High intensity focused ultrasound

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 (generally < 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 the United States, Canada, Israel, Europe, and Asia to treat uterine fibroids. And ultrasonography guided HIFU is currently used in the UK, Italy, Spain, Korea, Japan, Hong Kong, Malasia, Russia and China. 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 HIFUS 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 being called HIFU surgery. Because it destroys the diseased tissue non-invasively, it is also known as "Non-invasive HIFU surgery". Anesthesia is not required. 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. [ [http://www.insightec.com/11-en-r10/InSightec.aspx Insightec Information] ]

Cancer

HIFU has been successfully applied in treatment of cancer to destroy solid tumors of the bone, brain, breast, liver, pancreas, rectum, kidney, testes, prostate. [ [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VJW-4JWMT1W-1&_coverDate=05%2F06%2F2006&_alid=406180509&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=6105&_sort=d&view=c&_acct=C000038338&_version=1&_urlVersion=0&_userid=687471&md5=e85a589afd901f7d2baf01b89102952b Use in Urology, many references] ] [F Wu, Z-B Wang, Y-De Cao, W-Z Chen, J Bai, J-Z Zou and H Zhu. 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. [http://www.nature.com/bjc/journal/v89/n12/abs/6601411a.html;jsessionid=84749763531FA5510F2455132A1B3992] ] A lot of the initial studies have been performed by F. Wu and coworkers at the Chongqing Medical University, Chongqing, China. At this stage cancer treatments are still in the investigatory phases as there is a need to find more about their effectiveness.

One of the latest and most effective uses of HIFU is to use the method to provide hyperthemia not necessarily to treat the cancer alone, but in conjunction with targeted delivery of cancer drugs. For example, Celsion Corporation (www.celsion.com) has developed a technology that can use HIFU and other devices 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. 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.

The earliest widespread use of HIFU ablation was as a treatment for prostate cancer. Developed and refined by two companies in Europe and the United States, 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.

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. Currently, one of these devices has completed successful clinical trials for liver and kidney cancers at the Churchill Hospital, Oxford, UK, and now has CE Marking so can be used clinically in Europe and other countries where the CE Mark is accepted.

At International HIFU Centers in North & South America, physicians use HIFU 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.

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 U.S.

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 Champagne 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 Ablatherm, was developed by the French company EDAP-TMS (NASDAQ: EDAP) and launched in Europe in 2001 after receiving CE approval, bringing a first medical validation of the technology for localized prostate cancer. Comprehensive studies by practitioners at more than one site using the device have demonstrated clinical efficacy at more than 8 years with limited occurrence of side effects. Studies by Murat and colleagues at the Edouard Herriot Hospital in Lyon in 2006 showed that after treatment with Ablatherm, progression-free survival rates are very high for low- and intermediate- risk patients with recurrent prostate cancer (70% and 50% respectively) [ cite web |author= F-J Murat, L Poissonier and A Gelet| year=2006 |title= Recurrent Prostate Cancer After Radiotherapy - Slavage Treatment by High Intensity Focussed Ultrasound | url=http://www.urotoday.com/images/pdf_files/hifu/1-murat_european%20oncological%20disease_2006.pdf (pdf)] 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.

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.

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. 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.

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 surgeryVerify source|date=July 2007.Refimprove|date=July 2007

References

* More HIFU Information from Chongqing Haifu Technology Co., Ltd http://www.haifu.com.cn/en_main.asp

*" [http://bjr.birjournals.org/cgi/content/full/76/909/590 Full text] "

* Nakagawa M.D. PH.D., H, et al., "Initial Experience Using a Forward Directed, High-Intensity Focused Ultrasound Balloon Catheter for Pulmonary Vein Antrum Isolation in Patients with Atrial Fibrillation", "J Cardiovasc Electrophysiol", Vol 18, pp. 1&ndash;9, February 2007,

