marketing segment, PI Ceramic
If an external force with changing amplitude acts on an elastic medium such as a gas, a liquid or a solid, an undulating propagation of pressure and density fluctuation occurs in space and time, starting from the point where the force is applied. This is known as sound. The frequency of sound waves ranges from a few hertz up to several gigahertz (figure 1). Infrasound, the sound humans cannot hear, lies at frequencies below 16 Hz; it is followed by the hearing range, which reaches up to 20 kHz. Ultrasonic waves, which cannot be heard, lie in the frequency range from 20 kHz to 1.6 GHz, which equals 16 billion cycles per second. A prominent application example in medical technology is the use of ultrasound for diagnostic imaging techniques. In industry and research, ultrasound is mainly used in measurement technology, where sound waves with low power are used. The intensity of the sound describes the power that hits a certain surface. If it exceeds 10 W/cm2, it qualifies as power ultrasound, which often shows frequencies in the range of 20 to 800 kHz.
Figure 1
The frequency range of ultrasound.
Power ultrasound in medicine
Piezoelectric ceramics generate power ultrasound by using the piezoelectric effect to transform high frequency electric energy into mechanical energy and vice versa. The ultrasonic waves generated by a piezoelectric transducer can be used in fluids to generate so-called cavitation bubbles. These are created when acoustic waves generate rarefaction and compression zones with locally higher and lower material densities in a medium. The resulting high tensile and shear forces between the zones cause the fluid medium to be ripped apart, creating gas-filled cavities. Depending on the frequency and sound force of the applied ultrasonic sound waves, two different cavitation states can occur: a stable cavitation with small oscillating gas bubbles, i.e. they pulsate with the rhythm of the ultrasonic sound frequency and with that, increase or decrease in size; an instable cavitation, where such a high ultrasound power is used that the cavitation bubbles expand so much that they finally implode (figure 2). In the case of the latter, very high forces and pressures are released in the form of shock waves and extremely high temperatures of several 1,000°C as well as flashes of light can occur temporarily.
Figure 2
Cavitation in liquids caused by ultrasonic waves.
These physical effects of cavitation are used for various medical applications. For example, the stable cavitation is applied in medical imaging, when gas-filled microspheres are used as an ultrasound contrast medium. In addition to cavitation, power ultrasound can cause changes in material or even destroy it, which is used in medical applications but also in industrial material processing or ultrasonic cleaning.
Therapeutic ultrasound methods
Ultrasound opens up therapeutic possibilities that improve or even substitute many established procedures. Minimally or non-invasive and gentle treatment methods with improved therapy success and fewer side effects can be realised using piezoelectric components. In this case, therapeutic ultrasound refers to a group of methods in which ultrasound is not only a means of diagnosis but also the core element of therapy itself. By using piezoceramic ultrasonic transducers, minimally or non-invasive and gentle treatment methods with improved therapy success can be realised. These include methods that use focused but also unfocused ultrasound for, e.g., tissue ablation, targeted drug delivery and intravascular therapy. Further application examples using therapeutic ultrasound are cartilage therapy, administration of drugs through the skin and cosmetic treatments.
Tissue ablation
Focused ultrasound is used in a non-invasive procedure to help in the selective removal of certain tissue areas. Ultrasound-operated tools make this minimally or non-invasive surgery technique, often also referred to as incisionless, possible. Ultrasound-based ablation of tissue for, e.g., the removal of tumours in the prostate or uterus, is extracorporeal and therefore non-invasive. For this form of therapy, high-intensity focused ultrasound (HIFU) is projected into the body with the help of piezoelectric elements. The acoustic waves lead to a thermal ablation since the absorption of the ultrasonic wave energy generates heat above 42°C due to friction so that the proteins of the cell structures denaturise and entire tissue areas within the focus of the sound waves coagulate. HIFU can also be used to treat conditions such as tremor and epilepsy without medication by targeting specific brain structures with heat. Monitoring, in these cases, is performed simultaneously by magnetic resonance tomography (MRT).
