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.
Ultrasound Applications
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.
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
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
Thermal Ablation
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
Bioeffects
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
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
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
Cardiac pacing
Focused ultrasound can be used to trigger contraction of the heart.
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
Clot lysis
Focused ultrasound can be used to destroy targeted blood clots, or sensitize them to drug treatments. 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
Hemostasis
Focused ultrasound can be used to stop blood flow. 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
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
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
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
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
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
Sonoporation
Most drugs act from the inside of cells; however, cell membranes frequently prevent drugs 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
Stem cell trafficking
Treatment with focused ultrasound is capable of enhancing the homing, permeability, 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
Tissue destruction
Focused ultrasound can be used to permanently destroy tissue throughout the body.
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
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