Timeline of Focused Ultrasound

University of Oxford Named a Center of Excellence
The Focused Ultrasound Foundation designated the University of Oxford as Europe’s fifth Center of Excellence and the eleventh worldwide.

US FDA Clears Focused Ultrasound for Liver Tumors
The US Food and Drug Administration (FDA) cleared HistoSonics’ Edison^TM histotripsy platform to treat liver tumors. This is the ninth clinical indication for which focused ultrasound has been FDA cleared.

Focused Ultrasound for Veterinary Applications
A Foundation-funded clinical trial at Virginia Tech determined that focused ultrasound can safely ablate subcutaneous solid tumors in dogs. A team in Virginia also found that histotripsy safely and effectively treated osteosarcomas in client-owned dogs.

Breakthroughs in Parkinson’s Disease
Researchers in Spain successfully used focused ultrasound to open the blood-brain barrier (BBB) in people with Parkinson’s dementia. The results of a clinical trial investigating focused ultrasound to address a possible underlying cause of Parkinson’s disease were also published in Movement Disorders. Finally, researchers in Toronto tested the safety and efficacy of focused ultrasound–induced BBB opening to deliver enzyme replacement therapy.

New Brain Tumor Clinical Trials
In Milan, researchers used sonodynamic therapy (SDT) 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, also began a clinical trial using SDT to address diffuse intrinsic pontine gliomas.

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.

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 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 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 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 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.

Clinical Trial Results Published on Opening Blood-Brain Barrier
CarThera published the results from its clinical trial using the SonoCloud-1 ultrasound implant to open the blood-brain barrier (BBB) prior to carboplatin chemotherapy in patients with recurrent glioblastoma. Nature Communications also published clinical trial results showing it is possible to safely use MR-guided focused ultrasound to temporarily and reversibly open the BBB in patients with amyotrophic lateral sclerosis.

Ultrasound Device Earns FDA Approval to Treat the Prostate
Profound Medical’s TULSA-PRO® device earned US Food and Drug Administration (FDA) clearance 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.

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 also 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.

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).

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.

Partnering on Immunotherapy
The Foundation partnered with the Cancer Research Institute to further focused ultrasound and immunotherapy combination approaches for cancer, funding the first joint project in 2018. The first clinical trial combining focused ultrasound with an immunotherapy drug also began for patients with metastatic breast cancer at the University of Virginia.

John Grisham’s Focused Ultrasound Book
John Grisham wrote “The Tumor” 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 Depression Clinical Trial Begins
The first patient with depression was treated in a focused ultrasound clinical 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 clearance to ablate prostate tissue. This technique could be used to treat conditions like prostate cancer and BPH.

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.

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. also performed the first clinical trial using focused ultrasound to treat local advanced pancreatic cancer.

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.

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.

Brain Breakthrough
M. Kinoshita et al. demonstrated antibody delivery through the blood-brain barrier using MR-guided focused ultrasound.

First Clinical Trials in Women’s Health
C. Tempany et al. performed the first clinical trial of uterine fibroids using Insightec’s Exablate system. F. Wu et al. also 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 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 plus 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 also demonstrated noninvasive focusing through human skull using a phased array and CT based planning algorithm.

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 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.