Focused ultrasound

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Focused ultrasound
Diagram showing liver lesioning using a HIFU transducer 2.png
Diagram showing how HIFU can be used to destroy tissue in the body. An acoustic lens is used to focus sound to a small point in the body. The sound propagates through many layers of tissue. Because of the focal gain, only tissue at the focus is destroyed.
Other namesMagnetic resonance guided focused ultrasound surgery (MRgFUS), Focused Ultrasound Surgery (FUS)

High-intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique [1] that uses non-ionizing ultrasonic waves to heat or ablate tissue. HIFU can be used to increase the flow of blood or lymph or to destroy tissue, such as tumors, via thermal and mechanical mechanisms. Given the prevalence and relatively low cost of ultrasound generation mechanisms, the premise of HIFU is that it is expected to be a non-invasive and low-cost therapy that can at least outperform care in the operating room.

Contents

The technology is different from that used in ultrasonic imaging, though lower frequencies and continuous, rather than pulsed, waves are used to achieve the necessary thermal doses. However, pulsed waves may also be used if mechanical rather than thermal damage is desired. Acoustic lenses are often used to achieve the necessary intensity at the target tissue without damaging the surrounding tissue. The ideal pattern diagram is the beam-focusing of a magnifying glass of sunlight; only the focal point of the magnifying glass has high temperature.

HIFU is combined with other imaging techniques such as medical ultrasound or MRI to enable guidance of the treatment and monitoring.

History

Studies on localized prostate cancer showed that, after treatment, progression-free survival rates were high for low- and intermediate- risk patients with recurrent prostate cancer. [2] The InsighTec ExAblate 2000 was the first MRgFUS system to obtain FDA market approval, [3] US patent 5,247,935


Medical uses

There is no clear consensus on the boundaries between HIFU and other forms of therapeutic ultrasound. In particular literature, HIFU refers to the high levels of energy required to destroy tissue through ablation or cavitation, although it is also sometimes used to describe lower intensity applications such as occupational therapy and physical therapy.

Either way, HIFU is used to non-invasively heat tissue deep in the body without the need for an incision. [4] The main applications are the destruction of tissue caused by hypertharmia, increasing perfusion and physical therapy. The use of ultrasound in the treatment of musculoskeletal conditions is another use in the physiotherapy setting. [5]

Neurological disorders

Frontal MRI four days after MRgFUS (MRI-guided high-intensity focused ultrasound): Left ventral intermediate nucleus (Vim) thalamotomy. 79-year-old man with essential tremor. MRI-guided HIFU, essential tremor, 10-14 135, pointed.png
Frontal MRI four days after MRgFUS (MRI-guided high-intensity focused ultrasound): Left ventral intermediate nucleus (Vim) thalamotomy. 79-year-old man with essential tremor.

One of the first applications of HIFU was the treatment of Parkinson's disease in the 1940s. Although ineffective at the time, HIFU has the capacity to lesion pathology. A focused ultrasound system is approved in Israel, Canada, Italy, Korea and Russia to treat essential tremor, [6] neuropathic pain, [7] and Parkinsonian tremor. [8] This approach enables treatment of the brain without an incision or radiation. In 2016, the US Food and Drug Administration ( FDA ) approved Insightec's Exablate system to treat essential tremor. [9] Treatment for other thalamocortical dysrhythmias and psychiatric conditions are under investigation. [10]

Cancers

Prostate

HIFU may be effective for detecting prostate cancer. [11] [12] [13]

Liver

HIFU is studied in liver cancer and in many studies report a high response rate and positive outcome. [14] During the treatment of metastasized liver cancer with HIFU, immune responses have been observed in locations that are distant from the focal region. [15]

Prostate enlargement

Treatment of prostate enlargement (benign prostatic hyperplasia) by HIFU from inside the intestine (transrectal) has turned out to be unsuccessful. [16] [17]

In some countries, not in USA, HIFU has also been offered from the inside of the prostate, that is, via a catheter in the prostatic urethra. Evidence as of 2019 is lacking. [18]

In England the National Institute for Health and Care Excellence (NICE) in 2018 classified the method as "not recommended". [19]

Mechanism

HIFU beams are precisely focused on a small region of diseased tissue to locally deposit high levels of energy.