An alternative method for tissue ablation is histotripsy. In this case, HIFU generates cavitation bubbles, the high mechanical energy of which causes cells to burst without any significant heating of the affected tissue.
Targeted drug delivery
Ultrasound makes the targeted delivery as well as increased uptake of a drug at a specific location in the body possible. Various mechanisms are suitable. The basic method is the injection of microspheres filled with a drug or gas, which are distributed in the patient's bloodstream during treatment and can only be used where they are in the sound field focus. To target delivery of a drug, unstable cavitation generated by ultrasound causes drug-filled microspheres to burst and release the active substance directly at its destination.
To increase uptake of a drug, stable cavitation causes gas-filled microspheres to oscillate, producing microstreams that, in combination with the mechanical energy of the acoustic waves, increase permeability of, e.g., blood vessel walls, for the active substance. This mechanism is called sonoporation and is used for, e.g., the reversible opening of the blood-brain barrier, a process that can improve the medical therapy of neurodegenerative diseases such as Parkinson's or Alzheimer's significantly. In sonodynamic therapy, focused ultrasound waves induce the formation of reactive oxygen species (ROS), which act cytotoxically on cells in, e.g., cancer tumours.
Intravascular therapy
Ultrasound is used in a minimally invasive way to reduce atherosclerosis (the build-up of fatty deposits known as plaques) in blood vessels and thus treat stenosis (the narrowing of the arteries, resulting in restricted blood flow). In intravascular lithotripsy (IVL), ultrasound waves increase permeability of the blood vessel walls (sonoporation), allowing the drug to more easily penetrate and induce the dissolution of plaques. If a blood clot (thrombus) has already formed, the ultrasound waves help to loosen its structure. The drug can then more easily penetrate the thrombus and dissolve it. In this way, the flow of blood to vital organs is ensured and embolisms are prevented.
Suitability of piezoelectric transducers for therapeutic ultrasound applications
Generating and detecting ultrasound is a classic piezoelectric transducer application. When an AC voltage is applied, the piezoelectric elements start to oscillate at the frequency used. Ultrasound generation benefits from the short response times and the high dynamics of this motion. Piezoelectric elements (figure 3) are suitable for various ultrasound applications, especially in power ultrasound since they generate considerable power densities of up to several kW/cm2 for, e.g., lithotripsy (fragmentation of hardened masses such as kidney stones). The advantage here lies in the non-invasive execution of therapeutic procedures in patients. Ultrasound-operated medical devices are applied extracorporeal and are therefore even less stressful for the patients than established minimally invasive procedures.
Figure 3
Piezoelectric hemispheres or focus bowls for therapeutic ultrasound.
The selection of a suitable transducer for therapeutic ultrasound strongly depends on the specifications of the potential device such as focus depth, focus size, maximum electrical voltage, installation space, sound pressure and ambient conditions, e.g., strong magnetic fields. In the following paragraphs, the various transducer types that can be used for therapeutic ultrasound are discussed.
HIFU transducer with fixed focus point
Transducers with a device-specific fixed focus point (figure 4) are mainly used in ultrasonic handpieces for, e.g., cosmetic skin treatments or cartilage therapy. The focus depth, which is usually in the range of a few centimetres, is determined by the shape of the transducer. To generate focused ultrasound, piezoceramic focus bowls can be used. Their radius determines the ultrasound focus depth. Depending on the application, ferroelectric soft or hard ceramics such as PIC255, PIC155, PIC151 or PIC181 are used.
Figure 4
A HIFU transducer with fixed focus point.
The piezoceramic focus bowls can be customised from 2 to 130 mm outer diameter, in various designs and different quantities. Special shape variations are possible, e.g., collar, flattening, phases, spheres or application-specific designs. The electrode of such a focus bowl can be provided with one or more wraparound contacts in order to facilitate installation and cable routing in the end device. PI Ceramic also provides wires or soldered strands for the assembly.
