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Focused Ultrasound Therapy

Focused ultrasound is a noninvasive, therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients who are infected or who are at risk for infection because of foreign bodies (FB) that are present in their body. Infectious agents can infect FB or can produce biofilms that coat the surface of the FB and allow adherence of the infection to the biofilm, either of which can cause serious adverse impact to the patient. This novel technology focuses beams of ultrasound energy precisely and accurately on targets deep in the body without damaging surrounding normal tissue.

How it Works
Where the beams converge, the ultrasound produces precise ablation (thermal destruction of the target) potentially enabling biofilms and/or infection to be treated without surgery. Another option is to use focused ultrasound’s ability to temporarily open the blood-brain barrier (BBB) and allow therapeutic agents to treat infectious agents in the brain. Work is planned to insert CRISPR/Cas-9 aimed at targeting intracranial HIV. While significant work has been accomplished, there is still much to be done before this technology will be widely available.

The primary options for treatment of infection of FBs include medication or surgery to remove the FB.

For certain patients, focused ultrasound could provide a noninvasive alternative to surgery with less risk of complications – including surgical wound healing – at a lower cost.  It can also reach the desired target without damaging surrounding tissue and is repeatable, if necessary.

Clinical Trials

At the present time, there are no clinical trials recruiting patients for focused ultrasound treatment of infection or biofilms.

Regulatory Approval and Reimbursement 

Focused ultrasound treatment for infection or biofilms is not yet approved by regulatory bodies or covered by medical insurance companies.

Notable Papers

Ambekar PA, Wang YN, Khokhlova T, Bruce M, Leotta DF, Totten S, Maxwell AD, Chan K, Liles WC, Dellinger EP, Monsky W, Adedipe AA, Matula TJ. Comparative Study of Histotripsy Pulse Parameters Used to Inactivate Escherichia coli in Suspension. Ultrasound Med Biol. 2023 Sep 15:S0301-5629(23)00251-X. doi: 10.1016/j.ultrasmedbio.2023.08.004. PMID: 37718123 

Morse R, Childers C, Nowak E, Rao J, Vlaisavljevich E. Catheter-Based Medical Device Biofilm Ablation Using Histotripsy: A Parameter Study. Ultrasound Med Biol. 2023 Jul 1:S0301-5629(23)00203-X. doi: 10.1016/j.ultrasmedbio.2023.06.010. PMID: 37394375 

Ouyang M, Ouyang X, Peng Z, Liu M, Xu G, Zou Z, Zhang M, Shang Q. Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ. J Nanobiotechnology. 2022 Jun 7;20(1):263. doi: 10.1186/s12951-022-01457-y.

Wang G, Wu W, Zhu JJ, Peng D. The promise of low-intensity ultrasound: A review on sonosensitizers and sonocatalysts by ultrasonic activation for bacterial killing. Ultrason Sonochem. 2021 Nov;79:105781. doi: 10.1016/j.ultsonch.2021.105781. Epub 2021 Oct 9.

Matula TJ, Wang YN, Khokhlova T, Leotta DF, Kucewicz J, Brayman AA, Bruce M, Maxwell AD, MacConaghy BE, Thomas G, Chernikov VP, Buravkov SV, Khokhlova VA, Richmond K, Chan K, Monsky W. Treating Porcine Abscesses with Histotripsy: A Pilot Study. Ultrasound Med Biol. 2021 Mar;47(3):603-619. doi: 10.1016/j.ultrasmedbio.2020.10.011. Epub 2020 Nov 26.

Hu Y, Mo Y, Wei J, Yang M, Zhang X, Chen X. Programmable and monitorable intradermal vaccine delivery using ultrasound perforation array. Int J Pharm. 2022 Feb 18;617:121595. doi: 10.1016/j.ijpharm.2022.121595.

Childers C, Edsall C, Gannon J, Whittington A, Muelenaer A, Rao J, Vlaisavljevich E. Focused Ultrasound Biofilm Ablation: Investigation of Histotripsy for the Treatment of Catheter-Associated Urinary Tract Infections (CAUTIs). IEEE Trans Ultrason Ferroelectr Freq Control. 2021 May 5;PP. doi: 10.1109/TUFFC.2021.3077704.

Bharatula LD, Marsili E, Rice SA, Kwan JJ. Influence of High Intensity Focused Ultrasound on the Microstructure and c-di-GMP Signaling of Pseudomonas aeruginosa Biofilms. Front Microbiol. 2020 Dec 15;11:599407. doi: 10.3389/fmicb.2020.599407. eCollection 2020.

Apostolakis S. Use of Focused Ultrasound (Sonication) for the Diagnosis of Infections in Neurosurgical Operations: A Systematic Review and Meta-Analysis. World Neurosurg. 2020 Apr;136:364-373.e2. doi: 10.1016/j.wneu.2019.12.143. Epub 2019 Dec 30.

Bigelow TA, Thomas CL, Wu H, Itani KMF. Histotripsy Treatment of S. Aureus Biofilms on Surgical Mesh Samples Under Varying Pulse Durations. IEEE Trans Ultrason Ferroelectr Freq Control. 2017 Oct;64(10):1420-1428. doi: 10.1109/TUFFC.2017.2718841. Epub 2017 Jun 22.

Wardlow R, Bing C, VanOsdol J, Maples D, Ladouceur-Wodzak M, Harbeson M, Nofiele J, Staruch R, Ramachandran A, Malayer J, Chopra R, Ranjan A. Targeted antibiotic delivery using low temperature-sensitive liposomes and magnetic resonance-guided high-intensity focused ultrasound hyperthermia. Int J Hyperthermia. 2016 May;32(3):254-64. doi: 10.3109/02656736.2015.1134818. Epub 2016 Feb 18.

Iqbal K, Ohl SW, Khoo BC, Neo J, Fawzy AS. Effect of high-intensity focused ultrasound on Enterococcus faecalis planktonic suspensions and biofilms. Ultrasound Med Biol. 2013 May;39(5):825-33. doi: 10.1016/j.ultrasmedbio.2012.12.006. Epub 2013 Feb 27.

Xu J, Bigelow TA, Halverson LJ, Middendorf JM, Rusk B. Minimization of treatment time for in vitro 1.1 MHz destruction of Pseudomonas aeruginosa biofilms by high-intensity focused ultrasound. Ultrasonics. 2012 Jul;52(5):668-75. doi: 10.1016/j.ultras.2012.01.013. Epub 2012 Feb 1.

Bigelow TA, Northagen T, Hill TM, Sailer FC. The destruction of Escherichia coli biofilms using high-intensity focused ultrasound. Ultrasound Med Biol. 2009 Jun;35(6):1026-31. doi: 10.1016/j.ultrasmedbio.2008.12.001. Epub 2009 Jan 25.

Click here for additional references from PubMed.

Early Stage