Ideal temperature

The temperature of tissue at the focus will rise to between 65 and 85 °C, destroying the diseased tissue by coagulative necrosis. If tissue is elevated above the threshold of 60 °C for longer than 1 second this process is irreversible. [20] Each sonication (individual ultrasound energy deposition) treats a precisely defined portion of the targeted tissue. The entire therapeutic target is treated by using multiple sonications to create a volume of incompressible material, such as tap water. [21]

with the integral being over the treatment time, R=0.5 for temperatures over 43 °C and 0.25 for temperatures between 43 °C and 37 °C, a reference temperature of 43 °C, and time T is in minutes. The equations and methods described in this report are not intended to represent any clinical result, this is only an approach for thermal dose estimation in a incompressible material of just tap water; . [22]

As an ultrasound acoustic wave cannot propagates through the compressive tissue, such as rubber, human tissues part of it and the ultrasound energy will be turned to converted as heat, with focused beams, a very small region of heating can be achieved the part of shallow deep in tissues (usually on the order of 2~3 millimeters). Tissue occurs as a function of both the subtle shaking to which the water is heated and how long the part of water is exposed to this heat level in a metric referred to as "thermal dose". By focusing at more than one place or by scanning the focus, a volume can be thermally ablated. [23] [24] [25] Thermal doses of 120-240 min at 43 °C coagulate cellular protein and leads to irreversible tissue destruction.

There are some reports that HIFU could be applied to cancers to disrupt the tumor microenvironment and trigger an immune response, as well as possibly enhance the efficacy of immunotherapy. [26] [27]

Mechanical

Inertial cavitation

At high enough acoustic intensities, cavitation (microbubbles forming and interacting with the ultrasound field) can occur. Microbubbles produced in the field oscillate and grow (due to factors including rectified diffusion), and can eventually implode (inertial or transient cavitation). During inertial cavitation, very high temperatures occur inside the bubbles, and the collapse during the rarefaction phase is associated with a shock wave and jets that can mechanically damage tissue. [28]

Stable cavitation

Stable cavitation creates microstreaming which induces high shear forces on cells and leads to apoptosis. Elaborating, bubbles produced by the vaporization of water due to acoustic forces oscillate under a low-pressure acoustic field. Strong streaming may cause cell damage but also reduces tissue temperature via convective heat loss. [29]

Theory

There are several ways to focus ultrasound—via a lens (for example, a polystyrene lens, parabola curve transducer, a phased array, etc. The special patents and very precise technology solve the problem. This can be determined using an exponential model of ultrasound attenuation. The ultrasound intensity profile is bounded by an exponentially decreasing function where the decrease in ultrasound is a function of distance traveled through tissue:

is the initial intensity of the beam, is the attenuation coefficient (in units of inverse length), and z is distance traveled through the attenuating medium (e.g. tissue).

In ideal model, [30] is a measure of the power density of the heat absorbed from the ultrasound field. This demonstrates that tissue heating is proportional to intensity, and that intensity is inversely proportional to the area over which an ultrasound beam is spread—therefore, focusing the beam into a sharp point (i.e. increasing the beam intensity) creates a rapid temperature rise at the focus.[ citation needed ]

The ultrasound beam can be focused in these ways:

Beam delivery

Beam delivery consists of beam steering and image guidance. The beam has the ability to pass through overlying tissues without harm and focus on a localized area with size limit of 2-3 mm, that is determined the clinical frequency of the ultrasound. Following ablation a distinct boundary forms between healthy and necrotic tissue (width less than 50 microns). [31]

Beam steering

The most common transducer used is a concave focusing transducer with a fixed aperture and a fixed focal length. [31] Phased array transducers can also be used with different arrangements (flat/bowl). [31]

Image guidance

HIFU therapy requires careful monitoring and so it is usually performed in conjunction with other imaging techniques.

Pre-operative imaging, for instance CT and MRI, are usually used to identify general parameters of the target anatomy. Real-time imaging, on the other hand, is necessary for safe and accurate noninvasive targeting and therapy monitoring. Both MRI and Medical ultrasound imaging have been used for guidance in FUS treatment. These techniques are known as Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS) [32] [33] and Ultrasound guided Focused Ultrasound Surgery (USgFUS) respectively. [4] [34] MRgFUS is a 3D imaging technique which features high soft tissue contrast and provides information about temperature, thus allowing to monitor ablation. However, low frame rate makes this technique perform poorly in real-time imaging and high costs represent a significant limitation to its use. [35] USgFUS, differently, is a 2D imaging technique in which, although no system to provide quantitative information on temperature has been commercially developed so far, several benefits are exploited, such as high frame rate (up to 1000 images per second), low cost and minimal adverse health effects. Another reason why ultrasound is ideal for image guidance is it verifies the acoustic window in real time since it is the same modality as the therapy. [36] The implication of this is that if the target region is not visualized by ultrasound imaging before and during HIFU therapy, then it is unlikely that HIFU therapy will be effective in that specific region. [36] In addition, treatment outcomes can be estimated in real time through visual inspection of hyperechoic changes in standard B-mode images. [37]

Related Research Articles

<span class="mw-page-title-main">Ultrasound</span> Sound waves with frequencies above the human hearing range

Ultrasound is sound with frequencies greater than 20 kilohertz. This frequency is the approximate upper audible limit of human hearing in healthy young adults. The physical principles of acoustic waves apply to any frequency range, including ultrasound. Ultrasonic devices operate with frequencies from 20 kHz up to several gigahertz.

