Focused ultrasound

HIFU (high-Intensity Focused Ultrasound) (sometimes FUS or HIFUS) is a highly precise medical procedure using high-intensity focused ultrasound medical device 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).

This is under ultrasonography or computerized MRI. When MRI is used it is sometimes called Magnetic Resonance-guided Focused Ultrasound, often shortened to MRgFUS. When ultrasonography is used it 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. MRgFUS is currently used in Australia, the United States, Canada, Israel, Europe, and Asia to treat uterine fibroids. And 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 the technique 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.

Uses

Uterine fibroids

Development of this therapy significantly broadened the range of treatment options for patients suffering from uterine fibroids. HIFU treatment for uterine fibroids was approved by the Food and Drug Administration (FDA) in October 2004.^[1]

Currently available approved Uterine fibroids HIFU treatment devices are: 1- Philips Sonalleve MR-HIFU 2- GE Insightec ExAblate 2000

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.

Available devices for prostate cancer treatment

Ablatherm® Robotic HIFU

Developed in 1989 in France with Inserm (French National Institute of Medical Research),Edouard Herriot Hospital in Lyon and EDAP TMS (Nasdaq : EDAP), Ablatherm® HIFU was the first prostate cancer HIFU device to receive CE marking in 2000. The first treatments on men were performed in 1993 and as of January 2010, more than 21.000 treatments have been performed worldwide.

Sonablate® 500

Developed at the early 90s for the treatment of benign prostate hyperplasia (BPH) in the US by Misonix (Nasdaq : MSON), Sonablate® was then modified to treat prostate cancer at the end of the 90s. Sonablate® 500 received CE marking in 2001. As of January 2010, a total of more than 7.000 treatments have been performed for benign prostate hyperplasia and prostate cancer (1.600 treatments for prostate cancer as of February 2009).

Other cancers

HIFU has been successfully applied in treatment of cancer to destroy solid tumors of the bone, brain, breast, liver, pancreas, rectum, kidney, testes, prostate.^[2] ^[3] At this stage cancer treatments are still in the investigatory phases as there is a need to find more about their effectiveness.

HIFU may be used to create high temperatures not necessarily to treat the cancer alone, but in conjunction with targeted delivery of cancer drugs. For example, HIFU and other devices may be used to activate temperature-sensitive liposomes, filled with cancer drug "cargo" to release the drug in high concentrations only at the tumor site(s) only where triggered to do so by the hyperthermia device.^[4] This novel approach is resulting in drug concentrations 10 times or more than traditional chemo with a fraction of the side effects since the drug is not released system-wide.

In addition, several thousand patients with different types of tumors have been treated in China with HIFU using ultrasound imaging-guided devices built by several different companies.

Delivering drugs to brain

In current research, HIFU is being used to temporarily break up the blood-brain barrier, allowing an influx of drugs into the brain. It is most effective when used in combination with an inhibitor like verapamil.

Treatment of atrial fibrillation

HIFU has been used to treat the most common heart arrhythmia, atrial fibrillation (AF). A minimally invasive catheter based system designed to ablate heart tissue responsible for propagating AF has been approved for use in Europe and is undergoing an FDA approved phase III pivotal efficacy trial in the United States.

History

The first investigations of HIFU for non-invasive ablation were reported by Lynn et al. in the early 1940s. Extensive important early work was performed in the 1950s and 1960s by William Fry and Francis Fry at the University of Illinois and Carl Townsend, Howard White and George Gardner at the Interscience Research Institute of Champaign, Ill., culminating in clinical treatments of neurological disorders. In particular High Intensity ultrasound and ultrasound visualization was accomplished stereotaxically with a Cincinnati precision milling machine to perform accurate ablation of brain tumors. Until recently, clinical trials of HIFU for ablation were few (although significant work in hyperthermia was performed with ultrasonic heating), perhaps due to the complexity of the treatments and the difficulty of targeting the beam noninvasively. With recent advances in medical imaging and ultrasound technology, interest in HIFU ablation of tumors has increased.

