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Advanced Ultrasound in Diagnosis and Therapy ›› 2026, Vol. 10 ›› Issue (1): 51-58.doi: 10.26599/AUDT.2026.250050

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  • 收稿日期:2025-06-06 修回日期:2025-06-24 接受日期:2025-10-14 出版日期:2026-03-31 发布日期:2026-03-30

Focused Ultrasound Combined with Microbubbles for Inducing Blood-Brain Barrier Opening: Cavitation Monitoring and Control

Li Naa, Li Fanb,*()   

  1. aSchool of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
    bDepartment of Ultrasound, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Received:2025-06-06 Revised:2025-06-24 Accepted:2025-10-14 Online:2026-03-31 Published:2026-03-30
  • Contact: Department of Ultrasound, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, 241 West Huaihai Road, Shanghai, 200030, China (Fan Li), e-mail: medicineli@sjtu.edu.cn(F L)

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Abstract:

Focused ultrasound (FUS) represents an emerging non-invasive technique capable of achieving reversible and targeted opening of the blood-brain barrier (BBB) when combined with microbubbles (MBs), significantly enhancing drug permeability. This technology demonstrates considerable potential in preclinical studies for diagnosing and treating neurological disorders. Ensuring safe and effective BBB opening while preventing tissue injuries such as red blood cell extravasation remains a critical translational challenge. This review examines the mechanisms of FUS combined with MBs induced BBB opening, key influencing factors, and recent advances in strategies for monitoring and controlling in vivo cavitation activity, providing foundational insights for future research.

Key words: Focused ultrasound, Microbubbles, Blood-brain barrier, Control, Cavitation, Monitoring

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StudyModelUltrasound parametersFocus areaMicrobubbleMonitoring targetControl typeSonication termination
O'reilly (2012)RatsFrequency: 551.5 kHz
RPF: 2 Hz
Pulse duration: 10 ms
Total treatment time: 2 min		The top of the craniumDenity
0.02 mL/kg−1		1.5f0 and 2.5f0 ultraharmonicsOpen-loopStop with ultraharmonics
Tsai (2016)Ratsdual-frequency FUS transducer: 0.55 MHz and 1.1 MHz
Pulse duration: 10 ms
PRF = 1 Hz
Total treatment time: 90 s
power range: 2-7 W		The top of the craniumSonoVue
0.1 ml/kg−1		Subharmonics dose
(threshold method)		Open-loopSub-harmonics dose reached 0.55 MHz
Huang (2017)PigsFrequency: 230 kHz
RPF: 2 Hz
Total sonication time: 50 s
Power range: 3-10 W		The porcine brainDenity
4 ml/kg−1		Spectral integration of the subharmonic
(threshold method)		Open-loopDual-Threshold Consecutive Trigger
Kamimur (2019)MonkeysFrequency: 500 kHz
PRF: 5 Hz
Pulse length: 10 ms
Total treatment time: 2 min		Targe1: Hippocampus
Target 2: 2 cm caudal offset
Target 3: 2 cm rostral offset		SonoVue
0.3 ml/kg−1		The SCD and ICD
(threshold method)		Open-loopEnd of duration
Sun (2017)RatsFrequency: 274.3 kHz
PRF: 1 Hz/4 Hz
Pulse duration: 32.3 ms		Striatum and hippocampus.Optison
300 μl/kg−1		harmonic emission (HE) and broadband emission (BE)Open-loopDetected BE/HE threshold reached
Robin (2021)MiceFrequency: 1.5 MHz
PRF: 2 Hz
Pulse length: 10 ms		The left striatumDefinity
0.1 µL/g−1		the 3rd to 9th harmonic frequencies.Open-loopReach the preset target value
Bing (2018)RatsFrequency: 0.5 MHz
PRF: 1 Hz
Pulse length: 10 ms
Total treatment time: 125 s		Hippocampus on
both sides		Optison: 30 μl/kg−1
Denity: 6 μl/kg−1
Nanobubble: 737 μl/kg−1		AUC by summing at sub- or ultra- harmonics amplitudes within ± 0.05 MHz bandwidthReal-time closed-loopEnd of duration
Çavuşoğlu (2019)Micefrequency: 650 KHz
PRF: 1 Hz
Pulse duration: 10 ms
Total treatment time: 5 min		The top of the craniumBG8235
1.1-1.2 μl/kg−1		the broadband responseReal-time closed-loopEnd of duration
McDannol (2020)RatsFrequency: 660 kHz
PRF: 1.1 Hz
Pulse duration: 5 ms
Power range: 0.16-0.39 W
Total treatment time: 55 s		Most of the right
hemisphere of the brain		Denity: 20 μl/kg−1
BG8774: 20 μl/kg−1
MSB4: 20 μl/kg−1		subharmonic and
bandwidth		Real-time closed-loopEnd of duration
Chien (2022)MiceFrequency: 1.5 MHz|
Pulse length: 6.7 ms		The brainstemDenity
8 × 108 Mbs/ml		SC level: sum spectrum magnitude at the third harmonic
IC level: sum spectrum magnitude at 3.3 ± 0.02 MHz		Real-time closed-loopEnd of duration
Chien (2022)PigsFrequency: 2.25 MHz
PRF: 1 Hz
Pulse length: 10 ms
Total treatment time: 180 s		The cortical
brain region		Denity
10 μl/kg−1		SC level: sum spectrum magnitude at the fourth harmonic
IC level: sum spectrum magnitude at 2.1 ± 0.02 MHz		Real-time closed-loopEnd of duration
Lee (2022)MiceFrequency: 1.64 MHz
PRF: 1 Hz
Pulse length: 10 ms		The entire tumor
and its periphery		Denity/10 μl/kg−1The third harmonic levelReal-time closed-loopEnd of duration
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