HIFU (
high intensity focused ultrasound) (sometimes
FUS or
HIFUS) is a highly precise medical procedure using high-intensity focused
ultrasoundUltrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Although this limit varies from person to person, it is approximately 20 kilohertz in healthy, young adults and thus, 20 kHz serves as a useful lower limit in describing ultrasound...
medical deviceA medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery. If applied to the body, the effect of the medical device is primarily physical, in contrast to pharmaceutical drugs, which exert a biochemical effect. Specific regional definitions of...
to heat and destroy
pathogenA pathogen , infectious agent, or germ, is a biological agent that causes disease or illness to its host....
ic 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 imagingMagnetic Resonance Imaging , or nuclear magnetic resonance imaging , is primarily a medical imaging technique most commonly used in radiology to visualize the internal structure and function of the body...
(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 fibroidsA uterine fibroid is a non-cancerous tumor that originates from the smooth muscle layer and the accompanying connective tissue of the uterus...
. 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
ablationAblation means removal of material from the surface of an object by vaporization, chipping, or other erosive processes. The term occurs in space physics associated with atmospheric reentry, in glaciology, medicine, and passive fire protection.-Space physics:...
(HIFU) (for
tumorA tumor or tumour is the name for a swelling or lesion formed by an abnormal growth of cells . Tumor is not synonymous with cancer. A tumor can be benign, pre-malignant or malignant, whereas cancer is by definition malignant....
treatments, for example),
hyperthermiaHyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
treatments (low-level heating combined with radiation or chemotherapy), or the activation or enhanced delivery of
drugA drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s.
Aiming
The ultrasound beam can be focused in these ways:-
- Geometrically, for example with a lens
A lens is an optical device with perfect or approximate axial symmetry which transmits and refracts light, converging or diverging the beam. A simple lens is a lens consisting of a single optical element...
or with a spherically curved transducerA transducer is a device, electrical, electronic, electro-mechanical, electromagnetic, photonic, or photovoltaic, that converts one type of energy or physical attribute to another for various purposes including measurement or information transfer .There are two kinds of transducers...
.
- Electronically, by adjusting the relative phases of elements in an array of transducers (a "phased array
In wave theory, a phased array is a group of antennas in which the relative phases of the respective signals feeding the antennas are varied in such a way that the effective radiation pattern of the array is reinforced in a desired direction and suppressed in undesired directions...
"). 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,
cavitationCavitation is the formation of vapour bubbles of a flowing liquid in a region where the pressure of the liquid falls below its vapor pressure. Cavitation is usually divided into two classes of behavior: inertial cavitation, and noninertial cavitation. Inertial cavitation is the process where a...
(microbubbles forming and interacting with the
ultrasoundUltrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Although this limit varies from person to person, it is approximately 20 kilohertz in healthy, young adults and thus, 20 kHz serves as a useful lower limit in describing ultrasound...
field) can occur. Microbubbles produced in the field oscillate and grow (due to factors including rectified
diffusionMolecular diffusion, often called simply diffusion, is a net transport of molecules from a region of higher concentration to one of lower concentration by random molecular motion. The result of diffusion is a gradual mixing of material...
), 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 waveA shock wave is a type of propagating disturbance. Like an ordinary wave, it carries energy and can propagate through a medium or in some cases in the absence of a material medium, through a field such as the electromagnetic field...
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,
cavitationCavitation is the formation of vapour bubbles of a flowing liquid in a region where the pressure of the liquid falls below its vapor pressure. Cavitation is usually divided into two classes of behavior: inertial cavitation, and noninertial cavitation. Inertial cavitation is the process where a...
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
sonicationthumb|right|A sonicator at the [[Weizmann Institute of Science]] during sonicationSonication is the act of applying sound energy to agitate particles in a sample, for various purposes. In the laboratory, it is usually applied using an ultrasonic bath or an ultrasonic probe, colloquially known as...
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
ablationAblation means removal of material from the surface of an object by vaporization, chipping, or other erosive processes. The term occurs in space physics associated with atmospheric reentry, in glaciology, medicine, and passive fire protection.-Space physics:...
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.
Uterine fibroids
Development of this therapy significantly broadened the range of treatment options for patients suffering from
uterine fibroidsA uterine fibroid is a non-cancerous tumor that originates from the smooth muscle layer and the accompanying connective tissue of the uterus...
