Timeline of Focused Ultrasound

  • 1880

    Discovery of ultrasound technology:

    Pierre Curie and his brother, Jacques Curie, discovered the piezoelectric effect in certain crystals in Paris, France, leading to the evolution of high frequency echo-sounding techniques.

    J. Curie and P. Curie: Bulletin de la Société Minéralogique de France 3 (1880) 90. and also published in Comp. Rend. 91 (1880) 294 and 383.

  • 1915

    First ultrasound device:

    French professor Paul Langevin and Swiss physicist Constantin Chilowsky developed a high frequency ultrasonic device called a hydrophone. The hydrophone was deployed extensively in the surveillance of German U-boats and submarines.

  • 1917

    Paul Langevin discovered that a water tank insonated with high intensity ultrasound caused fish to be killed immediately, and certain observers experienced “a painful sensation on plunging the hand in this region."

    P. Langevin: French Patent No. 505,703 (filed September 17, 1917; issued August 5, 1920) H. Freundlich, K. Söllner and F. Rogowski: Klin. Wochenschr. 11 (1932) 1512.

  • 1932

    First thought of therapeutic use for ultrasound:

    H. Freundlich, K. Collner, and F. Rogowski suggested the application of ultrasound to therapeutically heat tissue.

    H. Freundlich, K. Söllner and F. Rogowski: Klin. Wochenschr. 11 (1932) 1512.

  • 1935

    First focusing of ultrasound:

    Johannes Gruetzmacher found that an ultrasound could be focused when he placed a concave surface to a piezoelectric generator.

    Gruetzmacher J. Piezoelektrischer kristall mit ultraschal- lkonvergenz. Z Phys. 1935;96:342-349.

  • 1942

    First tissue lesion:

    John G. Lynn et al. proposed the idea that ultrasound could be intensely focused to produce extreme heat and non-invasively destroy targeted diseased tissue within the body. They were able to produce lesions deep in bovine liver without damaging surrounding tissue.

    First focused ultrasound device:

    William Fry, a physicist veteran of naval sonar research, and his brother, Francis Fry, began civilian research at the Bioacoustic Research Laboratory (University of Illinois) and a research team developed a focused ultrasound device that mechanically aligned four focused ultrasound generators to produce a pinpoint lesion without damage to the surrounding tissue.

    J. G. Lynn, R. L. Zwemer, A. J. Chick and A. F. Miller: J. Gen. Physiol. 26 (1942) 179.

    W. J. Fry, J. W. Barnard, F. J. Fry, R. F. Krumins, and J. F. Brennan: Science 122 (1955) 517.

  • 1944

    First pre-clinical study:

    John G. Lynn and Tracy J. Putcham were able to destroy cerebral tissue in animals using focused ultrasound. They treated 37 animals in all and found well-circumscribed lesions on physical examination of the areas.

    J. G. Lynn and T. J. Putman: Am. J. Pathol. 20 (1944) 637.

  • 1950

    First therapeutic use:

    Lars Leksell designed a specially adapted frame and ultrasound transducer for the purpose of focused ultrasound lesioning and successfully used it on patients to treat psychiatric disorders. He eventually abandoned the method due to lack of imaging and the need for craniotomies.

  • 1952

    First focused ultrasound meeting:

    The first major symposium on Ultrasound in Biology and Medicine was held at the University of Illinois to examine phenomena of how ultrasonic energy interacted with and acted upon biological materials.

  • 1954

    Petter A. Lindstrom studied the effects of focused ultrasound-mediated lesioning as an alternative to a lobotomy procedure in patients with carcinomatosis and cancer-related pain.

    Lindstrom PA. Prefrontal ultrasonic irradiation--a substitute for lobotomy. Arch Neurol and Psychiatry. 1954;72:399–425.

  • 1955

    The “fathers” of HIFU:

    William Fry and his brother Francis Fry performed a partial ablation of the basal ganglia after a craniotomy using focused ultrasound.

    W. J. Fry, J. W. Barnard, F. J. Fry, R. F. Krumins, and J. F. Brennan: Science 122 (1955) 517.

  • 1957

    First research group dedicated to focused ultrasound:

    William Fry, Francis Fry, and Reginald C. Eggleton founded the Interscience Research Institute in Champaign, Illinois. The goals of the Institute were two-fold: to develop and apply high-intensity ultrasound instrumentation to treat neurological disorders; and to develop computer-based, low-intensity ultrasound instrumentation for visualization of the soft tissue.

  • 1962

    Russell Meyers and William Fry utilized focused ultrasound to treat numerous human patients suffering from various brain pathologies, in particular Parkinson’s disease.