* Dubinsky TJ, Cuevas C, Dighe MK, et al. High-Intensity Focused Ultrasound: Current Potential and Oncologic Applications. AJR 2008; 190:191-199

* Haar GT, Coussios C. High Intensity Focused Ultrasound: Past, present, present and future. Int J. Hyperthermia 2007; 23(2):85-87

* Coussios C, Farny CH, Haar GT et al. Role of acoustic cavitation in the delivery and monitoring of cancer treatment by high-intensity focused ultrasound (HIFU). Int. J. Hyperthermia 2007; 23(2):105-120

* Leslie TA, Kennedy JE. High intensity focused ultrasound in the treatment of abdominal and gynaecological disease. Int. J. Hyperthermia 2007; 23(2):173-182

* Wu F, Wang ZB, Chen WZ et al. Extracorporeal focused ultrasound surgery for treatment of human solid carcinomas: Early Chinese clinical experience. Ultrasound Med Biol 2004; 30:245-260

* Haar GT, Coussios C. High Intensity Focused Ultrasound: Physical principles and devices. Int J. Hyperthermia 2007; 23(2):89-104

* Lafon C, Melodelima D, Salomir R, et al. Interstitial devices for minimally invasive thermal ablation by high-intenstiy ultrasound. Int. J. Hyperthermia 2007; 23(2):153-163

* Stewart EA, Rabinovici J, Tempany CM, et al. Clinical outcomes of focused ultrasound surgery for the treatment of uterine fibroids. Fertil Steril 2006; 85:22-29

* Fosse E. Thermal ablation of benign and malignant tumours. Minim Invasive Ther Allied Technol 2006; 15:2-3

* Illing RO, Kennedy JE, Wu F, et al. The safety and feasibility of extracorporeal high.intensity focused ultrasound (HIFU) for the treatment of liver and kidney tumours in a Western population. Br J Canc 2005; 93:890-895

* Wu F, Wang ZB, Chen WZ, et al. Advanced hepatocellular carcinoma: Treatment with high-intensity focused ultrasound ablation combined with transcatheter arterial embolization. Radiology 2005; 235:659-667

* Wu F, Wang ZB Zhu H, et al. Feasibility of US-guided high-intensity focused ultrasound treatment in patients with advanced pancreatic cancer: Initial experience. Radiology 2005; 236:1034-1040

* Kennedy JE. High.intensity focused ultrasound in the treatment of solid tumours. Nature Reviews: Cancer 2005; doi10.1039/nrc1591

* Wu F,Wang ZB, Chen WZ, et al. Extracorporeal high intensity focused ultrasound ablation in the treatment of 1038 patients with solid carcinomas in China: an overview. Ultrasound Sonochemistry 11 2004; 149-154

* Kohrmann KU, Michel MS, Gaa J, et al. High intensity focused ultrasound as noinvasive therapy for multilocal renal cell carcinoma: Case study and review of the literature. J Urol 2002; 167:2397-2403

* Kennedy JE, Wu F, Haar TG, et al. High-intensity focused ultrasound for the treatment of liver tumors. Ultrasonics 2004; 42:931-935

* Wu F, Wang Z, Chen W, et al. Extracorporeal High-Intensity Focused Ultrasound for treatment of solid carcinomas: Four-year Chinese clinical experience. In: Andrew M, Crum L, Vaezy S, editors. Proceedings of the 2nd International Symposium on Therapeutic Ultrasound. Seattle: University of Washington; 2003; 34-43

* Wu F, Wang ZB, Chen WZ, et al. Preliminary experience using high intensity focused ultrasound for the treatment of patients with advanced stage renal malignancy. J Urol 2003; 170(6 Pt 1): 2237-2240

* Stewart EA, Gedroyc WM, Tempany CM, et al. Focused ultrasound treatment of uterine fibroid tumors: Safety and feasibility of a noninvasive thermoablative technique. Am J obstet Gynecol 2003; 189:48-54

