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.