The first commercial HIFU machine, called the Sonablate 200, was developed by the American company Focus Surgery, Inc. (Milipitas, CA) and launched in Europe in 1994 after receiving CE approval, bringing a first medical validation of the technology for benign prostatic hyperplasia (BPH). Comprehensive studies by practitioners at more than one site using the device demonstrated clinical efficacy for the destruction of prostatic tissue without bloodloss or long term side effects. Later studies on localized prostate cancer by Murat and colleagues at the Edouard Herriot Hospital in Lyon in 2006 showed that after treatment with the Ablatherm (EDAP TMS, Lyon, France), progression-free survival rates are very high for low- and intermediate- risk patients with recurrent prostate cancer (70% and 50% respectively)^[5] HIFU treatment of prostate cancer is currently an approved therapy in Europe, Canada, South Korea, Australia, and elsewhere. Clinical trials in the United States are expected to begin in 2006. Prostate cancer trials for the new Sonablate 500 are ongoing in the U.S.A. currently. Magnetic Resonance Guided Focused Ultrasound MRgFUS was first developed by Harvey Cline and Ronald Watkins at GE Corporate R&D lab in Niskayuna NY and Kullervo Hynynen at the University of Arizona, Tucson AZ. starting in 1991. This is described in U.S. Patent #5247935.(1992) The technology was later transferred to InsighTec in Haifa Israel in 2000. The InsighTec ExAblate 2000 was the first MR Guided focused ultrasound system to obtain FDA market approval and sold commercially in the United States. Haifu Model JC and JC200 by ChongQing Haifu Ltd. are complete ultrasound guided tumor treatment systems, and they are only CE approved for beningn and malignant tumors. HIFU-2001(By Sumo Corporation Ltd) is an enhanced technology treatment system that does not require anesthesia since 2001, which are famous in Asia countries. The treatment area included Liver/Pancreas/Bladder/Uterus/Kidney.

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.

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.

Focal HIFU treatment

With the latest improvements in biopsy techniques enabling to better locate cancer, focal HIFU treatment (i.e. partial HIFU ablation) is now starting to be investigated to further reduce the side effects of cancer treatment.

Organizations

The International Society for Therapeutic Ultrasound, founded in 2001, aims to promote clinical, academic and industrial advancement in Therapeutic Ultrasound. Its primary activity is the annual International Symposium on Therapeutic Ultrasound, which has attracted experts in HIFU from throughout the world.

The Foundation for Focused Ultrasound Research is an unincorporated association promoting research into medical uses of high intensity focused ultrasound, including HIFU.

The Focused Ultrasound Surgery Foundation (FUSF) is working to shorten the time from technology development to patient treatment, develop new applications and accelerate the worldwide adoption of MR-guided focused ultrasound surgery ^[6]

References

^ Insightec Information
^ Use in Urology, many references
^ "A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer", British Journal of Cancer (2003) 89, 2227-2233 {{citation}}: Cite uses deprecated parameter |authors= (help)
^ See, for example, Celsion's products at http://celsion.com
^ F-J Murat, L Poissonier and A Gelet (2006). "Recurrent Prostate Cancer After Radiotherapy - Salvage Treatment by High Intensity Focused Ultrasound" (PDF). (pdf)
^ http://www.fusfoundation.org

7. HIFU-2001 can be found at www.sumo.com.hk

External links

[1] Insightec Information

[2] Use in Urology, many references

[3] "A randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer", British Journal of Cancer (2003) 89, 2227-2233 {{citation}}: Cite uses deprecated parameter |authors= (help)

[4] See, for example, Celsion's products at http://celsion.com

[5] F-J Murat, L Poissonier and A Gelet (2006). "Recurrent Prostate Cancer After Radiotherapy - Salvage Treatment by High Intensity Focused Ultrasound" (PDF). (pdf)

[6] ttp://www.fusfoundation.org

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