Focused ultrasound (FUS) guided by magnetic resonance imaging (MRI) is an alternative to the standard treatment of neurological, oncological and musculoskeletal diseases. The technology enables targeted treatments across a wide range of FUS intensities that induce mechanical, thermal and neuroelectrical effects on tissues while sparing surrounding organs.1 Globally, FUS is approved for the treatment of over 30 indications. In the United States, use is approved for bone metastases, osteoid osteoma, tremor and dyskinesia in Parkinson’s disease, prostate cancer, benign prostatic hyperplasia, and uterine fibroids.2
The technology
“FUS is analogous to using a magnifying glass to focus beams of light onto a point to burn a hole in a sheet, but instead of an optical lens, an acoustic lens is used to focus multiple beams of ultrasound energy to direct it deep into the body with high of precision and accuracy while sparing the adjacent normal tissue,” said Neal Kassell, MD, founder and chairman of the Focused Ultrasound Foundation. “Each of the individual beams has the power of a diagnostic ultrasound only up to the focal point of convergence.”
Focused ultrasound uses acoustic lenses to precisely focus ultrasound beams at target points deep within tissues. [Focused Ultrasound Foundation].The therapeutic ultrasound intensity range is higher than that used in diagnostic ultrasound. The high intensity range, from 100 to >10,000 W/cm2, is used for tissue ablation, mainly by coagulation necrosis. Coagulation necrosis is a type of cell death in which tissue architecture is preserved for some time after cell death, potentially due to the denaturation of structural proteins and lysosomal enzymes and the inhibition of proteolysis of damaged cells. The lower intensity range, from 0.125–3 W/cm2, is used to induce mechanical effects at the cellular level.3
The application of MR-guidance in high-intensity focused ultrasound (HIFU) thermal ablation continues to be the subject of numerous studies and clinical trials.1 Although the potential clinical applications of HIFU were reported as early as the 1950s, the precise targeting is basically a problem. Finally, in 2004, the first MRI-guided HIFU application received FDA approval for the removal of uterine fibroids.3
Ultrasound enables deep tissue treatment, improves focus on target tissue through its short wavelengths, and offers precise control over the shape and location of energy deposition. It is non-invasive, extracorporeal and non-ionizing compared to conventional cancer treatment methods such as chemotherapy, radiotherapy and open surgery.4
At the other end of the acoustic spectrum, low-intensity FUS (LIFU) is often used to locally and reversibly induce excitatory and inhibitory neuromodulation or to facilitate drug and gene delivery by permeabilizing the blood-brain barrier.1
“We currently know 25 different ways that FUS affects the tissue at the focal point. A decade ago, we figured out three,” Cassel said. “This creates the opportunity to treat a wide variety of diseases compared to radiation therapy or a surgical robot.
“FUS can be used to destroy tissue and deliver therapeutic agents to the point in the body where they are needed, minimizing systemic side effects and thereby increasing the effectiveness and safety of treatment. “The effect is immediate and verifiable.”
Therapeutic potential
Today, globally, treatments for nearly 170 clinical indications are in various stages of R&D and commercialization, up from three a decade ago, according to Cassel. “We just started getting coverage and reimbursement from government and commercial organizations,” he said. “One of our challenges is that FUS is not one of medicine’s best-kept secrets. FUS is the most powerful sound you’ll never hear, but it’s the sound that could one day save your life.”
The use of FUS continues to grow. The applications that excite Kassell most are for brain indications such as Alzheimer’s, Parkinson’s, ALS, Huntington’s, OCD, depression and other neuropsychiatric disorders5, dystonia, epilepsy6, brain tumors, stroke, as well as oncology indications and immunotherapy.
In a certain area, FUS can reversibly open the blood-brain barrier to allow access of therapeutic agents. Microbubbles, hollow lipid spheres roughly one-tenth the diameter of a red blood cell, can be packaged with therapeutics and injected intravenously by the millions. They burst and release the pharmacological payload at the FUS convergence point. The great promise of FUS in combination with circulating microbubbles is reflected by the rapidly growing number of clinical trials for the treatment of various brain diseases.7,8
“FUS is disruptive to physician practices, referral patterns and manufacturers of replaceable legacy therapeutic equipment. The evolution of any highly disruptive technology from idea to widespread use as a global standard of care is a glacial process. “Every month that goes by that this incredible technology is not available results in unnecessary death, disability and suffering for countless people,” Cassell said.
References
- Kamimura HAS, Conti A, Toschi N, Konofagou EE. Ultrasound neuromodulation: mechanisms and potential of multimodal stimulation to assess neural function. Front Phys. 2020; 8:150.
- Focused Ultrasound Foundation, 2022 State of the Field.
- Shehata Elhelf IA, Albahar H, Shah U, Oto A, Cressman E and Almekkawy M. High Intensity Focused Ultrasound: Fundamentals, Clinical Applications and Research Trends. Diagnostic and Interventional Imaging 2018 99, 349—359.
- Izadifar Z, Izadifar Z, Chapman D and Babyn P. Introduction to high intensity ultrasound: a systematic review of principles, devices and clinical applications. Clin. Med. 2020, 9, 460; doi:10.3390/jcm9020460
- Wang JB, Di Ianni T, Vyas DB, Huang Z, Park S, Hosseini-Nassab N, Aryal M, and Airan RD. Focused ultrasound for noninvasive, focal pharmacological neurointervention. Neurosci. 2020 14:675.
- Lescrauwaet E, Vonck K, Sprengers M, Raedt R, Klooster D, Carrette E and Boon P. Recent advances in the use of focused ultrasound as a treatment for epilepsy. Neurosci. 2022 16:886584.
- Chen S, Nazeri A, Baek H, Ye D, Yang Y, Yuan J, Rubin JB, and Chen H. A review of bioeffects induced by focused ultrasound combined with microbubbles on the neurovascular unit. Journal of Cerebral Blood Flow & Metabolism 2022, Vol. 42 (1) 3–26. DOI: 10.1177/0271678X211046129
- Wu SK, Tsai CL, Huang Y and Hynynen Focused ultrasound and microbubble-mediated drug delivery to brain tumor. Pharmaceutics 2021, 13, 15
Add Comment