<span class="mw-page-title-main">Medical ultrasound</span> Diagnostic and therapeutic technique

Medical ultrasound includes diagnostic techniques using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints, blood vessels, and internal organs, to measure some characteristics or to generate an informative audible sound. The usage of ultrasound to produce visual images for medicine is called medical ultrasonography or simply sonography, or echography. The practice of examining pregnant women using ultrasound is called obstetric ultrasonography, and was an early development of clinical ultrasonography. The machine used is called an ultrasound machine, a sonograph or an echograph. The visual image formed using this technique is called an ultrasonogram, a sonogram or an echogram.

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<span class="mw-page-title-main">3D ultrasound</span> Rendering technique in medical imaging

3D ultrasound is a medical ultrasound technique, often used in fetal, cardiac, trans-rectal and intra-vascular applications. 3D ultrasound refers specifically to the volume rendering of ultrasound data. When involving a series of 3D volumes collected over time, it can also be referred to as 4D ultrasound or real-time 3D ultrasound.

Therapeutic ultrasound refers generally to any type of ultrasonic procedure that uses ultrasound for therapeutic benefit. Physiotherapeutic ultrasound was introduced into clinical practice in the 1950s, with lithotripsy introduced in the 1980s. Others are at various stages in transitioning from research to clinical use: HIFU, targeted ultrasound drug delivery, trans-dermal ultrasound drug delivery, ultrasound hemostasis, cancer therapy, and ultrasound assisted thrombolysis It may use focused ultrasound or unfocused ultrasound.

Ultrasound energy, simply known as ultrasound, is a type of mechanical energy called sound characterized by vibrating or moving particles within a medium. Ultrasound is distinguished by vibrations with a frequency greater than 20,000 Hz, compared to audible sounds that humans typically hear with frequencies between 20 and 20,000 Hz. Ultrasound energy requires matter or a medium with particles to vibrate to conduct or propagate its energy. The energy generally travels through most mediums in the form of a wave in which particles are deformed or displaced by the energy then reestablished after the energy passes. Types of waves include shear, surface, and longitudinal waves with the latter being one of the most common used in biological applications. The characteristics of the traveling ultrasound energy greatly depend on the medium that it is traveling through. While ultrasound waves propagate through a medium, the amplitude of the wave is continually reduced or weakened with the distance it travels. This is known as attenuation and is due to the scattering or deflecting of energy signals as the wave propagates and the conversion of some of the energy to heat energy within the medium. A medium that changes the mechanical energy from the vibrations of the ultrasound energy into thermal or heat energy is called viscoelastic. The properties of ultrasound waves traveling through the medium of biological tissues has been extensively studied in recent years and implemented into many important medical tools.

<span class="mw-page-title-main">Sonoporation</span> Technique in molecular biology

Sonoporation, or cellular sonication, is the use of sound in the ultrasonic range for increasing the permeability of the cell plasma membrane. This technique is usually used in molecular biology and non-viral gene therapy in order to allow uptake of large molecules such as DNA into the cell, in a cell disruption process called transfection or transformation. Sonoporation employs the acoustic cavitation of microbubbles to enhance delivery of these large molecules. The exact mechanism of sonoporation-mediated membrane translocation remains unclear, with a few different hypotheses currently being explored.

Treatment for prostate cancer may involve active surveillance, surgery, radiation therapy – including brachytherapy and external-beam radiation therapy, proton therapy, high-intensity focused ultrasound (HIFU), cryosurgery, hormonal therapy, chemotherapy, or some combination. Treatments also extend to survivorship based interventions. These interventions are focused on five domains including: physical symptoms, psychological symptoms, surveillance, health promotion and care coordination. However, a published review has found only high levels of evidence for interventions that target physical and psychological symptom management and health promotion, with no reviews of interventions for either care coordination or surveillance. The favored treatment option depends on the stage of the disease, the Gleason score, and the PSA level. Other important factors include the man's age, his general health, and his feelings about potential treatments and their possible side-effects. Because all treatments can have significant side-effects, such as erectile dysfunction and urinary incontinence, treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations.

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<span class="mw-page-title-main">Sonalleve MR-HIFU</span>

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<span class="mw-page-title-main">Focused ultrasound for intracranial drug delivery</span> Medical technique

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References

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