High Intensity Focused Ultrasound (HIFU)
HIFU (High-Intensity Focused Ultrasound) (sometimes FUS or HIFUS) is a highly precise medical procedure using high-intensity focused ultrasound to heat and destroy pathogenic tissue rapidly. It is one modality of therapeutic ultrasound, and, although it induces hyperthermia, it should not be confused with this technique, which heats much less rapidly and to much lower therapeutic temperatures (in general < 45°C).
Clinical HIFU procedures are typically image-guided to permit treatment planning and targeting before applying a therapeutic or ablative level of ultrasound energy. When MRI is used for guidance, the technique is sometimes called Magnetic Resonance-guided Focused Ultrasound, often shortened to MRgFU. When ultrasonography is used, the technique is sometimes called Ultrasound-guided Focused Ultrasound, often shortened to USgFUS. Magnetic resonance imaging (MRI) is used to identify tumors or fibroids in the body, before they are destroyed by the ultrasound. MRgFU is currently used in Australia, the United States, Canada, Israel, Europe, and Asia to treat uterine fibroids. Ultrasonography guided HIFU is currently used in the United Kingdom, Italy, Spain, Korea, Japan, Hong Kong, Malaysia, Russia, China, Romania and Bulgaria. Current clinical trials are underway, examining the possible use of HIFU in the treatment of cancers of the brain, breast, liver, bone, and prostate.
Therapeutic ultrasound is a minimally invasive or non-invasive method to deposit acoustic energy into tissue. Applications include tissue ablation (HIFU) (for tumor treatments, for example), hyperthermia treatments (low-level heating combined with radiation or chemotherapy), or the activation or enhanced delivery of drugs.
Aiming
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 due to tissue structures can be corrected.
How HIFU works
As an acoustic wave propagates through the tissue, part of it is absorbed and converted to heat. With focused beams, a very small focus can be achieved deep in tissues. When hot enough, the tissue is thermally coagulated. By focusing at more than one place or by scanning the focus, a volume can be thermally ablated. 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 eventually implode (inertial or transient cavitation). During inertial cavitation, very high temperatures inside the bubbles occur, and the collapse is associated with a shock wave and jets that can mechanically damage tissue. Because the onset of cavitation and the resulting tissue damage can be unpredictable, it has generally been avoided in clinical applications. However, cavitation is currently being investigated as a means to enhance HIFU ablation and for other applications.
Method of use
In HIFU therapy, ultrasound beams are focused on diseased tissue, and due to the significant energy deposition at the focus, temperature within the tissue rises to 65° to 85°C, destroying the diseased tissue by coagulation necrosis. Each sonication of the beams treats a precisely defined portion of the targeted tissue. The entire therapeutic target is treated by moving the applicator on its robotic arm in order to juxtapose multiple shots, according to a protocol designed by the physician. This technology can achieve precise ablation of diseased tissue, therefore it is called HIFU surgery. Because it destroys the diseased tissue non-invasively, it is also known as "Non-invasive HIFU surgery". Anesthesia is not required, but should be recommended. The treatment can be combined with radiotherapy or chemotherapy.
Prostate cancer
The earliest widespread use of HIFU ablation was as a treatment for prostate cancer. This treatment is administered through a trans-rectal probe and relies on heat developed by focusing ultrasound waves into the prostate to kill the tumor. Promising results approaching those of surgery have been reported in large series of prostate cancer patients. These treatments are performed under ultrasound imaging guidance, which allows for treatment planning and some minimal indication of the energy deposition. HIFU may also be used to ablate the entire prostate gland using a transrectal probe. This is an outpatient procedure that usually last 1–3 hours. Results show that it greatly reduces some of the side effects common with other treatments for prostate cancer.
During HIFU, the entire prostate is ablated, including the prostatic urethra. The urethra has regenerative ability because it is derived from a different type of tissue (bladder squamous-type epithelium) rather than prostatic tissue (glandular, fibrotic and muscular). While the urethra is an important anatomical structure, the sphincter and bladder neck are more important to maintaining the urinary function. During HIFU the sphincter and bladder neck are identified and avoided.
Advantages over other techniques
High Intensity Focused Ultrasound is often considered a promising technology within the non-invasive or minimally invasive therapy segments of medical technology. HIFU’s capacity to generate in-depth precise tissue necrosis using an external applicator, with no effect on the surrounding structures, is unique. The history of using therapeutic ultrasound dates back to early in the 20th century. Technology has continually improved and additional clinical applications, both diagnostic and therapeutic, have become an integral part of medicine today.
An important difference between HIFU and many other forms of focused energy, such as radiation therapy or radio surgery, is that the passage of ultrasound energy through intervening tissue has no apparent cumulative effect on that tissue.
The absence of cumulative effect of HIFU on the treated tissue means that the treatment can be repeated in case of first HIFU treatment failure or partial treatment of the prostate. As a clean treatment (= non-ionizing) HIFU is also an option to treat prostate cancer recurrence after radiation therapy failure.
Discoveries during use
Currently, the only proven imaging method to accurately quantify the heating produced during HIFU in vivo is Magnetic Resonance Imaging (MRI). MRI also has superior soft tissue contrast and can image in any orientation, making it the state of the art for guiding HIFU treatments. But MRI can't operate in real-time with HIFU, with the current state of the art being one image acquisition approximately every six seconds using a full scan of k-space. Researchers are working to reduce this image acquisition time through some of the speed enhancements common in other areas of MRI, including pulse sequences to scan a reduced k-space, constrained reconstruction, and model-based filtering using data from the bioheat equation.
Clinically, MRI-guided HIFU treatments have been tested for uterine fibroids, breast fibroadenomas, breast cancer, bone metastases, and liver tumors. The largest number of patients treated with MRI-guided HIFU have been with uterine fibroids.
USgFUS treatments have been approved with CE for wider range of benign and malignant tumors due to its higher power, precision and realtime monitoring system. The largest number of patients are uterine fibroids.
Ultrasound-guided HIFU treatments have been approved in Europe and Asia. MRI-guided treatments of uterine fibroids have been approved in Europe and Asia, and were granted FDA approval in the US in 2004.
