What ResoFUS treatments are based on?
Both MRgFUS and TULSA use ultrasound combined with magnetic resonance imaging to perform tissue ablation.
Ultrasound is sound waves with frequencies which are higher than those audible to humans. The frequencies used for diagnostic medical imaging are generally in the range of 1 to 18 MHz. With INSIGHTEC technology, ultrasound is used therapeutically. High intensity focused ultrasound energy generates heat at a focal point of up to 85○C to ablate targeted tissue. The frequencies used for therapeutic ultrasound are in the range of 220KHz to 680KHz.
Magnetic Resonance Imaging (MRI) is a medical imaging technique that uses magnetic fields and radio waves to form images of the body. The technique is widely used in hospitals for medical diagnosis, staging of disease and follow-up with no exposure to ionizing radiation. An MRI advantage is that it can also provide a temperature measurement (Thermometry) of a scanned organ. MRgFUS uses focused ultrasound to ablate the target tissue under the image and temperature guidance of the MR. This enables the physician to perform a safe and effective non-invasive treatment with little to no harm to the surrounding tissue and with minimal side effects.
How does it work?
A multi-element phased array transducer adjusts to a focal point electronically. The treating physician defines the region of treatment and the system creates a treatment plan accordingly. During treatment, up to 1000 rays of ultrasound are emitted to a focal point. While transforming energy to heat, the ultrasound rays ablate targeted tissue. Guided by MRI, a clear vision of the treated tissue is acquired. Furthermore, thermal data is analyzed to determine the cumulative thermal impact on the tissue. If necessary, parameters are adjusted to ensure a safe and effective response.
The fundamental principle is analogous to using a magnifying glass to focus beams of sunlight on a single point to burn a hole in a leaf. With focused ultrasound, an acoustic lens is used to concentrate multiple intersecting beams of ultrasound on a target deep in the body with extreme precision and accuracy. Depending on the design of the lens and the ultrasound parameters, the target can be as small as 1×1.5mm or as large as 10x16mm in diameter.
Where each of the individual beams passes through the tissue, there is no effect. But, at the focal point, the convergence of the multiple beams of focused ultrasound energy results in many important biological effects, creating the possibility of treating a variety of medical disorders.
Focused ultrasound treatments can be performed on an outpatient basis, require no incisions, and can result in minimal discomfort and few complications, allowing for rapid recovery.
TULSA PRO is a rigit transurethral device that incorporates a linear array of 10 independent ultrasound transducers that emit directional (but not focused) high-intensity ultrasound energy directly into the adjacent prostate. In this configuration, the ultrasound beams expose a large volume of tissue, resulting in short treatment times and creating a continuous region of thermal ablation without risk of cold spots. A fluid circuit flows water through the UA, providing 1–2 mm of urethral tissue preservation and a passive endorectal cooling device (ECD).
The device is held in situ with a positioning system (PS) that also provides remote linear and rotational motion of the device within the prostatic urethra. A treatment delivery console (TDC) includes customized software to outline the target prostate boundary during planning, monitor the thermal therapy delivery in real time during treatment, and implement the proprietary temperature feedback control algorithm.
Mechanism of action
Transmitting ultrasonic energy continuously raises tissue temperature at the focal point in the body. The level and duration of this temperature elevation is quantified as the tissue’s “thermal dose.”
Thermal effects can be used to create either a low level thermal rise over several hours (local hyperthermia) or, conversely, a short, highly localized high temperature rise that cooks the tissue (thermal ablation). The graph below illustrates different levels of thermal dose and their biological outcome.
Focused ultrasound’s thermal ablation effect may be used to non-invasively treat a variety of clinical conditions, including symptomatic uterine fibroids; tumors in the prostate, breast, and liver; low back pain; and brain disorders such as essential tremor, Parkinson’s disease, and epilepsy.
Thermal ablation allows for cell death in a targeted area with minimal damage to the surrounding normal tissue. Tissue damage can be accurately controlled, and magnetic resonance imaging allows for the monitoring of temperature in real time. Depending on the equipment and parameters used, high-intensity exposure to focused ultrasound can occur in a volume as small as a grain of rice (10 cubic millimeters). This allows for an extremely localized treatment and a sharp border between treated and untreated areas.
Mechanical tissue destruction
The non thermal effects of focused ultrasound can also be used for the destruction of tissue in a precise location.
As ultrasound propagates through tissue, it interacts with dissolved gases in a process known as cavitation. In its stable form, cavitation forms as oscillating bubbles of gas.
When ultrasound is used at high enough intensities, these bubbles can be made to collapse and release an enormous amount of pressure. This phenomenon, known as inertial cavitation, releases a shockwave capable of causing damage and even liquefying cells. The use of inertial cavitation to destroy regions of tissue is known as histotripsy, and is usually the compounded effect of multiple cavitation collapses.
In procedures, microbubbles will often be injected into a targeted location to negate the need for their spontaneous generation. This lowers the threshold for inertial cavitation and aids in the process of histotripsy.
Histotripsy has been used to generate lesions with sharp borders and completely liquefy tumors. Microbubbles are clearly visible with the use of ultrasound imaging which allows for the accurate targeting of a region of tissue. As thermal effects are kept minimal through the use of pulsed focused ultrasound, the destruction of tissue through inertial cavitation can be a precise process that causes minimal damage to surrounding tissue.
Research, Development, and Commercialization
Some applications of the technology are approved for commercial use and are available in medical treatment centers around the world. Other uses are still undergoing research, with opportunities for patients to participate in clinical trials at leading medical research institutions. Even more potential uses of the technology are in the early stages of technical research.
The following charts summarize the state of research and regulatory approval of focused ultrasound for nearly 50 medical conditions around the globe.