HIFU transducer with steerable focus point
To move an ultrasound focus, phased array transducers are used. These transducers are usually made of many piezoelectric elements (arrays) that can be controlled individually. Using a time-shift electrical control (phase), interferences are created in the sound field, enabling a defined and steerable focus point. The motion of the ultrasound focus in these phased array transducers can be controlled by appropriate electronics. Transducers typically used for therapeutic ultrasound are annular phased arrays or curved phased arrays.
Annular phased arrays are a group of transducers, the main element of which is a piezoelectric ceramic disk, plate or focus bowl. The applied electrode can be chosen from various material systems, e.g., thick silver (Ag) films or thin copper (Cu) or copper-nickel (CuNi) films. Annular phased arrays have a structured electrode that can, e.g., be structured using a laser. In this case, the electrode is divided into concentric surfaces in the shape of a central ring with surrounding rings. The width of the electrode rings diminishes from the inner to the outer ring since all electrode segments have the same surface area (figure 5). At the front, these annular arrays have an electrode that covers the entire surface. Electronic focus control of annular arrays is possible along the ultrasound beam axis by way of phase-shift control of the individual electrodes. Annular arrays are used in, e.g., handpieces for prostate tumour ablation.
Figure 5
The electrode rings of a HIFU annular phased array transducer with steerable focus point.
Curved phased arrays are the most complex sound transducers used for therapeutic ultrasound. They are mainly used for thermal or histotripsy-induced tissue ablation in the treatment of, e.g., breast cancer, abdominal tumours, tremor and epilepsy. To generate a directed ultrasound wave, a few to over several 1,000 piezoelectric elements, depending on the application, are arranged on a concave dome and excited synchronously (figure 6). This focuses the energy in the shock wave. Commonly used shapes are plates or disks. Although piezoelectric plates make use of the entire space in the transducer, they still lead to distortions in the sound field and a softening of the sound focus. In contrast, piezoelectric disks have a more homogenous single sound field and are thus better suited for generating the most accurate focusing possible. Special shapes such as pentagons or hexagons are also suitable for lining a HIFU phased array transducer with piezoelectric elements. The electrodes of these sound transducers can be, e.g., thick Ag films or thin Cu or CuNi films.
Figure 6
A HIFU curved phased array transducer with steerable focus point.
Structuring the electrode surfaces with wraparound contacts is the best solution to lead any electrical contact to the rear of the transducer. The numerous piezoelectric elements can be individually soldered or glued with stranded wires or cables. Furthermore, customised flexible circuit boards can be used for contacting these complex transducers. In most cases, the sound focus is controlled using the phase offset of the individual signals in the drive electronics. Concave HIFU phased array transducers are always used in conjunction with a water bellow, since this is the only way to overcome the impedance jump between the piezoelectric elements and the surrounding environment with as little loss as possible.
Transducers in minimally invasive catheters
Minimally invasive catheters use ultrasonic sound waves for therapy, e.g., removal of blood vessel deposits (figure 7) or targeted tissue ablation for the treatment of atrial fibrillation of the heart. In this case, individual piezoelectric elements such as miniaturised tubes or plates, are used (figure 8). Freely defined shapes with dimensions of only a few millimetres also offer high effective force in a minimal installation space. For transducer applications, it is furthermore possible to assemble several elements in a catheter by soldering or gluing them together. In this case, it is important that the piezoelectric elements do not come into direct contact with tissues or bodily fluids. An electrically insulating protective layer made of silicon or parylene, for example, protects against an electrical short circuit and prevents the piezoelectric elements from corrosion.
Figure 7
A minimally invasive catheter that uses ultrasonic sound waves to remove blood vessel deposits.
Klaus Kerth
Figure 8
Miniaturised piezoelectric elements for integration into minimally invasive catheters.
Conclusion
Therapeutic ultrasound opens up numerous applications for the treatment of neurodegenerative, cardiovascular and cancer diseases. PI Ceramic supports customers in manufacturing customised transducers for their applications, affording considerable expertise in piezoelectric technology and exceptional competence in assembly and connection technologies.
PI Ceramic