Timeline of Focused Ultrasound

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.

First Ultrasound Device

French professor Paul Langevin and Swiss physicist Constantin Chilowsky developed a high-frequency ultrasonic device called a hydrophone, which was used in German U-boat and submarine surveillance.

Paul Langevin Discovery

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.”

First Thought Of Therapeutic Use for Ultrasound

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

First Focusing of Ultrasound

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

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.

First Preclinical 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.

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.

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.

Focused Ultrasound as Lobotomy Alternative

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.

The “Fathers” of Focused Ultrasound

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

First Research Group Dedicated to Focused Ultrasound

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.

Focused Ultrasound and the Brain

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

First Cancer Application

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

First Brain Cancer Treatment

Dr. Robert Heimburger was the first neurosurgeon to use a focused ultrasound device to treat brain cancer, under ultrasound guidance.

HIFU Ablative Research by Francis Fry and Colleagues

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

First 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.

Focused Ultrasound for BPH

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

Focused Ultrasound for Brain Tumors

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

First Combination with MRI

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.

First Blood-brain Barrier Application

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

Transcranial Research

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.

Manufacturer Milestones

Chongqing Haifu and INSIGHTEC were founded. EDAP TMS‘s Ablatherm device earns CE Mark.

First Volumetric Hyperthermia with MR-guided Focused Ultrasound

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

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.

Breakthroughs in Brain Research

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.

First Clinical Trials in Women’s Health

C. Tempany et al. performed the first clinical trial of uterine fibroids using INSIGHTEC’S Exablate system and found the procedure feasible and safe.

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

Focused Ultrasound and Immune Response

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.

First US Approval of an MRgFUS Device

The FDA approved INSIGHTEC’s Exablate 2000 to treat uterine fibroids.

Foundation Began

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

First Brain Clinical Trial

Z. Ram et al. initiated a clinical trial to treat patients with recurrent gliomas and demonstrated that it was a potentially effective way of destroying tissue.

Demonstrating Drug Delivery

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

Philips Enters the Industry

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

First Focused Ultrasound Foundation Symposium

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.

Focused Ultrasound for Pain

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

First Movement Disorder Trial

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.

Regulatory Wins

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.

Addressing Challenging Cancers

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.

Focused Ultrasound for Bone Cancer Pain

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

First Pediatric Patient in North America

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.

First Depression Clinical Trial Begins

The first patient with depression was treated in a focused ultrsaound clinicial trial led by Jin Woo Chang, MD, at Yonsei University College of Medicine in Seoul, Korea.

First-in-Man Hyperthermia Treatment with MR-guided Focused Ultrasound

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.

Approvals to Treat the Prostate

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

In 2016, Profound Medical’s TULSA-PRO device earned CE approval to ablate prostate tissue.

John Grisham’s Focused Ultrasound Book

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.

Essential Tremor Approval

Insightec’s Exablate Neuro device is approved to treat essential tremor in the US and Canada. The Centers for Medicare and Medicaid Services subsequently assigned the procedure a payment level, the first step toward Medicare reimbursement.

First Focused Ultrasound Pediatric Brain Tumor Clinical Trial Begins

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

First Alzheimer’s Disease Trial

The first clinical trial for Alzheimer’s disease began at Sunnybrook Health Sciences Centre in Toronto, Canada. The trial was one of the first to explore using focused ultrasound to temporarily disrupt the blood-brain barrier (BBB).

Partnering on Immunotherapy

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.

Veterinary Applications

The Foundation launched a veterinary program and funded initial trials in canine cancer and wound healing.

Profound Medical Transforms Industry

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

First Histotripsy Clinical Trial

A first-in-human clinical trial – the “THERESA” study – took place at three sites in Barcelona, Spain, under the direction of Joan Vidal-Jové, MD, PhD, Head of Focused Ultrasound Ablation Oncology at Barcelona University Hospital.

Focused Ultrasound Drug Delivery Clinical Trial Published

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.