    Fry WJ, Meyers R. Ultrasonic method of modifying brain structures. Confin Neurol. 1962;22:315–327.

  • 1964

    First cancer application:

    M. Oka reported on the successful use of focused ultrasound to treat thyroid and breast cancers.

    Oka M. Progress in studies of the potential use of medical ultrasonics. Wakayama Medical Report (Japan). 1977;20:1-50.

    Oka M. Application of intense focused ultrasound in brainsurgery and other fields. Clinica All-Round (Japan). 1964;13:1514.

  • 1968

    Dr. Robert Heimburger from Dept. of Neurosurgery from IU Medical School in Indianapolis, IN was the first neurosurgeon to use a focused ultrasound device to treat brain cancer, under US guidance.

    Heimburger RF: Ultrasound augmentation of central nervous system tumor therapy. Indiana Med 78:469–476, 1985.

  • 1980's

    First focused ultrasound device to earn FDA approval:

    Coleman and Lizzie developed the Sonocare CST-100 Therapeutic Ultrasound System which was designed to treat glaucoma. It was the first focused ultrasound system to earn FDA approval. However, it was ultimately outdated by laser surgery.

    Silverman R. Focused ultrasound in ophthalmology. Clin Ophthalmol. 2016; 10: 1865–1875.

  • 1990

    N. Sanghvi et al. developed and implemented a clinical protocol for focused ultrasound treatment of benign prostatic hyperplasia.

    Sanghvi NT, Foster RS, Bihrle R, et al. Noninvasive surgery of prostate tissue by high intensity focused ultrasound: an updated report. Eur J Ultrasound. 1999;9(1):19-29.

  • 1991

    A. Guthkelch and K. Hynynen et al. reported on the treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation.

    Guthkelch AN, Carter LP, Cassady JR, Hynynen KH, Iacono RP, Johnson PC, et al: Treatment of malignant brain tumors with focused ultrasound hyperthermia and radiation: results of a phase I trial. J Neurooncol 10:271-284, 1991.

  • 1992

    First combination with MRI:

    K. Hynynen et al. proposed the use of non-invasive focused ultrasound surgery in a magnet using magnetic resonance imaging to guide and monitor tissue damage. The term Magnetic Resonance Guided Focused Ultrasound (MRgFUS) was first coined.

    Yang R, Reilly CR, Rescorla FJ, et al. Effects of high-intensity focused ultrasound in the treatment of experimental neuroblastoma. J Pediatr Surg. 1992;27(2):246-250; discussion. 250-241.

  • 1996

    First blood-brain barrier application:

    K. Hynynen et al. first described a controlled, reversible, and reproducible manner of opening the blood-brain barrier (BBB) while being monitored by MRI.

    Hynynen K, Colucci V, Chung A, Jolesz F. Noninvasive arterial occlusion using MRI-guided focused ultrasound. Ultrasound Med Biol. 1996;22:1071–1077.

  • 1998

    K.Hynynen and F. Jolesz demonstrated the feasibility of using a large phased array applicator for through skull focusing and ablation and proposed the benefits of using cavitation for through skull treatments.

  • 1999

    Chongqing Haifu Medical Technology Co. Ltd. is founded to manufacture non-invasive ultrasound therapeutic systems for both malignant and benign tumors.

    INSIGHTEC is founded by GE Healthcare and Elbit Medical Imaging to transform MRgFUS into a clinically viable technology.

  • 2001

    First focused ultrasound society:

    The International Society for Therapeutic Ultrasound (ISTU) was formed to increase and diffuse knowledge of therapeutic ultrasound to the scientific and medical community.

    K. Hynynen et al. determined that focused ultrasound, when combined with microbubbles, can cause localized and reversible disruption of the blood brain barrier (BBB), a historically major obstacle in the treatment of brain diseases.

    G.Clement and K.Hynynen demonstrated noninvasive focusing through human skull using a phased array and CT based planning algorithm.

  • 2003

    First clinical trial:

    C. Tempany et al. performed the first clinical trial of uterine leiomyomas using INSIGHTEC'S ExAblate system and found the procedure feasible and safe.

    H. Zheng et al. found focused ultrasound treatment may evoke a strong immune response to combat residual tumor cells and suppress remote metastasis in cancer patients.

    F. Wu et al. performed the first randomized focused ultrasound clinical trial for breast cancer, concluding it could be effective, safe, and feasible in the extracorporeal treatment of localized breast cancer.

    Tempany, et al., MR imaging-guided focused ultrasound surgery of uterine leiomyomas. Radiology. Mar 2003;226(3):897-905.

