Timeline of Focused Ultrasound

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.

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

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

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.

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.

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.

William Fry, Francis Fry, and Reginald C. Eggleton founded the Interscience Research Institute in Champaign, Illinois. Its goals 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.

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

Between 1972 and 1984, Francis Fry and colleagues continued to carry out laboratory research on focused ultrasound for solid tumors in preclinical models.

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

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

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.

C. Moonen and colleagues demonstrate volumetric heating for local hyperthermia with MR-guided focused ultrasound and real time temperature feedback in preclinical studies.

K. Hynynen et al. determined that focused ultrasound, 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.

In 2006, M. Kinoshita et al. demonstrated antibody delivery through the BBB using MRgFUS.

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.

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

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

The Focused Ultrasound Foundation hosted the first biennial Focused Ultrasound Symposium, October 6-7, 2008, in Tyson’s Corner, Virginia. The meeting attracted 300 attendees from around the world.

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

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

HF. Gao et al. performed the first clinical trial using focused ultrasound to treat local advanced pancreatic cancer.

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

W. Chu, in the Department of Radiation Oncology at Sunnybrook Health Sciences Centre in Toronto, reported the feasibility and safety of MR-guided focused ultrasound hyperthermia in a pilot study on 10 patients with recurrent rectal cancer.

John Grisham wrote “The Tumor,” a book about the potential for focused ultrasound, to raise awareness of the technology. In a year, more than 800,000 copies were distributed.

In 2019, the audiobook version of the book was released, pushing the number of total books distributed over 1 million.

A team at Nicklaus Children’s Hospital in Miami, Florida, treated the first patient in a pediatric and young adult brain tumor study.

The Focused Ultrasound Foundation partnered with the Cancer Research Institute to further focused ultrasound and immunotherapy combination approaches to treat cancer. The pair funded their first joint project in 2018.

The first clinical trial combining focused ultrasound with an immunotherapy drug began for patients with metastatic breast cancer at the University of Virginia.

Toronto-based Profound Medical announced that it will acquire Philips’ Sonalleve MR-HIFU business.

The first clinical trial demonstrating local drug delivery using focused ultrasound and temperature sensitive liposomes was performed in Oxford and published in Lancet Oncology in 2018.

On December 18, 2018, Insightec’s Exablate Neuro device earned approval from the US Food and Drug Administration (FDA) to treat patients with tremor-dominant Parkinson’s disease.

Profound Medical’s TULSA-PRO® device earned US Food and Drug Administration (FDA) approval to ablate prostate tissue. This is the first transurethral ultrasound device approved in the US, and it allows physicians to predictably ablate whole-gland or partial prostate tissue.

A $150 million funding round made device manufacturer, Insightec, the first focused ultrasound unicorn (a privately held company valued over $1 billion.)

HistoSonics received approval to begin its first clinical trial in the US – called #HOPE4LIVER. The trial investigated the safety and efficacy of using the company’s Edison platform – a sonic beam therapy platform utilizing histotripsy – to noninvasively and mechanically destroy liver tumors. The company began a similar study in Europe in early 2021.

The Edison device earned Breakthrough Device Designation in October 2021.

The US FDA expanded its 2018 approval of focused ultrasound to treat tremor-dominant Parkinson’s disease to include the treatment of patients with advanced Parkinson’s disease suffering with mobility, rigidity, or dyskinesia symptoms.

The FDA also cleared Insightec’s Exablate Prostate focused ultrasound system to ablate prostate tissue.

Profound Medical’s Sonalleve system received the CE mark for the treatment of desmoid tumors.

Results of a first-in-human study – published in Neuro-Oncology – found that focused ultrasound increased the amount of brain tumor biomarkers in the blood. The results suggest that focused ultrasound could reduce the need for invasive brain tumor biopsies and allow better monitoring of glioblastoma treatment responses.

A Foundation-funded clinical trial at Virginia Tech determined that high-intensity focused ultrasound (HIFU) can safely ablate subcutaneous solid tumors in dogs.

A team at the Virginia-Maryland College of Veterinary Medicine found that histotripsy safely and effectively treated the targeted volumes within osteosarcomas in client-owned dogs, with no significant adverse events.

In Milan, researchers will use sonodynamic therapy in patients with newly diagnosed glioblastomas.

Four sites across the US and Canada began a clinical trial to investigate focused ultrasound’s role in enhancing immunotherapy for non-small cell lung cancer that has spread to the brain.

Researchers in Washington, DC, began a clinical trial using sonodynamic therapy to address deadly pediatric brain tumors called diffuse intrinsic pontine gliomas (DIPG).