* Wu F, Chen WZ, Bai J, et al. Tumor vessel destruction resulting from high intensity focused ultrasound in patients with solid malignancies. Ultrasound Med Biol 2002; 28:535-542

* Chen WS. Investigations on the destruction of ultrasound contrast agents: fragmentation thresholds, inertial cavitation and bioeffects [dissertation] . Seattle, WA:University of Washington 2002

* Wu F, Chen WZ, Bai J, et al. Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound. Ultrasound Med Biol 2001; 27:1099-1106

* Sibille A, Prat F, Chapelon JY, et al. Extracorporeal ablation of liver tissue by high intensity focused ultrasound. Oncology 1993: 50:375-379

* Haar TG, Kennedy JE, Wu F. Physical characterization of extra corporeal high intensity focused ultrasound (HIFU) treatments of cancer. Ultrasound Med Biol (in press)

* Chen J, Zhou D, Liu Y, Peng J, Li C, Chen W, Wang Z. A Comparison Between Ultrasound Therapy and Laser Therapy for Symptomatic Cervical Ectopy. Ultrasound Med Biol 2008 May 8.

* Li YY, Sha WH, Zhou YJ, Nie YQ. Short and long term efficacy of high intensity focused ultrasound therapy for advanced hepatocellular carcinoma. J Gastroenterol Hepatol. 2007 Dec;22(12):2148-2154

* Pan JY, Liu YH, Yang QH, Jia L, Ma J. Toxicity attenuation and efficacy potentiation effects of FU Zheng Yang Yin Decoction with HIFU on the experimental model of VX2 cancer in rabbits' liver. Zhong Yao Cai. 2007 Nov;30(11):1425-1429. [Article in Chinese]

* Yu T, Xu C. Hyperecho as the Indicator of Tissue Necrosis During Microbubble-Assisted High Intensity Focused Ultrasound: Sensitivity, Specificity and Predictive Value. Ultrasound Med Biol. 2008 Mar; 29.

* Qiao L, Song WQ. Research on data management of medical equipments in HIFU. Zhongguo Yi Liao Qi Xie Za Zhi. 2007 Sep;31(5):333-337.

* Yang Z, Cao YD, Hu LN, Wang ZB. Feasibility of laparoscopic high-intensity focused ultrasound treatment for patients with uterine localized adenomyosis. Fertil Steril. 2008 Apr 26.

ee also

*Magnetic resonance imaging
*Medical ultrasonography
*Uterine fibroids

External links

* [http://www.istus.org International Society of Therapeutic Ultrasound]
* [http://www.haifu.com.cn/en_about.asp?x_newsort=197&newsort=180 HAIFU Model-JC Focused Ultrasound Tumor Therapeutic System]
* [http://www.pinestreetfoundation.org/avenues/avenues16/hifu16.html Pine Street Foundation Review Article (Winter 2006)]
* [http://www.insightec.com/Overview.aspx?region=10&docID=66&FolderID=36&lang=EN ExAblate 2000, an example of MRgFUS]
* [http://www.focused-ultrasound.org Foundation for Focused Ultrasound]
* [http://dmoz.org/Science/Technology/Acoustics,_Ultrasound_and_Vibration/Ultrasound/Therapeutic_Ultrasound/ Open Directory - Science: Technology: Acoustics, Ultrasound and Vibration: Ultrasound: Therapeutic Ultrasound]
* [http://cimu.apl.washington.edu/ The Center for Industrial and Medical Ultrasound]
* [http://www.fusfoundation.org Focused Ultrasound Surgery Foundation]
* [http://www.urotoday.com/379/browse_categories/hifu_resource_center/1712/ UROTODAY Hifu Resource center]
* [http://www.bubl.org.uk Biomedical Ultrasonics and Biotherapy Laboratory, Oxford, UK]
* [http://www.cancercompass.com/message-board/message/all,3457,0.htm HIFU Message Board]
* [http://www.prorhythm.com Information on the company and device used to treat atrial fibrillation using HIFU]