Mechanisms of Action

Focused ultrasound is a platform technology that can interact with the body in a number of different ways. It can produce both mechanical and thermal energy, and may deliver this energy through either high or low pressure waves. These various focused ultrasound applications induce a wide range of bioeffects on the treated tissue. Some effects like tissue destruction and clot lysis are permanent, while others such as blood-brain barrier opening and neuromodulation are transitory and reversible. Multiple types of ultrasound applications may produce the same bioeffect, further enhancing focused ultrasound’s versatility in the treatment of disease.

To learn more about the current research related to the various mechanisms of action, please see Chapter 3 in the 2023 State of the Field Report.

Tissue Destruction

Thermal Ablation

Thermal ablation occurs when high power ultrasound waves are applied to the tissue over a few seconds to minutes, depositing energy in the form of heat. Heating tissue denatures proteins and leads to death of all cells, regardless of whether they are normal or abnormal (i.e., tumors). The thermal dose required to produce irreversible damage and coagulative necrosis depends on the cell type, temperature and duration of exposure, ranging from one second at 56°C (130°F) to 240 minutes at 43°C (109.4°F). Read More

Histotripsy

High pressure focused ultrasound capable of destroying tissue through mechnical effects rather than thermal. This effect relies on the production and destruction of tiny air bubbles in the targeted tissue, a process called cavitation. Histotripsy induces controlled cavitation to mechanically homogenize targeted tissue. Read More

Sonodynamic therapy

Certain chemical agents induce cell death when exposed to specific wavelengths of light or ultrasound. This mechanism is thought to be caused by the production of reactive oxygen species in cells exposed to such photosensitive and sonosensitive agents. Read More

Clot lysis

Focused ultrasound can be used to destroy targeted blood clots, or sensitize them to drug treatments. Read More

Nonthermal

Low intensity ultrasound applied such that it produces less than 2°C increase in temperature and bioeffects are mediated by mechanical forces. Ultrasound may be pulsed or continuous.

Therapeutic Delivery

Increased vascular permeability

The endothelium creates a barrier to movement of molecules (including drugs) from the inside of the blood vessel to the surrounding tissue. Ultrasound increases the permeability of the blood vessels, which allows drugs to enter tissue in higher concentrations. Read More

Blood-brain barrier opening

The blood-brain barrier is a protective layer of tightly joined cells that line the blood vessels of the brain to prevent harmful toxins from entering. It also prevents the delivery of beneficial drugs to diseased brain tissue. Focused ultrasound can be used to increase the permeability of this barrier in a safe, non-invasive, targeted, and reversible manner. This process can enhance the delivery of drugs, immune or stem cells, immunotherapeutics, genes, and therapeutic delivery vehicles such as nanoparticles. Read More

Sonoporation

Most drugs act from the inside of cells; however, cell membranes frequently prevent drugs or genetic material from entering their interior. Focused ultrasound can temporarily create pores in the cell membrane, allowing drugs to pass through the membrane and reach the interior of the cell. Read More

Vasodilation

Focused ultrasound has been shown to cause blood vessels to widen in a targeted location. This effect is most likely caused by the release of nitric oxide. Vasodilation increases the volume of blood flowing through a targeted region, peak systolic velocity, and permeability of blood vessels. Read More

Drug delivery

Focused ultrasound can be used to enhance the local delivery of drugs, immune or stem cells, immunotherapeutics, genes, and therapeutic delivery vehicles such as nanoparticles. This enhanced delivery may be due to increased vascular permeability, vasodilation, or ultrasound-triggered drug release from a therapeutic delivery vehicle such as a lipsome. Read More

Immunomodulation

Amplification of cancer biomarkers

Tumors release cancer-associated biomarkers into surrounding tissue and the bloodstream that indicate their presence in the body. These markers are usually released in very small quantities. Focused ultrasound can amplify the release of biomarkers and aid in diagnosing and monitoring cancer. Read More

Enhanced Glymphatic Drainage

Studies have suggested that focused ultrasound can enhance glymphatic function by promoting the clearance of waste products from the brain. Read More

Immune cell trafficking

Treating tissues with focused ultrasound can cause the release of various cytokines that can attract immune cells to the targeted tissue. Read More

Immunomodulation

After a focused ultrasound procedure, the exposed proteins and cellular debris that remain in the body can trigger an increased immune response to the treated tumor. Read More

Hyperthermia

A mild temperature elevation to 42°C (107°F) performed continuously over a few minutes to induce hyperperfusion, a physiological response that increases delivery of blood and drugs in the bloodstream to the targeted region. Read More

Chemosensitization

Treating tumors with focused ultrasound can make them more susceptible to chemotherapy, an effect known as sensitization. Sensitization can increase the transportation of chemotherapeutic agents to the tumor and enhance their local effects while diminishing systemic damage by decreasing the dose needed to achieve clinical benefit. Read More

Neuromodulation

Ultrasound can stimulate or block neural activity without damaging the nerves. This effect has potential to block epileptic seizures and induce muscular contractions. Read More

Radiation Sensitization

Radiosensitization

Focused ultrasound can increase the delivery of oxygen to tumors and enhance their metabolic rate. These effects make tumors more susceptible to radiotherapy. Read More

Other

Angiogenesis

Focused ultrasound can interact with endothelial cells in a manner that induces angiogenesis – the process through which new blood vessels form from pre-existing vessels. Read More

Cardiac pacing

Focused ultrasound can be used to trigger contraction of the heart.

Hemostasis

Focused ultrasound can be used to stop blood flow. Read More

Kidney Stone Fragmentation

Focused ultrasound can non-invasively break kidney stones into smaller pieces, making it easier for them to pass through the ureter. Read More

Kidney Stone Propulsion

Kidney stones may get trapped throughout the kidney and ureter, causing obstructions. Focused ultrasound may be applied to reposition the stones and relieve the obstruction. Read More

Liquid biopsy

Treating a tumor with focused ultrasound can enhance the release of cancer antigens, cells, and DNA into the blood stream to permit cancer diagnosis and monitoring. Read More

Stem cell trafficking

Treatment with focused ultrasound is capable of enhancing the homing, penetration, and retention of stem cells at a targeted site. This action occurs through an increased expression of cellular adhesion molecules and the release of chemoattractants. Read More

Vascular occlusion

Focused ultrasound can thermally coagulate and thereby occlude blood vessels. Read More

Vasoconstriction

When focused ultrasound interacts with blood vessels, it can temporarily cause blood vessels to narrow, reducing blood flow. Similarly, the thermal effects of focused ultrasound can produce long term vasoconstriction, allowing for the potential to correct venous abnormalities. Read More