    Zheng, et al., Heat shock factor 1-independent activation of dendritic cells by heat shock... Eur J Immunol. 2003;33:1754–1762.

    Wu, et al., Randomised clinical trial of high-intensity focused ultrasound ablation for the treatment of patients with localised breast cancer. Br J Cancer. 2003; 15; 89 (12): 2227-33.

  • 2004

    The FDA approved INSIGHTEC's ExAblate 2000 for treatment of uterine fibroids. This is the first MRgFUS system to obtain approval in the US.

  • 2006

    The Focused Ultrasound Foundation was founded in Charlottesville, VA to help accelerate the development and adoption of focused ultrasound.

    First brain clinical study:

    Z. Ram et al. initiated a clinical study to treat patients with recurrent gliomas using MRgFUS. It was demonstrated to be a potentially effective way of destroying tissue.

    M.Kinoshita et al. demonstrated antibody delivery through the BBB using MRgFUS.

  • 2007

    L. Treat et al., demonstrated chemotherapy delivery (Doxil) into the brain.

  • 2008

    Philips unveiled MRgFUS system Sonalleve, initially used to treat uterine fibroids.

  • 2009

    E. Martin, D. Jeanmonod et al. conducted successful clinical trials that used focused ultrasound targeting the thalamus for treatment of neuropathic pain.

    E. Martin, et al., "High-intensity focused ultrasound for noninvasive functional neurosurgery," Annals of Neurology, vol. 66, pp. 858-861, 2009.

  • 2010

    W. Elias et al. successfully treated the first 15 patients with essential tremor at the University of Virginia as part of a pilot trial. All patients noted a significant decrease in their tremors.

    J. Jordao et al. demonstrated the effectiveness of antibodies delivered using MRgFUS in reducing amyloid load in mice modeling Alzheimer's Disease.

    Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. England Journal of Medicine. 2013 Aug 15;369(7):640-8.

  • 2012

    Second FDA win

    The FDA approved focused ultrasound for the treatment of pain from bone metastases.

    Theraclion's EchoPulse received CE marking in Europe to treat breast fibroadenoma.

    Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. England Journal of Medicine. 2013 Aug 15;369(7):640-8.

  • 2013

    M. Aryal, Y. Zhang et al. demonstrated that focused ultrasound can be used to enhance delivery of anti-cancer drugs (Doxirubicin) and can have a therapeutic effect on gliomas in a rat model.

    HF. Gao et al. performed the first clinical trial using HIFU to treat local advanced pancreatic cancer and revealed that it is a promising mode of treatment

    Aryal M, Vykhodtseva N, Zhang YZ, Park J, McDannold N. Multiple treatments with liposomal doxorubicin and ultrasound-induced disruption of blood-tumor and blood-brain barriers improve outcomes in a rat glioma model. J Control Release. 2013; 169(1-2):103-11.

    Gao HF, Wang K, Meng ZQ, Chen Z, Lin JH, Zhou ZH, Wang P, Shi WD, Sheng YH. High intensity focused ultrasound treatment for patients with local advanced pancreatic cancer. Hepatogastroenterology. 2013; 60(128):1906-10.

  • 2014

    Hurwitz et al. demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases.

    First pediatric patient in North America:

    First pediatric bone tumor (osteoid osteoma) was treated with the Philips Sonalleve system in a clinical trial conducted by The Hospital for Sick Children (SickKids) and Sunnybrook Health Sciences Centre and funded by the Foundation.

    Hurwitz MS, Ghanouni P, Kanaev SV, Iozeffi D, Gianfelice D, Fennessy FM, Kuten A, Meyer JE, LeBlang SD, Roberts A, Choi J, Larner JM, Napoli A, Turkevich VG, Inbar Y, Tempany CM, Pfeffer RM. Magnetic resonance-guided focused ultrasound for patients with painful bone metastases: phase III trial results. J Natl Cancer Inst. 2014; 106(5).

  • 2015

    Two focused ultrasound devices - EDAP’s Ablatherm Robotic HIFU and SonaCare Medical’s Sonablate 450 - earn FDA approval to ablate prostate tissue. This technique could be used to treat conditions like prostate cancer and BPH.

  • 2016

    Insightec's Exablate Neuro device earns approval to treat essential tremor in the US and Canada.

  • 2017

    The first clinical trial of focused ultrasound for Alzheimer's disease begins at Sunnybrook Health Sciences Centre in Toronto, Canada

    The Focused Ultrasound Foundation partners with the Cancer Research Insitute to futher focused ultrasound and immunotherapy combination approaches to treat cancer.

    Read the Alzheimer's study press release.

    Read the CRI Partnership press release.