Neurological Clinical Trials

A multisite clinical trial to treat the motor symptoms of Parkinson’s disease began at Weill Cornell in New York.

University of Maryland researchers began the first US trial to open the blood-brain barrier in brain tumor patients.

FDA Approval for Parkinson’s Disease

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.

Clinical Trial Results Published on Opening Blood-Brain Barrier

French device manufacturer CarThera published the results from its Phase I/IIa clinical trial using the SonoCloud-1 ultrasound implant to open the blood-brain barrier (BBB) prior to carboplatin chemotherapy in patients with recurrent glioblastoma (GBM).

Nature Communications published the findings of a clinical trial at Sunnybrook Health Sciences Centre in Toronto to assess the feasibility and safety of using focused ultrasound in patients with amyotrophic lateral sclerosis (ALS). The results showed it is possible to safely use MR-guided focused ultrasound to temporarily and reversibly open the blood-brain barrier (BBB) in patients with ALS.

Ultrasound Device Earns FDA Approval to Treat the Prostate

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.

Reimbursement Wins

In February, the US Centers for Medicare and Medicaid Services (CMS) began covering focused ultrasound for tremor-dominant Parkinson’s disease for many patients in the Southeast.

In July, CMS began covering focused ultrasound for essential tremor nationwide. By 2023, private payors like Aetna, Blue Cross Blue Shield, and Anthem reimbursed the procedure.

First Focused Ultrasound “Unicorn”

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

Focused Ultrasound for Psychiatric Disorders: Clinical Trial Results Published

Researchers at Sunnybrook Health Sciences Centre published data indicating that focused ultrasound is safe and effective in addressing the symptoms of treatment-resistant major depression and obsessive-compulsive disorder (OCD).

First Liver Tumor Clinical Trial Begins in the US

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.

Focused Ultrasound Approved to Treat Osteoid Osteomas

The US FDA approved Profound Medical’s Sonalleve MR-guided High Intensity Focused Ultrasound (MR-HIFU) system for the treatment of painful bone tumors – called osteoid osteomas – in the extremities. This marked the first focused ultrasound regulatory approval that directly impacts pediatric patients, and it was the sixth indication to earn approval in the US.

Regulatory Updates for Parkinson’s, Prostate, and Soft Tissue Tumors

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.

World-First for Metastatic Breast Cancer

In a first-in-world clinical trial, researchers at Sunnybrook Health Sciences Centre in Toronto, Canada, demonstrated that MR-guided focused ultrasound can be used to safely deliver antibody therapy to breast cancer that has metastasized to the brain.

Focused Ultrasound and Liquid Biopsies

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.

Pioneering Clinical Trials

Researchers at West Virginia University have treated the first patient in a first-in-the-world clinical trial investigating focused ultrasound to address opioid use disorder.

Theraclion also received approval for its first US trial to noninvasively address varicose veins using their SONOVEIN device.

Focused Ultrasound for Veterinary Applications

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.

Breakthroughs in Parkinson’s Disease

A collaborative team of researchers in Spain successfully used focused ultrasound to open the blood-brain barrier in people with Parkinson’s dementia, and the procedure was well tolerated.

The results of an early-stage clinical trial investigating focused ultrasound to address a possible underlying cause of Parkinson’s disease were published in Movement Disorders. Researchers in Toronto tested the safety and efficacy of focused ultrasound–induced blood-brain barrier opening to deliver enzyme replacement therapy.

New Brain Tumor Clinical Trials

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).

University of Oxford Named a Center of Excellence

The Focused Ultrasound Foundation has designated the University of Oxford a Center of Excellence in focused ultrasound. Oxford has become Europe’s fifth Center of Excellence and eleventh worldwide.

US FDA Clears Focused Ultrasound for Liver Tumors

The US Food and Drug Administration (FDA) has cleared HistoSonics’ novel therapy platform – called EdisonTM – to treat liver tumors. This is the ninth clinical indication for which focused ultrasound treatment has been approved by the FDA.*