. HIFU treatment for uterine fibroids was approved by the
Food and Drug AdministrationThe Food and Drug Administration is a Government agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, tobacco products, dietary supplements, Medication drugs, vaccines, Biopharmaceutical, blood transfusion,...
(FDA) in October 2004.
Cancer
HIFU has been successfully applied in
treatment of cancerOncology is the branch of medicine dealing with tumors . A medical professional who practices oncology is an oncologist. The term originates from the Greek "Ογκολογία" derived from onkos , meaning bulk, mass, or tumor, and the suffix -logy , meaning "study of" or "to talk about".Oncology is...
to destroy solid tumors of the bone, brain, breast, liver, pancreas, rectum, kidney, testes, prostate. 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. 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. 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.
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 barrierThe blood-brain barrier is a separation of circulating blood and cerebrospinal fluid maintained by the choroid plexus in the central nervous system . Endothelial cells restrict the diffusion of microscopic objects The blood-brain barrier (BBB) is a separation of circulating blood and...
, allowing an influx of drugs into the brain. It is most effective when used in combination with an inhibitor like
verapamilVerapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
.
Treatment of atrial fibrillation
HIFU has been used to treat the most common heart arrhythmia,
atrial fibrillationAtrial fibrillation is the most common cardiac arrhythmia and involves the two upper chambers of the heart. Its name comes from the fibrillating of the heart muscles of the atria, instead of a coordinated contraction...
(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 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-Technomed, Lyon, France), progression-free survival rates are very high for low- and intermediate- risk patients with recurrent prostate cancer (70% and 50% respectively) HIFU treatment of prostate cancer is currently an approved therapy in Europe, Canada, South Korea, Australia, and elsewhere. Clinical trials in the
United StatesThe United States of America is a federal constitutional republic comprising fifty states and a federal district...
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 which don't 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.
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.
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 ResearchThe Foundation for Focused Ultrasound Research is an American non-profit 501 charity designed to promote both education and research within the area of medical applications of focused ultrasound .- History :...
is an unincorporated association promoting research into medical uses of high intensity focused ultrasound, including HIFU.
The
Focused Ultrasound Surgery FoundationThe Focused Ultrasound Surgery Foundation is a medical device foundation based in Charlottesville, Virginia, United States, that promotes the use of magnetic resonance guided focused ultrasound , which uses high intensity focused ultrasound...
(
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
Further reading
- Magnetic Resonance Guided Focused Ultrasound Surgery, United States Patent #5247935 Harvey Cline, Robert Ettinger, Kenneth Rohling Ronald Watkins, filed March 1992
- H. E. Cline, J. F. Schenck, K. Hynynen, R. D. Watkins, S. P. Souza, and F. A. Jolesz. “MR-guided focused ultrasound surgery,” J Comput Assist Tomogr 16(6), 956-65 (1992).
- Focused US system for MR imaging-guided tumor ablation HE Cline, K Hynynen, RD Watkins, WJ Adams, JF Schenck, RH Ettinger, WR Freund, JP Vetro and FA Jolesz Radiology 1995 194: 731-737
- More HIFU Information from Chongqing Haifu Technology Co., Ltd http://www.haifu.com.cn/en_main.asp
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. 1–9, 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.
- Loulou T, Scott E. Thermal Dose Optimization in Hyperthermia Treatments by Using The Conjugate Gradient Method. Numerical Heat Transfer, Part A. 42; 661-683, 2002.
- Tempany CMC, Stewart EA, McDannold N, Quade B, Jolesz F, Hynynen K. MRI guided focused ultrasound surgery (FUS) of uterine leiomyomas: A Feasibility study. Radiology 2003; 226:897-905.
See also
- Magnetic resonance imaging
Magnetic Resonance Imaging , or nuclear magnetic resonance imaging , is primarily a medical imaging technique most commonly used in radiology to visualize the internal structure and function of the body...
- Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used to visualize subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions. Obstetric sonography is commonly used during pregnancy and is widely...
- Uterine fibroids
A uterine fibroid is a non-cancerous tumor that originates from the smooth muscle layer and the accompanying connective tissue of the uterus...
- Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery. If applied to the body, the effect of the medical device is primarily physical, in contrast to pharmaceutical drugs, which exert a biochemical effect. Specific regional definitions of...
External links