High-intensity focused ultrasound
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 names	Magnetic-resonance-guided focused ultrasound surgery (MRgFUS), focused ultrasound surgery (FUS), MR-guided focused ultrasound ablation
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High-intensity focused ultrasound (HIFU), or MR-guided focused ultrasound surgery (MR-guided focused ultrasound ablation), is an incisionless therapeutic technique^[1] that uses non-ionizing ultrasonic waves to heat orablate tissue. HIFU can be used to increasethe flow of blood or lymph or to destroy tissue, such astumors, 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.

The technology is different from that used inultrasonic 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 ifmechanical rather than thermal damage is desired. Acoustic lenses are often used to achieve the necessaryintensity 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 otherimaging techniques such asmedical ultrasound orMRI to enable guidance of the treatment and monitoring.

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Studies on localized prostate cancer showed that, after treatment, progression-free survival rates were high for low- and intermediate- risk patients with recurrentprostate cancer.^[2]

In 2009, the Insightec ExAblate 2000 was the first MRgFUS system to obtain FDA market approval, applyingUS 5,247,935 ^[3]

In 2016, the US Food and Drug Administration (FDA) approved Insightec's Exablate system to treat essential tremor.^[4] Treatment for otherthalamocortical dysrhythmias and psychiatric conditions are under investigation.^[5]

In 2023, Edison histotripsy developer Histosonics was approved by the FDA to use the technique to destroy tumors and tissue under real-time image guidance In 2025 the company closed a $250M investment round.^[6]

This sectionneeds morereliable medical references forverification or relies too heavily onprimary sources. Please review the contents of the section andadd the appropriate references if you can. Unsourced or poorly sourced material may be challenged andremoved.Find sources: "Focused ultrasound" – news ·newspapers ·books ·scholar ·JSTOR(April 2016)

There is no accepted boundary between HIFU and other forms oftherapeutic ultrasound. In some literature, HIFU refers to the high levels of energy required to destroy tissue throughablation orcavitation, although it is also sometimes used to describe lower intensity applications such asoccupational andphysical therapy.

Either way, HIFU is used to non-invasively heat or ablate tissue deep in the body without an incision.^[1] The main applications are the destruction of tissue caused byhyperthermia, increasingperfusion and physical therapy. It later found use to treat tumors of the liver, with clinical trials underway for other sites,^[7] as well as musculoskeletal conditions.^[8]

One of the first applications of HIFU was forParkinson's disease in the 1940s. Although ineffective at the time, HIFU has the capacity to lesion pathology. Focused ultrasound is approved in Israel, Canada, Italy, Korea and Russia to treatessential tremor,^[9]neuropathic pain,^[10] andParkinsonian tremor.^[11] This approach enables treatment of the brain without an incision or radiation.

HIFU applied to cancers can disrupt thetumor microenvironment and trigger an immune response, as well as possibly enhance the efficacy ofimmunotherapy.^[12][13]

HIFU may be effective for treatingprostate cancer.^[14][15][16]

HIFU has been studied inliver cancer and many studies report a high response rate and positive outcome.^[17] During the treatment of metastasized liver cancer with HIFU, immune responses have been observed in locations distant from the focal region.^[18] A 2024 clinical trial of histotripsy on liver tumors, researchers reported a 95% success rate.^[19] Clinical trials are underway for treating tumors of the pancreas and kidney.^[20]

Histotripsy is a form of non-thermal HIFU for use on the liver that shows some therapeutic potential.^[21] Histotripsy mechanically destroys tissue throughcavitation.^[22]

Focused ultrasound may be used to dissolvekidney stones bylithotripsy.

Ultrasound may be used to treatcataracts byphacoemulsification.

This sectionneeds morereliable medical references forverification or relies too heavily onprimary sources. Please review the contents of the section andadd the appropriate references if you can. Unsourced or poorly sourced material may be challenged andremoved.Find sources: "Focused ultrasound" – news ·newspapers ·books ·scholar ·JSTOR(April 2016)

Multiple HIFU beams are precisely focused on a small region of diseased tissue to locally deposit high levels of energy. Focused ultrasound can generate localized heating. Focusing can be guided byMagnetic Resonance Imaging (MRgFUS). These procedures generally use lower frequencies than diagnostic ultrasound (0.7 to 2 MHz), but the higher frequency means lower focusing energy.

