High-intensity focused ultrasound

A focused ultrasound system is approved in Israel, Canada, Europe, Korea and Russia to treat essential tremor,[3] neuropathic pain,[4] and Parkinsonian tremor.[5] 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.[6] Treatment for other thalamocortical dysrhythmias and psychiatric conditions are under investigation.[7]

Treatment for symptomatic uterine fibroids became the first approved application of HIFU by the US Food and Drug Administration (FDA) in October 2004.[8] Studies have shown that HIFU is safe and effective, and that patients have sustained symptomatic relief is sustained for at least two years without the risk of complications involved in surgery or other more invasive approaches.[9] Up to 16-20% of patients will require additional treatment.[10]

HIFU is being studied in men with prostate cancer.[11][12] HIFU was approved in the United States for prostate tissue ablation in 2015.[13][14][15] HIFU is also being used for ablation of prostate cancer.[16][17][18]

HIFU has been successfully applied in treatment of cancer to destroy solid tumors of the bone, brain, breast, liver,[19] pancreas, rectum, kidney, testes, prostate.[20]

HIFU has been found to have palliative effects. CE approval has been given for palliative treatment of bone metastasis.[21] Experimentally, a palliative effect was found in cases of advanced pancreatic cancer.[22]

Treatment of prostate enlargement (benign prostatic hyperplasia) by HIFU from inside the intestine (transrectal) has turned out to be unsuccessful.[23][24]

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.[25]

In England the National Institute for Health and Care Excellence (NICE) in 2018 classified the method as "not recommended".[26] In the US (as of 2019) not even the technical device needed for the treatment has been approved.[27]

The temperature of tissue at the focus will rise to between 65 and 85 °C, destroying the diseased tissue by coagulative necrosis. Higher temperatures are usually avoided to prevent boiling of liquids inside the tissue. 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 treated tissue, according to a protocol developed by the physician. Anesthesia is not required, but sedation is generally recommended.[29]

As an acoustic wave propagates through the tissue, part of it is absorbed and converted to heat. With focused beams, a very small region of heating can be achieved deep in tissues (usually on the order of millimeters). Tissue damage occurs as a function of both the temperature to which the tissue is heated and how long the tissue 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.[30][31][32]

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.[33][34]

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 is associated with a shock wave and jets that can mechanically damage tissue.[35] Because the onset of cavitation and the resulting tissue damage can be unpredictable, it has generally been avoided in clinical applications thus far. However, researchers have been working on a method of controlling this cavitation, called histotripsy which often involves adding an agent that lowers the temperature at which cavitation occurs.[36][37][38]

There are several ways to focus ultrasound—via a lens (for example, a polystyrene lens), a curved transducer, a phased array, or any combination of the three. This concentrates it into a small focal zone; it is similar in concept to focusing light through a magnifying glass. 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 this model, ${\displaystyle {\frac {-\partial I}{\partial \mathrm {z} }}=2\alpha I=Q}$[39] is a measure of the power density of the heat absorbed from the ultrasound field. Sometimes, SAR is also used to express the amount of heat absorbed by a specific medium, and is obtained by dividing Q by the tissue density. 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 amount of damage caused in the tissue can be modeled using Cumulative Equivalent Minutes (CEM). Several formulations of the CEM equation have been suggested over the years, but the equation currently in use for most research done in HIFU therapy comes from a 1984 paper by Dewey and Sapareto:[40]

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

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 in minutes. This formula is an empirical formula derived from experiments performed by Dewey and Sapareto by measuring the survival of cell cultures after exposure to heat. 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.