High-intensity focused ultrasound

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, Europe, Korea and Russia to treat essential tremor,[7] neuropathic pain,[8] and Parkinsonian tremor.[9] 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.[10] Treatment for other thalamocortical dysrhythmias and psychiatric conditions are under investigation.[11]

Treatment for symptomatic uterine fibroids became the first approved application of HIFU by the US Food and Drug Administration (FDA) in October 2004.[5]

HIFU is an attractive option for tumors in locations that are hard to reach or non-resectable.[12] Of particular interest are intestinal cancers and brain cancer. When recommending treatment, a clinician must consider other modalities to determine if HIFU is a viable option [supposing commercial statement].

HIFU is being studied in men with prostate cancer.[13][14] Sonacare company received the precaution note from FDA if it is Medical Device, it is needed to 501k procedure with multiple safety clinical data because of it will classified to the class 2 medical device, that is not meant of any registration or the permission. But some commercial magazine showed as it have been registered.[15][16][17][18][19][20]

HIFU is well studied in liver cancer and in many studies report a high response rate and positive patient outcome.[21]

During the treatment of metastasized liver cancer with HIFU, immune responses have been observed in locations that are distant from the focal region.[22][23] Although the mechanism of this systemic response is unknown, it is thought to be elicited by the release of tumor antigens with retained immunogenicity through histotripsy.[24]

HIFU has been applied in treatment of cancer to destroy solid tumors of the pancreas. Xiaolin Yang of Beijing Yuande Bio-Medical Engineering Co., Ltd. represented the big parabola transducer HIFU system named FEP-BY.北京源徳生物医学工程有限公司

HIFU has been found to have palliative effects. CE approval has been given for palliative treatment of bone metastasis.[25] Experimentally, a palliative effect was found in cases of advanced pancreatic cancer.[26]

Treatment of prostate enlargement (benign prostatic hyperplasia) by HIFU from inside the intestine (transrectal) has turned out to be unsuccessful.[27][28]

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.[29]

In England the National Institute for Health and Care Excellence (NICE) in 2018 classified the method as "not recommended".[30]

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.[31] 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, sea water...The treatment will be done by means of the shape of the cylinder in the part, therefore, it is assumed to be adopted of the formula of Bessel's (Cylinder) function. The ideal "IN-VITRO", just in tap water examination, formulations of the CEM equation have been supposed as Dewey and Sapareto:[32]

${\displaystyle {\mathit {CEM}}=\int _{t_{o}}^{t_{f}}R^{T_{\mathrm {reference} }-T}dt}$

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 approach for thermal dose estimation in incompressive material of just a tap water; .[33]

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 3~5 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.[34][35][36] Thermal doses of 120-240 min at 43 °C coagulate cellular protein and leads to irreversible tissue destruction.

There is some evidence that HIFU can be applied to cancers to disrupt the tumor microenvironment and trigger an immune response, as well as possibly enhance the efficacy of immunotherapy.[37][38]

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.[39]

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.[40]

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:

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

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

In ideal model, ${\displaystyle {\frac {-\partial I}{\partial \mathrm {z} }}=2\alpha I=Q}$[41] 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.

The ultrasound beam can be focused in these ways:

• Geometrically, for example with a lens or with a spherically curved transducer.
• Electronically, by adjusting the relative phases of elements in an array of transducers (a "phased array"). By dynamically adjusting the electronic signals to the elements of a phased array, the beam can be steered to different locations, and aberrations in the ultrasound beam due to tissue structures can be corrected.
• Above ideal assumption is adopted with the condition of no reflection, no absorption and no diffusion of intermediate tissue.The ultrasound itself can penetrate the incompressive material such as tap water, sea water, but the compressive material such as air, rubber, human tissue,fat, fiber, hollow bone, fascia, those tissue are reflect, absorb and diffuse the ultrasund energy.

The most common transducer used is a concave focusing transducer with a fixed aperture and a fixed focal length.[42] Phased array transducers can also be used with different arrangements (flat/bowl).[42]

HIFU therapy requires careful monitoring and so 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)[43] and Ultrasound guided Focused Ultrasound Surgery (USgFUS) respectively.[1][44] 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.[45] 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.[46] 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.[46] In addition, treatment outcomes can be estimated in real time through visual inspection of hyperechoic changes in standard B-mode images.[47]