The temperature of tissue at the focus can be increased to between 65 and 85 °C. This inducescoagulative necrosis, destroying the tissue. Tissue heated above 60 °C for longer than 1 second becomes irreversibly damaged.^[23] Eachsonication (individual ultrasound energy deposition) treats a precisely defined portion of tissue. Multiple sonications cover a larger area, creating a volume of incompressible material, such as tap water.^[24]

${\displaystyle \mathit{C}\mathit{E}\mathit{M}={\int }_{t_o}^{t_f}{R}^{T_{\mathrm{r}\mathrm{e}\mathrm{f}\mathrm{e}\mathrm{r}\mathrm{e}\mathrm{n}\mathrm{c}\mathrm{e}}-T}dt}$

with theintegral 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 represent an approach for thermal dose estimation in an incompressible material such as tap water.^[25]

An ultrasound acoustic wave cannot propagate through compressible tissue, such as rubber or human tissues. In that case the ultrasound energy is converted to heat. Using focused beams, a small region of heating can be achieved deep in tissues (usually on the order of 2~3 mm). Tissue changes as a function of the subtle shaking from the heated water within and the duration of this heating according to the thermal dose metric. Focusing at more than one place or by scanning, a volume can be ablated.^[26][27][28] Thermal doses of 120-240 min at 43 °C coagulate cellular protein and lead to irreversible tissue destruction.

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 rectifieddiffusion), and can eventually implode (inertial or transient cavitation). During inertial cavitation, temperatures increase inside the bubbles. The ultimate collapse during the rarefaction phase is associated with ashock wave and jets that can mechanically damage tissue.^[29]

Stable cavitation creates microstreaming, which induces high shear forces on cells and leads toapoptosis. 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.^[30]

Ultrasound can be focused in several ways—via a lens (for example, apolystyrene lens, parabola curvetransducer, or aphased array). This can be calculated using an exponential model ofultrasound 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:

${\displaystyle I=I_o{e}^{-2\alpha \mathrm{z}}}$

${\displaystyle I_o}$ is the initial intensity of the beam,${\displaystyle \alpha }$ is theattenuation coefficient (in units of inverse length), and z is the distance traveled through the attenuating medium (e.g. tissue).

In this ideal model,${\displaystyle \frac{-\mathrm{\partial }I}{\mathrm{\partial }\mathrm{z}}=2\alpha I=Q}$^[31] is a measure of thepower 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, narrowly focusing the beam or increasing the beam intensity creates a rapid temperature rise at the focus.^{[citation needed]}

The ultrasound beam can be focused in several ways:

• Geometrically, with alens or with a spherically curvedtransducer.
• Electronically, by adjusting the relative phases of elements in an array of transducers (a "phased array"). This steers the beam to different locations. Aberrations in the ultrasound beam due to tissue structures can be corrected.^{[citation needed]} This assumes no reflection, no absorption and no diffusion in intermediate tissue. The ultrasound itself can penetrate incompressible materials such as water, but compressible materials such as air, rubber, human tissue, fat, fiber, hollow bone, and fascia reflect, absorb, and diffuse the energy.

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 of 2–3 mm (at most), that determines the frequency of the ultrasound. Following ablation a distinct boundary (less than 50 microns wide) forms between healthy and necrotic tissue.^[32]

The most commontransducer is a concave focusing transducer with a fixed aperture and a fixed focal length.^[32] Phased array transducers can be used with different arrangements (flat/bowl).^[32]

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

Pre-operative imaging, for instanceCT andMRI, are used to identify general parameters of the target anatomy. Real-time imaging provides safe and accurate noninvasive targeting and monitoring. Both MRI andmedical ultrasound have been used. These techniques are known respectively as Magnetic Resonance guided Focused Ultrasound Surgery (MRgFUS)^[33][34] and Ultrasound guided Focused Ultrasound Surgery (USgFUS) respectively.^[1][35]

MRgFUS is a 3D imaging technique. It features high soft tissue contrast and provides information about temperature, thus allowing ablation to be monitored. However, low frame rates make this technique perform poorly in real-time imaging while high costs limit its use.^[36]

USgFUS is a 2D imaging technique. While no quantitative temperature measurement system is available, benefits such as highframe rate (up to 1000 images per second), low cost and minimal adverse health effects commend it. Ultrasound verifies the acoustic window in real time using the same modality as the therapy.^[37] This implies that if the target region is not visualized by ultrasound imaging before and during therapy, then it is unlikely that the therapy will be effective in that specific region.^[37] In addition, treatment outcomes can be estimated in real time through visual inspection ofhyperechoic changes in standardB-mode images.^[38]

• Medical ultrasonography
• Magnetic resonance imaging
• Medical physics

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